@article {3040926,
	title = {Homeostasis of mucosal glial cells in human gut is independent of microbiota},
	journal = {Sci Rep},
	volume = {11},
	year = {2021},
	month = {2021 Jun 17},
	pages = {12796},
	abstract = {In mammals, neural crest cells populate the gut and form the enteric nervous system (ENS) early in embryogenesis. Although the basic ENS structure is highly conserved across species, we show important differences between mice and humans relating to the prenatal and postnatal development of mucosal enteric glial cells (mEGC), which are essential ENS components. We confirm previous work showing that in the mouse mEGCs are absent at birth, and that their appearance and homeostasis depends on postnatal colonization by microbiota. In humans, by contrast, a network of glial cells is already present in the fetal gut. Moreover, in xenografts of human fetal gut maintained for months in immuno-compromised mice, mEGCs persist following treatment with antibiotics that lead to the disappearance of mEGCs from the gut of the murine host. Single cell RNAseq indicates that human and mouse mEGCs differ not only in their developmental dynamics, but also in their patterns of gene expression.},
	issn = {2045-2322},
	doi = {10.1038/s41598-021-92384-9},
	author = {Inlender, Timna and Nissim-Eliraz, Einat and Stavely, Rhian and Hotta, Ryo and Goldstein, Allan M and Yagel, Simcha and Gutnick, Michael J and Shpigel, Nahum Y}
}
@article {3040928,
	title = {Hyperinflammation evokes different antiviral TMPRSS2 and ADAM17 expression responses in human gut xenograft versus host mouse gut although overall genomic responses are similar},
	journal = {bioRxiv},
	year = {2021},
	month = {2021/01/01},
	pages = {2021.05.09.443289},
	abstract = {The global spread of the newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the pandemic outbreak of coronavirus disease 2019 (COVID-19), an inflammatory disease that is primarily affecting the respiratory system. However, gastrointestinal symptoms in COVID-19 patients suggests that the gut may present another viral target organ. Disease development and severity is dependent on viral interaction with two cell surface human proteins, ACE2 and TMPRSS2, and on antiviral response which may lead to systemic hyperinflammatory syndrome and multiorgan dysfunction. Understanding the host response to SARS-CoV-2 infection and the pathology of the disease will be greatly enhanced by the development of appropriate animal models. Laboratory mice have been the mainstay of therapeutic and vaccine development, however, the virus does not grow in wild type mice and only induced mild disease in transgenic animals expressing human ACE2. As there are known differences between immune response in laboratory mice and humans we evaluated the response of human gut developed as xenografts and host mouse gut following systemic LPS injections as a hyperinflammation model system. The orthologous gene expression levels in the mouse and human gut were highly correlated (Spearman{\textquoteright}s rank correlation coefficient: 0.28{\textendash}0.76) and gene set enrichment analysis of significantly upregulated human and mouse genes revealed that a number of inflammatory and immune response pathways are commonly regulated in the two species. However, species differences were also observed, most importantly, in the inflamed human gut but not in the mouse gut, there was clear upregulation of mRNAs coding for TMPRSS2, ADAM17 and for RIG-I-like receptors, which are involved in the recognition of viruses and in antiviral innate immune response. Moreover, using species-specific immunofluorescence microscopy, we demonstrated the expression and localization of human ACE2 and TMPRSS2 proteins, which are essential elements of the molecular machinery that enables SARS-CoV-2 to infect and replicate in human gut cells. Our findings demonstrate that the intestinal immune response to inflammation in humans and mice are generally very similar. However, certain human-specific diseases, such as COVID-19, can only be successfully studied in an experimental model of human tissue, such as the gut xenograft.Competing Interest StatementThe authors have declared no competing interest.},
	url = {http://biorxiv.org/content/early/2021/05/10/2021.05.09.443289.abstract},
	author = {Morris, Lorna and Einat Nisim-Eliraz, and Schouten, Iftach and Fran{\c c}ois Bergey, and Nigel Dyer, and Hiroshi Momiji, and Nir, Eilam and Marsiano, Noga and Raheleh Sheibani Tezerji, and Yagel, Simcha and Rosenstiel, Philip and Rand, David and dos Santos, Vitor A.P. Martins and Shpigel, Nahum Y. and ,}
}
@article {3040927,
	title = {NF-kappa-B activation unveils the presence of inflammatory hotspots in human gut xenografts},
	journal = {PLoS One},
	volume = {16},
	year = {2021},
	month = {2021},
	pages = {e0243010},
	abstract = {The single-epithelial cell layer of the gut mucosa serves as an essential barrier between the host and luminal microflora and plays a major role in innate immunity against invading pathogens. Nuclear factor kB (NF-κB), a central component of the cellular signaling machinery, regulates immune response and inflammation. NF-κB proteins are activated by signaling pathways downstream to microbial recognition receptors and cytokines receptors. Highly regulated NF-κB activity in intestinal epithelial cells (IEC) is essential for normal gut homeostasis; dysregulated activity has been linked to a number of disease states, including inflammatory bowel diseases (IBD) such as Crohn{\textquoteright}s Disease (CD). Our aim was to visualize and quantify spatial and temporal dynamics of NF-κB activity in steady state and inflamed human gut. Lentivirus technology was used to transduce the IEC of human gut xenografts in SCID mice with a NF-κB luminescence reporter system. NF-κB signaling was visualized and quantified using low resolution, intravital imaging of the whole body and high resolution, immunofluorescence microscopic imaging of the tissues. We show that NF-κB is activated in select subset of IEC with low "leaky" NF-κB activity. These unique inflammatory epithelial cells are clustered in the gut into discrete hotspots of NF-κB activity that are visible in steady state and selectively activated by systemic LPS and human TNFα or luminal bacteria. The presence of inflammatory hotspots in the normal and inflamed gut might explain the patchy mucosal lesions characterizing CD and thus could have important implications for diagnosis and therapy.},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0243010},
	author = {Nissim-Eliraz, Einat and Nir, Eilam and Marsiano, Noga and Yagel, Simcha and Shpigel, Nahum Y}
}
@article {764333,
	title = {NF-kappa-B activation unveils the presence of inflammatory hotspots in human gut xenografts},
	journal = {bioRxiv},
	year = {2020},
	pages = {2020.07.23.212621},
	abstract = {The single-epithelial cell layer of the gut mucosa serves as an essential barrier between the host and luminal microflora and plays a major role in innate immunity against invading pathogens. Nuclear factor kB (NF-kB), a central component of the cellular signaling machinery, regulates immune response and inflammation. NF-kB proteins are activated by signaling pathways downstream to microbial recognition receptors and cytokines receptors. Highly regulated NF-kB activity in intestinal epithelial cells (IEC) is essential for normal gut homeostasis; dysregulated activity has been linked to a number of disease states, including inflammatory bowel diseases (IBD) such as Crohns Disease (CD). Our aim was to visualize and quantify spatial and temporal dynamics of NF-kB activity in steady state and inflamed human gut. Lentivirus technology was used to transduce the IEC of human gut xenografts in SCID mice with a NF-kB luminescence reporter system. NF-kB signaling was visualized and quantified using low resolution, intravital imaging of the whole body and high resolution, immunofluorescence microscopic imaging of the tissues. We show that NF-kB is activated in select subset of IEC with low leaky NF-kB activity. These unique inflammatory epithelial cells are clustered in the gut into discrete hotspots of NF-kB activity that are visible in steady state and selectively activated by systemic LPS and human TNFa; or luminal bacteria. The presence of inflammatory hotspots in the normal and inflamed gut might explain the patchy mucosal lesions characterizing CD and thus could have important implications for diagnosis and therapy.Competing Interest StatementThe authors have declared no competing interest.},
	doi = {10.1101/2020.07.23.212621},
	url = {https://www.biorxiv.org/content/biorxiv/early/2020/07/24/2020.07.23.212621.full.pdf},
	author = {Nissim-Eliraz, Einat and Nir, Eilam and Marsiano, Noga and Yagel, Simcha and Shpigel, Nahum Y}
}
@article {241017,
	title = {Homeostasis of Mucosal Glial Cells in Human Gut is Independent of Microbiota},
	journal = {NEURON-D-20-00496. Available at SSRN: https://ssrn.com/abstract=3564977 or http://dx.doi.org/10.2139/ssrn.3564977},
	year = {2020},
	author = {Inlender T. Nissim-Eliraz E. Stavely R. Hotta R. Goldstein A.M. Yagel S. Gutnick M.J. Shpigel N.Y.}
}
@article {764335,
	title = {The role of O-polysaccharide chain and complement resistance of Escherichia coli in mammary virulence},
	journal = {Vet Res},
	volume = {51},
	year = {2020},
	month = {2020},
	pages = {77},
	abstract = {Mastitis, inflammation of the mammary gland, is a common disease of dairy animals. The disease is caused by bacterial infection ascending through the teat canal and mammary pathogenic Escherichia coli (MPEC) are common etiology. In the first phase of infection, virulence mechanisms, designated as niche factors, enable MPEC bacteria to resist innate antimicrobial mechanisms, replicate in milk, and to colonize the mammary gland. Next, massive replication of colonizing bacteria culminates in a large biomass of microbe-associated molecular patterns (MAMPs) recognized by pattern recognition receptors (PRRs) such as toll-like receptors (TLRs) mediating inflammatory signaling in mammary alveolar epithelial cells (MAEs) and macrophages. Bacterial lipopolysaccharides (LPSs), the prototypical class of MAMPs are sufficient to elicit mammary inflammation mediated by TLR4 signaling and activation of nuclear factor kB (NF-kB), the master regulator of inflammation. Using in vivo mastitis model, in low and high complements mice, and in vitro NF-kB luminescence reporter system in MAEs, we have found that the smooth configuration of LPS O-polysaccharides in MPEC enables the colonizing organisms to evade the host immune response by reducing inflammatory response and conferring resistance to complement. Screening a collection of MPEC field strains, we also found that all strains were complement resistant and 94\% (45/48) were smooth. These results indicate that the structure of LPS O-polysaccharides chain is important for the pathogenesis of MPEC mastitis and provides protection against complement-mediated killing. Furthermore, we demonstrate a role for complement, a key component of innate immunity, in host-microbe interactions of the mammary gland.},
	isbn = {1297-9716},
	url = {https://doi.org/10.1186/s13567-020-00804-x},
	author = {Salamon, Hagit and Nissim-Eliraz, Einat and Ardronai, Oded and Nissan, Israel and Shpigel, Nahum Y.}
}
@article {74817,
	title = {Correction of Defective T-regulatory Cells From Patients With Crohn{\textquoteright}s Disease by Ex Vivo Ligation of Retinoic Acid Receptor Alpha.},
	journal = {Gastroenterology},
	year = {2019},
	month = {2019 Jan 17},
	abstract = {BACKGROUND \& AIMS: Crohn{\textquoteright}s disease (CD) is characterized by an imbalance of effector and regulatory T cells in the intestinal mucosa. The efficacy of anti-adhesion therapies led us to investigate whether impaired trafficking of T-regulatory (Treg) cells contributes to the pathogenesis of CD. We also investigated whether proper function could be restored to Treg cells by ex vivo expansion in the presence of factors that activate their regulatory activities.

METHODS: We measured levels of the integrin α4β7 on Treg cells isolated from peripheral blood or lamina propria of patients with CD and healthy individuals (controls). Treg cells were expanded ex vivo and incubated with rapamycin with or without agonists of the retinoic acid receptor alpha (RARA) and their gene expression profiles were analyzed. We also studied the cells in cytokine challenge, suppression, and flow chamber assays and in SCID mice with human intestinal xenografts.

RESULTS: We found that Treg cells from patients with CD express lower levels of the integrin α4β7 than Treg cells from control patients. The pathway that regulates expression of integrin subunit alpha is induced by retinoic acid (RA). Treg cells from patients with CD incubated with rapamycin and an agonist of RARA (RAR568) expressed high levels of integrin α4β7, as well as CD62L and FOXP3, compared to cells incubated with rapamycin or rapamycin and ATRA. These Treg cells had increased suppressive activities in assays and migrated under conditions of shear flow; they did not produce inflammatory cytokines and RAR568 had no effect on cell stability or lineage commitment. Fluorescently labelled Treg cells incubated with RAR568 were significantly more likely to traffic to intestinal xenografts than Treg cells expanded in control medium.

CONCLUSIONS: Treg cells from patients with CD express lower levels of the integrin α4β7 than Treg cells from control patients. Incubation of patients{\textquoteright} ex vivo expanded Treg cells with rapamycin and an RARA agonist induced expression of α4β7 and had suppressive and migratory activities in culture and in intestinal xenografts in mice. These cells might be developed for treatment of CD. clinicaltrials.gov no: NCT03185000.},
	issn = {1528-0012},
	doi = {10.1053/j.gastro.2019.01.025},
	author = {Goldberg, Rimma and Scotta, Cristiano and Cooper, Dianne and Nissim-Eliraz, Einat and Nir, Eilam and Tasker, Scott and Irving, Peter M and Sanderson, Jeremy and Lavender, Paul and Ibrahim, Fowzia and Corcoran, Jonathan and Prevost, Toby and Shpigel, Nahum Y and Marelli-Berg, Federica and Lombardi, Giovanna and Lord, Graham M}
}
@article {88718,
	title = {Intraepithelial neutrophils in mammary, urinary and gall bladder infections},
	journal = {Vet Res},
	volume = {50},
	year = {2019},
	month = {2019 Jul 19},
	pages = {56},
	abstract = {Neutrophil mobilization is a crucial response to protect the host against invading microorganisms. Neutrophil recruitment and removal have to be tightly regulated to prevent uncontrolled inflammation and excessive release of their toxic content causing tissue damage and subsequent organ dysfunctions. We show here the presence of live and apoptotic neutrophils in the cytoplasm of inflamed mammary, urinary and gall bladder epithelial cells following infection with E. coli and Salmonella bacteria. The entry process commenced with adherence of transmigrated neutrophils to the apical membrane of inflamed epithelial cells. Next, nuclear rearrangement and elongation associated with extensive actin polymerization enabled neutrophils to crawl and invaginate the apical membrane into cytoplasmic double membrane compartments. Scission of the invaginated cell membrane from the entry point and loss of these surrounding membranes released intracellular neutrophils into the cytoplasm where they undergone apoptotic death. The co-occurrence of this observation with bacterial invasion and formation of intracellular bacterial communities (IBCs) might link entry of infected neutrophils to the formation of IBCs and chronic carriage in E. coli mastitis and cystitis and Salmonella cholecystitis.},
	issn = {1297-9716},
	doi = {10.1186/s13567-019-0676-5},
	author = {Mintz, Dvir and Salamon, Hagit and Mintz, Michal and Rosenshine, Ilan and Shpigel, Nahum Y}
}
@article {62842,
	title = {Microbial communities and inflammatory response in the endometrium differ between normal and metritic dairy cows at 5-10 days post-partum},
	journal = {Vet ResVet Res},
	volume = {49},
	number = {1},
	year = {2018},
	note = {Sicsic, RonGoshen, TamirDutta, RahulKedem-Vaanunu, NoaKaplan-Shabtai, VeronicaPasternak, ZoharGottlieb, YuvalShpigel, Nahum YRaz, Taleng668-0093-10/The Israel Dairy Board Fund/International705-0064-14/The Israel Dairy Board Fund/InternationalResearch Support, Non-U.S. Gov{\textquoteright}tEngland2018/08/03 06:00Vet Res. 2018 Aug 2;49(1):77. doi: 10.1186/s13567-018-0570-6.},
	month = {Aug 2},
	pages = {77},
	abstract = {Post-partum metritis is among the most prevalent disease in dairy cows affecting animal welfare and inflicting considerable economic loses. While post-partum contamination of the uterus is rife in dairy cows, only a fraction of these animals will develop metritis. Our main objective was to compare the bacterial communities and the inflammatory response in the endometrium of healthy and metritic dairy cows. Holstein-Friesian cows (n = 35) were sampled immediately following clinical classification as healthy (n = 21), suffering from metritis (n = 13) or septic metritis (n = 1), based on veterinary examination at 5-10 days post-partum. Polymorphonuclear cells (PMN) percentage in endometrial cytology was significantly higher in cows with metritis. Full-thickness uterine biopsy analysis revealed that the luminal epithelium in inter-caruncle areas was preserved in healthy cows, but in metritis it was compromised, with marked PMN infiltration particularly in the apical endometrium. Gram staining revealed that bacterial load and spatial distribution was associated with disease severity. 16S-rDNA bacterial community analysis revealed unique endometrial bacterial community composition in metritic cows, as compared to more diverse communities among healthy cows. The most abundant phyla in healthy cows were Proteobacteria (31.8 +/- 9.3\%), Firmicutes (27.9 +/- 8.4\%) and Bacteroidetes (19.7 +/- 7.2\%), while Bacteroidetes (60.3 +/- 10.3\%), Fusobacteria (13.4 +/- 5.9\%) and Firmicutes (10.5 +/- 3.3\%) were most abundant in the endometrial mucosa of metritic cows. Relative abundance of Bacteroidetes (19.7 +/- 7.2\% vs. 60.3 +/- 10.3\%), Fusobacteria (7.5 +/- 5.2\% vs. 13.4 +/- 5.9\%) and Proteobacteria (31.8 +/- 9.3\% vs. 7.3 +/- 5.6\%) phyla differed significantly between healthy and metritic cows. In summary, endometrial PMN abundance, spatial distribution and bacterial communities differed between healthy and metritic dairy cows at early post-partum.},
	isbn = {1297-9716 (Electronic)0928-4249 (Linking)},
	author = {Sicsic, R. and Goshen, T. and Dutta, R. and Kedem-Vaanunu, N. and Kaplan-Shabtai, V. and Pasternak, Z. and Gottlieb, Y. and Shpigel, N. Y. and Raz, T.}
}
@article {72714,
	title = {Transplantation of Human Intestine into the Mouse: A Novel Platform for Study of Inflammatory Enterocutaneous Fistulas.},
	journal = {J Crohns Colitis},
	year = {2018},
	month = {2018 Dec 24},
	abstract = {Background and Aims: Enteric fistulas represent a severe and medically challenging co-morbidity commonly affecting Crohn{\textquoteright}s disease [CD] patients. Gut fistulas do not develop in animal models of the disease. We have used transplantation of the human fetal gut into mice as a novel platform for studying inflammatory enterocutaneous fistulas.

