Coexpression of leptin receptor and preproneuropeptide Y mRNA in arcuate nucleus of mouse hypothalamus

Leptin, the protein product of the adipose tissue-specific ob (obese) gene (1), reduces the body weight, adiposity and food intake of obese ob/ob mice on peripheral or central injection (2, 3, 4). [125I]leptin binding has been detected in mouse choroid plexus (5), from which a leptin receptor gene was expression cloned (5). The gene has at least 6 splice variants (6, 7). Leptin receptor mRNA was localized in the hypothalamus by in situ hybridization being particularly abundantly expressed in the arcuate nucleus (8). There is evidence linking the physiological effects of injected leptin with hypothalamic neuropeptide Y (9, 10) (NPY), which has potent central effects on food intake and energy balance (11), and is also expressed in the arcuate nucleus. Here we report dual in situ hybridization studies for leptin receptor and NPY gene expression in the mouse arcuate nucleus, where the majority of cells examined expressed both genes. This provides the first direct evidence that leptin acts on cells that express NPY mRNA.     

Overview of randomized trials of intravenous heparin in patients with acute myocardial infarction treated with thrombolytic therapy

Intravenous heparin is routinely given after thrombolytic therapy for patients with acute myocardial infarction in the United States and in some, but by no means all, other countries. Several trials have documented improved infarct-artery patency in patients treated with heparin; however, none was large enough individually to assess the effect of heparin on clinical outcomes. We performed a systematic overview of the 6 randomized controlled trials (1,735 patients) to summarize the available data concerning the risks and benefits of intravenous heparin versus no heparin after thrombolytic therapy. Mortality before hospital discharge was 5.1% for patients allocated to intravenous heparin compared with 5.6% for controls (relative risk reduction of 9%, odds ratio 0.91, 95% confidence interval 0.59 to 1.39). Similar rates of recurrent ischemia and reinfarction were observed among those allocated to heparin therapy or control. The rates of total stroke, intracranial hemorrhage, and severe bleeding were similar in patients allocated to heparin; however, the risk of any severity of bleeding was significantly higher (22.7% vs 16.2%; odds ratio 1.55, 95% confidence interval 1.21 to 1.98). There was no significant difference in the observed effects of heparin between patients receiving tissue-type plasminogen activator and those receiving streptokinase or anisoylated plasminogen streptokinase activator complex, or between patients who did and did not receive aspirin. The findings of this overview demonstrate that insufficient clinical outcome data are available to support or to refute the routine use of intravenous heparin therapy after thrombolysis. It is not known if these findings are due to lack of statistical power, inappropriate levels of anticoagulation, or lack of benefit of intravenous heparin. Large randomized studies of heparin (and of new antithrombotic regimens) are needed to establish the role of such therapy.     

Volunteer facilitators assist community practices with enhancing cancer control

OBJECTIVE: To explore the feasibility of recruiting, training, and placing in the field volunteers to assist community practices in enhancing the provision of preventive care. DESIGN: A case series design followed up a cohort of volunteers prospectively as they were recruited, trained, and assigned to practices. SETTING: The New Hampshire Division of the American Cancer Society recruited and trained the volunteer facilitators. INTERVENTION: Assistance from the volunteers in implementing a preventive services office system served as the intervention for practices. Volunteers were trained and supported by professional staff and an implementation manual. MAIN OUTCOME MEASURES: Recruitment, training, and volunteer experiences in working with practices, as well as the costs of supporting the program, were assessed. RESULTS: Twenty-six volunteers were trained. Of the 15 assigned to practices, 11 had begun to assist their assigned practices to establish a preventive services office system. Extensive planning, patience, and support were required. CONCLUSION: Volunteers recruited and supported by an intermediary organization can provide assistance to practices in implementing a preventive services office system.     

Physical and genetic map of the mitochondrial genome of Cryphonectria parasitica Ep155

In the chestnut-blight fungus, Cryphonectria parasitica, a cytoplasmically transmissible (infectious) form of hypovirulence is associated with mitochondrial DNA (mtDNA) mutations that cause respiratory deficiencies. To facilitate the characterization of such mutations, a restriction map including the probable location of 13 genes was constructed for a relatively well-characterized virulent strain of the fungus, Ep155. The physical map is based on the order of all fragments generated by cleavage of the mtDNA by the PstI restriction endonuclease and includes some of the cleavage sites for HindIII, EcoRI, and XbaI. It was constructed from hybridization patterns of cloned mtDNA fragments with Southern blots of mtDNA digested with the four restriction enzymes. On this map, the probable locations of genes commonly found in the mitochondrial genomes of ascomycetes were determined by low-stringency hybridization of cloned Neurospora crassa mitochondrial gene probes to Southern blots of C. parasitica mtDNA. The data indicate that the mtDNA of strain Ep155 is a circular molecule of approximately 157 kbp and ranks among the largest mitochondrial chromosomes observed so far in fungi. The mtDNAs of 11 different C. parasitica isolates range in size from 135 to 157 kbp and in relatedness from 68 to 100 percent, as estimated from restriction-fragment polymorphisms. In addition to the typical mtDNA, the mitochondria of some isolates of the fungus contain double-stranded DNA plasmids consisting of nucleotide sequences not represented in the mtDNA of Ep155.     

