Spontaneous autoimmune gastritis and hypochlorhydria are manifest in the ileitis-prone SAMP1/YitFcs mice.

SAMP1/YitFcs mice serve as a model of Crohn's disease, and we have used them to assess gastritis. Gastritis was compared in SAMP1/YitFcs, AKR, and C57BL/6 mice by histology, immunohistochemistry, and flow cytometry. Gastric acid secretion was measured in ligated stomachs, while anti-parietal cell antibodies were assayed by immunofluorescence and enzyme-linked immunosorbent spot assay. SAMP1/YitFcs mice display a corpus-dominant, chronic gastritis with multifocal aggregates of mononuclear cells consisting of T and B lymphocytes. Relatively few aggregates were observed elsewhere in the stomach. The infiltrates in the oxyntic mucosa were associated with the loss of parietal cell mass. AKR mice, the founder strain of the SAMP1/YitFcs, also have gastritis, although they do not develop ileitis. Genetic studies using SAMP1/YitFcs-C57BL/6 congenic mice showed that the genetic regions regulating ileitis had comparable effects on gastritis. The majority of the cells in the aggregates expressed the T cell marker CD3 or the B cell marker B220. Adoptive transfer of SAMP1/YitFcs CD4(+) T helper cells, with or without B cells, into immunodeficient recipients induced a pangastritis and duodenitis. SAMP1/YitFcs and AKR mice manifest hypochlorhydria and anti-parietal cell antibodies. These data suggest that common genetic factors controlling gastroenteric disease in SAMP1/YitFcs mice regulate distinct pathogenic mechanisms causing inflammation in separate sites within the digestive tract.

Henipavirus: a review of laboratory animal pathology.

The genus Henipavirus contains two members-Hendra virus (HeV) and Nipah virus (NiV)-and each can cause fatal disease in humans and animals. HeV and Niv are currently classified as biosafety level 4, and NiV is classified as a category C priority pathogen. The aim of this article is to discuss the pathology of laboratory animal models of henipavirus infection and to assess their suitability as animal models for the development and testing of human therapeutics and vaccines. There has been considerable progress in the development of animal models for henipavirus disease. Suitable animal models include the golden hamster, ferrets, cats, and pigs, which develop disease resembling that observed in humans. Guinea pigs are a less reliable model for henipavirus disease, but they do develop henipavirus-induced encephalitis. Because human efficacy studies with henipaviruses are not permitted, animal studies are critical for the development of antiviral therapeutics and vaccines. Current research indicates that passive immunotherapy using monoclonal antibodies is protective of ferrets against NiV infection and that passive immunotherapy using NiV antibodies protects hamsters from HeV. Recombinant vaccines have been used to protect cats and pigs against NiV infection. Ribavirin and 6-aza-uridine were able to delay but not prevent NiV-induced mortality in hamsters. Further research is needed to develop a model and therapy for late-onset henipavirus encephalitis.

An in situ hybridization and immunohistochemical study of cytauxzoonosis in domestic cats.

Cytauxzoonosis, caused by the protozoan parasite, Cytauxzoon felis, is a tick-borne disease of domestic cats causing high mortality. The reservoir is wild felids. In this study, 7 archived cases of the disease were examined through in situ hybridization for localization of the parasite and by immunohistochemistry for various cell markers to characterize infected cells. The riboprobe used was specific for the 16S-like rRNA subunit of Babesia microti, which shares 91% identity with the same gene for C. felis. In situ hybridization highlighted the presence of the organism in several tissues, most prominently lung and spleen, and, in general, there were 2 to 10 times more infected cells seen with in situ hybridization than with HE. Parasite-laden cells were usually found within vessels. These cells were often tightly packed and frequently formed parasitic thrombi. Immunohistochemistry with an antilysozyme antibody confirmed the macrophage origin of the infected cells. Using an antibody specific for calprotectin (Mac387), parasitized cells were markedly devoid of this protein, which may explain the lack of diapedesis and vascular crowding of parasitized cells, providing more circulating parasites for the tick vector. Immunohistochemical labeling for 2 proliferation markers, proliferating cell nuclear antigen (PCNA) and p53, indicated that parasitized cells have a heightened replicative ability, which is probably an additional parasite-driven modification to facilitate survival and transmission.

Localization of fibropapilloma-associated turtle herpesvirus in green turtles (Chelonia mydas) by in-situ hybridization.

Fibropapilloma-associated turtle herpesvirus (FPTHV) is the presumed aetiological agent of sea turtle fibropapillomatosis (FP). Intralesional DNA and RNA of the virus have been detected by polymerase chain reaction (PCR) and reverse transcriptase-PCR (RT-PCR), respectively, but the exact location and distribution of the virus within the tumours have not been addressed. In this study, in-situ hybridization (ISH) was used to investigate viral transcriptional activity and localization of FPTHV. Twenty-five tumours were obtained from the skin or conjunctiva of 105 green turtles (Chelonia mydas) examined on two islands in Puerto Rico (Culebra and Culebrita). These lesions comprised 19 fibropapillomas and six fibromas. FPTHV mRNA transcripts were detected by ISH in three fibropapillomas, with positive reactions confined to the nuclei of clusters of epithelial cells. Viral DNA was detected by riboprobe ISH combined with denaturation in 14 tumours, including both fibropapillomas and fibromas. Signals were confined to the nuclei of acanthotic epithelial cells and were not seen in the subepithelial fibrous areas of the tumours. These results suggest that FPTHV is present in epithelial cells and transcriptionally active in fibropapillomas.

Histopathologic and immunohistochemical characterization of Nipah virus infection in the guinea pig.

Mortality rate in humans infected with Nipah virus (NiV) has been reported as high as 92%. Humans infected with NiV show a widespread multisystemic vasculitis with most severe clinical and pathologic manifestations in the brain, lungs, and spleen. The purpose of this study was to study pathologic and immunohistochemical findings in guinea pigs infected with NiV. Of 28 animals inoculated intraperitoneally, only 2 survived the infection, and most died between 4 and 8 days postinoculation (dpi). Viral antigen with minimal pathologic changes was first detected 2 dpi in lymph nodes and spleen. More severe changes were noted in these organs 4-8 dpi, where pathologic damage had a vasocentric distribution and viral antigen was abundant in vascular endothelium, tunica media, adventitia, as well as in macrophages lining sinuses. The urinary bladder, uterus, and ovaries were also affected with necrosis and acute inflammation. In these organs, immunohistochemical positive staining was intense in blood vessels, epithelial cells, and ovarian follicles. Approximately 50% of the animals that died or were euthanized in extremis had evidence of viral antigen and histopathologic changes in brain, especially involving meninges and ependymal cells, with lesser changes in the neural parenchyma. A unifying feature of the damage for all affected tissues was necrosis and inflammation of the vasculature, chiefly in arterioles, capillaries, and venules. Inoculation of guinea pigs intraperitoneally with NiV produces a disease with considerable resemblance to the disease in humans, but with reduced pulmonary involvement and marked infection of urinary bladder and the female reproductive tract.