Is Theiler's murine encephalomyelitis virus infection of mice an autoimmune disease?

Viruses can initiate disease by many different means. Direct viral, immune mediated and host factors all play important parts. Molecular mimicry or having cross-reacting determinants that result in immune responses which have the potential to cause damage can be incorporated into this framework. Here, autoimmune responses generated by virus infection have been presented in relation to these other parameters. The cross-reacting immune response originally generated by virus would have to be directed toward or involve a disease inducing site such as an EAE (encephalitogenic), thyroiditis, or diabetogenic site. If the cross-reaction took place at a nondisease inducing site, the ensuring immune response may result in the production of autoantibodies, however no disease would occur. In other systems autoantibodies can potentiate an ongoing inflammatory response. This may be the case that is described here with Theiler's murine encephalomyelitis virus infection. Lastly, viruses having common determinants with MHC determinants may modify immune responses leading to immunosuppression and allowing virus to persist. In addition, similar determinants may lead to disease by an alternative route. For example, we have described a region of human cytomegalovirus that has a common determinant with HLA DR beta chain. This region is associated with diabetes in humans (Todd et al. 1988). Thus, many factors are involved in the outcome of disease induction by viruses of which autoimmunity is one.     

Body protein and lipid deficit in tumour-bearing rats in relation to age.

Cancer cachexia is among the most dramatic situations of depletion in body energy reserves. To ascertain whether the pattern of body composition alteration during tumour development is influenced by aging as in uncomplicated starvation, we compared the difference of body composition between Yoshida sarcoma bearing rats and young (200 g, 7 weeks) and adult (400 g, 13 weeks) control rats. After the same duration of tumour bearing, mass and composition of tumours were similar in adult and young rats, indicating that they are independent of host age. Food intake decreased to a remarkably similar value in both young and adults. Body water content was elevated in hosts of both ages. The relative deficit of body lipid vs controls was similar for both, the absolute lipid deficit being therefore larger in adult than in young tumour-bearing rats (14.3 +/- 4.4 g vs 6.8 +/- 0.9 g; P < 0.01). In contrast, there was a relatively larger deficit of body protein in young rats. Paradoxically, these rats still maintained a positive nitrogen balance whereas this balance was negative in adult tumour-bearing rats. In conclusion, as previously shown in uncomplicated undernutrition, the anorexia induced by Yoshida sarcoma development is still associated with some protein accretion in young rats whereas cachexia develops in adults.     

Low molecular weight chitosan inhibits obesity induced by feeding a high-fat diet long-term in mice

Three low molecular weight chitosans (molecular weight: 21, 46 and 130 kDa) obtained by enzymatic hydrolysis of a high molecular weight chitosan (average molecular weight: 650 kDa) had low viscosity and were water-soluble. The effects of these water-soluble chitosans on pancreatic lipase (in-vitro) and the elevation of plasma triacylglycerol concentration after the oral lipid tolerance test were examined in mice. The water-soluble 46-kDa chitosan was the most effective at inhibiting pancreatic lipase activity (in-vitro) and plasma triacylglycerol elevation after the oral lipid tolerance test. Based on this result, the effects of the 46-kDa chitosan on increases in bodyweight, various white adipose tissue weights, and plasma and liver lipids were examined in mice fed a high-fat diet for 20 weeks. Water-soluble 46-kDa chitosan (300 mg kg(-1), twice daily) prevented increases in bodyweight, various white adipose tissue weights and liver lipids (cholesterol and triacylglycerol) in mice fed a high-fat diet, and further increased the faecal bile acid and fat. The results suggest that the lipid-lowering effects of the 46-kDa chitosan may be mediated by increases in faecal fat and/or bile acid excretion resulting from the binding of bile acids, and by a decrease in the absorption of dietary lipids (triacylglycerol and cholesterol) from the small intestine as a result of the inhibition of pancreatic lipase activity. Water-soluble 46-kDa chitosan (100 and 300 mg kg(-1), twice daily) did not cause liver damage with the elevation of glutamic oxaloacetic transaminase and glutamic pyruvic transaminase, or kidney damage with the elevation of blood nitrogen urea. It was concluded that water-soluble 46-kDa chitosan is a safe functional food.     

Neuroserpin (PI-12) is upregulated in high-grade prostate cancer and is associated with survival

We carried out Genechip analysis using prostate cancer and non-malignant tissue to identify specific genes related to prostate cancer. We focused on neuroserpin (PI-12), which has been identified as one of the genes with high expression in prostate cancer. We analyzed the relationship between its expression pattern and clinical characteristics. Prostate cancer and normal prostate tissue were analyzed by Affymetrix GeneChip technology. We carried out real-time quantitative PCR on a total of 102 specimens: 45 of normal prostate, 45 of previously untreated prostate cancer (constituting 45 pairs of samples obtained at radical prostatectomy, with each pair dissected from the same prostate specimen) and 12 of recurrent hormone refractory prostate cancer (HRPC). Results showed that the neuroserpin gene was more highly expressed in prostate cancer than in normal prostate tissue. Neuroserpin expression in untreated prostate cancer was significantly higher than that in normal prostate. In HRPC it was significantly higher than that in untreated prostate cancer and normal prostate. In untreated prostate cancer, neuroserpin expression was significantly higher in high grade tumors such as poorly differentiated adenocarcinoma than in lower grade tumors such as well or moderately differentiated adenocarcinoma. Higher neuroserpin expression was associated with shorter recurrence-free survival after radical prostatectomy, shorter recurrence-free survival in HRPC patients and shorter overall survival in HRPC patients. The neuroserpin gene may be associated with the development, progression and aggressiveness of prostate cancer. Our present data suggests that higher neuroserpin expression may predict an unfavorable outcome after radical prostatectomy or hormone therapy.     

Acute encephalopathy in inherited metabolic diseases

Acute encephalopathy, regardless of the cause, is a medical emergency. In addition to being a common manifestation of a variety of acquired medical or surgical conditions, it is a presenting feature of number of inherited metabolic diseases, particularly in young children. Because of the importance of identifying treatable inherited metabolic diseases early, initial investigation must not be delayed. In addition, it is important to keep their serum and urine for investigation later.