Methods: Human fetal gut segments were transplanted subcutaneously into mature SCID mice, where they grew and fully developed over the course of several months. We first analyzed the resident immune cells and inflammatory response elicited by systemic LPS in normal, fully developed human gut xenografts. Thereafter, we used immunostaining to analyze fully-developed xenografts that spontaneously developed enterocutaneous fistulas.

Results: Resident human innate and adaptive immune cells were demonstrated in gut xenografts during steady state and inflammation. The expression of human IL-8, IL-1β, IL-6, TNF-α, A20 and IkBα was significantly elevated in response to LPS with no change in IL-10 gene expression. Approximately 17\% [19/110] of fully developed subcutaneous human gut xenografts spontaneously developed enterocutaneous fistulas revealing striking histopathological similarities with CD fistula specimens. Immunohistochemical analyses of fistulating xenografts revealed transmural lymphocytic enteritis associated with massive expansion of resident human CD4 + lymphocytes and their migration into the intraepithelial compartment. Regionally, mucosal epithelial cells assumed spindle-shaped mesenchymal morphology and formed fistulous tracts towards chronic non-healing wounds in the host mouse skin overlying the transplants.

Conclusions: Inflammation and fistulas developed in human gut xenografts lacking IL-10 gene response. This novel model system will enable systematic studies of the inflamed and fistulating human gut in live animals.},
	issn = {1876-4479},
	doi = {10.1093/ecco-jcc/jjy226},
	author = {Bruckner, Ramona S and Nissim-Eliraz, Einat and Marsiano, Noga and Nir, Eilam and Shemesh, Hadar and Leutenegger, Martin and Gottier, Claudia and Lang, Silvia and Spalinger, Marianne R and Leibl, Sebastian and Rogler, Gerhard and Yagel, Simcha and Scharl, Michael and Shpigel, Nahum Y}
}
@article {62788,
	title = {Xenotransplantation of human intestine into mouse abdomen or subcutaneous tissue: Novel platforms for the study of the human enteric nervous system},
	journal = {Neurogastroenterol MotilNeurogastroenterol Motil},
	volume = {30},
	number = {3},
	year = {2018},
	note = {Nagy, NMarsiano, NBruckner, R SScharl, MGutnick, M JYagel, SArciero, EGoldstein, A MShpigel, N YengR01 DK103785/DK/NIDDK NIH HHS/England2017/09/09 06:00Neurogastroenterol Motil. 2018 Mar;30(3). doi: 10.1111/nmo.13212. Epub 2017 Sep 8.},
	month = {Mar},
	abstract = {BACKGROUND: Current efforts to develop stem cell therapy as a novel treatment for neurointestinal diseases are limited by the unavailability of a model system to study cell transplantation in the human intestine. We propose that xenograft models support enteric nervous system (ENS) development in the fetal human intestine when transplanted into mice subcutaneously or intra-abdominally. METHODS: Fetal human small and large intestine were grafted onto the small intestinal mesentery and into the subcutaneous tissue of immunodeficient mice for up to 4 months. Intestinal cytoarchitecture and ENS development were studied using immunohistochemistry. KEY RESULTS: In both abdominal and subcutaneous grafts, the intestine developed normally with formation of mature epithelial and mesenchymal layers. The ENS was patterned in two ganglionated plexuses containing enteric neurons and glia, including cholinergic and nitrergic neuronal subtypes. c-Kit-immunoreactive interstitial cells of Cajal were present in the gut wall. CONCLUSIONS \& INFERENCES: Abdominal xenografts represent a novel model that supports the growth and development of fetal human intestine. This in vivo approach will be a useful method to study maturation of the ENS, the pathophysiology of neurointestinal diseases, and the long-term survival and functional differentiation of neuronal stem cells for the treatment of enteric neuropathies.},
	keywords = {enteric nervous system, enteric neuropathies, fetal human intestine, xenotransplant},
	isbn = {1365-2982 (Electronic)1350-1925 (Linking)},
	author = {Nagy, N. and Marsiano, N. and Bruckner, R. S. and Scharl, M. and Gutnick, M. J. and Yagel, S. and Arciero, E. and Goldstein, A. M. and Shpigel, N. Y.}
}
@article {62789,
	title = {Characterization and identification of microbial communities in bovine necrotic vulvovaginitis},
	journal = {The Veterinary JournalThe Veterinary Journal},
	volume = {219},
	year = {2017},
	month = {1//},
	pages = {34-39},
	abstract = {Bovine necrotic vulvovaginitis (BNVV) is a severe and potentially fatal disease of post-partum cows that emerged in Israel after large dairy herds were merged. While post-partum cows are commonly affected by mild vulvovaginitis (BVV), in BNVV these benign mucosal abrasions develop into progressive deep necrotic lesions leading to sepsis and death if untreated. The etiology of BNVV is still unknown and a single pathogenic agent has not been found. We hypothesized that BNVV is a polymicrobial disease where the normally benign vaginal microbiome is remodeled and affects the local immune response. To this end, we compared the histopathological changes and the microbial communities using 16S rDNA metagenetic technique in biopsies taken from vaginal lesions in post-partum cows affected by BVV and BNVV. The hallmark of BNVV was the formation of complex polymicrobial communities in the submucosal fascia and abrogation of neutrophil recruitment in these lesions. Additionally, there was a marked difference in the composition of bacterial communities in the BNVV lesions in comparison to the benign BVV lesions. This difference was characterized by the abundance of Bacteroidetes and lower total community membership in BNVV. Indicator taxa for BNVV were Parvimonas, Porphyromonas, unclassified Veillonellaceae, Mycoplasma and Bacteroidetes, whereas unclassified Clostridiales was an indicator for BVV. The results support a polymicrobial etiology for BNVV.},
	keywords = {16S metagenetics, Dairy cows, Microbiome, Neutrophils, Vaginitis},
	isbn = {1090-0233},
	author = {Shpigel, N. Y. and Adler-Ashkenazy, L. and Scheinin, S. and Goshen, T. and Arazi, A. and Pasternak, Z. and Gottlieb, Y.}
}
@article {62792,
	title = {New Human Gut Xenograft Mouse Model for Intestinal Fistulas},
	journal = {GastroenterologyGastroenterology},
	volume = {152},
	number = {5},
	year = {2017},
	month = {2017/04/01/},
	pages = {S784},
	isbn = {0016-5085},
	author = {Bruckner, Ramona and Marsiano, Noga and Nissim-Eliraz, Einat and Nir, Eilam and Lang, Silvia and Spalinger, Marianne and Rogler, Gerhard and Yagel, Simcha and Scharl, Michael M. and Shpigel, Nahum Y.}
}
@article {62791,
	title = {OP028 Gut specific regulatory T cells {\textendash} a new frontier for Crohn{\textquoteright}s disease therapy},
	journal = {Journal of Crohn{\textquoteright}s and ColitisJournal of Crohn{\textquoteright}s and Colitis},
	volume = {11},
	number = {suppl_1},
	year = {2017},
	note = {10.1093/ecco-jcc/jjx002.027},
	pages = {S17-S17},
	abstract = {Background: We have recently shown that Tregs isolated from the peripheral blood of patients with Crohn{\textquoteright}s Disease (CD) play a critical role in controlling both phenotype and expansion of auto-reactive T cells (1). This is a critical step to developing cell based therapy for Crohn{\textquoteright}s disease, where where primary and secondary non response rates to biologics remain unacceptably high. The immune system used retinoic acid (ATRA) to induce a4b7 and thus prime Tregs to home to the gut. We sought use ATRA in-vitro in order to engineer gut specific Tregs for our Phase 1 trial in Crohn{\textquoteright}s Disease. We then validated our findings in-vitro and in-vivo.Methods: Tregs were isolated from peripheral blood of CD patients. ATRA supplementation was tested in standard culture conditions. The expression of a4b7 was assessed by flow cytometry. Suppression assays were performed using autologous effector T cells (Teff). An ibidi flow chamber system coated with recombinant human MAdCAM-1 was used for in-vitro trafficking experiments. SCID mice xenografted with foetal intestinal small bowel were used for in-vivo experiments. Parametric and non-parametric data were calculated as the mean {\textpm} s.d. and median (IQR). For comparison of parametric and non-parametric data, t-test, or ANOVA were used.Results:Ex-vivo expansion of Tregs in the presence of ATRA significantly induced the expression of a4b7 compared to Rapamycin alone (5.57\%{\textpm}3.12 vs 82.8\%{\textpm}9.5, p=0.0057) Cells treated with Rapa+ATRA maintained their superior suppressive ability compared to Rapamycin treated Tregs (95.8\%{\textpm}3.5\% vs 91.15\%{\textpm}10.1\% p=ns; at Treg:Teff 1:1 ratio). RAPA+ATRA Tregs did not produce IFNy or IL17 under pro-inflammatory cytokine challenge. When flowed through a MAdCAm-1 coated chamber, significantly higher numbers of Rapa+ATRA treated cells were observed to roll (Rapa 0.83{\textpm}0.40 vs Rapa+ATRA 10.17{\textpm}2.54 p=0.005), crawl (Rapa 0 vs Rapa+ATRA 4{\textpm}0.89 p=0.001) and firmly adhere (Rapa 0.33{\textpm}0.21 vs Rapa+ATRA 36.8{\textpm}1.78, p\&lt;0.001) than those treated with Rapa alone. When Tregs were transferred into mice, a higher proportion of Tregs were found in xenografts of animals treated with Rapa+ATRA Tregs compared Rapa Tregs (12.10 (7.54{\textendash}22.83) vs 4.97 (1.72{\textendash}7.63), p=0.0056). Importantly there was a higher proportion of Tregs in inflamed xenografts of animals treated with Rapa+ATRA Tregs compared to those treated with Rapa Tregs (18.35 (12.95{\textendash}28.63) vs 6.78 (2.65{\textendash}9.61), p=0.0095).Conclusions: The addition of ATRA to Treg culture in-vitro confers a gut homing phenotype. This is functionally relevant in-vitro and in-vivo. The treatment maintains the highly suppressive and phenotypically stable phenotype of these cells. These gut specific Tregs will be implemented in our first in man trial Treg therapy for Crohn{\textquoteright}s disease.},
	isbn = {1873-9946},
	author = {Goldberg, R. and Scotta, C. and Cooper, D. and Eliraz, E. and Nir, E. and Irving, P. and Sanderson, J. and Shpigel, N. and Marelli-Berg, F. and Lombardi, G. and Lord, G.}
}
@article {62790,
	title = {T3SS-dependent microvascular thrombosis and ischemic enteritis in human gut xenografts infected with enteropathogenic Escherichia coli},
	journal = {Infect ImmunInfect Immun},
	year = {2017},
	note = {Nissim-Eliraz, EinatNir, EilamShoval, IritMarsiano, NogaNissan, IsraelShemesh, HadarNagy, NandorGoldstein, Allan MGutnick, MichaelRosenshine, IlanYagel, SimchaShpigel, Nahum Yeng2017/08/09 06:00Infect Immun. 2017 Aug 7. pii: IAI.00558-17. doi: 10.1128/IAI.00558-17.},
	month = {Aug 07},
	abstract = {Enteropathogenic Escherichia coli (EPEC) is a leading cause of severe intestinal disease and infant mortality in developing countries. Virulence is mediated by a type three secretion system (T3SS) causing the hallmark lesions of attaching and effacing (AE) and actin-rich pedestal formation beneath the infecting bacteria on the apical surface of enterocytes. EPEC is a human-specific pathogen whose pathogenesis cannot be studied in animal models. We therefore established an EPEC infection model in human gut xenografts in SCID mice and used it to study the role of T3SS in the pathogenesis of the disease. Following EPEC O127:H6 strain E2348/69 infection, T3SS-dependent AE lesions and pedestals were demonstrated in all infected xenografts. We report here the development of T3SS-dependent intestinal thrombotic microangiopathy (iTMA) and ischemic enteritis in approximately 50\% of infected human gut xenografts. Using species-specific CD31 immunostaining, we showed that iTMA was limited to the larger human-mouse chimeric blood vessels which are located between the muscularis mucosa and circular muscular layer of the human gut. These blood vessels were massively invaded by bacteria which adhered to and formed pedestals on endothelial cells and aggregated with mouse neutrophils in the lumen. We conclude that endothelial infection, iTMA and ischemic enteritis might be central mechanisms underlying severe EPEC-mediated disease.},
	isbn = {1098-5522 (Electronic)0019-9567 (Linking)},
	author = {Nissim-Eliraz, E. and Nir, E. and Shoval, I. and Marsiano, N. and Nissan, I. and Shemesh, H. and Nagy, N. and Goldstein, A. M. and Gutnick, M. and Rosenshine, I. and Yagel, S. and Shpigel, N. Y.}
}
@article {62795,
	title = {Developing in vitro expanded CD45RA+ regulatory T cells as an adoptive cell therapy for Crohn{\textquoteright}s disease},
	journal = {GutGut},
	volume = {65},
	number = {4},
	year = {2016},
	note = {Canavan, James BScotta, CristianoVossenkamper, AnnaGoldberg, RimmaElder, Matthew JShoval, IritMarks, EllenStolarczyk, EmilieLo, Jonathan WPowell, NickFazekasova, HenrietaIrving, Peter MSanderson, Jeremy DHoward, Jane KYagel, SimchaAfzali, BehdadMacDonald, Thomas THernandez-Fuentes, Maria PShpigel, Nahum YLombardi, GiovannaLord, Graham MENG88245/Medical Research Council/United KingdomG0802068/Medical Research Council/United KingdomRG/13/12/30395/British Heart Foundation/United KingdomMR/J006742/1/Medical Research Council/United KingdomMR/K025538/1/Medical Research Council/United KingdomG0801537/ID/Medical Research Council/United KingdomMR/M003493/1/Medical Research Council/United KingdomWT088747MA/Wellcome Trust/United KingdomMR/K002996/1/Medical Research Council/United KingdomG0801537/Medical Research Council/United Kingdom091009/Wellcome Trust/United KingdomResearch Support, Non-U.S. Gov{\textquoteright}tEngland2015/02/26 06:00Gut. 2016 Apr;65(4):584-94. doi: 10.1136/gutjnl-2014-306919. Epub 2015 Feb 24.},
	month = {Apr},
	pages = {584-94},
	abstract = {BACKGROUND AND AIM: Thymus-derived regulatory T cells (Tregs) mediate dominant peripheral tolerance and treat experimental colitis. Tregs can be expanded from patient blood and were safely used in recent phase 1 studies in graft versus host disease and type 1 diabetes. Treg cell therapy is also conceptually attractive for Crohn{\textquoteright}s disease (CD). However, barriers exist to this approach. The stability of Tregs expanded from Crohn{\textquoteright}s blood is unknown. The potential for adoptively transferred Tregs to express interleukin-17 and exacerbate Crohn{\textquoteright}s lesions is of concern. Mucosal T cells are resistant to Treg-mediated suppression in active CD. The capacity for expanded Tregs to home to gut and lymphoid tissue is unknown. METHODS: To define the optimum population for Treg cell therapy in CD, CD4(+)CD25(+)CD127(lo)CD45RA(+) and CD4(+)CD25(+)CD127(lo)CD45RA(-) Treg subsets were isolated from patients{\textquoteright} blood and expanded in vitro using a workflow that can be readily transferred to a good manufacturing practice background. RESULTS: Tregs can be expanded from the blood of patients with CD to potential target dose within 22-24 days. Expanded CD45RA(+) Tregs have an epigenetically stable FOXP3 locus and do not convert to a Th17 phenotype in vitro, in contrast to CD45RA(-) Tregs. CD45RA(+) Tregs highly express alpha4beta7 integrin, CD62L and CC motif receptor 7 (CCR7). CD45RA(+) Tregs also home to human small bowel in a C.B-17 severe combined immune deficiency (SCID) xenotransplant model. Importantly, in vitro expansion enhances the suppressive ability of CD45RA(+) Tregs. These cells also suppress activation of lamina propria and mesenteric lymph node lymphocytes isolated from inflamed Crohn{\textquoteright}s mucosa. CONCLUSIONS: CD4(+)CD25(+)CD127(lo)CD45RA(+) Tregs may be the most appropriate population from which to expand Tregs for autologous Treg therapy for CD, paving the way for future clinical trials.},
	keywords = {*Adoptive Transfer, Animals, Antigens, CD45/immunology, Cell- and Tissue-Based Therapy/*methods, Crohn Disease/immunology/*therapy, DNA Methylation, Enzyme-Linked Immunosorbent Assay, Forkhead Transcription Factors/genetics, Humans, Ibd, Ibd basic research, Ibd clinical, Immunotherapy, In Vitro Techniques, Interleukin-17/metabolism, Intestinal t cells, Mice, Mice, SCID, Phenotype, Polymerase Chain Reaction, T-Lymphocytes, Regulatory/*immunology, Transplantation, Heterologous},
	isbn = {1468-3288 (Electronic)0017-5749 (Linking)},
	author = {Canavan, J. B. and Scotta, C. and Vossenkamper, A. and Goldberg, R. and Elder, M. J. and Shoval, I. and Marks, E. and Stolarczyk, E. and Lo, J. W. and Powell, N. and Fazekasova, H. and Irving, P. M. and Sanderson, J. D. and Howard, J. K. and Yagel, S. and Afzali, B. and MacDonald, T. T. and Hernandez-Fuentes, M. P. and Shpigel, N. Y. and Lombardi, G. and Lord, G. M.}
}
@article {62793,
	title = {Genome-wide comparative transcriptome analysis of steady state and inflamed human and mouse gut},
	journal = {1st Conference of the European Association of System Medicine, 26th-28th October 2016 Berlin.1st Conference of the European Association of System Medicine, 26th-28th October 2016 Berlin.},
	year = {2016},
	author = {Shpigel N.Y., and Nigel Dyer, and Hiroshi Momiji, and Einat Nisim-Eliraz, and Nir, Eilam and Marsiano, Noga and Raheleh Sheibani Tezerji, and Fran{\c c}ois Bergey, and Alexander Kel,}
}
@article {62794,
	title = {Whole-Genome Draft Sequences of Six Commensal Fecal and Six Mastitis-Associated Escherichia coli Strains of Bovine Origin},
	journal = {Genome AnnouncGenome Announc},
	volume = {4},
	number = {4},
	year = {2016},
	note = {Leimbach, AndreasPoehlein, AnjaWitten, AnikaWellnitz, OlgaShpigel, NahumPetzl, WolframZerbe, HolmDaniel, RolfDobrindt, UlrichENG2016/07/30 06:00Genome Announc. 2016 Jul 28;4(4). pii: e00753-16. doi: 10.1128/genomeA.00753-16.},
	month = {Jul 28},
	abstract = {The bovine gastrointestinal tract is a natural reservoir for commensal and pathogenic Escherichia coli strains with the ability to cause mastitis. Here, we report the whole-genome sequences of six E. coli isolates from acute mastitis cases and six E. coli isolates from the feces of udder-healthy cows.},
