Within-individual stability of obesity-related biomarkers among women.

OBJECTIVE: Novel biomarkers including proinflammatory cytokines and adipokines are being explored as potential mediators of cancer and other obesity-related conditions. Prospective studies linking biomarker levels with disease outcomes often measure biomarkers at a single time point and assume that the within-individual variation in levels is small compared with the interindividual variation. However, this assumption is seldom tested. METHODS: This study examined the within-individual stability over time of plasma adiponectin, resistin, leptin, plasma activator inhibitor type 1, hepatocyte growth factor, tumor necrosis factor alpha, interleukin 6, and insulin among healthy young women. RESULTS: The study included 17 women (9 Black non-Hispanic, 2 Black Hispanic, 2 White Hispanic, and 4 other race/ethnicity) with mean age of 32.3 years, mean body mass index of 31.2 kg/m2, and 76% prevalence of smoking. Analysis of intraclass correlation (ICC) suggested high to moderate correlation over repeated samples taken over 3 years in levels of resistin (ICC = 0.95), hepatocyte growth factor (0.91), plasma activator inhibitor type 1 (0.84), adiponectin (0.73), insulin (0.62), and leptin (0.58). ICCs were weaker for levels of proinflammatory cytokines, tumor necrosis factor alpha (0.39), and interleukin 6 (0.47). CONCLUSION: In this population of minority young females with a high prevalence of overweight and smoking, several obesity-related endocrine markers were stable over a period of 3 years. This supports the feasibility of longitudinal studies relating these biomarkers to the future occurrence of cancer and other health consequences of obesity.     

Fish consumption and breast cancer risk

The omega-3 fatty acids, especially long-chain eicosapentaenoic acid (20:5n-3) and docosahexaenoic (22:6n-3) contained in "fatty" fish, have consistently been shown to retard the growth of breast cancer in vitro and in animal experiments. In contrast, studies of the association between fish consumption and breast cancer risk in human populations have not consistently shown inverse associations. However, previous studies have not considered the specific types of fish consumed. Using data from a large, nationwide case-control study conducted in Sweden, we examined the association between consumption of fatty and lean fish and breast cancer risk. Odds ratios (OR) and 95% confidence intervals were computed from unconditional logistic regression models. High consumption of fish was weakly associated with reduced breast cancer risk, and the association was not statistically significant. With multivariate adjustment, the OR for women with the highest consumption (> or =3.5 servings/wk) compared with women with the lowest (virtually none) was 0.88 (95% confidence interval = 0.60-1.29, P for trend = 0.15). When type of fish was examined separately, the association was similar for fatty and lean fish.     

Implications for altered glutamate and GABA metabolism in the dorsolateral prefrontal cortex of aged schizophrenic patients

OBJECTIVE: Pharmacological, clinical, and postmortem studies suggest altered gamma-aminobutyric acid (GABA)-ergic and glutamatergic function in patients with schizophrenia. The dorsolateral prefrontal cortex is one key locus of abnormality. The precise neurochemical mechanisms underlying neurotransmitter alterations, such as hypoglutamatergia or GABA dysfunction, are not well understood. This study investigated key biochemical elements of GABA and glutamate metabolism in brain specimens from schizophrenic patients. The activities of nine principal GABA and glutamate-associated metabolic enzymes were measured concurrently in the dorsolateral prefrontal cortex of antemortem-assessed and neuropathologically characterized schizophrenic and comparison subjects. METHOD: Postmortem dorsolateral prefrontal cortex specimens from schizophrenia, Alzheimer's disease, and normal nonpsychiatric comparison subjects were assayed to determine activities of the principal glutamate and GABA-metabolizing enzymes glutamine synthetase, glutamate dehydrogenase, alpha-ketoglutarate dehydrogenase, phosphate-activated glutaminase, alanine aminotransferase, aspartate aminotransferase, glutamic acid decarboxylase, GABA-transaminase, and succinic semialdehyde dehydrogenase. RESULTS: Glutamic acid decarboxylase activities were twofold greater and phosphate-activated glutaminase activities were fourfold greater in the schizophrenic group than in the comparison group. Differences in postmortem interval, tissue pH, inhibition of phosphate-activated glutaminase, and medication effects could not account for the differences. Differences in phosphate-activated glutaminase and glutamic acid decarboxylase activities in equivalent specimens from Alzheimer's patients were not observed. The activities of the remaining enzymes were unchanged. CONCLUSIONS: Greater phosphate-activated glutaminase and glutamic acid decarboxylase activities, specific to schizophrenia patients, provide additional biochemical evidence that dorsolateral prefrontal cortex glutamate and GABA metabolism is altered in schizophrenic subjects. These greater activities are consistent with models of a dysregulated glutamatergic/GABA-ergic state in schizophrenia.     

Abnormalities of the RB1 pathway in ovarian serous papillary carcinoma as determined by overexpression of the p16(INK4A) protein.

Dysfunction of proteins involved in the G1 to S transition of the cell cycle, such as p16(INK4A) and RB1, is common in many cancer types. A screen of p16 protein expression was performed in benign, borderline, and invasive ovarian tumors, together with endometrial cancers, aligned on a tissue microarray. We observed frequent p16 overexpression in serous papillary carcinomas of ovarian and endometrial origin. An extended cohort of ovarian serous papillary carcinomas was examined to further evaluate the frequency of p16 overexpression. Strong, uniform staining in the majority of cancer cells occurred commonly in invasive serous papillary ovarian cancers, particularly in grade 3 carcinomas. RB1 protein expression abnormalities were rare. Our data indicate that abnormalities in the retinoblastoma pathway, as determined by p16 overexpression, are common in serous papillary carcinomas and are probably an early event.     

A BPA survey of recently appointed consultants

A postal survey of recently appointed consultant paediatricians was undertaken to determine whether they perceived their training had adequately equipped them for their current job. The response rate was 69% (207/299). After excluding replies from consultants trained outside the UK the analysis was carried out on 167 replies. Trainees held a mean 5.2 posts during general and higher professional training, necessitating a mean 1.8 house moves. Altogether 82% felt moves were beneficial to training but 46% found moves 'very disruptive' to family life. Only 12% of district general hospital and 22% of teaching hospital senior registrars took two research sessions a week. Supervision and training in research was absent or poor for more than 60%; 24% felt major changes and 55% moderate changes were needed to current training. Training in non-clinical skills was particularly in demand and a curriculum for both trainers and trainees with regular appraisals is required. Research at senior registrar level needs review and educational methods improved to achieve better training in a shorter period.