Continuity of care and delivery of ambulatory services to children in community health clinics

This study assesses how continuity of care influences receipt of preventive care and overall levels of ambulatory care among children and adolescents in community health clinics (CHCs). It is a secondary data analysis of the 1988 Child Health Supplement to the National Health Interview Survey. Of 17,110 children in the sample population, the 1465 who identified CHCs as their routine source of care formed the study population. Continuity of site was defined as identification of a CHC as a source of both routine and sick care, and continuity with a clinician was defined as identification of a specific clinician for sick visits. In bivariate analyses both continuity with the CHC and with a specific clinician were associated with increased levels of preventive care and overall ambulatory care. In logistic regression models, continuity of care was associated with nearly a two-fold increase in the odds of receiving age-appropriate preventive care. Alternatively, insurance status was a better predictor of receipt of overall levels of ambulatory care. We conclude that expanding financial access alone is unlikely to sufficiently improve low-income children's access to Community Health Clinics. Additional emphasis on localizing the delivery of both routine and sick care services in a single site or with a specific clinician may be needed to achieve higher levels of both preventive care and overall ambulatory care.     

Zinc modulates mononuclear cellular calcitriol metabolism in peritoneal dialysis patients

Zinc has long been known to play a role in maintaining immunologic function. Hypozincemia, however, is common in patients with end-stage renal disease (ESRD) treated with continuous ambulatory peritoneal dialysis (CAPD). We previously demonstrated that zinc depletion limits the ability of animals to achieve maximum circulating calcitriol levels in response to the stress of calcium or phosphorus depletion. It was unclear, however, whether changes in the circulating levels of calcitriol in these settings was associated with a direct effect on renal 1-alpha hydroxylase activity, or whether the zinc dependence of the stimulated calcitriol response involved an integrated systemic response in intact animals. In addition it was unclear whether circulating zinc levels or zinc nutritional status modified calcitriol metabolism in humans. To better understand the role zinc plays in the immune response in patients with ESRD, we studied IL-1, calcitriol and tumor necrosis factor-alpha production by mononuclear cells from blood and peritoneal effluents of 22 patients with ESRD treated with CAPD. Macrophages from peritoneal effluents and peripheral blood mononuclear cells were isolated and pulsed with phytohemagglutinin in medium to which different concentrations of zinc chloride, copper chloride, and carbonyl cyanide p-(trifluoromethoxy)-phenyl-hydrazone (FCCP), an inhibitor of mitochondrial function were added. Supernatant interleukin-1, calcitriol, and tumor necrosis factor-alpha levels were subsequently measured. We demonstrated a zinc concentration dependent increase in stimulated IL-1 alpha and -beta, and TNF-alpha release in both peripheral mononuclear cells and peritoneal macrophages from patients with ESRD treated with CAPD. The effect is zinc specific, as it is not reproduced by copper or chloride supplementation. A zinc concentration dependent increase in peritoneal macrophage calcitriol release was also noted. FCCP blocked the cellular production of IL-1 alpha, IL-1 beta, and TNF-alpha, but had little effect on zinc-induced stimulated mononuclear cell supernatant calcitriol levels. The different shape of the zinc dose response curve, and the lack of correlation between paired IL-1 and calcitriol supernatant levels suggests the effect of zinc on mononuclear cellular cytokine and calcitriol production is mediated through different pathways.     

The organization of leg movements in preterm and full-term infants after term age

In a sample of 13 full-term and 10 preterm infants, the development of kicking movements was studied at 6, 12, and 18 weeks (corrected) age. In healthy full-term infants some characteristics are strikingly stable, such as the duration of the flexion and extension phase and the within-joint organization. These parameters did not differ in preterm compared to full-term infants. For other features, however, developmental changes and differences were observed. Full-term infants tended to decrease their kick frequencies slightly with age. In preterm infants much higher initial kick rates were found, followed by a steep decrease, which resulted in kick frequencies comparable to the full-term levels after the (corrected) age of 12 weeks. There is a tight coupling between the movements in the different joints of the leg in full-term newborns. Preterm infants, in contrast, initially show much lower cross-correlations between hip and ankle and between knee and ankle. This is particularly the case for those preterm infants who were born before 32 weeks gestation. Again, the differences resolved after the age of 12 weeks, which might be related to a transformation in neural functions reported previously around this age. The initial differences in the characteristics of kicking appeared to be more readily explainable by differences in neurological condition than by contrasts in leg volume or postural control.     

Dual-energy X-ray absorptiometry derived structural geometry for stress fracture prediction in male U.S. Marine Corps recruits

OBJECTIVES: To evaluate the effects of losartan administration on cardiovascular mass, systemic and coronary hemodynamics (rest, maximal treadmill exercise, and dipyridamole infusion) and on resting regional hemodynamics in conscious spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. RESULTS: Although losartan administration (two doses: 10 and 30 mg/kg per day for 3 weeks by gavage) reduced left ventricular mass at the higher dose in WKY rats and with both doses in SHR, only the higher dose reduced arterial pressure in SHR. Losartan administration did not affect cardiac index, myocardial or other organ flows (radiomicrosphere) at rest in both strains. Significant increases in cardiac index and coronary flow and decreases in coronary vascular resistance were observed during exercise in both strains and these responses were not affected by losartan administration. Compared with those in WKY rats, coronary flow and flow reserve (dipyridamole) were decreased and minimal coronary vascular resistance was increased in untreated SHR. Administration of a higher losartan dose increased coronary flow reserve and decreased minimal coronary vascular resistance (measured during dipyridamole infusion) in SHR. CONCLUSIONS: These data demonstrated that losartan administration reduced left ventricular mass, a response that did not seem to be solely dependent on afterload. Furthermore, cardiac and stroke indices and coronary flow reserve were not changed in SHR during maximal treadmill exercise after hypertrophy reversal, even with the lower dose of losartan and when the ventricular afterload was similar to that of untreated SHR.