	author = {Leimbach, A. and Poehlein, A. and Witten, A. and Wellnitz, O. and Shpigel, N. and Petzl, W. and Zerbe, H. and Daniel, R. and Dobrindt, U.}
}
@article {62798,
	title = {Comparison of the efficacy of Neethling lumpy skin disease virus and x10RM65 sheep-pox live attenuated vaccines for the prevention of lumpy skin disease - The results of a randomized controlled field study},
	journal = {VaccineVaccineVaccine},
	volume = {33},
	number = {38},
	year = {2015},
	note = {Ben-Gera, JKlement, EKhinich, EStram, YShpigel, N YengNetherlands2015/08/05 06:00Vaccine. 2015 Sep 11;33(38):4837-42. doi: 10.1016/j.vaccine.2015.07.071. Epub 2015 Aug 1.},
	month = {Sep 11},
	pages = {4837-42},
	abstract = {Lumpy skin disease (LSD) is a viral disease of cattle and buffalo, caused by a Capripox virus. A field study was performed during an LSD epidemic which occurred in 2012-2013 in Israel, in order to assess the efficacy of two commercial vaccines for protection against LSD. Fifteen dairy herds, vaccinated 2-5 months prior to study onset with a single dose of 10(2.5) TCID50 of RM65 attenuated sheep-pox vaccine, and not affected previously, were enrolled in the study. 4694 cows were randomized to be either vaccinated with a 10(3.5) TCID50/dose of RM65 vaccine (x10RM65) or with a same dose of an attenuated Neethling LSD virus vaccine. A case of LSD was defined as the appearance of at least 5 lesions typical to LSD and a severe case was defined if this sign was accompanied by either fever (>39.5 degrees C) or/and a 20\% reduction in milk production. Deep lesion biopsies and blood samples were collected from 64.5\% of the cases in an attempt to detect DNA of LSD virus by PCR and to differentiate between the wild strain and the vaccine Neethling strain. Seventy-six cows were affected by LSD in 8 herds with an incidence of 0.3-5.7\%. Mantel-Haenszel relative risk (RRMH) for LSD morbidity at least 15 days after vaccination in x10RM65 vs. Neethling was 2.635 (CI95\%=1.44-4.82) and 11.2 (2.3-54.7) for severe morbidity. RRMH for laboratory confirmed cases was 4.28 (1.59-11.53). An incidence of 0.38\% (9/2356) of Neethling associated disease was observed among Neethling vaccinated cows while no such disease occurred in x10RM65 vaccinated cows. We conclude that the Neethling vaccine is significantly more effective than x10RM65 in preventing LSD morbidity, though it might cause a low incidence of Neethling associated disease. No transmission of the Neethling strain to non-Neethling vaccinated cows was observed in this study.},
	isbn = {1873-2518 (Electronic)0264-410X (Linking)},
	author = {Ben-Gera, J. and Klement, E. and Khinich, E. and Stram, Y. and Shpigel, N. Y.}
}
@article {62796,
	title = {Diversity of Bacterial Biofilm Communities on Sprinklers from Dairy Farm Cooling Systems in Israel},
	journal = {PLoS OnePLoS OnePLoS One},
	volume = {10},
	number = {9},
	year = {2015},
	note = {Shpigel, Nahum YPasternak, ZoharFactor, GiladGottlieb, Yuvaleng2015/09/26 06:00PLoS One. 2015 Sep 25;10(9):e0139111. doi: 10.1371/journal.pone.0139111. eCollection 2015.},
	pages = {e0139111},
	abstract = {On dairy farms in hot climates worldwide, cows suffer from heat stress, which is alleviated by the use of water cooling systems. Sprinklers and showerheads are known to support the development of microbial biofilms, which can be a source of infection by pathogenic microorganisms. The aim of this study was to investigate the presence of microbial biofilms in dairy cooling systems, and to analyze their population compositions using culture-independent technique, 16S rRNA gene sequencing. Biofilm samples were collected on eight dairy farms from 40 sprinklers and the microbial constituents were identified by deep sequencing of the 16S rRNA gene. A total of 9,374 operational taxonomic units (OTUs) was obtained from all samples. The mean richness of the samples was 465 +/- 268 OTUs which were classified into 26 different phyla; 76\% of the reads belonged to only three phyla: Proteobacteria, Actinobacteria and Firmicutes. Although the most prevalent OTUs (Paracoccus, Methyloversatilis, Brevundimonas, Porphyrobacter, Gp4, Mycobacterium, Hyphomicrobium, Corynebacterium and Clostridium) were shared by all farms, each farm formed a unique microbial pattern. Some known potential human and livestock pathogens were found to be closely related to the OTUs found in this study. This work demonstrates the presence of biofilm in dairy cooling systems which may potentially serve as a live source for microbial pathogens.},
	isbn = {1932-6203 (Electronic)1932-6203 (Linking)},
	author = {Shpigel, N. Y. and Pasternak, Z. and Factor, G. and Gottlieb, Y.}
}
@article {62797,
	title = {Identification of pluripotent cells in bovine uterus: in situ and in vitro studies},
	journal = {ReproductionReproduction},
	volume = {149},
	number = {4},
	year = {2015},
	note = {Lupicka, MartynaBodek, GabrielShpigel, NahumElnekave, EhudKorzekwa, Anna JengResearch Support, Non-U.S. Gov{\textquoteright}tEngland2015/01/04 06:00Reproduction. 2015 Apr;149(4):317-27. doi: 10.1530/REP-14-0348. Epub 2015 Jan 2.},
	month = {Apr},
	pages = {317-27},
	abstract = {The aim of this study was to identify uterine pluripotent cells both in bovine uterine tissues as well in epithelial, stromal, and myometrial uterine cell populations. Moreover, the relationship of pluripotent markers expression with age and the uterine horn side was considered. Uterine tissue was collected from ipsilateral and contralateral horns (days 8-10 of the estrous cycle). Immunohistostaining for C-KIT, OCT3/4, NANOG, and SOX2 in uterine tissue was determined. mRNA expression of C-KIT, OCT3/4, NANOG and SOX2 was evaluated in uterine tissue relative to the age of the cow and uterine horn side. Gene and protein expression of these markers in the uterine luminal epithelial, stromal, and myometrial cells was evaluated by real-time PCR and western blotting respectively. The expression of pluripotent cell markers OCT3/4, NANOG, and SOX2 was identified by flow cytometry assay in epithelial, stromal, and myometrial cells. Multilineage differentiation of the bovine uterine cells was performed. mRNA expression of OCT3/4, NANOG, and SOX2 in uterine tissue was higher in the ipsilateral horn than in the contralateral horn. Flow cytometry assay revealed positive fluorescence for OCT3/4, NANOG, and SOX2 in all uterine cell types. Results showed the age-dependent expression of pluripotent markers in uterine tissue. Beside, the different expression of pluripotent cells in each horn of uterus suggests the influence of ovarian hormones on these characteristics. The highest mRNA and protein expression for pluripotent markers was observed in stromal cells among uterine cells, which indicates this population of cells as the main site of pluripotent cells in the cow uterus.},
	keywords = {*Cell Differentiation, *Cell Lineage, *Gene Expression Regulation, Developmental, Animals, Biomarkers/*metabolism, Blotting, Western, Cattle, Cells, Cultured, Enzyme-Linked Immunosorbent Assay, Female, Immunoenzyme Techniques, Pluripotent Stem Cells/*cytology/metabolism, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, RNA, Messenger/genetics, Uterus/*cytology/metabolism},
	isbn = {1741-7899 (Electronic)1470-1626 (Linking)},
	author = {Lupicka, M. and Bodek, G. and Shpigel, N. Y. and Elnekave, E. and Korzekwa, A. J.}
}
@article {62799,
	title = {Generation and screening of a comprehensive Mycobacterium avium subsp. paratuberculosis transposon mutant bank},
	journal = {Front Cell Infect MicrobiolFront Cell Infect MicrobiolFront Cell Infect Microbiol},
	volume = {4},
	year = {2014},
	note = {Rathnaiah, GovardhanLamont, Elise AHarris, N BethFenton, Robert JZinniel, Denise KLiu, XiaofeiSotos, JoshFeng, ZhengyuLivneh-Kol, AyalaShpigel, Nahum YCzuprynski, Charles JSreevatsan, SrinandBarletta, Raul GengResearch Support, U.S. Gov{\textquoteright}t, Non-P.H.S.Switzerland2014/11/02 06:00Front Cell Infect Microbiol. 2014 Oct 15;4:144. doi: 10.3389/fcimb.2014.00144. eCollection 2014.},
	pages = {144},
	abstract = {Mycobacterium avium subsp. paratuberculosis (MAP) is the etiologic agent of Johne{\textquoteright}s Disease in ruminants. This enteritis has significant economic impact and worldwide distribution. Vaccination is one of the most cost effective infectious disease control measures. Unfortunately, current vaccines reduce clinical disease and shedding, but are of limited efficacy and do not provide long-term protective immunity. Several strategies have been followed to mine the MAP genome for virulence determinants that could be applied to vaccine and diagnostic assay development. In this study, a comprehensive mutant bank of 13,536 MAP K-10 Tn5367 mutants (P > 95\%) was constructed and screened in vitro for phenotypes related to virulence. This strategy was designated to maximize identification of genes important to MAP pathogenesis without relying on studies of other mycobacterial species that may not translate into similar effects in MAP. This bank was screened for mutants with colony morphology alterations, susceptibility to D-cycloserine, impairment in siderophore production or secretion, reduced cell association, and decreased biofilm and clump formation. Mutants with interesting phenotypes were analyzed by PCR, Southern blotting and DNA sequencing to determine transposon insertion sites. These insertion sites mapped upstream from the MAP1152-MAP1156 cluster, internal to either the Mod operon gene MAP1566 or within the coding sequence of lsr2, and several intergenic regions. Growth curves in broth cultures, invasion assays and kinetics of survival and replication in primary bovine macrophages were also determined. The ability of vectors carrying Tn5370 to generate stable MAP mutants was also investigated.},
	keywords = {*Biological Specimen Banks, *DNA Transposable Elements, *DNA, Bacterial, *Mutation, Animals, Cattle, Cycloserine/pharmacology, Macrophages/immunology/microbiology, Microbial Sensitivity Tests, Microbial Viability/immunology, Mutagenesis, Insertional, Mycobacterium avium subsp. paratuberculosis/drug effects/*genetics/immunology, Paratuberculosis/immunology/*microbiology, Phenotype},
	isbn = {2235-2988 (Electronic)2235-2988 (Linking)},
	author = {Rathnaiah, G. and Lamont, E. A. and Harris, N. B. and Fenton, R. J. and Zinniel, D. K. and Liu, X. and Sotos, J. and Feng, Z. and Livneh-Kol, A. and Shpigel, N. Y. and Czuprynski, C. J. and Sreevatsan, S. and Barletta, R. G.}
}
@article {62800,
	title = {Pam3CSK4/TLR2 signaling elicits neutrophil recruitment and restricts invasion of Escherichia coli P4 into mammary gland epithelial cells in a murine mastitis model},
	journal = {Vet Immunol ImmunopatholVet Immunol ImmunopatholVet Immunol Immunopathol},
	volume = {152},
	number = {1-2},
	year = {2013},
	note = {Mintz, MichalMintz, DvirIlia-Ezra, RaayaShpigel, Nahum YengResearch Support, Non-U.S. Gov{\textquoteright}tNetherlands2012/10/18 06:00Vet Immunol Immunopathol. 2013 Mar 15;152(1-2):168-75. doi: 10.1016/j.vetimm.2012.09.030. Epub 2012 Sep 26.},
	month = {Mar 15},
	pages = {168-75},
	abstract = {Mastitis-inflammation of the mammary gland is an important disease affecting dairy animals worldwide. The disease is caused by mammary pathogenic bacteria, and Escherichia coli is frequently implicated. Intramammary challenge with bacterial LPS is sufficient to elicit the disease. However, using toll-like receptor (TLR) 4-deficient mice, we previously found that mammary pathogenic E. coli is still able to elicit neutrophil recruitment, indicating the presence of bacterial virulence factors other than LPS. To date, no specific virulence factors have been identified in E. coli isolates associated with mastitis, and other microbe-associated molecular patterns (MAMPs), such as bacterial lipoproteins, are prime candidates. The synthetic analog of bacterial lipopeptides, Pam3CSK4, is recognized by TLR2 and mimics the proinflammatory properties of triacylated lipoproteins of Gram-negative bacteria. The aim of the present work was to determine the role of bacterial lipoproteins recognized by TLR2 on mammary cells as virulence factors in the mammary gland. Using the murine mastitis model, we previously showed that following intramammary LPS challenge, neutrophil recruitment is strictly dependent on alveolar macrophages. Thus, the role of alveolar macrophages in the response to intramammary bacterial lipoprotein challenge was also studied. Here, Pam3CSK4 infusion induced mastitis in wild-type mice, but not in TLR2-deficient mice. The wild-type phenotype was not restored by adoptive transfer of TLR2-expressing macrophages into the alveolar milk space of TLR2-deficient mice, indicating that cells other than alveolar macrophages are essential for Pam3CSK4/TLR2 signaling. In contrast to the Pam3CSK4 treatment, infection with E. coli P4 resulted in inflammation, even in the absence of TLR2 signaling, indicating that lipoproteins are sufficient, but not essential virulence factors in the pathogenesis of the intact bacteria. However, in the absence of TLR2, the infecting E. coli P4 invaded the alveolar epithelial cells and formed intracellular bacterial communities, indicating that intact lipoprotein/TLR2 signaling is essential to restricting bacterial invasion.},
	keywords = {Animals, Cell Line, Colony Count, Microbial, Disease Models, Animal, Escherichia coli Infections/immunology/microbiology/*veterinary, Escherichia coli/*immunology, Female, Macrophages, Mastitis/immunology/microbiology/*veterinary, Mice, Mice, Knockout, Microscopy, Confocal, Neutrophil Infiltration/*immunology, Signal Transduction, Toll-Like Receptor 2/*immunology},
	isbn = {1873-2534 (Electronic)0165-2427 (Linking)},
	author = {Mintz, M. and Mintz, D. and Ilia-Ezra, R. and Shpigel, N. Y.}
}
@article {62801,
	title = {Ly6C hi monocytes in the inflamed colon give rise to proinflammatory effector cells and migratory antigen-presenting cells},
	journal = {ImmunityImmunity},
	volume = {37},
	number = {6},
	year = {2012},
	note = {Zigmond, EhudVarol, ChenFarache, JuliaElmaliah, ElinorSatpathy, Ansuman TFriedlander, GilgiMack, MatthiasShpigel, NahumBoneca, Ivo GMurphy, Kenneth MShakhar, GuyHalpern, ZamirJung, SteffenENGResearch Support, Non-U.S. Gov{\textquoteright}t2012/12/12 06:00Immunity. 2012 Dec 14;37(6):1076-90. doi: 10.1016/j.immuni.2012.08.026. Epub 2012 Dec 6.},
	month = {Dec 14},
	pages = {1076-90},
	abstract = {Ly6C(hi) monocytes seed the healthy intestinal lamina propria to give rise to resident CX(3)CR1(+) macrophages that contribute to the maintenance of gut homeostasis. Here we report on two alternative monocyte fates in the inflamed colon. We showed that CCR2 expression is essential to the recruitment of Ly6C(hi) monocytes to the inflamed gut to become the dominant mononuclear cell type in the lamina propria during settings of acute colitis. In the inflammatory microenvironment, monocytes upregulated TLR2 and NOD2, rendering them responsive to bacterial products to become proinflammatory effector cells. Ablation of Ly6C(hi) monocytes ameliorated acute gut inflammation. With time, monocytes differentiated into migratory antigen-presenting cells capable of priming naive T cells, thus acquiring hallmarks reminiscent of dendritic cells. Collectively, our results highlight cellular dynamics in the inflamed colon and the plasticity of Ly6C(hi) monocytes, marking them as potential targets for inflammatory bowel disease (IBD) therapy.},
	keywords = {Animals, Antigen-Presenting Cells/*immunology/metabolism, Antigens, Ly/immunology/*metabolism, Cell Movement/*immunology, Colitis/*immunology/metabolism/pathology, Disease Models, Animal, Gene Expression Profiling, Immunophenotyping, Macrophages/immunology/metabolism, Mice, Mice, Transgenic, Monocytes/*immunology/metabolism, Nod2 Signaling Adaptor Protein/immunology/metabolism, Receptors, CCR2/immunology/metabolism, Receptors, Chemokine/metabolism, T-Lymphocytes/immunology, Toll-Like Receptor 2/immunology/metabolism},
	isbn = {1097-4180 (Electronic)1074-7613 (Linking)},
	author = {Zigmond, E. and Varol, C. and Farache, J. and Elmaliah, E. and Satpathy, A. T. and Friedlander, G. and Mack, M. and Shpigel, N. and Boneca, I. G. and Murphy, K. M. and Shakhar, G. and Halpern, Z. and Jung, S.}
}
@article {62802,
	title = {Mathematical modelling and evaluation of the different routes of transmission of lumpy skin disease virus},
	journal = {Vet ResVet ResVet Res},
	volume = {43},
	year = {2012},
	note = {Magori-Cohen, ReumaLouzoun, YoramHerziger, YaelOron, EldadArazi, AlonTuppurainen, EevaShpigel, Nahum YKlement, EyalengResearch Support, Non-U.S. Gov{\textquoteright}tEngland2012/01/13 06:00Vet Res. 2012 Jan 11;43:1. doi: 10.1186/1297-9716-43-1.},
	pages = {1},
	abstract = {Lumpy skin disease (LSD) is a severe viral disease of cattle. Circumstantial evidence suggests that the virus is transmitted mechanically by blood-feeding arthropods. We compared the importance of transmission via direct and indirect contact in field conditions by using mathematical tools. We analyzed a dataset collected during the LSD outbreak in 2006 in a large dairy herd, which included ten separated cattle groups. Outbreak dynamics and risk factors for LSD were assessed by a transmission model. Transmission by three contact modes was modelled; indirect contact between the groups within a herd, direct contact or contact via common drinking water within the groups and transmission by contact during milking procedure. Indirect transmission was the only parameter that could solely explain the entire outbreak dynamics and was estimated to have an overall effect that was over 5 times larger than all other possible routes of transmission, combined. The R0 value induced by indirect transmission per the presence of an infectious cow for 1 day in the herd was 15.7, while the R0 induced by direct transmission was 0.36. Sensitivity analysis showed that this result is robust to a wide range of assumptions regarding mean and standard deviation of incubation period and regarding the existence of sub-clinically infected cattle. These results indicate that LSD virus spread within the affected herd could hardly be attributed to direct contact between cattle or contact through the milking procedure. It is therefore concluded that transmission mostly occurs by indirect contact, probably by flying, blood-sucking insects. This has important implications for control of LSD.},
