Adhesion molecule expression on B-cell chronic lymphocytic leukemia cells: malignant cell phenotypes define distinct disease subsets

Expression of surface adhesion molecules of the Ig superfamily (CD54 and CD58), of the integrin family (beta 1, beta 2, and beta 3 chains), of the selectin family (L-selectin), and of the lymphocyte homing receptor (CD44) was analyzed on B-cell chronic lymphocytic leukemia (B- CLL) cells from 74 patients. The aim of the study was the definition of phenotypically distinct disease subsets and the correlation of adhesion molecule phenotypes with clinical parameters. Expression of CD58 on B- CLL cells defined more advanced disease stages. In comparison with beta chain-positive cases, patients whose cells did not express beta 1, beta 2, and beta 3 integrin chains fell into the most favorable prognostic group, with lower lymphocytosis and the absence of splenomegaly, diffuse bone marrow infiltration, and therapy requirement. A novel finding was the expression of beta 3 chains on cells from a minority (12 of 74) of B-CLL cases. beta 3 chains were always coexpressed with beta 1 and beta 2 chains. Two-color immunofluorescence analyses of adhesion molecules such as alpha x beta 2 integrin (LeuM5) and L- selectin (Leu8) showed that these markers were detectable on variable proportions of leukemic cells, thus confirming the intraclonal phenotypic heterogeneity of B-CLL. Differences in the intensity of CD44 expression were also shown among the various B-CLL clones. Finally, no major variations were shown by comparison of adhesion molecule phenotypes of leukemic cells simultaneously obtained from blood and bone marrow, and of CD5+ versus CD5- clones.     

Energy balance and type 2 diabetes: a report from the Shanghai Women's Health Study

BACKGROUND AND AIMS: The combined effect of the components of energy balance (energy intake and physical activity) and the development of type 2 diabetes (T2D) has not been adequately investigated. The aim of this study was to examine the components of energy balance and the incidence of T2D in a cohort of middle-aged women. METHODS AND RESULTS: A population-based prospective study of 64,227 middle-aged Chinese women who had no prior history of diabetes or chronic disease at study recruitment. Participants completed in-person interviews at baseline and follow-up surveys that collected information on diabetes risk factors including dietary and physical activity habits and disease occurrence. Anthropometric measurements were taken by trained interviewers at recruitment. Average follow-up time was 4.6 years. During 297,755 person-years of follow-up, 1608 new cases of T2D were documented. Body mass index (BMI) and weight gain (since age 20) were strongly associated with T2D incidence. Energy intake (EI) was associated with modestly increased risk, while physical activity (PA) was associated with decreased risk of T2D. Less active women with higher EI had higher risk of T2D (RR=1.96; 95% CI: 1.44, 2.67) than active women with lower EI (P(interaction)=0.02). The EI to PA (EI:PA) ratio was positively associated with T2D risk; the association was more evident among overweight and obese women (BMI > or = 23 kg/m(2)). CONCLUSION: These data suggest that energy balance plays an important role in the development of T2D, and this effect may be modified by BMI.     

Intravascular tumors: transvenous biopsy

A technique is described for transfemoral biopsy of intravenous tumors. Positive results were obtained at biopsy in three patients who had an intraluminal mass in the inferior vena cava and in one patient with a mass in the iliac vein. Transvenous biopsy is helpful in obtaining a histologic diagnosis and provides an alternative method to surgery or percutaneous transabdominal needle biopsy.     

Medullary carcinoma of thyroid gland in a girl aged 10 years

A healthy girl of 10 years presented with lumps on her tongue, shown on biopsy to be neuromas. She had had operations to her feet for pes cavus and was relatively long-limbed but had no other 'Marfanoid' features. She had a high plasma calcitonin level. At operation a normal sized thyroid gland was totally removed. It contained two discrete masses of malignant C-cells and diffuse foci elsewhere. The plasma calcitonin fell slowly to normal on follow-up but was noted to be rising 2 1/2 years later. We stress the importance of making this diagnosis as early as possible and mention briefly another child aged 15 months, similarly diagnosed and operated upon.     

SNAP-25 deficit and hippocampal connectivity in schizophrenia

Regional abnormalities of brain connectivity may be an important substrate for the expression of schizophrenia, a severe form of mental illness. Brain imaging and postmortem morphometric studies indicate hippocampal structure is abnormal in schizophrenia. To study molecular components of hippocampal connectivity the presynaptic proteins SNAP-25 and synaptophysin were assayed in postmortem samples. Immunocytochemical studies indicated reduced SNAP-25 immunoreactivity in schizophrenia compared to controls, particularly in the terminal fields of entorhinal cortex projections. Although there were no overall changes in synaptophysin immunoreactivity, in the granule cell layer of the dentate gyrus synaptophysin immunoreactivity was increased in schizophrenia. These results indicate that disconnection of a subset of hippocampal circuitry from the entorhinal cortex, as well as intrinsic changes in hippocampal connectivity, may contribute to the mechanism of illness in schizophrenia.