Diaphragmatic Hernia Induced in Rat Fetuses by Administration of Bisdiamine

Administration of N, N'-bis (dichloroacetyl)-l,8-octamethylenediamine, bisdiamine, to pregnant Donryu rats on a single day of gestation induced unilateral and bilateral diaphragmatic hernias in fetuses with high incidence. The protruded liver was not covered with a serous membrane or a muscular layer. Incidence of unilateral diaphragmatic hernia on the left side was high when bisdiamine was administered on day 9 or 13 of gestation, and that on the right side was high when administered on day 12 of gestation. Incidence of bilateral diaphragmatic hernia was high when bisdiamine was administered on day 12 of gestation. Differences in sensitivity to hernia formation according to day of bisdiamine administration between right and left sides may reflect differences in developmental chronology between the two sides. Two distinct times for induction of left diaphragmatic hernia might be attributed to at least two different mechanisms. The present model is expected to help analyzing not only anatomical characteristics of congenital diaphragmatic hernia but also possible mechanisms responsible for their development.     

Malignant transformation of renal angiomyolipoma

In the present paper, two cases of malignant transformation of renal angiomyolipoma without tuberous sclerosis are reported. Pathological examination revealed that, in both cases, in addition to the areas affected by typical angiomyolipoma, there were areas that contained elevated numbers of perivascular epithelioid cells with prominent nuclear pleomorphism. Immunohistochemical examination revealed that both cases were negative for keratin and epithelial membrane antigen, but were positive for the melanogenesis-related marker HMB-45. Metastatic diseases appeared 40 months after radical nephrectomy in the first case and 18 months in the second case.     

CASE REPORT: Insulin - like growth factor II expression in hepatocellular carcinoma with alcoholic liver fibrosis accompanied by hypoglycaemia

This case of hepatocellular carcinoma (HCC) with alcoholic liver fibrosis, which was not associated with hepatitis viruses, was accompanied by hypoglycaemia. The immunoreactive insulin level was low and other hormonal examinations were almost normal. Immunohistochemical studies showed a high level of insulin-like growth factor II (IGF2) peptide in the HCC section and the size heterogeneity of serum IGF2 investigated by western blot revealed a large form at approximately 15 kDa. These results suggest that the HCC with alcoholic liver fibrosis produced IGF2 and that the hypoglycaemia was caused by tumour-associated IGF2.     

Short and long-term effects of interferon on serum markers of hepatitis C virus replication

Abstract Hepatitis C virus RNA (HCV-RNA) and serological markers of HCV infection were measured in 30 patients with chronic hepatitis C who had been treated with interferon (IFN). Patients were classified into four groups according to serum alanine aminotransferase (ALT) levels after treatment. These were: as complete responders (CR); partial responders (PR); transient responders (TR); and non-responders (NR). In all 11 patients in the CR group, HCV-RNA disappeared from serum for at least 24 months and anti-c100-3 decreased progressively during this time. In the PR group, four of five patients were positive for HCV-RNA in spite of the improvement of ALT levels and decline of anti-c100-3. In the TR and NR groups, HCV-RNA disappeared transiently or remained persistently positive. The results indicate that IFN-mediated improvement of ALT and decrease of anti-HCV (anti-c100-3) were not always related to the disappearance of HCV-RNA from serum. On the other hand, sustained disappearance of HCV-RNA from serum was demonstrated in the patients who did not have post-treatment ALT relapse. This indicates that IFN can eradicate HCV from serum in some patients and provide a clinical remission of chronic hepatitis C.     

Clinical features and course of type A and type B vitiligo

Four hundred and eighty one cases of vitiligo (acquired idiopathic depigmentation) were studied clinically. They were divided into two types, type B, in which depigmented patches are confined to a definite dermatome in the same manner as herpes zoster, and type A, which included all cases of vitiligo not classified as type B. The ratio of type A:type B was approximately 3:1. Onset of type A vitiligo could occur at any age, whereas type B generally affected the young. The activity of type B vitiligo usually ceased after one year, following rapid spread over the particular dermatomal area. However, in type A vitiligo new depigmented patches continued to appear throughout the patients’lives. Association with halo naevus and Köbner's phenomenon were observed exclusively in type A. Association with diseases with a proven or suggested allergic or immunological aetiology was more often found in type A. These findings support our hypothesis that type A and type B vitiligo have a different pathogenesis and that autoimmune mechanisms play a role only in type A.     

TNF-α, nitric oxide and IFN-γ are all critical for development of necrosis in the small intestine and early mortality in genetically susceptible mice infected perorally with Toxoplasma gondii

We previously reported that genetic susceptibility of mice to peroral infection with T. gondii is associated with CD4+ T cell-dependent, interferon (IFN)-gamma-mediated necrosis of their small intestine. We examined the role of tumour necrosis factor (TNF)-alpha and nitric oxide (NO), in addition to IFN-gamma. At 7 days after infection, a marked increase in CD4+ T cells was observed in lamina propria mononuclear cells (LPC) of the small intestine as compared with normal mice, and significantly greater amounts of mRNA for IFN-gamma, TNF-alpha, and inducible NO synthase (iNOS) were detected in LPC of the small intestine of infected than uninfected animals. Treatment of infected mice with anti-TNF-alpha monoclonal antibody (mAb) or the iNOS inhibitor, aminoguanidine, prevented necrosis and prolonged time to death. Infected iNOS-targeted mutant mice did not develop the disease whereas infected, control mice did. Treatment with anti-TNF-alpha mAb did not affect the expression of IFN-gamma in the LPC but inhibited expression of iNOS in the infected mice, indicating the role of TNF-alpha in the induction of iNOS. These results suggest that NO induced by a combination of IFN-gamma and TNF-alpha through activation of iNOS is a critical mediator of intestinal pathology and contributes to early mortality in genetically susceptible mice.