	keywords = {*Models, Biological, Animals, Cattle, Disease Outbreaks/*veterinary, Female, Incidence, ISRAEL, Lumpy skin disease virus/*physiology, Lumpy Skin Disease/*epidemiology/*transmission/virology, Microscopy, Electron/veterinary, Polymerase Chain Reaction/veterinary, Risk Factors},
	isbn = {1297-9716 (Electronic)0928-4249 (Linking)},
	author = {Magori-Cohen, R. and Louzoun, Y. and Herziger, Y. and Oron, E. and Arazi, A. and Tuppurainen, E. and Shpigel, N. Y. and Klement, E.}
}
@article {62803,
	title = {Comparison of the epidemiology of epizootic haemorrhagic disease and bluetongue viruses in dairy cattle in Israel},
	journal = {Vet JVet JVet J},
	volume = {190},
	number = {1},
	year = {2011},
	note = {Kedmi, MaorGalon, NadavHerziger, YaelYadin, HagaiBombarov, VelizarBatten, CarrieShpigel, Nahum YKlement, EyalengResearch Support, Non-U.S. Gov{\textquoteright}tEnglandLondon, England : 19972010/11/26 06:00Vet J. 2011 Oct;190(1):77-83. doi: 10.1016/j.tvjl.2010.10.003. Epub 2010 Nov 18.},
	month = {Oct},
	pages = {77-83},
	abstract = {An outbreak of epizootic haemorrhagic disease virus (EHDV) in cattle in Israel in 2006 enabled a comparison of the spatial distribution of epidemic exposure to EHDV with that of exposure to bluetongue virus (BTV), which is endemic in the country. The seroprevalence of both viruses was examined in 1650 serum samples collected from 139 farms representative of the spatial distribution of dairy cattle in Israel. A significant association between exposure to EHDV and BTV was demonstrated in both univariate and multivariate analyses. Recent exposure to BTV and EHDV (demonstrated by seroprevalence in calves) was clustered in different geographical locations, indicating that the two viruses had different patterns of spread, that of EHDV being influenced by winds and terrain barriers and that of BTV by herd immunity.},
	keywords = {*Bluetongue virus, *Hemorrhagic Disease Virus, Epizootic, Animals, Bluetongue/*epidemiology/transmission, Cattle, Cattle Diseases/epidemiology/*transmission, Dairying, Disease Outbreaks/*veterinary, Disease Transmission, Infectious/*veterinary, Female, Israel/epidemiology, Prevalence, Reoviridae Infections/epidemiology/transmission/*veterinary, Seroepidemiologic Studies},
	isbn = {1532-2971 (Electronic)1090-0233 (Linking)},
	author = {Kedmi, M. and Galon, N. and Herziger, Y. and Yadin, H. and Bombarov, V. and Batten, C. and Shpigel, N. Y. and Klement, E.}
}
@article {62804,
	title = {Enterohemorrhagic Escherichia coli induce attaching and effacing lesions and hemorrhagic colitis in human and bovine intestinal xenograft models},
	journal = {Dis Model MechDis Model MechDis Model Mech},
	volume = {4},
	number = {1},
	year = {2011},
	note = {Golan, LilachGonen, ErezYagel, SimchaRosenshine, IlanShpigel, Nahum YengResearch Support, Non-U.S. Gov{\textquoteright}tEngland2010/10/21 06:00Dis Model Mech. 2011 Jan;4(1):86-94. doi: 10.1242/dmm.005777. Epub 2010 Oct 19.},
	month = {Jan},
	pages = {86-94},
	abstract = {Enterohemorrhagic Escherichia coli (EHEC) O157:H7 is an important cause of diarrhea, hemorrhagic colitis and hemolytic uremic syndrome in humans worldwide. The two major virulence determinants of EHEC are the Shiga toxins (Stx) and the type III secretion system (T3SS), including the injected effectors. Lack of a good model system hinders the study of EHEC virulence. Here, we investigated whether bovine and human intestinal xenografts in SCID mice can be useful for studying EHEC and host tissue interactions. Fully developed, germ-free human and bovine small intestine and colon were established by subcutaneous transplantation of human and bovine fetal gut into SCID mice. Xenografts were allowed to develop for 3-4 months and thereafter were infected by direct intraluminal inoculation of Stx-negative derivatives of EHEC O157:H7, strain EDL933. The small intestine and colon xenografts closely mimicked the respective native tissues. Upon infection, EHEC induced formation of typical attaching and effacing lesions and tissue damage that resembled hemorrhagic colitis in colon xenografts. By contrast, xenografts infected with an EHEC mutant deficient in T3SS remained undamaged. Furthermore, EHEC did not attach to or damage the epithelium of small intestinal tissue, and these xenografts remained intact. EHEC damaged the colon in a T3SS-dependent manner, and this model is therefore useful for studying the molecular details of EHEC interactions with live human and bovine intestinal tissue. Furthermore, we demonstrate that Stx and gut microflora are not essential for EHEC virulence in the human gut.},
	keywords = {*Bacterial Adhesion, Animals, Cattle, Cell Differentiation, Colitis/complications/*microbiology/pathology, Colon/microbiology/pathology/transplantation/ultrastructure, Disease Models, Animal, Enterohemorrhagic Escherichia coli/*cytology, Epithelial Cells/microbiology/pathology/ultrastructure, Escherichia coli Infections/complications/*microbiology/*pathology, Escherichia coli Proteins/secretion, Fetus, Gastrointestinal Hemorrhage/*complications/pathology, Humans, Intestine, Small/microbiology/pathology/*transplantation/ultrastructure, Mice, Morphogenesis, Organ Specificity, Transplantation, Heterologous},
	isbn = {1754-8411 (Electronic)1754-8403 (Linking)},
	author = {Golan, L. and Gonen, E. and Yagel, S. and Rosenshine, I. and Shpigel, N. Y.}
}
@article {62806,
	title = {Essential role of neutrophils but not mammary alveolar macrophages in a murine model of acute Escherichia coli mastitis},
	journal = {Vet ResVet ResVet Res},
	volume = {41},
	number = {4},
	year = {2010},
	note = {Elazar, SharonGonen, ErezLivneh-Kol, AyalaRosenshine, IlanShpigel, Nahum YengResearch Support, Non-U.S. Gov{\textquoteright}tFrance2010/04/27 06:00Vet Res. 2010 Jul-Aug;41(4):53. doi: 10.1051/vetres/2010025. Epub 2010 Apr 26.},
	month = {Jul-Aug},
	pages = {53},
	abstract = {Mastitis, the inflammation of the mammary gland, is an important disease affecting dairy animals worldwide. The disease is caused by mammary pathogenic bacteria and Escherichia coli are frequently implicated. Virulence factors of mammary pathogenic E. coli are only partially known and intramammary challenge with LPS elicits neutrophil recruitment in experimental bovine and murine mastitis models. We have previously shown that neutrophil recruitment in LPS-induced murine mastitis is strictly dependent on mammary alveolar macrophages. However, the relative role of alveolar macrophages and blood neutrophils in E. coli mastitis is not well defined. To this end, we selectively depleted mammary alveolar macrophages or blood neutrophils before intramammary challenge with E. coli strain P4 (ECP4). Mice depleted of alveolar macrophages prior to intramammary challenge recruited neutrophils normally and restricted bacterial growth and interstitial invasion. Importantly however, upon depletion of alveolar macrophages, ECP4 invaded the mammary alveolar epithelial cells and formed intracellular bacterial communities. In contrast, neutrophil depletion prior to intramammary infection with ECP4 was associated with unrestricted bacterial growth, tissue damage, severe sepsis and mortality. This study suggests that neutrophils but not alveolar macrophages provide essential antimicrobial defense against mammary pathogenic E. coli. Furthermore, we show here similar invasion after depletion of alveolar macrophages as in our previous studies showing that LPS/TLR4 signaling on alveolar macrophages abrogates ECP4 invasion of the mammary epithelium. Interestingly, similar ECP4 invasion and formation of intracellular communities were also observed following intramammary infection of either iNOS gene-deficient or IL-1 receptor type 1 gene-deficient mice.},
	keywords = {Animals, Escherichia coli Infections/*immunology/microbiology, Escherichia coli/classification, Female, Gene Expression Regulation/immunology, Interleukin-1beta/metabolism, Macrophages/*physiology, Mammary Glands, Animal/*cytology, Mastitis/*immunology/microbiology, Mice, Mice, Knockout, Neutrophils/*physiology, Nitric Oxide Synthase Type II/genetics/metabolism, Receptors, Interleukin-1/genetics/metabolism, Signal Transduction, Toll-Like Receptor 4/genetics/metabolism},
	isbn = {0928-4249 (Print)0928-4249 (Linking)},
	author = {Elazar, S. and Gonen, E. and Livneh-Kol, A. and Rosenshine, I. and Shpigel, N. Y.}
}
@article {62805,
	title = {Neutrophil recruitment in endotoxin-induced murine mastitis is strictly dependent on mammary alveolar macrophages},
	journal = {Vet ResVet ResVet Res},
	volume = {41},
	number = {1},
	year = {2010},
	note = {Elazar, SharonGonen, ErezLivneh-Kol, AyalaRosenshine, IlanShpigel, Nahum YehudaengResearch Support, Non-U.S. Gov{\textquoteright}tFrance2009/10/16 06:00Vet Res. 2010 Jan-Feb;41(1):10. doi: 10.1051/vetres/2009058. Epub 2009 Oct 14.},
	month = {Jan-Feb},
	pages = {10},
	abstract = {Mastitis, inflammation of the mammary tissue, is a common disease in dairy animals and mammary pathogenic Escherichia coli (MPEC) is a leading cause of the disease. Lipopolysaccharide (LPS) is an important virulence factor of MPEC and inoculation of the mammary glands with bacterial LPS is sufficient to induce an inflammatory response. We previously showed using adoptive transfer of normal macrophages into the mammary gland of TLR4-deficient C3H/HeJ mice that LPS/TLR4 signaling on mammary alveolar macrophages is sufficient to elicit neutrophil recruitment into the alveolar space. Here we show that TLR4-normal C3H/HeN mice, depleted of alveolar macrophages, were completely refractory to LPS intramammary challenge. These results indicate that alveolar macrophages are both sufficient and essential for neutrophil recruitment elicited by LPS/TLR4 signaling in the mammary gland. Using TNFalpha gene-knockout mice and adoptive transfer of wild-type macrophages, we show here that TNFalpha produced by mammary alveolar macrophages in response to LPS/TLR4 signaling is an essential mediator eliciting blood neutrophil recruitment into the milk spaces. Furthermore, using the IL8 receptor or IL1 receptor gene-knockout mice we observed abrogated recruitment of neutrophils into the mammary gland and their entrapment on the basal side of the alveolar epithelium in response to intramammary LPS challenge. Adoptive transfer of wild-type neutrophils to IL1 receptor knockout mice, just before LPS challenge, restored normal neutrophil recruitment into the milk spaces. We conclude that neutrophil recruitment to the milk spaces is: (i) mediated through TNFalpha, which is produced by alveolar macrophages in response to LPS/ TLR4 signaling and (ii) is dependent on IL8 and IL1beta signaling and regulated by iNOS-derived NO.},
	keywords = {Animals, Cytokines/genetics/metabolism, Endotoxins/*toxicity, Female, Interleukin-1beta/genetics/metabolism, Interleukin-8/genetics/metabolism, Lipopolysaccharides/toxicity, Macrophages/*physiology, Mammary Glands, Animal/*cytology, Mastitis/chemically induced/*veterinary, Mice, Mice, Inbred Strains, Mice, Knockout, Neutrophils/*physiology, Nitric Oxide Synthase Type II/genetics/metabolism, Signal Transduction, Toll-Like Receptor 4/genetics/metabolism, Tumor Necrosis Factor-alpha/genetics/metabolism},
	isbn = {0928-4249 (Print)0928-4249 (Linking)},
	author = {Elazar, S. and Gonen, E. and Livneh-Kol, A. and Rosenshine, I. and Shpigel, N. Y.}
}
@article {62807,
	title = {Associations among patterns in daily body weight, body condition scoring, and reproductive performance in high-producing dairy cows},
	journal = {J Dairy SciJ Dairy SciJ Dairy Sci},
	volume = {92},
	number = {9},
	year = {2009},
	note = {van Straten, MShpigel, N YFriger, Meng2009/08/25 09:00J Dairy Sci. 2009 Sep;92(9):4375-85. doi: 10.3168/jds.2008-1956.},
	month = {Sep},
	pages = {4375-85},
	abstract = {The objective was to investigate the associations between body condition scores (BCS) and daily body weight (BW) in the first 150 d of lactation (DIM) and reproductive performance in high-producing dairy cows. Data included automated daily BW measurements and BCS of 2,020 Israeli Holstein cows from 7 commercial farms. Individual BW series were smoothed using penalized cubic splines, and variables representing BW patterns were generated. The presence of 7- and 21-d cycles in BW was determined using time-series analysis. Associations between BW and BCS and conception at first artificial insemination (AI) were analyzed using generalized estimating equations. Multivariate survival analysis was used for associations between BW and BCS and the calving-to-first AI interval, first AI-to-conception interval, and calving-to-conception interval. First-parity cows that lost >or=12\% and second-parity cows that lost >or=15\% of their BW from calving to nadir BW were less likely to conceive at first AI. Cows without 7-d cycles in BW were 1.48 times more likely to conceive at first AI relative to cows with 7-d cycles. The odds of conceiving at first AI increased by 53\% for each additional unit in BCS from 40 to 60 DIM. In the multivariate survival analysis, a BCS of <or=2.5 between 40 and 60 DIM, the percentage of BW lost from calving to nadir BW, and a BW loss of >or=7\% from calving to 10 DIM were associated with reduced reproductive performance. The presence of 21-d cycles in BW was associated with high reproductive performance in first-parity [odds ratio (OR) = 1.18] and second-parity cows (OR = 1.22). The presence of 7-d cycles in BW was associated with low reproductive performance in first-parity cows (OR = 0.77), but not in older cows. Based on previous findings and on the associations found in this study, we postulate that 21-d cycles are probably related to the sexual cycle and could be used as a proxy for assessing ovarian activity. Variables representing relative BW loss (\%) were better predictors for impaired reproductive performance than those representing absolute BW loss (kg) and may be more suitable for estimating individual adaptation to negative energy balance in herds for which automated daily BW is available.},
	keywords = {*Dairying, Animals, Body Constitution/*physiology, Body Weight/*physiology, Cattle/*physiology, Energy Metabolism, Female, Fertilization/physiology, Insemination, Artificial/veterinary, Multivariate Analysis, Odds Ratio, Pregnancy, Reproduction/*physiology, Time Factors},
	isbn = {1525-3198 (Electronic)0022-0302 (Linking)},
	author = {van Straten, M. and Shpigel, N. Y. and Friger, M.}
}
@article {62808,
	title = {Events of elevated somatic cell counts in high-producing dairy cows are associated with daily body weight loss in early lactation},
	journal = {J Dairy SciJ Dairy SciJ Dairy Sci},
	volume = {92},
	number = {9},
	year = {2009},
	note = {van Straten, MFriger, MShpigel, N Yeng2009/08/25 09:00J Dairy Sci. 2009 Sep;92(9):4386-94. doi: 10.3168/jds.2009-2204.},
	month = {Sep},
	pages = {4386-94},
	abstract = {The objective of this study was to determine associations between body weight (BW) and body condition score (BCS) variables indicating a more severe negative energy balance in early lactation and events of somatic cell counts (SCC) >250,000 cells/mL and SCC >400,000 cells/mL in dairy cows. We studied lactations from 634 primiparous and 1,086 multiparous Israeli Holstein dairy cows originating from 7 commercial dairy farms. Generalized mixed models with a random herd effect were used to quantify the effects of BW and BCS variables in early lactation on events of elevated SCC. Data were analyzed using 2 different approaches. In the first approach, only first events in a lactation were taken into account, whereas in the second approach, all events in a lactation were analyzed and repeated events from the same cow were accounted for. Although no associations were found between the different BW and BCS variables and first events of elevated SCC, associations were present between these variables and events of elevated SCC when all events were analyzed. The cumulative incidence of a lactation with multiple events of SCC >250,000 cells/mL was 8.8 and 27.7\% for primiparous and multiparous cows, respectively. The odds of an event of SCC >250,000 cells/mL were 25\% greater for cows belonging to the upper quartile in relative BW loss from calving to nadir BW (loss >12.3, 15.0, and 15.7\% for first-, second-, and third- parity and greater cows, respectively) compared with cows losing less relative BW. Odds of an event were 44\% greater for cows with ketosis when compared with cows without. The cumulative incidence of a lactation with multiple events of SCC >400,000 cells/mL was 4.1 and 14.3\% for primiparous and multiparous cows, respectively. The odds of an event of SCC >400,000 cells/mL were 43\% greater for cows belonging to the upper quartile in relative BW loss from calving to nadir BW compared with cows losing less relative BW. Odds of an event were 33\% greater for cows with ketosis when compared with cows without. Assuming that extreme BW loss and ketosis in early lactation indicate a more severe negative energy balance, our findings support the hypothesis that greater negative energy balance in early lactation predisposes dairy cows to udder inflammation. Considering the fact that many of the events were recurring, we stress the importance of including all events in the analysis and postulate the possibility of long-term detrimental effects of negative energy balance on udder health.},
	keywords = {Animals, Body Constitution/*physiology, Body Weight/*physiology, Cattle/*physiology, Cell Count, Dairying, Energy Metabolism, Female, Lactation/*physiology, Linear Models, Milk/cytology/secretion, Time Factors, Weight Loss/physiology},
