Differential expression of two forms of GABAA receptor gamma 2-subunit in mice.

The gamma-aminobutyric acid type A (GABAA) receptor gamma 2-subunit is important for benzodiazepine action. In previous studies, two forms of gamma 2-subunit have been found which are generated by RNA alternative splicing (gamma 2L and gamma 2S) and differ by the presence or absence of an 8-amino acid insertion in the major intracellular loop between proposed transmembrane domains M3 and M4. We have used the RNase protection assay to study regulation of expression of the two forms of gamma 2-subunit in mouse brain, as judged from mRNA levels. We find that gamma 2L and gamma 2S are differentially expressed in brain regions and that gamma 2S is expressed at a fairly constant level during brain development while gamma 2L increases dramatically with maturation. Their differentially regulated expression suggests further that gamma 2L and gamma 2S form receptors with important functional differences.     

Day-to-Day Variation in Iron Status Indexes is Similar for Most Measures in Elderly Women With and Without Rheumatoid Arthritis

Objective To determine the day-to-day variation in biochemical measures of iron status in a group of elderly women with rheumatoid arthritis compared with a group of healthy elderly women.Design Venous blood samples were collected from each subject on 3 nonconsecutive days during a 2-week study period; subjects had fasted overnight. Variability in hemoglobin level, hematocrit value, serum iron concentration, total iron-binding capacity, transferrin saturation, serum ferritin concentration, and plasma transferrin receptor level was determined.Subjects Two groups of women, one with rheumatoid arthritis (n=10) and another that was apparently healthy (n=10).Statistical analyses Variance component analysis was used to estimate the biological variation (σ²_day) and analytic variation (σ²_rep) for each iron index. The coefficient of variation (CV) for each variance component was calculated: coefficient of biological variation = CV_day, coefficient of analytic variation = CV_rep, and coefficient of a single future determination = CV_fd.Results The CV_rep for all iron indexes was smaller than the CV_day in both groups. The CV_day was considerably higher for serum iron concentration and for transferrin saturation than for the other indexes in both groups (16.6% arid 16.6% in healthy subjects and 33.6% and 28.2%, respectively, in subjects with rheumatoid arthritis). The higher CV_day for serum iron concentration and transferrin saturation translated into a higher CV_fd for these indexes. Because of the higher variance for these two indexes, more sampling days were required for reliable estimates. CV_da and CV_fd for plasma transferrin receptor level were relatively low.Conclusions These findings corroborate our previous finding that variation of serum ferritin concentration in the elderly is lower than that demonstrated in younger populations. This aging effect persists in the presence of rheumatoid arthritis. Fasting appeared to improve reliability in the determinations for serum iron concentration and transferrin saturation. Variability estimates for the indexes other than serum iron concentration and transferrin saturation were not altered by the inflammation of rheumatoid arthritis. Plasma transferrin receptor level is a reliable index for assessing iron status in populations with rheumatoid arthritis. J Am Diet Assoc. 1996; 96:247-251.     

Change in Nutrient Intakes, Number of Servings, and Contributions of Total Fat from Food Groups in 4- to 10-Year-Old Children Enrolled in a Nutrition Education Study

Objective To determine change in nutrient intakes, number of servings, and contributions of total fat from food groups in children who lowered their dietary fat intake.Design A research and demonstration study designed to lower plasma low-density lipoprotein cholesterol level. There were four study groups: two intervention and two control groups. All children had hypercholesterolemia except for those in one control group. Three 24-hour dietary recalls were collected on randomly assigned days over a 2-week period at baseline and 3 months after the intervention.Subjects Three hundred three 4- to 10-year old children from suburbs north of Philadelphia, Pa.Interventions One intervention involved a home-based, parent-child autotutorial program (PCAT group) with audiotaped stories and print materials for the children and their families; the other intervention involved one face-to-face counseling session with a registered dietitian (counseling group).Outcome measures Change in mean nutrient intakes compared with the Recommended Dietary Allowance (RDA); change in number of servings and mean grams of total fat contributed from 10 different food groups.Statistical analyses performed Analyses of variance and χ² analyses.Results Children in every study group had mean intakes of all nutrients (except vitamin D) greater than 67% of the RDA 3 months after the baseline measurement. Several food groups (ie, meats, dairy products, fats/oils, and desserts) provided less total fat to the diets of children who reduced their dietary lipid intake after 3 months (ie, PCAT and counseling groups). These children also reduced the mean number of servings selected from these food groups. Within these same food groups, some children consumed fewer servings of higher fat foods and more servings of lower fat foods.Applications/conclusions Children who lowered their dietary fat intake after intervention reported both quantitative and qualitative changes in food choices from several food groups. These choices did not significantly reduce their nutrient intakes. J Am Diet Assoc. 1996; 96:865-873.     

