Multiple-trait quantitative trait loci analysis using a large mouse sibship

Quantitative trait loci influencing several phenotypes were assessed using a genetically heterogeneous mouse population. The 145 individuals were produced by a cross between (BALB/cJ x C57BL/6J)F1 females and (C3H/HeJ x DBA/2J)F1 males. The population is genetically equivalent to full siblings derived from heterozygous parents, with known linkage phase. Each individual in the population represents a unique combination of alleles from the inbred grandparents. Quantitative phenotypes for eight T cell measures were obtained at 8 and 18 mo of age. Single-marker locus, repeated measures analysis of variance identified nine marker-phenotype associations with an experimentwise significance level of P < 0.05. Six of the eight quantitative phenotypes could be associated with at least one locus having experiment-wide significance. Composite interval, repeated measures analysis of variance identified 13 chromosomal regions with comparisonwise (nominal) significance associations of P < 0.001. The heterozygous-parent cross provides a reproducible, general method for identification of loci associated with quantitative trait phenotypes or repeated phenotypic measures.     

The mammalian brain high-affinity L-proline transporter is enriched preferentially in synaptic vesicles in a subpopulation of excitatory nerve terminals in rat forebrain

The expression of a brain-specific high-affinity Na+-dependent (and Cl--dependent) L-proline transporter (PROT) in subpopulations of putative glutamatergic neurons in mammalian brain suggests a physiological role for this carrier in excitatory neurotransmission (). To gain insights into potential sites where PROT may function, we used a C-terminal domain antipeptide antibody to determine the regional distribution and subcellular localization of PROT in rat forebrain. PROT immunoreactivity was seen in processes having a regional light microscopic distribution comparable to that of known glutamatergic projections within the cortex, caudate putamen nucleus (CPN), hippocampal formation, and other forebrain regions. In all regions examined by electron microscopy (cortex, CPN, and the stratum oriens of CA1), PROT labeling was observed primarily within subpopulations of axon terminals forming asymmetric excitatory-type synapses. Immunogold labeling for PROT was detected in close contact with membranes of small synaptic vesicles (SSVs) and more rarely with the plasma membrane in these axon terminals. Subcellular fractionation studies confirmed the preferential distribution of PROT to synaptic vesicles. The topology of PROT in synaptic vesicles was found to be inverted with respect to the plasma membrane, suggesting that PROT-containing vesicles are generated by a process involving endocytosis from the plasma membrane. Because PROT lacks any of the known characteristics of other vesicular transporters, these results suggest that certain excitatory terminals have a reserve pool of PROT associated with SSVs. The delivery of PROT to the plasma membrane by exocytosis could play a critical role in the plasticity of certain glutamatergic pathways.     

Inorganic arsenic in cooked rice and vegetables from Bangladeshi households

Many Bangladeshi suffer from arsenic-related health concerns. Most mitigation activities focus on identifying contaminated wells and reducing the amount of arsenic ingested from well water. Food as a source of arsenic exposure has been recently documented. The objectives of this study were to measure the main types of arsenic in commonly consumed foods in Bangladesh and estimate the average daily intake (ADI) of arsenic from food and water. Total, organic and inorganic, arsenic were measured in drinking water and in cooked rice and vegetables from Bangladeshi households. The mean total arsenic level in 46 rice samples was 358 microg/kg (range: 46 to 1,110 microg/kg dry weight) and 333 microg/kg (range: 19 to 2,334 microg/kg dry weight) in 39 vegetable samples. Inorganic arsenic calculated as arsenite and arsenate made up 87% of the total arsenic measured in rice, and 96% of the total arsenic in vegetables. Total arsenic in water ranged from 200 to 500 microg/L. Using individual, self-reported data on daily consumption of rice and drinking water the total arsenic ADI was 1,176 microg (range: 419 to 2,053 microg), 14% attributable to inorganic arsenic in cooked rice. The ADI is a conservative estimate; vegetable arsenic was not included due to limitations in self-reported daily consumption amounts. Given the arsenic levels measured in food and water and consumption of these items, cooked rice and vegetables are a substantial exposure pathway for inorganic arsenic. Intervention strategies must consider all sources of dietary arsenic intake.     

Increased urine catecholamines and cortisol in women with irritable bowel syndrome

OBJECTIVES: There are few data on the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis in individuals with chronic GI symptoms. The current study was designed to describe and compare urine catecholamine (norepinephrine, epinephrine) and cortisol levels in women diagnosed with irritable bowel syndrome (IBS-patients), women who report similar symptom levels but had not sought health care services (IBS-nonpatients; IBS-NP), and asymptomatic (control) women. METHODS: Seventy-three women (24 IBS; 24 IBS-NP; 25 controls) were interviewed for demographic, GI, gynecological, and psychological data and then followed for two menstrual cycles with a daily health diary. Urine samples were obtained in the evening and morning at specific phases across two menstrual cycles. RESULTS: Women in the IBS group had significantly higher PM and AM urine norepinephrine levels. Urine epinephrine and cortisol levels were also generally higher in women with IBS. Differences in neuroendocrine indicators of arousal were not accounted for by differences in demographic variables, lifestyle characteristics, menstrual distress, or average daily measures of anxiety or depression. CONCLUSIONS: Increases in indicators of sympathetic nervous system activation in women seeking health care for IBS may reflect greater symptom distress or may contribute to increased symptom distress.     