	isbn = {1525-3198 (Electronic)0022-0302 (Linking)},
	author = {van Straten, M. and Friger, M. and Shpigel, N. Y.}
}
@article {62809,
	title = {Mycobacterium avium paratuberculosis invades human small-intestinal goblet cells and elicits inflammation},
	journal = {J Infect DisJ Infect DisJ Infect Dis},
	volume = {199},
	number = {3},
	year = {2009},
	note = {Golan, LLivneh-Kol, AGonen, EYagel, SRosenshine, IShpigel, N YengResearch Support, Non-U.S. Gov{\textquoteright}t2009/01/13 09:00J Infect Dis. 2009 Feb 1;199(3):350-4. doi: 10.1086/596033.},
	month = {Feb 1},
	pages = {350-4},
	abstract = {Crohn disease is a chronic inflammatory bowel disease of unknown etiology. Mycobacterium avium paratuberculosis (MAP) was found in the gut of patients with Crohn disease, but causality was not established. Fully developed, germ-free human small intestine and colon were established by subcutaneous transplantation of fetal gut into SCID (severe combined immunodeficiency) mice thereafter infected by direct intraluminal inoculation of MAP. We have found that MAP actively invades the human gut epithelial goblet cells of the small intestine, inducing severe tissue damage and inflammation. These observations indicate that MAP can specifically colonize the normal human small intestine and can elicit inflammation and severe mucosal damage.},
	keywords = {Animals, Crohn Disease/microbiology, Goblet Cells/*microbiology, Humans, Inflammation/*microbiology, Intestine, Small/*cytology/metabolism, Mice, Mice, SCID, Mycobacterium avium subsp. paratuberculosis/*physiology, Paratuberculosis/microbiology/pathology, Transplantation, Heterologous},
	isbn = {0022-1899 (Print)0022-1899 (Linking)},
	author = {Golan, L. and Livneh-Kol, A. and Gonen, E. and Yagel, S. and Rosenshine, I. and Shpigel, N. Y.}
}
@article {62810,
	title = {Analysis of daily body weight of high-producing dairy cows in the first one hundred twenty days of lactation and associations with ovarian inactivity},
	journal = {J Dairy SciJ Dairy SciJ Dairy Sci},
	volume = {91},
	number = {9},
	year = {2008},
	note = {van Straten, MShpigel, N YFriger, Meng2008/09/04 09:00J Dairy Sci. 2008 Sep;91(9):3353-62. doi: 10.3168/jds.2008-1020.},
	month = {Sep},
	pages = {3353-62},
	abstract = {The objective of this study was to investigate, describe, and quantify daily body weight (BW) changes in the first 120 d of lactation in high-producing dairy cows. Data included 255,287 daily BW measurements from 2,167 Israeli Holstein dairy cows originating from 7 commercial dairy farms. Individual series of measurements were first smoothed using cubic splines for generating variables representing BW changes in early lactation and further analysis of the data. To construct standard BW curves stratified by parity and adjusted for farm, mixed models for repeated measurements were fit to the smoothed data, and least squares means for day in lactation were plotted. Time-series analysis techniques using polynomial functions of day in lactation and pairs of sine and cosine functions representing 7- and 21-d cycles were performed separately on each individual series of measurements. Additionally, generalized estimating equations were used to perform similar analysis on the data set as a whole. Mean days from calving to nadir BW increased significantly from first to later parities, as did mean BW loss from calving to nadir. The first-parity cow lost 6.5\% of her BW from calving to d 29 in lactation, and second-parity and greater-parity cows lost 8.5 and 8.4\% of their BW to d 34 and 38 in lactation, respectively. After nadir BW was reached, first-parity cows regained relative BW at a greater rate than did older parity cows. The trend in BW was nonlinear. A 7-d cycle was present in 247 cows (11.4\%) and a 21-d cycle was present in 715 cows (33.0\%). Presence of a 21-d cycle was associated with a 33\% reduction in the risk of being diagnosed with inactive ovaries. Fewer days from calving to nadir BW and smaller BW loss from calving to nadir, coupled with a faster post-nadir increase in relative BW in first-parity cows compared with older cows indicated a smaller energy deficit in early lactation. Association between 21-d cycles in BW and ovarian activity suggest that these cycles were physiological and related to the estrous cycle. Therefore, monitoring them could be useful for indirectly assessing ovarian activity in a herd.},
	keywords = {*Dairying, Animals, Body Constitution, Body Weight/*physiology, Cattle/*physiology, Cohort Studies, Female, Lactation/*physiology, Odds Ratio, Ovary/*physiology, Parity, Parturition, Pregnancy, Time Factors},
	isbn = {1525-3198 (Electronic)0022-0302 (Linking)},
	author = {van Straten, M. and Shpigel, N. Y. and Friger, M.}
}
@article {62812,
	title = {Beta-hydroxybutyrate abrogates formation of bovine neutrophil extracellular traps and bactericidal activity against mammary pathogenic Escherichia coli},
	journal = {Infect ImmunInfect ImmunInfect Immun},
	volume = {76},
	number = {6},
	year = {2008},
	note = {Grinberg, NavitElazar, SharonRosenshine, IlanShpigel, Nahum YengResearch Support, Non-U.S. Gov{\textquoteright}t2008/04/16 09:00Infect Immun. 2008 Jun;76(6):2802-7. doi: 10.1128/IAI.00051-08. Epub 2008 Apr 14.},
	month = {Jun},
	pages = {2802-7},
	abstract = {Escherichia coli is an important bacterial species isolated from bovine mastitis. The rate of neutrophil recruitment into the mammary gland and their bactericidal activity largely affect the severity and outcome of the disease. Ketosis is a common metabolic disease, and affected dairy cows are known to have increased risk for mastitis and other infectious conditions. The disease is associated with high blood and milk levels of beta-hydroxybutyrate (BHBA), previously shown to negatively affect neutrophil function by unknown mechanisms. We show here that the mammary pathogenic E. coli strain P4 activates normal bovine neutrophils to form neutrophil extracellular traps (NETs), which are highly bactericidal against this organism. Preincubation of these neutrophils with increasing concentrations (0.1 to 8 mmol/liter) of BHBA caused a fivefold decrease of E. coli P4 phagocytosis, though intracellular killing was unaffected. Furthermore, BHBA caused a 10-fold decrease in the NETs formed by E. coli P4-activated neutrophils and a similar decrease in NET bactericidal activity against this organism. These negative effects of BHBA on bovine neutrophils might explain the increased susceptibility of ketotic cows to mastitis and other infectious conditions.},
	keywords = {3-Hydroxybutyric Acid/*pharmacology, Animals, Cattle, Dairying, Escherichia coli Infections/microbiology/veterinary, Escherichia coli/*immunology, Female, Ketosis/blood/complications/veterinary, Mammary Glands, Animal/*microbiology, Mastitis, Bovine/*microbiology, Neutrophils/*drug effects/immunology, Phagocytosis/drug effects/immunology},
	isbn = {1098-5522 (Electronic)0019-9567 (Linking)},
	author = {Grinberg, N. and Elazar, S. and Rosenshine, I. and Shpigel, N. Y.}
}
@article {62813,
	title = {CD44 is highly expressed on milk neutrophils in bovine mastitis and plays a role in their adhesion to matrix and mammary epithelium},
	journal = {Vet ResVet ResVet Res},
	volume = {39},
	number = {3},
	year = {2008},
	note = {Gonen, ErezNedvetzki, ShlomoNaor, DavidShpigel, Nahum YengResearch Support, Non-U.S. Gov{\textquoteright}tFrance2008/02/16 09:00Vet Res. 2008 May-Jun;39(3):29. doi: 10.1051/vetres:2008005. Epub 2008 Feb 15.},
	month = {May-Jun},
	pages = {29},
	abstract = {Mastitis, inflammation of the mammary gland, is a common and economically important disease in dairy animals. Mammary pathogenic organisms, such as Escherichia coli, invade the teat canal,milk ducts, and mammary alveolar space, replicate in mammary secretions, and elicit a local inflammatory response characterized by massive recruitment of blood polymorphonuclear neutrophil leukocytes (PMN) into the alveoli and milk ducts. CD44 is a trans-membrane glycoprotein previously shown to play a role in mediation and control of blood PMN recruitment in response to inflammatory signals. Here we show, for the first time, increased expression of CD44 on recruited milk PMN in bovine mastitis and the expression of a CD44 variant, CD44v10, on these PMN. Furthermore, we demonstrate that CD44 mediates specific adhesion of bovine blood PMN to hyaluronic acid and mammary epithelial cells. Our results suggest that in mastitis CD44 plays a role in recruiting blood PMN into the mammary glands, the exact nature of this role needs to be elucidated.},
	keywords = {Animals, Antigens, CD44/genetics/*immunology, Bacterial Adhesion/physiology, Cattle, Dairying, Epithelium/immunology/physiology, Escherichia coli/immunology/pathogenicity/physiology, Female, Flow Cytometry/veterinary, Mammary Glands, Animal/immunology/microbiology, Mastitis, Bovine/blood/*immunology/microbiology, Milk/*cytology/microbiology, Neutrophils/*immunology/physiology, Reverse Transcriptase Polymerase Chain Reaction/veterinary, RNA/analysis},
	isbn = {0928-4249 (Print)0928-4249 (Linking)},
	author = {Gonen, E. and Nedvetzki, S. and Naor, D. and Shpigel, N. Y.}
}
@article {62811,
	title = {Mammary pathogenic Escherichia coli},
	journal = {Curr Opin MicrobiolCurr Opin MicrobiolCurr Opin Microbiol},
	volume = {11},
	number = {1},
	year = {2008},
	note = {Shpigel, Nahum YElazar, SharonRosenshine, IlanengResearch Support, Non-U.S. Gov{\textquoteright}tReviewEngland2008/02/23 09:00Curr Opin Microbiol. 2008 Feb;11(1):60-5. doi: 10.1016/j.mib.2008.01.004. Epub 2008 Mar 4.},
	month = {Feb},
	pages = {60-5},
	abstract = {Pathogenic Escherichia coli can be classified into several pathotypes, and it is believed that each pathotype carries one or more specific gene repertoire (or virulence factors combination) that distinguishes them from non-pathogenic E. coli strains and from other pathotypes. In contrast to this notion, it was proposed that this is not the case for E. coli mastitis, a common disease in farm animals and that any given E. coli isolate can cause this disease, even strains that are considered non-pathogenic. In this review we will re-examine this latter concept and recent advances in the study E. coli mastitis.},
	keywords = {Animal Diseases/*microbiology, Animals, Animals, Domestic, Escherichia coli Infections/*microbiology/*veterinary, Escherichia coli/*isolation \& purification, Mastitis/*microbiology/*veterinary, Models, Biological},
	isbn = {1369-5274 (Print)1369-5274 (Linking)},
	author = {Shpigel, N. Y. and Elazar, S. and Rosenshine, I.}
}
@article {62816,
	title = {Cattle immune response to botulinum type D toxoid: results of a vaccination study},
	journal = {VaccineVaccineVaccine},
	volume = {25},
	number = {44},
	year = {2007},
	note = {Steinman, AGalon, NArazi, ABar-Giora, YShpigel, N YengResearch Support, Non-U.S. Gov{\textquoteright}tNetherlands2007/10/05 09:00Vaccine. 2007 Nov 1;25(44):7636-40. Epub 2007 Sep 17.},
	month = {Nov 1},
	pages = {7636-40},
	abstract = {Cattle botulism is a food-borne intoxication caused by the ingestion of preformed botulinum neurotoxins (BoNT) of serotypes B, C, or D. Protection in cattle against botulinum intoxication is based on the presence of specific serum neutralizing antibodies upon exposure. Outbreaks in vaccinated cattle have raised concerns about vaccine quality and efficacy. To this end, three different immunization protocols and the effect of maternal anti-BoNT/D antibodies, at the priming dose, were analyzed in 2-month-old dairy calves. Based on previously determined protective anti-BoNT/D antibody levels analyzed in field outbreaks, the immune response to type D toxoids was analyzed using an in-house ELISA system. Here we show that using the current vaccination strategy of using a priming dose in 2-month-old calves followed by booster doses after 4 weeks and annually thereafter, did not result in continuous protective levels of anti-BoNT/D antibodies. As a result of this vaccination protocol, only 15-31\% of cattle in parities 1-3 were protected at the time of the annual booster. Vaccination study in calves indicated that adding a 6-month booster dose to the current protocol resulted in continuous protective levels of anti-BoNT/D antibodies well above the cut-off protective levels. The presence of maternally derived anti-BoNT/D antibodies did not interfere with the immune response to toxoids that can be administered to 2-month-old calves.},
	keywords = {Animals, Antibodies, Bacterial/blood, Botulinum Toxins/*immunology, Botulism/prevention \& control/*veterinary, Cattle, Cattle Diseases/*prevention \& control, Female, Immunity, Maternally-Acquired, Immunization, Secondary, Toxoids/*immunology, Vaccination/*veterinary},
	isbn = {0264-410X (Print)0264-410X (Linking)},
	author = {Steinman, A. and Galon, N. and Arazi, A. and Bar-Giora, Y. and Shpigel, N. Y.}
}
@article {62814,
	title = {Presence of antibotulinum neurotoxin antibodies in selected wild canids in Israel},
	journal = {J Wildl DisJ Wildl DisJ Wildl Dis},
	volume = {43},
	number = {3},
	year = {2007},
	note = {Steinman, AmirMillet, NetaFrenkel, ChanaKing, RoniShpigel, Nahum Yeng2007/08/19 09:00J Wildl Dis. 2007 Jul;43(3):548-50.},
	month = {Jul},
	pages = {548-50},
	abstract = {Serum samples from 35 golden jackals (Canis aureus syriacus), eight wolves (Canis lupus), and four red foxes (Vulpes vulpes) from various regions of Israel were collected during the years 2001-04 and tested for antibodies to Clostridium botulinum neurotoxin (BoNT) types C and D. Antibodies against BoNT types C and D were detected in 10 (29\%) and in 3 (9\%) of 35 golden jackals, respectively, using enzyme-linked immunosorbent assay. This report describes detection of anti BoNT antibodies in wild canids other than coyotes (Canis latrans) for the first time and demonstrates that C. botulinum type C is prevalent in Israel.},
	keywords = {Animals, Animals, Wild/microbiology, Antibodies, Bacterial/*blood, Botulinum Toxins/*immunology, Botulism/epidemiology/*veterinary, Canidae/*microbiology, Clostridium botulinum type C/*immunology/metabolism, Clostridium botulinum type D/*immunology/metabolism, Disease Reservoirs/veterinary, Foxes/microbiology, Israel/epidemiology, Jackals/microbiology, Seroepidemiologic Studies, Wolves/microbiology},
	isbn = {0090-3558 (Print)0090-3558 (Linking)},
	author = {Steinman, A. and Millet, N. and Frenkel, C. and King, R. and Shpigel, N. Y.}
}
@article {62815,
	title = {Seroprevalence of antibotulinum neurotoxin type C antibodies in horses in Israel},
	journal = {Equine Vet JEquine Vet JEquine Vet J},
	volume = {39},
	number = {3},
	year = {2007},
	note = {Steinman, AKachtan, ILevi, OShpigel, N YengEngland2007/05/25 09:00Equine Vet J. 2007 May;39(3):232-5.},
	month = {May},
	pages = {232-5},
	abstract = {REASONS FOR PERFORMING STUDY: Clostridium botulinum type C is prevalent in Israel and outbreaks recorded in many species, other than horses. Association between levels of anti-BoNT/C antibodies and equine grass sickness (EGS) have been demonstrated but seroprevalence of anti-BoNT/C antibodies in horses has not been reported nor has EGS been reported in Israel. OBJECTIVES: To determine the seroprevalence of specific anti-BoNT/C antibodies in horses in Israel and to determine whether age, breed and gender, or geographical region of farms are potential risk factors for exposure to BoNT/C. HYPOTHESIS: Anti-BoNT/C antibodies are prevalent among horses in Israel and farm and horse-level variables are associated with increased risk for exposure. METHODS: Serum samples from 198 horses were collected and the levels of specific anti-BoNT/C antibodies were determined using enzyme-linked immunosorbent assay (ELISA). For each categorical variable indicator variables were created and the odds ratio (OR) and 95\% confidence intervals (95\% CI) for the outcome variable were calculated using a univariable and multivariable logistic regression models. RESULTS: A total of 61 (30.8\%) horses were ELISA positive for anti-BoNT/C IgG antibodies. The farm and its geographical region were associated significantly with seropositivity, horse-level variables, such as gender and breed, were also associated with seropositivity. Quarter Horse and Warmblood mares placed in the southern region of Israel had the highest odds to be tested positive for anti-BoNT/C IgG antibodies. CONCLUSIONS AND POTENTIAL RELEVANCE: Several farm and various horse-level risk factors for exposure to BoNT/C, found in this study, could be correlated to previously reported risk factors of EGS. Studies are required to determine the predisposing factors that cause EGS, which is apparently not present in Israel.},
	keywords = {*Clostridium botulinum type C/immunology/metabolism, Animals, Antibodies, Bacterial/*blood, Autonomic Nervous System Diseases/epidemiology/veterinary, Botulinum Toxins/*immunology, Botulism/epidemiology/*veterinary, Confidence Intervals, Enzyme-Linked Immunosorbent Assay/methods/veterinary, Female, Horse Diseases/*epidemiology, Horses, Israel/epidemiology, Logistic Models, Male, Odds Ratio, Risk Factors, Seroepidemiologic Studies},
	isbn = {0425-1644 (Print)0425-1644 (Linking)},
	author = {Steinman, A. and Kachtan, I. and Levi, O. and Shpigel, N. Y.}
}
@article {62817,
	title = {Toll-like receptor 4 is needed to restrict the invasion of Escherichia coli P4 into mammary gland epithelial cells in a murine model of acute mastitis},
	journal = {Cell MicrobiolCell MicrobiolCell Microbiol},
	volume = {9},
	number = {12},
	year = {2007},
	note = {Gonen, ErezVallon-Eberhard, AlexandraElazar, SharonHarmelin, AlonBrenner, OriRosenshine, IlanJung, SteffenShpigel, Nahum YengResearch Support, Non-U.S. Gov{\textquoteright}tEngland2007/07/05 09:00Cell Microbiol. 2007 Dec;9(12):2826-38. Epub 2007 Jun 29.},
	month = {Dec},
	pages = {2826-38},