Vegetables, Fruit, and Cancer Prevention: A Review

In this review of the scientific literature on the relationship between vegetable and fruit consumption and risk of cancer, results from 206 human epidemiologic studies and 22 animal studies are summarized. The evidence for a protective effect of greater vegetable and fruit consumption is consistent for cancers of the stomach, esophagus, lung, oral cavity and pharynx, endometrium, pancreas, and colon. The types of vegetables or fruit that most often appear to be protective against cancer are raw vegetables, followed by allium vegetables, carrots, green vegetables, cruciferous vegetables, and tomatoes. Substances present in vegetables and fruit that may help protect against cancer, and their mechanisms, are also briefly reviewed; these include dithiolthiones, isothiocyanates, indole-3-carbinol, allium compounds, isoflavones, protease inhibitors, saponins, phytosterols, inositol hexaphosphate, vitamin C, D-limonene, lutein, folic acid, beta carotene, lycopene, selenium, vitamin E, flavonoids, and dietary fiber. Current US vegetable and fruit intake, which averages about 3.4 servings per day, is discussed, as are possible noncancer-related effects of increased vegetable and fruit consumption, including benefits against cardiovascular disease, diabetes, stroke, obesity, diverticulosis, and cataracts. Suggestions for dietitians to use in counseling persons toward increasing vegetable and fruit intake are presented. J Am Diet Assoc. 1996; 96:1027-1039.     

Increased circulating interleukin-7 levels in HIV-1-infected women

Sex-based differences in CD4 T-cell (CD4) counts are well recognized, but the basis for these differences has not been identified. Conceivably, homeostatic factors may play a role in this process by regulating T-cell maintenance and repletion. Interleukin (IL)-7 is essential for normal T-cell production and homeostasis. We hypothesized that differences in IL-7 might contribute to sex-based differences in CD4 counts. Circulating IL-7 levels were analyzed in 299 HIV-1-infected women and men. Regression analysis estimated that IL-7 levels were 40% higher in women than in men (P = 0.0032) after controlling for CD4 count, age, and race. Given the important role of IL-7 in T-cell development and homeostasis, these findings suggest that higher IL-7 levels may contribute to higher CD4 counts in women.     

The use of urine proteomic and metabonomic patterns for the diagnosis of interstitial cystitis and bacterial cystitis

The advent of systems biology approaches that have stemmed from the sequencing of the human genome has led to the search for new methods to diagnose diseases. While much effort has been focused on the identification of disease-specific biomarkers, recent efforts are underway toward the use of proteomic and metabonomic patterns to indicate disease. We have developed and contrasted the use of both proteomic and metabonomic patterns in urine for the detection of interstitial cystitis (IC). The methodology relies on advanced bioinformatics to scrutinize information contained within mass spectrometry (MS) and high-resolution proton nuclear magnetic resonance (1H-NMR) spectral patterns to distinguish IC-affected from non-affected individuals as well as those suffering from bacterial cystitis (BC). We have applied a novel pattern recognition tool that employs an unsupervised system (self-organizing-type cluster mapping) as a fitness test for a supervised system (a genetic algorithm). With this approach, a training set comprised of mass spectra and 1H-NMR spectra from urine derived from either unaffected individuals or patients with IC is employed so that the most fit combination of relative, normalized intensity features defined at precise m/z or chemical shift values plotted in n-space can reliably distinguish the cohorts used in training. Using this bioinformatic approach, we were able to discriminate spectral patterns associated with IC-affected, BC-affected, and unaffected patients with a success rate of approximately 84%.     

Macrophage and perisinusoidal cell kinetics in acute liver injury.

Perisinusoidal cells (PSCs) are currently regarded as the major source of extracellular matrix proteins during hepatic fibrogenesis in response to liver injury. However, the cellular mechanisms underlying their response to injury are not fully understood. One hypothesis is that the PSCs are stimulated by peptide growth factors produced by hepatic macrophages (Kupffer cells) in response to parenchymal cell damage. In this study we have investigated the kinetics of the PSC and macrophage populations in acute carbon tetrachloride-induced hepatic injury in rats. PSCs were identified immunohistochemically by detection of cytoplasmic desmin; monocytes and macrophages were detected using the monoclonal antibodies ED1 and ED2; cells in S phase were identified by immunohistochemical detection of nuclear-incorporated bromodeoxyuridine. The results showed an expansion of the desmin-positive PSC population, predominantly within the damaged perivenular zones, which reached a peak on days 3 and 4 following administration of carbon tetrachloride; this was contributed to by local PSC proliferation. The PSC response was preceded by an expansion of the macrophage population resulting from both local macrophage proliferation and influx of blood monocytes. These results are in keeping with the hypothesis that the PSC response to acute liver injury is mediated, at least in part, by hepatic macrophages.