Age-dependent changes in the susceptibility to apoptosis of peripheral blood CD4+ and CD8+ T lymphocytes with virgin or memory phenotype

Susceptibility to apoptosis changes with age and most of the available data on lymphocytes refer to mitogen stimulated cells. We studied this susceptibility in quiescent, purified CD4+ or CD8+ T cells from a group of Italian old people compared with a group of young people. We found that an apoptotic agent such as 2-deoxy-D-ribose (dRib), which acts via glutathione depletion and oxidative stress, was more effective in CD4+ T cells from young donors, while no difference was found in CD8+ T cells. On the contrary, another agent such as TNF-alpha, which acts via receptor engagement, was more effective in CD8+ T cells from old subjects, and no difference was found in CD4+ T cells. When marker of activation-memory were investigated, no difference between young and old subjects was found when dRib was used. Differently, when TNF-alpha was used, memory and activated CD4+ T cells from old donors were less sensitive than younger counterparts, while memory CD8+ T cells from old donors were more sensitive than younger counterparts. This suggests that age-related changes in susceptibility to apoptosis of resting T cells largely depend on the type of the apoptotic stimulus which is used as well as on the memory phenotype of the cells. These results may also account, at least in part, for the deep remodelling of T cell repertoire that occurs during ageing.     

DTNBP1 haplotype influences baseline assessment scores of schizophrenic in-patients

Dysbindin gene (DTNBP1) has been associated with schizophrenia, but literature findings are inconsistent, and further analyses are required. This study is aimed to investigate if a set of DTNBP1 variations might influence clinic psychotic phenotype or treatment response in a sample of 240 Korean schizophrenic in-patients. Four variants have been selected (rs3213207; rs1011313; rs16876759; rs2619522) on the basis of previous findings of association with schizophrenia, bipolar disorder and antidepressant response. Single marker analysis gave marginal results. Haplotype analysis identified a significant association between A–A (rs3213207(A/G), rs1011313(A/G)) haplotype and lower PANSS total and positive scores at baseline (p = 0.01; 0.02) and at discharge (p = 0.008; 0.005). Covariate analysis revealed a more stable significant association between A–A haplotype and baseline scores. These results suggest a protective effect of A–A haplotype on psychotic positive symptoms at baseline.     

Influence of diabetic treatment regimens on vitamin D metabolism in elderly patients

The influence of diabetic treatment regimens on vitamin D metabolism and on bone mineral content has been explored in 41 elderly patients with normal renal and hepatic functions. The data obtained suggest that oral treatment with hypoglycemic compounds exerts a negative influence on vitamin D metabolism. It is possible that the reduction of 25-OH-hydroxy-vitamin D levels depends on a high conversion rate to the active 1,25-dihydroxy-vitamin D, as a consequence of parathormone-stimulated increase of 1-alpha-hydroxylase activity. On the other hand, no differences in bone mineral densities were observed in correlation with the diabetic treatment regimens. Therefore, oral treatment with hypoglycemic compounds can only be associated with an accelerated vitamin D metabolism.     

Inflammatory pseudotumor of the lung. Diagnostic-therapeutic effectiveness of its radical resection

Clinical, therapeutical observations and experience in 3 cases of pulmonary inflammatory pseudotumors (PIP) are presented. A retrospective analysis is made of cases with pulmonary "mass" suspected as malignant tumor, resected in a general surgery department between 1988 and 1995, and finally diagnosed as inflammatory pseudotumor. Three of the 10 cases originally diagnosed as malignant lung tumor were inflammatory pseudotumor (30%). Pulmonary inflammatory pseudotumors, may be a pitfall diagnosing a lung mass and implicate legal problems. Surgical resection leads to the final diagnosis in doubtful cases. A wide resection has a diagnostic aim and may preserve healthy parenchyma. Clinicians, pathologists and surgeons should accurately inform patients with doubtful diagnosis of pulmonary malignancy. Any decision should be kept altogether either choosing the simple observation or the timely surgical diagnostic and therapeutical approach.     

Proliferating cell nuclear antigen assessed by a computer-assisted image analysis system in patients with chronic viral hepatitis and cirrhosis

BACKGROUND: Assessment of liver cell proliferation by immunodetection of proliferating cell nuclear antigen may predict regenerative potential and survival of liver and hepatocellular carcinoma risk in patients with chronic viral hepatitis. AIM: To evaluate proliferating cell nuclear antigen status and its clinical significance in a large cohort of patients with chronic viral hepatitis and different degree of liver damage by a computer assisted imaging analysis system. MATERIALS: Liver biopsies from 358 patients with chronic hepatitis (259 males, 49 years, 63% with hepatitis C infection, 27% with hepatitis B virus, 10% with multiple infections) were studied. METHODS: Proliferating cell nuclear antigen was localised by immunoperoxidase on microwave oven pre-treated formalin-fixed, paraffin embedded sections using PC10 monoclonal antibody. Proliferating cell nuclear antigen labelling index was calculated by an automated imaging system (Immagini e Computers, Milan, Italy). RESULTS: Mean proliferating cell nuclear antigen labelling index ranged from 0.1% for patients with minimal changes to 3.6% for those with cirrhosis and hepatocellular carcinoma. Overall, proliferating cell nuclear antigen labelling index was higher in males, in older patients, in multiple infections and in hepatitis C virus compared to hepatitis B virus related cases. By linear regression analysis, proliferating cell nuclear antigen labelling index correlated with older age, male gender; higher transaminase levels, hepatitis C virus, higher histological gradIng and staging: by multivariate analysis male gender, hepatitis C virus, higher grading and staging resulted as independent variables. Both hepatitis C virus or hepatitis B virus cirrhotics had similar liver cell proliferation rate but those with hepatitis B virus had higher prevalence of liver cell dysplasia with respect to those with hepatitis C virus. CONCLUSIONS: Proliferating cell nuclear antigen labelling index was a reliable assay for assessing liver cell proliferation rate in patients with chronic viral hepatitis and correlated with liver disease severity