	abstract = {Mastitis, an inflammatory response of the mammary tissue to invading pathogenic bacteria, is a common disease in breast-feeding women and dairy animals. Escherichia coli is a leading cause of mastitis in dairy animals. During the course of the disease the host mounts a strong inflammatory response, but specific bacterial virulence factors have not yet been identified. Here we report the use of a murine mastitis model to investigate the innate inflammatory reaction of the mammary gland. We show that lipopolysaccharide (LPS) infusion induces mastitis in wild-type mice (C3H/HeN), but not in mice expressing mutated Toll-like receptor 4 (TLR4) (C3H/HeJ). The wild-type phenotype was restored by adoptive transfer of TLR4-expressing macrophages into the alveolar milk space of C3H/HeJ mice. In contrast to the LPS treatment, infection with E. coli P4 (ECP4) resulted in inflammation even in the absence of LPS/TLR4 signalling, indicating that additional factors play a role in the pathogenesis of the intact bacteria. Furthermore, in the absence of functional TLR4 the infecting ECP4 invade the epithelial cells with high efficiency, forming intracellular microcolonies. However, adoptive transfer with TLR4-expressing macrophages drastically reduced the epithelial invasion. Taken together, these results indicate that ECP4 has an invasive potential, which is restricted by alveolar macrophages in response to the LPS/TLR4 signalling.},
	keywords = {Adoptive Transfer, Animals, Cytosol/microbiology, Disease Models, Animal, Epithelial Cells/immunology/*microbiology, Escherichia coli Infections/*immunology, Escherichia coli/immunology, Female, Macrophages/immunology, Mammary Glands, Animal/*immunology/microbiology, Mastitis/*immunology/*microbiology, Mice, Mice, Inbred C3H, Toll-Like Receptor 4/deficiency/*immunology},
	isbn = {1462-5814 (Print)1462-5814 (Linking)},
	author = {Gonen, E. and Vallon-Eberhard, A. and Elazar, S. and Harmelin, A. and Brenner, O. and Rosenshine, I. and Jung, S. and Shpigel, N. Y.}
}
@article {62821,
	title = {A comparative randomized field trial on intramammary and intramuscular dry cow antibiotic treatment of subclinical Staphylococcus aureus mastitis in dairy cows},
	journal = {J Vet Med A Physiol Pathol Clin MedJ Vet Med A Physiol Pathol Clin MedJ Vet Med A Physiol Pathol Clin Med},
	volume = {53},
	number = {8},
	year = {2006},
	note = {Shpigel, N YKass, P HSaran, AengComparative StudyGermany2006/09/15 09:00J Vet Med A Physiol Pathol Clin Med. 2006 Oct;53(8):418-22.},
	month = {Oct},
	pages = {418-22},
	abstract = {The efficacy of two dry cow treatment (DCT) regimens for subclinical Staphylococcus aureus mastitis was evaluated in naturally infected dairy cows. At dry-off, cows were assigned to two treatment groups by randomized blocks on the basis of parity and somatic cell count (SCC). Two antibiotic DCT regimens were used, namely: (1) a single intramammary infusion containing sodium nafcillin, procaine benzylpenicillin and dihydrostreptomycin; and (2) systemic cefquinome administered intramuscularly, twice at a 24-h interval. In the intramammary (IMM) treatment group, the S. aureus intramammary infection (IMI) rate was reduced from 40\% (56/140 quarters) before dry-off to 20\% (28/140) after calving. Seventy per cent (39/56) of the S. aureus-positive quarters were negative after calving, and 13\% (11/84) of the negative quarters were positive after calving. In the systemic treatment group, the S. aureus IMI rate increased from 39\% (29/74 quarters) before dry-off to 55\% (41/74) after calving. Twenty-eight per cent (8/29) of the S. aureus-positive quarters were negative after calving and 45\% (20/45) of the negative quarters were positive after calving. The odds ratio of an S. aureus-positive quarter being negative after calving in the IMM group relative to the systemic therapy group was 44.6 (95\% confidence interval = 2.1-909.1, P < 0.01). Parity, quarter, milk SCC and N-acetyl-beta-D-glucosaminidase were tested in the model, and were found to have no significant effect on S. aureus cure rates or new IMI rates. The IMM treatment resulted in a higher cure rate compared with that observed in previous studies. The very low cure rate after systemic cefquinome treatment was comparable to the spontaneous cure rate observed in untreated controls in previous studies. The unfavourable results of the cefquinome systemic DCT might reflect inadequate pharmacokinetic properties of the drug regarding poor udder penetration in subclinical mastitis and short antimicrobial effect compared with the IMM treatment.},
	keywords = {Animals, Anti-Bacterial Agents/*therapeutic use, Cattle, Cell Count/veterinary, Female, Injections, Intramuscular/veterinary, Mastitis, Bovine/*drug therapy/prevention \& control, Milk/cytology/microbiology, Random Allocation, Staphylococcal Infections/drug therapy/prevention \& control/*veterinary, Treatment Outcome},
	isbn = {0931-184X (Print)0931-184X (Linking)},
	author = {Shpigel, N. Y. and Kass, P. H. and Saran, A.}
}
@article {62822,
	title = {Evaluation of intrauterine antibiotic treatment of clinical metritis and retained fetal membranes in dairy cows},
	journal = {TheriogenologyTheriogenologyTheriogenology},
	volume = {66},
	number = {9},
	year = {2006},
	note = {Goshen, TamirShpigel, Nahum YengRandomized Controlled TrialResearch Support, Non-U.S. Gov{\textquoteright}t2006/09/12 09:00Theriogenology. 2006 Dec;66(9):2210-8. Epub 2006 Sep 7.},
	month = {Dec},
	pages = {2210-8},
	abstract = {Retained fetal membranes (RFM) and clinical metritis (CM) are frequently diagnosed disease conditions in dairy cows and considered of major economic impact due to negative effect on reproduction and milk production. The objective of this study was to evaluate the efficacy of i.u. tetracycline for the treatment of RFM and CM in dairy cows. Affected cows were randomly assigned to two groups; treatment group animals received i.u. 5g chlortetracycline twice weekly for 2 wks, and no treatment group. A total of 1416 cows and 804 heifers in 5 herds calved during the study period. CM was diagnosed in 18.6\% (inter farm range; 15.2-23.5\%) and 30\% (19.4-42.3\%) of cows and heifers, respectively. RFM was diagnosed in 13.1\% (9.4-18.1\%) and 9.2\% (3.6-13.8\%) of cows and heifers, respectively. Conception rates after first insemination were 38.3\%, 42.5\% and 18\% in normal, treated and non-treated CM cows, respectively. Numbers of days open were 140.5, 136.2 and 165.5 in normal, treated and non-treated CM cows, respectively. Based on 305-d corrected milk yield, cows and heifers affected by RFM and CM produced 300-500kg less milk compared with their normal herd mates. Cows treated for CM produced 654kg more milk per 305-d corrected lactation compared to non-treated control cows. Treatment of RFM had no effect on reproductive performance or milk production. In conclusion, i.u. chlortetracycline treatment was proven to prevent the detrimental effect of CM on reproductive performance in heifers and cows and on milk production in cows only.},
	keywords = {Age Factors, Animals, Anti-Bacterial Agents/administration \& dosage/*therapeutic use, Cattle, Cattle Diseases/*drug therapy, Chlortetracycline/administration \& dosage/*therapeutic use, Endometritis/drug therapy/*veterinary, Female, Lactation/drug effects/physiology, Parity, Placenta, Retained/drug therapy/*veterinary, Postpartum Period, Pregnancy, Reproduction/drug effects/physiology, Treatment Outcome},
	isbn = {0093-691X (Print)0093-691X (Linking)},
	author = {Goshen, T. and Shpigel, N. Y.}
}
@article {62820,
	title = {Experimental infection of common garter snakes (Thamnophis sirtalis) with West Nile virus},
	journal = {Vector Borne Zoonotic DisVector Borne Zoonotic DisVector Borne Zoonotic Dis},
	volume = {6},
	number = {4},
	year = {2006},
	note = {Steinman, AmirBanet-Noach, CarolineSimanov, LubovGrinfeld, NuritAizenberg, ZachiLevi, OhadLahav, DanMalkinson, MertynPerk, ShimonShpigel, Nahum YengLarchmont, N.Y.2006/12/26 09:00Vector Borne Zoonotic Dis. 2006 Winter;6(4):361-8.},
	month = {Winter},
	pages = {361-8},
	abstract = {The role of various reptilian species in the infectious cycle of several arboviruses is documented, but their role in that of West Nile virus (WNV) is uncertain. Common garter snakes (Thamnophis sirtalis) were infected subcutaneously with 10(5) plaque forming units (PFU) WNV-Isr 98, five of nine snakes became viremic, and five exhibited persistent low levels of neutralizing antibodies. Four of the parentally infected snakes died and high titers of virus were found in multiple organ samples. In contrast, orally infected garter snakes did not become viremic, but viral RNA was detected in cloacal swabs. Since oral infection of predator birds by WNV is known, their ingestion of infected snakes may also result in their becoming infected.},
	keywords = {*Disease Reservoirs, Administration, Oral, Animals, Antibodies, Viral/*biosynthesis/blood, Colubridae/*virology, Humans, Immunohistochemistry/veterinary, Infusions, Parenteral/veterinary, Injections, Subcutaneous/veterinary, Neutralization Tests/veterinary, Organ Specificity, Reverse Transcriptase Polymerase Chain Reaction/veterinary, RNA, Viral/analysis, Viremia/veterinary, Virus Replication, West Nile Fever/pathology/transmission/*veterinary/virology, West Nile virus/*pathogenicity},
	isbn = {1530-3667 (Print)1530-3667 (Linking)},
	author = {Steinman, A. and Banet-Noach, C. and Simanov, L. and Grinfeld, N. and Aizenberg, Z. and Levi, O. and Lahav, D. and Malkinson, M. and Perk, S. and Shpigel, N. Y.}
}
@article {62818,
	title = {Low seroprevalence of antibodies to Neospora caninum in wild canids in Israel},
	journal = {Vet ParasitolVet ParasitolVet Parasitol},
	volume = {137},
	number = {1-2},
	year = {2006},
	note = {Steinman, AShpigel, N YMazar, SKing, RBaneth, GSavitsky, IShkap, VengNetherlands2006/01/27 09:00Vet Parasitol. 2006 Apr 15;137(1-2):155-8. Epub 2006 Jan 24.},
	month = {Apr 15},
	pages = {155-8},
	abstract = {The role of domestic dogs in the epidemiology of Neospora caninum as well as the relationship between N. caninum infection of farm dogs and cattle were demonstrated, however, evidence is scarce regarding the role of wild canids in domestic animal neosporosis. The present study was undertaken to evaluate the role of wild canids in the epidemiology of bovine neosporosis in Israel by analyzing the prevalence of antibodies to N. caninum in wild canids. Sera samples were collected from 114 free ranging wild golden jackals (Canis aureus), 24 red foxes (Vulpes vulpes) and nine wolves (Canis lupus), which were collected in Israel during the years 1999-2004. Of a total of 147 wild canids tested antibodies to N. caninum were only found in two golden jackals with IFAT titers of 1:50, and in one red fox and one wolf with IFAT titer of 1:400. The low seroprevalence found in this study (2.7\%) indicated that wild canids probably do not have an important role in the epidemiology of N. caninum in Israel. However, since the diet of different species of wild canids and even diverse populations of the same canid species vary, it is possible that other results might be obtained from specific wild canids populations, which scavenge in the vicinity of infected bovines.},
	keywords = {Animals, Animals, Domestic/parasitology, Animals, Wild/parasitology, Antibodies, Protozoan/*blood, Cattle, Cattle Diseases/*epidemiology/transmission, Coccidiosis/epidemiology/transmission/*veterinary, Disease Reservoirs/veterinary, Dogs, Female, Fluorescent Antibody Technique, Indirect/methods/veterinary, Foxes/*parasitology, Israel/epidemiology, Jackals/*parasitology, Male, Neospora/*immunology, Seroepidemiologic Studies, Wolves/*parasitology},
	isbn = {0304-4017 (Print)0304-4017 (Linking)},
	author = {Steinman, A. and Shpigel, N. Y. and Mazar, S. and King, R. and Baneth, G. and Savitsky, I. and Shkap, V.}
}
@article {62819,
	title = {Quantitative analysis of levels of serum immunoglobulin G against botulinum neurotoxin type D and association with protection in natural outbreaks of cattle botulism},
	journal = {Clin Vaccine ImmunolClin Vaccine ImmunolClin Vaccine Immunol},
	volume = {13},
	number = {8},
	year = {2006},
	note = {Steinman, AChaffer, MElad, DShpigel, N YengResearch Support, Non-U.S. Gov{\textquoteright}t2006/08/09 09:00Clin Vaccine Immunol. 2006 Aug;13(8):862-8.},
	month = {Aug},
	pages = {862-8},
	abstract = {The recent outbreaks of cattle botulism in vaccinated Israeli dairy cattle prompted us to determine vaccine efficacy and reasons for vaccine failure. Analysis of clinical signs, feeding practice, vaccination history, and epidemic curves enabled us to define a study population in two outbreaks, where high doses of Clostridium botulinum neurotoxin type D (BoNT/D) were evenly consumed by the affected animal groups. Attack rates among unvaccinated 6- to 24-month-old heifers were 96\% (55/57) and 85\% (53/62). The attack rates in vaccinated parity 1, 2, and >or=3 cows were 40.4\% (21/52), 14.3\% (4/28), and 5.6\% (3/54), respectively. Vaccine efficacies for these cow groups were 52.5\%, 83.2\%, and 93.4\%, respectively. In younger, unvaccinated 2- to 6-month-old calves, presumably protected by maternal antibodies, the attack rate was 24\% (17/71). These differences correlated with significant differences in levels of specific anti-BoNT/D antibody in serum by an enzyme-linked immunosorbent assay (ELISA). The ELISA performance for predicting protection was analyzed by receiver operating characteristic analysis and was found to be highly significant, with an area under the curve of 0.941 (standard error, 0.034; 95\% confidence interval, 0.875 to 1.008; P < 0.000). No animals with serum ELISA unit levels above 0.33 were affected in these exposed groups. At this cutoff level, the specificity of the ELISA was 100\%, sensitivity was 67\%, and accuracy was 92\%. We concluded that botulinum toxoids can confer adequate protection against natural exposure to lethal doses of BoNT/D; however, the vaccination protocols should be optimized. Our in-house ELISA system will enable us to optimize vaccination protocols in the animal population.},
	keywords = {*Disease Outbreaks, Animals, Antibodies/blood, Botulinum Toxins/*immunology, Botulism/epidemiology/prevention \& control/*veterinary, Cattle, Cattle Diseases/blood/epidemiology/*prevention \& control, Clostridium botulinum type D/*immunology, Enzyme-Linked Immunosorbent Assay, Feces/microbiology, Female, Immunoglobulin G/*blood, Injections, Subcutaneous, Israel/epidemiology, Male, ROC Curve, Sensitivity and Specificity, Toxoids/administration \& dosage},
	isbn = {1556-6811 (Print)1556-679X (Linking)},
	author = {Steinman, A. and Chaffer, M. and Elad, D. and Shpigel, N. Y.}
}
@article {62823,
	title = {Toxicological, bacteriological and serological diagnosis of botulism in a dog},
	journal = {Vet RecVet RecVet Rec},
	volume = {158},
	number = {22},
	year = {2006},
	note = {Bruchim, YSteinman, AMarkovitz, MBaneth, GElad, DShpigel, N YengCase ReportsEngland2006/06/06 09:00Vet Rec. 2006 Jun 3;158(22):768-9.},
	month = {Jun 3},
	pages = {768-9},
	keywords = {Animals, Antibodies, Bacterial/blood, Biological Assay/veterinary, Botulinum Toxins/blood/immunology, Botulism/diagnosis/therapy/*veterinary, Clostridium botulinum/immunology/*isolation \& purification/pathogenicity, Diagnosis, Differential, Dog Diseases/*diagnosis/therapy, Dogs, Enzyme-Linked Immunosorbent Assay/veterinary, Feces/microbiology, Fluid Therapy/veterinary, Male, Mice, Neurologic Examination/veterinary},
	isbn = {0042-4900 (Print)0042-4900 (Linking)},
	author = {Bruchim, Y. and Steinman, A. and Markovitz, M. and Baneth, G. and Elad, D. and Shpigel, N. Y.}
}
@article {62824,
	title = {Haematological and biochemical measurements in healthy, adult, free-ranging golden jackals (Canis aureus syriacus) held in captivity},
	journal = {Vet RecVet RecVet Rec},
	volume = {157},
	number = {11},
	year = {2005},
	note = {Aroch, IShpigel, N YAvidar, YYakobson, BKing, RShamir, MengEngland2005/09/13 09:00Vet Rec. 2005 Sep 10;157(11):317-21.},
	month = {Sep 10},
	pages = {317-21},
	abstract = {Blood from 31 healthy, free-ranging golden jackals held in captivity for seven days was collected while they were anaesthetised. Haematological and serum biochemical measurements were analysed and the 95 per cent confidence interval for each variable was compared with the reference value for domestic dogs. The measurements of their red blood cells were within the reference interval for dogs, but the jackals had higher white blood cell counts and eosinophil counts than dogs. The male jackals had a higher haematocrit, red blood cell count, mean corpuscular volume and mean corpuscular haemoglobin concentration, and a lower red blood cell distribution width than the female jackals. High activities of muscle enzymes were detected in many of the jackals, in several of which the activity of creatine kinase exceeded 5000 U/l; these were considered abnormal.},
	keywords = {Animals, Animals, Wild/*blood, Blood Cell Count/*veterinary, Blood Chemical Analysis/*veterinary, Female, ISRAEL, Jackals/*blood, Male, Reference Values, Sex Factors, Species Specificity},
	isbn = {0042-4900 (Print)0042-4900 (Linking)},
	author = {Aroch, I. and Shpigel, N. Y. and Avidar, Y. and Yakobson, B. and King, R. and Shamir, M.}
}
@article {62827,
	title = {Experimental Corynebacterium pseudotuberculosis mastitis in dairy cows},
	journal = {Vet RecVet RecVet Rec},
	volume = {153},
	number = {24},
	year = {2003},
	note = {Aroch, IHarmelin, ASaran, ALevin, DShpigel, N YengResearch Support, Non-U.S. Gov{\textquoteright}tEngland2004/01/02 05:00Vet Rec. 2003 Dec 13;153(24):746-50.},
	month = {Dec 13},
	pages = {746-50},