Interlaboratory comparison of the assessment of P450 activities in human hepatic microsomal samples

The present study had 3 goals: (a) to provide a preliminary investigation of the dimensions involved in the capacity for intimacy toward the best friend and the sexual partner during adolescence; (b) to determine whether the specific areas of the capacity for intimacy toward the best friend are the same as toward the sexual partner; and (c) to consider the usefulness of conceiving the capacity for intimacy as a multidimensional concept. Canadian high school students (N = 465; 257 girls, 208 boys) completed a questionnaire on the capacity for intimacy, best friend version; 232 of them completed the partner version of the questionnaire. Factorial analysis on the best friend version of the questionnaire identified 3 factors: Social Intimacy, Positive Intimacy, and Negative Intimacy. Factorial analysis on the partner version of the questionnaire identified 4 factors: Social Intimacy, Positive Intimacy, Negative Intimacy, and Sexual Intimacy.     

Neurone-glia interactions in the hypothalamus and pituitary

Research in the hypothalamus and pituitary has provided compelling evidence that neurone-glia interactions are important in regulating the activity of both neurones and glia. These interactions involve receptor-mediated signalling, intracellular Ca2+ signalling, growth factor-steroid actions and activity-dependent modifications in neurone-glia anatomical relationships. This review focuses on neuroendocrine systems, such as the intermediate lobe of the pituitary and the hypothalamo-neurohypophysial system, which exemplify some of these activities. Although their functional significance has not been fully elucidated, the synaptic responses, release of bioactive factors and changing morphology of certain glia highlight their integral role in hypothalamic function.     

Retinal detachment in a battered infant

A 12-week-old battered infant boy had bilateral retinal detachments. The retina in the left eye was considered inoperable, but retinal detachment surgery was performed in the right eye. This retina was reattached and limited vision was restored. The history, the location of the retinal pathology, and the absence of a lens coloboma helped differentiate this result of physical abuse from a congenital retinal detachment.     

Reduction of S-T segment elevation with infusion of nitroprusside in patients with acute myocardial infarction

It is pointed out that the arrival or fixation probability of a mutant gene can be easily inferred analytically. The mean first arrival time for a single overdominant mutation to reach frequency y attains its maximum when x is close to but still slightly less than y/2, where x is the equilibrium frequency of the mutant gene in an infinitely large population. For an advantageous mutation, the mean first arrival time decreases with an increasing degree of dominance if selection is strong, but it first increases, after reaching a maximum, then decreases as the degree of dominance increases, if selection is weak. Contrary to our intuition, the mean age of an advantageous mutant gene increases with increasing degree of dominance, except when selection is very strong. A simple explanation is given in terms of the sojourn time at a particular gene frequency.     

Glucocorticoid therapy for immune-mediated diseases: basic and clinical correlates

Glucocorticoids are pleiotropic hormones that at pharmacologic doses prevent or suppress inflammation and other immunologically mediated processes. At the molecular level, glucocorticoids form complexes with specific receptors that migrate to the nucleus where they interact with selective regulatory sites within DNA; this results in positive and negative modulation of several genes involved in inflammatory and immune responses. At the cellular level, glucocorticoids inhibit the access of leukocytes to inflammatory sites; interfere with the functions of leukocytes, endothelial cells, and fibroblasts; and suppress the production and the effects of humoral factors involved in the inflammatory response. Clinically, several modes of glucocorticoid administration are used, depending on the disease process, the organ involved, and the extent of involvement. High doses of daily glucocorticoids are usually required in patients with severe diseases involving major organs, whereas alternate-day regimens may be used in patients with less aggressive diseases. Intravenous glucocorticoids (pulse therapy) are frequently used to initiate therapy in patients with rapidly progressive, immunologically mediated diseases. The benefits of glucocorticoid therapy can easily be offset by severe side effects; even with the greatest care, side effects may occur. Moreover, for certain complications (for example, infection diathesis, peptic ulcer, osteoporosis, avascular necrosis, and atherosclerosis), other drug toxicities and pathogenic factors overlap with glucocorticoid effects. Minimizing the incidence and severity of glucocorticoid-related side effects requires carefully decreasing the dose; using adjunctive disease-modifying immunosuppressive and anti-inflammatory agents; and taking general preventive measures.