Pathogenesis of renal disease due to enterohemorrhagic Escherichia coli in germ-free mice.

Enterohemorrhagic Escherichia coli (EHEC) is a food-borne pathogen that causes hemorrhagic colitis and acute renal failure. We used a germ-free mouse model to investigate the role of host factors, Shiga toxin 2 (Stx2), and bacterial strain in disease due to EHEC. Germ-free male and female Swiss-Webster mice that were 3 days to 12 weeks old were orally inoculated with 1 of 10 EHEC strains or derivatives of two of these strains with Stx2 deleted. All inoculated mice became infected regardless of the inoculum dose. All bacterial strains colonized the intestines, reaching levels of 10(9) to 10(12) CFU/g of feces by 4 days after inoculation. Seven of the 10 wild-type strains caused disease. However, the two Stx2 deletion mutants, unlike the Stx2(+) parental strains, did not cause disease. The clinical signs of disease in mice included lethargy, dehydration, polyuria, polydypsia, and death. Postmortem examination of affected mice revealed dehydration and luminal cecal fluid accumulation. Histologic examination revealed close adherence of bacteria to the intestinal epithelium in the ileum and cecum but not in the colon. Other lesions included progressive renal tubular necrosis, glomerular fibrin thrombosis, and red blood cell sludging. The severity of disease varied according to the bacterial strain and age, but not sex, of the host. This study demonstrated that EHEC colonizes germ-free mice in large numbers, adheres to the intestinal epithelium, and causes luminal cecal fluid accumulation and progressive renal failure. The disease in mice was Stx2 and bacterial strain dependent. This animal model should be a useful tool for studying the pathogenesis of renal disease secondary to EHEC infection.

Role of transcription factor T-bet expression by CD4+ cells in gastritis due to Helicobacter pylori in mice.

Gastritis due to Helicobacter pylori is induced by a Th1-mediated response that is CD4 cell and gamma interferon (IFN-gamma) dependent. T-bet is a transcription factor that directs differentiation of and IFN-gamma secretion by CD4+ Th1 T cells. The goal of this study was to use two mouse models to elucidate the role of T-bet in gastritis due to H. pylori. C57BL/6J mice, congenic T-bet knockout (KO) mutants, or congenic SCID (severe, combined immunodeficient) mutants were given live H. pylori by oral inoculation. SCID mice were given CD4+ splenocytes from C57BL/6J or T-bet KO mice by intraperitoneal injection. Twelve or 24 weeks after bacterial inoculation, C57BL/6J mice developed moderate gastritis but T-bet KO mice and SCID mice did not. In contrast, SCID recipients of either C57BL/6J T cells or T-bet KO T cells developed gastritis 4 or 8 weeks after adoptive transfer. In recipients of C57BL/6J CD4+ cells but not recipients of T-bet KO cells, gastritis was associated with a delayed-type hypersensitivity response to H. pylori antigen and elevated gastric and serum IFN-gamma, interleukin 6, and tumor necrosis factor alpha. In spite of the absence of IFN-gamma expression, indicating failure of Th1 differentiation, CD4+ T cells from T-bet KO mice induce gastritis in H. pylori-infected recipient SCID mice. This indicates that Th1-independent mechanisms can cause gastric inflammation and disease due to H. pylori.

Tibiotarsal fracture repair in a bald eagle (Haliaeetus leucocephalus) using an interlocking nail.

A 14-yr-old, 5.13-kg bald eagle (Haliaeetus leucocephalus) was hit by a car and presented to the Michigan State University Small Animal Clinic with an open, grade II, transverse, midshaft, Winquist-Hansen type-II-comminuted left tibiotarsal fracture. The fracture was reduced and fixation established with a 4.7-mm-diameter, 112-mm-long, four-hole veterinary intramedullary interlocking nail maintained in position by single 2-mm transcortical screws placed in the main proximal and distal fragments. The bird was weight bearing on the bandaged limb 48 hr postoperatively. Radiographs obtained 4 wk postoperatively revealed bridging callus over three of four cortices. The bird was released after 5 mo of rehabilitation.