	abstract = {The inoculation of 2000 colony-forming units of Corynebacterium pseudotuberculosis into one teat canal of each of three cows resulted in severe, chronic, pyogranulomatous mastitis. Within three days the cows had a reduced haematocrit, haemoglobin concentration and red cell count. The anaemia was initially normocytic, normochromic and non-regenerative, and was associated with a brief peak of neutrophilia; a regenerative response became evident two to three weeks later. Clinical signs of mastitis appeared seven to 14 days after the inoculation, with a peak of high fever, more severe anaemia, a second peak of neutrophilia and the complete cessation of milk production from all quarters; extensive and severe pyogranulomatous mastitis developed in the inoculated quarters. No other lesions were detected postmortem, and C pseudotuberculosis was cultured from the affected quarters but not from the supramammary lymph nodes and viscera.},
	keywords = {Anemia/microbiology/pathology/veterinary, Animals, Cattle, Cell Count/veterinary, Corynebacterium Infections/blood/microbiology/pathology/*veterinary, Corynebacterium pseudotuberculosis/*pathogenicity, Female, Lactation, Mammary Glands, Animal/microbiology/pathology, Mastitis, Bovine/blood/*microbiology/pathology, Milk/cytology/microbiology, Neutrophils/pathology},
	isbn = {0042-4900 (Print)0042-4900 (Linking)},
	author = {Aroch, I. and Harmelin, A. and Saran, A. and Levin, D. and Shpigel, N. Y.}
}
@article {62826,
	title = {In vitro antimicrobial susceptibility of Escherichia coli isolates from clinical bovine mastitis in Finland and Israel},
	journal = {J Dairy SciJ Dairy SciJ Dairy Sci},
	volume = {86},
	number = {12},
	year = {2003},
	note = {Lehtolainen, TShwimmer, AShpigel, N YHonkanen-Buzalski, TPyorala, SengResearch Support, Non-U.S. Gov{\textquoteright}t2004/01/27 05:00J Dairy Sci. 2003 Dec;86(12):3927-32.},
	month = {Dec},
	pages = {3927-32},
	abstract = {Minimal inhibition concentration (MIC) values of 100 Finnish and 100 Israeli Escherichia coli isolated from clinical bovine mastitis were determined for ampicillin, cephalexin, ceftazidime, dihydrostreptomycin, gentamicin, tetracycline, trimethoprim-sulfadiazine, and ciprofloxacin by an agar dilution method. The in vitro antimicrobial susceptibility of the E. coli isolates was high; only 27\% showed resistance to one or more tested antimicrobial agents. Fifteen percent of the Israeli isolates and 14\% of the Finnish isolates were resistant to tetracycline, 3 and 16\% to cephalexin, 10 and 7\% to ampicillin, 13 and 9\% to dihydrostreptomycin, and 4 and 2\% to trimethoprim-sulfadiazine. No gentamicin-, ceftazidime-, or ciprofloxacin-resistant isolates were detected. Eleven percent of all the isolates were resistant to two or more antimicrobial agents. Tetracycline was most often associated with multiresistant patterns. Most of the multiresistant isolates had very high MIC values, whereas most of those that were resistant to only one tested antibiotic had MIC values close to the susceptibility breakpoint. Antimicrobial resistance appeared to pose no problem in E. coli isolated from mastitic milk of both countries. This is probably due to the controlled use of antimicrobial agents in the treatment of dairy herds. Some differences were present in the resistance patterns, which may reflect the different use of antimicrobial agents in these two countries.},
	keywords = {Ampicillin/pharmacology, Animals, Anti-Bacterial Agents/*pharmacology, Cattle, Ceftazidime/pharmacology, Cephalexin/pharmacology, Ciprofloxacin/pharmacology, Dihydrostreptomycin Sulfate/pharmacology, Drug Combinations, Drug Resistance, Microbial, Escherichia coli/*drug effects/isolation \& purification, Female, Finland, Gentamicins/pharmacology, ISRAEL, Mastitis, Bovine/*microbiology, Microbial Sensitivity Tests, Sulfadiazine/pharmacology, Tetracycline/pharmacology, Trimethoprim/pharmacology},
	isbn = {0022-0302 (Print)0022-0302 (Linking)},
	author = {Lehtolainen, T. and Shwimmer, A. and Shpigel, N. Y. and Honkanen-Buzalski, T. and Pyorala, S.}
}
@article {62825,
	title = {Value of measurements of the serum activities of creatine phosphokinase, aspartate aminotransferase and lactate dehydrogenase for predicting whether recumbent dairy cows will recover},
	journal = {Vet RecVet RecVet Rec},
	volume = {152},
	number = {25},
	year = {2003},
	note = {Shpigel, N YAvidar, YBogin, EengEngland2003/07/09 05:00Vet Rec. 2003 Jun 21;152(25):773-6.},
	month = {Jun 21},
	pages = {773-6},
	abstract = {Over a period of seven years, 262 recumbent dairy cows were investigated, and serum samples were analysed for creatine phosphokinase (CPK), lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) activities. The results from cows for which all three measurements were available, were analysed statistically by the non-parametric receiver operating characteristic (ROC) method, to evaluate the value of the serum enzyme activities for predicting a failure to recover. The sensitivity and specificity of the activity levels were calculated over all cut-off points, and ROC curves were created by plotting sensitivity as a function of 1--specificity at each cut-off point for samples grouped by the interval after the cows became recumbent. The predictive values of the tests were compared by calculating the areas under the curves, and the positive and negative predictive values of the tests were calculated and plotted against the prevalence of a failure to recover. The results from each of the enzymes were significantly better than from a random test with no discriminatory ability. The optimal cut-off points maximising the sensitivity and specificity of the tests were 2330, 2225 and 171 U/litre for CPK, LDH and AST, respectively. The predictive value of AST was significantly better than that of CPK or LDH, and measures made on the second and third day of recumbency were significantly better with optimal cut-off points of 128 and 189 U/litre, respectively.},
	keywords = {Animals, Aspartate Aminotransferases/*blood/metabolism, Bayes Theorem, Cattle, Cattle Diseases/*blood/*diagnosis, Creatine Kinase/*blood/metabolism, Female, L-Lactate Dehydrogenase/*blood/metabolism, Prognosis},
	isbn = {0042-4900 (Print)0042-4900 (Linking)},
	author = {Shpigel, N. Y. and Avidar, Y. and Bogin, E.}
}
@article {62828,
	title = {Virulence factors of Escherichia coli isolated from bovine clinical mastitis},
	journal = {Vet MicrobiolVet MicrobiolVet Microbiol},
	volume = {85},
	number = {1},
	year = {2002},
	note = {Kaipainen, TPohjanvirta, TShpigel, N YShwimmer, APyorala, SPelkonen, SengResearch Support, Non-U.S. Gov{\textquoteright}tNetherlands2002/01/17 10:00Vet Microbiol. 2002 Feb 26;85(1):37-46.},
	month = {Feb 26},
	pages = {37-46},
	abstract = {Escherichia coli isolates from bovine mastitis were examined for a selection of virulence factors. The strains originated from Finland and Israel, which have differences in the proportion of mastitis caused by E. coli, clinical pictures of coliform mastitis, environmental conditions and herd management. The genes of nine virulence factors were detected by polymerase chain reaction. Presence of K1 and K5 capsules was assessed by use of specific bacteriophages. Serum resistance was tested by a turbidimetric assay. Out of 160 Finnish isolates, 37\% had traT, 14\% cnf2, 8\% cnf1, 11\% aer, 9\% f17, 8\% sfa, 7\% pap, 1\% afa8D and 1\% afa8E. Out of 113 Israeli isolates, 41\% had traT, 4\% aer, 3\% cnf2, 1\% cnf1, 1\% sfa and 1\% f17. Some of the genes were distributed among two major pathotype groups, with either f17 family or sfa, pap and cnf1 as major determinants. Genes for F17a, CS31A, Afa7D and Afa7E were not detected. Altogether 49\% of Finnish and 42\% of Israeli isolates had at least one virulence gene, but genes other than traT were present in only 24\% of Finnish and 5\% of Israeli isolates. Serum resistance was more common among Finnish (94/160) than Israeli isolates (19/113). K1 and K5 capsules were not detected.},
	keywords = {Animals, Bacterial Capsules/*genetics, Bacterial Outer Membrane Proteins/genetics, Base Sequence, Blood Bactericidal Activity, Cattle, DNA Primers, Escherichia coli Proteins/genetics, Escherichia coli/genetics/*pathogenicity, Finland, Genes, Bacterial, ISRAEL, Mastitis, Bovine/*microbiology, Nephelometry and Turbidimetry/veterinary, Polymerase Chain Reaction/veterinary, Virulence/genetics},
	isbn = {0378-1135 (Print)0378-1135 (Linking)},
	author = {Kaipainen, T. and Pohjanvirta, T. and Shpigel, N. Y. and Shwimmer, A. and Pyorala, S. and Pelkonen, S.}
}
@article {62829,
	title = {Mammary infection with Staphylococcus aureus in cows: progress from inoculation to chronic infection and its detection},
	journal = {J Dairy ResJ Dairy ResJ Dairy Res},
	volume = {67},
	number = {2},
	year = {2000},
	note = {Shoshani, ELeitner, GHanochi, BSaran, AShpigel, N YBerman, AengENGLAND2000/06/07 09:00J Dairy Res. 2000 May;67(2):155-69.},
	month = {May},
	pages = {155-69},
	abstract = {The progress of Staphylococcus aureus infection from inoculation to the early chronic stage was examined in 12 Israeli-Holstein cows (four primiparous and eight multiparous) for up to 48 d after inoculation. Before inoculation, the primiparous cows were free from any infection and the multiparous cows were infected by coagulase-negative staphylococci. Two quarters in each cow were inoculated intracisternally following milking with 2000 cfu of a local prevailing Staph. aureus strain, VL-8407. Infection was established in 21 out of 24 quarters. The control quarters remained free from infection during the study, with no significant change in function. No statistically significant differences were found between primiparous and multiparous cows in the responses examined. Somatic cell count (SCC) increased within 24 h of inoculation and remained high for the duration of the study. In the infected quarters mean ln (SCC) increased within 24 h from 9.9 +/- 0.5 before inoculation to 13.0 +/- 0.2 after inoculation; most of the cells were neutrophils. N-acetyl-beta-glucosaminidase activity, expressed as ln (nnmol/min per l), was increased from 0.9 +/- 0.6 to 2.4 +/- 0.2 by inoculation, and was highly correlated with SCC. The Staph. aureus count fluctuated with no particular relationship with SCC. The phagocytic activity of neutrophils was significantly lower in the inoculated than in the control quarters and this difference increased with time after inoculation. CD8+ T lymphocytes were the main subpopulation of lymphocytes found in inoculated quarters. After inoculation, maximum but not minimum electrical conductivity (EC) recorded during milking increased significantly. The rises in maximum EC varied significantly among cows. The rises in SCC were associated with a persistent increase in EC in only one of the eight cows examined. No clinical signs were observed, and milk yield and composition were not affected during the study period. The results suggest that some strains of Staph. aureus may induce a relatively mild response in mammary glands of cows in mid lactation, and that the concomitant development of such chronic Staph. aureus infections in two quarters may not be detected by changes in the EC of composite milk and in the yield of the cow.},
	keywords = {*Staphylococcal Infections, Acetylglucosaminidase/metabolism, Animals, Cattle, CD8-Positive T-Lymphocytes, Cell Count, Electric Conductivity, Female, Flow Cytometry, Lactation, Mastitis, Bovine/*diagnosis/*microbiology, Milk/chemistry/cytology, Neutrophils, Phagocytosis},
	isbn = {0022-0299 (Print)0022-0299 (Linking)},
	author = {Shoshani, E. and Leitner, G. and Hanochi, B. and Saran, A. and Shpigel, N. Y. and Berman, A.}
}
@article {62830,
	title = {Serum electrolyte concentrations in bitches with eclampsia},
	journal = {Vet RecVet RecVet Rec},
	volume = {145},
	number = {11},
	year = {1999},
	note = {Aroch, ISrebro, HShpigel, N YengENGLAND1999/10/09Vet Rec. 1999 Sep 11;145(11):318-20.},
	month = {Sep 11},
	pages = {318-20},
	keywords = {Animals, Dog Diseases/*blood, Dogs, Eclampsia/blood/*veterinary, Electrolytes/*blood, Female, Pregnancy, Retrospective Studies},
	isbn = {0042-4900 (Print)0042-4900 (Linking)},
	author = {Aroch, I. and Srebro, H. and Shpigel, N. Y.}
}
@article {62832,
	title = {Clinical, bacteriological and epidemiological aspects of clinical mastitis in Israeli dairy herds},
	journal = {Prev Vet MedPrev Vet MedPrev Vet Med},
	volume = {35},
	number = {1},
	year = {1998},
	note = {Shpigel, N YWinkler, MZiv, GSaran, AengNETHERLANDS1998/06/25Prev Vet Med. 1998 Apr 16;35(1):1-9.},
	month = {Apr 16},
	pages = {1-9},
	abstract = {A 4-year retrospective study was performed to determine the clinical, bacteriological and epidemiological aspects of acute clinical mastitis in seven Israeli dairy herds. A total of 1124 clinical mastitis cases were detected by abnormal changes in the milk and udder with concurrent decrease of at least 25\% in daily milk production. A total of 1190 quarters were affected with clinical mastitis in 1089 cows. The rear quarters had a higher incidence risk (64.7\% of quarter cases) than the front quarters. The annual herd-year-incidence varied from 4.2 to 126.8 cases/100 cows/year. The whole-lactation incidence risk (LIR) was 20.8 per 100 lactations. LIR increased from the first to fifth lactation and then decreased. Most clinical mastitis cases were associated with coliform bacteria (60.2\% of cases), environmental streptococci (18.6\%), coagulase-negative staphylococci (8.7\%) and samples from which no bacterial growth was detected (8.1\%). Most cases of clinical mastitis occurred in the early stages of lactation, with 51.4\% of all cases, 52.3\% of coliform cases and 54.6\% of environmental streptococci mastitis cases occurring during the first 4 months of lactation. The median days in milk at diagnosis was 118 days. The incidence was lower in the dry summer months. The ratio of peak to low incidence was 1.62 with a calculated peak incidence in January.},
	keywords = {Animals, Cattle, Female, ISRAEL, Mastitis, Bovine/*epidemiology/microbiology, Milk/microbiology, Retrospective Studies, Seasons},
	isbn = {0167-5877 (Print)0167-5877 (Linking)},
	author = {Shpigel, N. Y. and Winkler, M. and Ziv, G. and Saran, A.}
}
@article {62831,
	title = {Relationship between in vitro sensitivity of coliform pathogens in the udder and the outcome of treatment for clinical mastitis},
	journal = {Vet RecVet RecVet Rec},
	volume = {142},
	number = {6},
	year = {1998},
	note = {Shpigel, N YWinkler, MZiv, GSaran, AengENGLAND1998/03/21Vet Rec. 1998 Feb 7;142(6):135-7.},
	month = {Feb 7},
	pages = {135-7},
	abstract = {The relationship between in vitro sensitivity to antimicrobials and the outcome of treatment was studied in 228 cows with coliform mastitis. All the cows were treated with a preparation containing sulphonamide and trimethoprim, and 197 of them were also treated with a non-steroidal anti-inflammatory drug (NSAID). The relationship between in vitro sensitivity to sulphonamide/trimethoprim and recovery was analysed by multivariate logistic regression. The possible confounding effects of treatment with an NSAID, days in lactation, parity, herd, and type of infecting organism were tested. Only treatment with an NSAID had a significant confounding effect and was included in the final statistical model. The recovery rate of the 165 cows infected by coliforms that were sensitive to sulphonamide/trimethoprim (89.1 per cent) was higher than that of the 63 cows infected by coliforms that were resistant to sulphonamide/trimethoprim (74.6 per cent). The odds ratio of recovery for the cases associated with organisms that were sensitive to sulphonamide/trimethoprim relative to the cases associated with organisms that were resistant to sulphonamide/trimethoprim was 2.75, with a 95 per cent confidence from 1.25 to 5.85. The odds ratio of recovery for the cases treated with an NSAID relative to the cases treated with sulphonamide/trimethoprim only was 2.76 with a 95 per cent confidence interval from 1.12 to 6.79.},
	keywords = {Animals, Anti-Inflammatory Agents, Non-Steroidal/*therapeutic use, Antimalarials/*therapeutic use, Cattle, Cattle Diseases/*drug therapy/microbiology, Enterobacteriaceae Infections/drug therapy/*veterinary, Enterobacteriaceae/*pathogenicity, Female, In Vitro Techniques, Mastitis/drug therapy/microbiology/*veterinary, Microbial Sensitivity Tests, Prognosis, Sulfonamides/*therapeutic use, Treatment Outcome, Trimethoprim/*therapeutic use},
	isbn = {0042-4900 (Print)0042-4900 (Linking)},
	author = {Shpigel, N. Y. and Winkler, M. and Ziv, G. and Saran, A.}
}
@article {62834,
	title = {[Contribution to the treatment of acute bovine mastitis with cefquinome]},
	journal = {Tierarztl PraxTierarztl PraxTierarztl Prax},
	volume = {25},
	number = {3},
	year = {1997},
	note = {Shpigel, N YSchmid, PgerEnglish AbstractReviewGERMANY1997/05/01Tierarztl Prax. 1997 May;25(3):200-6.},
	month = {May},
	pages = {200-6},
	abstract = {Cefquinome is the first 4th generation cephalosporin antibiotic developed for use in veterinary medicine. A European multicentre study established a high in vitro activity for this modern antimicrobial drug against a wide spectrum of bovine pathogens. Gram-positive and gram-negative mastitis agents were inactivated even at very low active ingredient concentrations, including Enterobacteriaceae which are often resistant to other drugs. The results of clinical trials using experimental E. coli mastitis as an example demonstrate the efficacy of cefquinome in vivo. Parenteral administration at a dose rate of 1 mg/kg body weight when compared with conventional therapy using a control drug with equally good in vitro activity, produced significantly better therapeutic results.},
	keywords = {Animals, Cattle, Cephalosporins/*therapeutic use, Clinical Trials as Topic, Enterobacteriaceae Infections/drug therapy/veterinary, Escherichia coli Infections/drug therapy/veterinary, Female, Gram-Negative Bacterial Infections/drug therapy/veterinary, Gram-Positive Bacterial Infections/drug therapy/veterinary, Mastitis, Bovine/*drug therapy/microbiology, Multicenter Studies as Topic},
	isbn = {0303-6286 (Print)0303-6286 (Linking)},
	author = {Shpigel, N. Y. and Schmid, P.}
}
@article {62833,
	title = {Corynebacterium pseudotuberculosis infection in Israeli cattle: clinical and epidemiological studies},
	journal = {Vet RecVet RecVet Rec},
	volume = {140},
	number = {16},
	year = {1997},
	note = {Yeruham, IElad, DVan-Ham, MShpigel, N YPerl, SengENGLAND1997/04/19Vet Rec. 1997 Apr 19;140(16):423-7.},
	month = {Apr 19},
	pages = {423-7},
	abstract = {Morbidity due to Corynebacterium pseudotuberculosis infection occurred in 29 dairy herds in Israel during 1989 to 1995. The disease occurred sporadically in 17 of the herds with a morbidity of up to 5 per cent, and was epidemic in 12, with a morbidity of 5 to 35 per cent. Cutaneous abscesses were diagnosed in 609 animals. Young cattle appeared to be less susceptible to the disease than older cows. Beef cattle herds were not affected. The disease appeared in the cutaneous form in 92.5 per cent of cases, the cutaneous and mastitic form in 5.9 per cent and the cutaneous and visceral form in 1.6 per cent. The cutaneous form appeared as deep subcutaneous abscesses on various parts of the body, with granulating ulcers exuding pus and blood. In 10 of the herds, C pseudotuberculosis was isolated from 33 mastitic cows which also had cutaneous lesions. The visceral form of the disease was detected when severely affected animals were slaughtered. In 23 of the herds, the disease occurred during the spring and summer dry season, from March to October; the highest prevalence was in the semi-arid Negev region. In 25 herds, the infection lasted for up to five months. The skin lesions on individual cows healed on average in 23.4 days, after either local or parenteral treatment. No significant difference was observed between the effect of systemic antibiotic treatment and local antiseptic treatment. One hundred and two (16.7 per cent) severely affected animals were culled. There was a decrease in milk production and large increases in somatic cell counts in the 12 herds in which the disease was epidemic. None of the strains of isolated C pseudotuberculosis reduced nitrate.},
	keywords = {*Corynebacterium pseudotuberculosis, Animals, Cattle, Cattle Diseases/*epidemiology/microbiology/pathology, Corynebacterium Infections/epidemiology/pathology/*veterinary, Disease Outbreaks/*veterinary, Female, Israel/epidemiology, Prevalence},
	isbn = {0042-4900 (Print)0042-4900 (Linking)},
	author = {Yeruham, I. and Elad, D. and Van-Ham, M. and Shpigel, N. Y. and Perl, S.}
}
@article {62835,
	title = {Efficacy of cefquinome for treatment of cows with mastitis experimentally induced using Escherichia coli},
	journal = {J Dairy SciJ Dairy SciJ Dairy Sci},
	volume = {80},
	number = {2},
	year = {1997},
	note = {Shpigel, N YLevin, DWinkler, MSaran, AZiv, GBottner, Aeng1997/02/01J Dairy Sci. 1997 Feb;80(2):318-23.},
	month = {Feb},
	pages = {318-23},
	abstract = {The efficacy of intramuscularly and intramammarily administered cefquinome was evaluated in experimental Escherichia coli mastitis in dairy cows. Forty-seven multiparous, Israeli Holstein cows in early lactation that produced at least 25 L/d of milk were used, and 400 to 750 cfu of E. coli were infused into two healthy quarters of each cow. Cows were randomly assigned to one of the following treatment groups: 1) 75 mg of cefquinome administered intramammarily three times at 12-h intervals, 2) 75 mg of cefquinome administered intramammarily three times at 12-h intervals and 1 mg/kg of cefquinome administered intramuscularly two times at a 24-h interval, 3) 1 mg/kg of cefquinome administered intramuscularly two times at a 24-h interval, and 4) 75 mg of ampicillin and 200 mg of cloxacillin administered intramammarily three times at 12-h intervals. All cows developed typical signs of acute clinical mastitis by 12 to 16 h postinoculation. Parenteral cefquinome therapy, with or without intramammary cefquinome (groups 2 and 3), significantly improved clinical recovery and return to milk production. The bacteriological cure rates were considerably and significantly higher for cows in the groups treated with cefquinome than for cows in the group treated with ampicillin and cloxacillin. This study supported the efficacy of cefquinome in the treatment of clinical coliform mastitis in dairy cows.},
	keywords = {Animals, Anti-Bacterial Agents/*therapeutic use, Cattle, Cephalosporins/administration \& dosage/*therapeutic use, Escherichia coli Infections/*drug therapy, Escherichia coli/isolation \& purification, Female, Injections, Intramuscular, Lactation, Mammary Glands, Animal/drug effects, Mastitis, Bovine/*drug therapy/*microbiology/physiopathology},
	isbn = {0022-0302 (Print)0022-0302 (Linking)},
	author = {Shpigel, N. Y. and Levin, D. and Winkler, M. and Saran, A. and Ziv, G. and Bottner, A.}
}
@article {62837,
	title = {The anti-inflammatory drugs phenylbutazone and dipyrone in the treatment of field cases of bovine mastitis},
	journal = {Zentralbl Veterinarmed AZentralbl Veterinarmed AZentralbl Veterinarmed A},
	volume = {43},
	number = {6},
	year = {1996},
	note = {Shpigel, N YWinkler, MSaran, AZiv, GengClinical TrialRandomized Controlled TrialGERMANY1996/08/01Zentralbl Veterinarmed A. 1996 Aug;43(6):331-6.},
	month = {Aug},
	pages = {331-6},
	abstract = {The efficacy of phenylbutazone vs. dipyrone for the treatment of acute clinical mastitis were compared in a clinical trial. All cows were treated with 20 g sulfadiazine and 4 g trimethoprim i.m. upon diagnosis and half dosage once daily thereafter. In addition, the NSAIDs treated cows received once daily either 4 g phenylbutazone or 20 g dipyrone i.m. for the duration of the antimicrobial therapy. In all treatment groups the major causative organisms were coliforms. Recovery rates for the controls, the phenylbutazone and dipyrone treatment groups were 81.8\%, 89.4\% and 86.6\%, respectively. Recovery was evaluated by the logistic regression analysis, the odds ratios (OR) and their 95\% confidence interval (CI) of treatment success for phenylbutazone and dipyrone treatments relative to the control treatment were calculated. Odds ratio of recovery was high for phenylbutazone (OR = 2.42; CI = 0.98-5.96; P = 0.054) as well as for dipyrone (OR = 1.71; CI = 0.98-3.00; P = 0.060), demonstrating a strong trend towards improved recovery in NSAID groups. The odds of treatment failure for the phenylbutazone group relative to the dipyrone group was 0.71 with 95\% CI of 0.28-1.78. Clearly no significant difference could be demonstrated between phenylbutazone and dipyrone in this field trial.},
	keywords = {Animals, Anti-Infective Agents/therapeutic use, Anti-Inflammatory Agents, Non-Steroidal/*therapeutic use, Cattle, Dipyrone/*therapeutic use, Drug Combinations, Drug Therapy, Combination, Female, Mastitis, Bovine/*drug therapy, Phenylbutazone/*therapeutic use, Sulfadiazine/therapeutic use, Trimethoprim/therapeutic use},
	isbn = {0514-7158 (Print)0514-7158 (Linking)},
	author = {Shpigel, N. Y. and Winkler, M. and Saran, A. and Ziv, G.}
}
@article {62836,
	title = {Mastitis in dairy cattle caused by Corynebacterium pseudotuberculosis and the feasibility of transmission by houseflies. I},
	journal = {Vet QVet QVet Q},
	volume = {18},
	number = {3},
	year = {1996},
	note = {Yeruham, IBraverman, YShpigel, N YChizov-Ginzburg, ASaran, AWinkler, MengNETHERLANDS1996/09/01Vet Q. 1996 Sep;18(3):87-9.},
	month = {Sep},
	pages = {87-9},
	abstract = {Morbidity due to Corynebacterium pseudotuberculosis infection occurred in 29 dairy herds. The disease appeared basically in three clinical forms: cutaneous, mastitic, and visceral. The appearance of the disease showed a marked seasonality: in 23 herds it occurred during the spring and summer months (dry season) (March-October). The mastitic form occurred in only 10 herds and the causative bacterium was isolated from 33 cows (5.8\%). All the strains of C. pseudotuberculosis isolated from the milk samples were found not to be nitrate reducers. The bacterium was excreted in the milk of six cows from herd B during a period of 11 months. In the mastitic cows, a decrease in milk production and considerable increases in the somatic cell count were noted. C. pseudotuberculosis was isolated from houseflies collected over a cow lesion. Laboratory-reared houseflies were successfully infected with C. pseudotuberculosis-contaminated milk, broth and sugar cubes. Flies infected with the bacterium from contaminated milk excreted the bacterium in their droppings for up to 4 h and from their saliva for up to 3 h post infection. The bacterium survived on the external organs of houseflies for no longer than 10 min post infection, after the flies had been dipped in contaminated broth.},
	keywords = {Animals, Cattle, Cattle Diseases/microbiology/pathology/*transmission, Corynebacterium Infections/complications/pathology/*veterinary, Corynebacterium pseudotuberculosis/*isolation \& purification/*physiology, Female, Houseflies/*microbiology, Mastitis, Bovine/*etiology/pathology, Milk/microbiology, Morbidity, Seasons},
	isbn = {0165-2176 (Print)0165-2176 (Linking)},
	author = {Yeruham, I. and Braverman, Y. and Shpigel, N. Y. and Chizov-Ginzburg, A. and Saran, A. and Winkler, M.}
}
@article {62838,
	title = {Use of corticosteroids alone or combined with glucose to treat ketosis in dairy cows},
	journal = {J Am Vet Med AssocJ Am Vet Med AssocJ Am Vet Med Assoc},
	volume = {208},
	number = {10},
	year = {1996},
	note = {Shpigel, N YChen, RAvidar, YBogin, EengClinical TrialComparative StudyControlled Clinical Trial1996/05/15J Am Vet Med Assoc. 1996 May 15;208(10):1702-4.},
	month = {May 15},
	pages = {1702-4},
	abstract = {OBJECTIVE: To compare relative efficacy of dexamethasone and flumethasone alone or in combination with rapid IV infusion of glucose for treatment of ketosis in cattle. DESIGN: Clinical trial. ANIMALS: 127 cows with urine acetoacetate concentration > or = 60 mg/dl. PROCEDURE: Cows were treated with 500 ml of 50\% glucose solution. IV, and 40 mg of dexamethasone, IM (group 1), 40 mg of dexamethasone, IM (group 2), 5 mg of flumethasone (group 3), or 500 ml of 50\% glucose solution, IV, and 5 mg of flumethasone (group 4). Treatment success was defined as recovery after a single treatment without relapse during the same lactation. Uterine disease (retained placenta or metritis), parity, and pretreatment plasma glucose, serum beta-hydroxybutyric acid, and urine acetoacetate concentrations were evaluated as possible confounding factors affecting recovery. RESULTS: Only uterine disease was found to have a significant effect on recovery. Treatments 1 and 4 were significantly more efficacious than was treatment 2, but efficacy of treatment 2 was not significantly different from that of treatment 3. Regardless of treatment, cows with uterine disease were less likely to have a successful outcome than were cows without uterine disease. In all treatment groups, plasma glucose concentration increased and serum beta-hydroxybutyric acid and urine acetoacetate concentrations decreased following treatment. CLINICAL IMPLICATIONS: In this study, treatment of ketosis in dairy cattle with a corticosteriod alone was less efficacious than treatment with glucose and a corticosteroid.},
	keywords = {3-Hydroxybutyric Acid, Acetoacetates/urine, Animals, Blood Glucose/analysis, Cattle, Cattle Diseases/*drug therapy, Dexamethasone/administration \& dosage/*therapeutic use, Drug Therapy, Combination, Female, Flumethasone/administration \& dosage/*therapeutic use, Glucocorticoids/administration \& dosage/*therapeutic use, Glucose/administration \& dosage/*therapeutic use, Hydroxybutyrates/blood, Infusions, Intravenous/veterinary, Injections, Intramuscular/veterinary, Ketosis/drug therapy/*veterinary, Lactation, Odds Ratio, Regression analysis, Solutions},
	isbn = {0003-1488 (Print)0003-1488 (Linking)},
	author = {Shpigel, N. Y. and Chen, R. and Avidar, Y. and Bogin, E.}
}
@article {62839,
	title = {Feed contamination with Candida krusei as a probable source of mycotic mastitis in dairy cows},
	journal = {J Am Vet Med AssocJ Am Vet Med AssocJ Am Vet Med Assoc},
	volume = {207},
	number = {5},
	year = {1995},
	note = {Elad, DShpigel, N YWinkler, MKlinger, IFuchs, VSaran, AFaingold, Deng1995/09/01J Am Vet Med Assoc. 1995 Sep 1;207(5):620-2.},
	month = {Sep 1},
	pages = {620-2},
	abstract = {Over 3 months, yeasts were isolated in pure culture from milk samples obtained from 8 lactating cows with acute mastitis and from 1 cow with subacute mastitis. Eight of the isolates were identified as Candida krusei; 1 isolate was not submitted for identification. The affected cows were assigned to separate milking groups and had not been treated by intramammary administration of antibiotic before the outbreak. Remission of disease without treatment was observed, followed by shedding of the yeast in milk for 2 to 5 weeks. Median somatic cell counts in the affected cows before, during, and 2 months after the onset of clinical signs were 93,000; 1,793,000; and 135,000 cells/ml, respectively. Wheat silage was found to be the probable source of the infecting microorganism, whereas inadequate milking hygiene resulted in its persistence in the herd. Following replacement of the silage and improvement of the milking hygiene, the outbreak ceased. Candida krusei thus may cause mastitis in cattle not only following intramammary antibiotic treatment, but also in conditions of heavy environmental contamination, in conjunction with inadequate milking hygiene.},
	keywords = {*Food Microbiology, Animal Feed/*microbiology, Animal Husbandry, Animals, Candida/*isolation \& purification, Candidiasis/epidemiology/microbiology/*veterinary, Cattle, Cell Count/veterinary, Disease Outbreaks/veterinary, Female, Israel/epidemiology, Mastitis, Bovine/epidemiology/*microbiology, Milk/cytology/microbiology},
	isbn = {0003-1488 (Print)0003-1488 (Linking)},
	author = {Elad, D. and Shpigel, N. Y. and Winkler, M. and Klinger, I. and Fuchs, V. and Saran, A. and Faingold, D.}
}
@article {62840,
	title = {Anti-inflammatory ketoprofen in the treatment of field cases of bovine mastitis},
	journal = {Res Vet SciRes Vet SciRes Vet Sci},
	volume = {56},
	number = {1},
	year = {1994},
	note = {Shpigel, N YChen, RWinkler, MSaran, AZiv, GLongo, FengClinical TrialRandomized Controlled TrialENGLAND1994/01/01Res Vet Sci. 1994 Jan;56(1):62-8.},
	month = {Jan},
	pages = {62-8},
	abstract = {The efficacy of ketoprofen in the treatment of acute clinical mastitis was evaluated in a clinical trial comprising a non-blind controlled study and a blind, placebo-controlled study. All the cows were treated with 20 g sulphadiazine and 4 g trimethoprim intramuscularly upon diagnosis, and half the dosage was given once daily thereafter. In addition, the ketoprofen treatment groups received 2 g ketoprofen intramuscularly once daily for the duration of the antimicrobial therapy. Recovery rates for the non-blind contemporary controls and the blind placebo-controls were 83.7 per cent and 70.7 per cent, respectively. In the non-blind controlled ketoprofen and the placebo-controlled ketoprofen treatment groups, recovery rates were 94.7 per cent and 92.3 per cent, respectively. The odds ratio (OR) of recovery was significantly (P < or = 0.01) high in the placebo-controlled study (OR = 6.75, confidence interval [CI] = 1.45 to 31.4), and high but not significant in the non-blind controlled study (OR = 2.64, CI = 0.53 to 13.10). It was concluded that ketoprofen significantly improved recovery in clinical mastitis in dairy cows.},
	keywords = {Animals, Cattle, Drug Combinations, Female, Ketoprofen/*therapeutic use, Mastitis, Bovine/*drug therapy, Single-Blind Method, Sulfadiazine/therapeutic use, Trimethoprim/therapeutic use},
	isbn = {0034-5288 (Print)0034-5288 (Linking)},
	author = {Shpigel, N. Y. and Chen, R. and Winkler, M. and Saran, A. and Ziv, G. and Longo, F.}
}
@article {62841,
	title = {An outbreak of Corynebacterium pseudotuberculosis infection in an Israeli dairy herd},
	journal = {Vet RecVet RecVet Rec},
	volume = {133},
	number = {4},
	year = {1993},
	note = {Shpigel, N YElad, DYeruham, IWinkler, MSaran, AengResearch Support, Non-U.S. Gov{\textquoteright}tENGLAND1993/07/24Vet Rec. 1993 Jul 24;133(4):89-94.},
	month = {Jul 24},
	pages = {89-94},
	abstract = {An outbreak of Corynebacterium pseudotuberculosis infection in an Israeli dairy herd appeared in four clinical forms: cutaneous, mastitic, visceral and a mixed form. Only cows were affected and susceptibility increased with age. Most cases occurred during a short period in the summer months. The total morbidity rate was 13.7 per cent involving 41 cows. Thirty cows were affected by the cutaneous form, five by the mastitic form, four by the mastitic and cutaneous forms, one by the mastitic and visceral forms and one by the visceral form. The cutaneous form appeared as one or two pyogranulomatous lesions affecting the body or head. Subclinical to severe clinical mastitis was found in the mastitic form. In the visceral form the upper and lower respiratory system were affected by multiple purulent lymphadenitis. All the cutaneous lesions recovered irrespective of treatment. Mastitis did not respond to treatment and severely affected milk production in most cases. All the isolates of C pseudotuberculosis were nitrate reductase negative. Most isolates were sensitive to norfloxacin, cephalothin, methicillin, kanamycin and furazolidone and resistant to ampicillin, lincomycin and neomycin.},
	keywords = {Age Factors, Animals, Cattle, Corynebacterium Infections/epidemiology/pathology/*veterinary, Corynebacterium pseudotuberculosis/*isolation \& purification, Dairying, Disease Outbreaks/*veterinary, Female, Israel/epidemiology, Male, Mastitis, Bovine/*epidemiology, Sex Factors, Skin Diseases, Bacterial/epidemiology/pathology/*veterinary},
	isbn = {0042-4900 (Print)0042-4900 (Linking)},
	author = {Shpigel, N. Y. and Elad, D. and Yeruham, I. and Winkler, M. and Saran, A.}
}
