Exploring the genetic etiology of low general cognitive ability from 14 to 36 months

The genetic and environmental etiology of low general cognitive ability (g) during infancy and early childhood has not previously been investigated. The current study examined the genetic etiology of low cognitive ability at 14, 20, 24, and 36 months with twins from the MacArthur Longitudinal Twin Study. Low g groups were formed from the lowest 10th percentile at each age. Univariate probandwise concordance rates and DeFries-Fulker (J. C. DeFries & D. W. Fulker, 1985, 1988) multiple regression techniques suggest genetic etiology in low general cognitive ability groups. The stability of low general cognitive ability over time also appears to be primarily due to genetic factors. Although replication is necessary, these results suggest that the genetic etiology of low g during infancy and early childhood is at least as great as the heritability of g in the unselected population.     

Psychoneuroendocrinology of depression. Prolactin

Prolactin provides us with a window to the brain in our quest for understanding the psychobiology of depression, since the regulation of its release involves some of the monamine neurotransmitter systems that have been implicated in the pathophysiology of depression. Investigation examining basal prolactin plasma concentrations in depressed patients, including assessments of the rhythm of prolactin release, have not provided clear, consistent findings. Further exploration of the precise mechanisms involved in serotonin-stimulated prolactin release should shed light on the pathophysiology of abnormal prolactin responsivity in depression, and by extension, the psychobiologic basis of depression.     

Regional CNS densities of serotonin and dopamine receptors in high alcohol-drinking (HAD) and low alcohol-drinking (LAD) rats

A model of membrane potential-dependent distribution of oxonol VI to estimate the electrical potential difference deltapsi across Schizosaccharomyces pombe plasma membrane vesicles (PMV) has been developed. deltapsi was generated by the H+-ATPase reconstituted in the PMV. The model treatment was necessary since the usual calibration of the dye fluorescence changes by diffusion potentials (K+ + valinomycin) failed. The model allows for fitting of fluorescence changes at different vesicle and dye concentrations, yielding deltapsi in ATP-energized PMV of 80 mV. The described model treatment to estimate deltapsi may be applicable for other reconstituted membrane systems.     

A sequence in the 5'' flanking region confers progestin responsiveness on the human c-myc gene

Sarcoidosis is a systemic granulomatous disease of undetermined etiology in which the immune system is overstimulated. Management of the patient with sarcoidosis entails continuity of patient care far beyond disease, even into remission. Care is comprehensive, including all involved organ systems, coordination of specialty consultations and services, and includes diagnostic tests. Therapeutic decisions are the responsibility of the primary care practitioner. Prognosis of sarcoidosis is not uniformly good. Patients can die. Subacute sarcoidosis patients usually do not require pharmacologic therapy. Chronic sarcoidosis may require long-term treatment for years to indefinitely. Corticosteroids are still the drugs of choice and other therapy is now available. Health organizations and private nonprofit support groups are available for patient education and assistance. Close support must still come from the family unit. Sarcoidosis may occur in family members in different cohorts at all ages in life and in any racial or ethnic group. The second in a two-part series on management of the patient with sarcoidosis, this article describes coordination of care and considers community, prevention, and family aspects of the disease.     

Antigen-unspecific B cells and lymphoid dendritic cells both show extensive surface expression of processed antigen-major histocompatibility complex class II complexes after soluble protein exposure in vivo or in vitro

Intravenous (i.v.) injection of high amounts of soluble proteins often results in the induction of antigen-specific tolerance or deviation to helper rather than inflammatory T cell immunity. It has been proposed that this outcome may be due to antigen presentation to T cells by a large cohort of poorly costimulatory or IL-12-deficient resting B cells lacking specific immunoglobulin receptors for the protein. However, previous studies using T cell activation in vitro to assess antigen display have failed to support this idea, showing evidence of specific peptide-major histocompatibility complex (MHC) class II ligand only on purified dendritic cells (DC) or antigen-specific B cells isolated from protein injected mice. Here we reexamine this question using a recently derived monoclonal antibody specific for the T cell receptor (TCR) ligand formed by the association of the 46-61 determinant of hen egg lysozyme (HEL) and the mouse MHC class II molecule I-Ak. In striking contrast to conclusions drawn from indirect T cell activation studies, this direct method of TCR ligand analysis shows that i.v. administration of HEL protein results in nearly all B cells in lymphoid tissues having substantial levels of HEL 46-61-Ak complexes on their surface. DC readily isolated from spleen also display this TCR ligand on their surface. Although the absolute number of displayed ligands is greater on such DC, the relative specific ligand expression compared to total MHC class II levels is similar or greater on B cells. These results demonstrate that in the absence of activating stimuli, both lymphoid DC and antigen-unspecific B cells present to a similar extent class II-associated peptides derived from soluble proteins in extracellular fluid. The numerical advantage of the TCR ligand-bearing B cells may permit them to interact first or more often with naive antigen-specific T cells, contributing to the induction of high-dose T cell tolerance or immune deviation.     

How accurate is the recall of bowel habits in children with defaecation disorders?

The aim was to assess in children with defaecation disorders, the accuracy of recalled information as provided by the child and/or parents compared to diary information and to evaluate its effect on diagnostic grouping. In this prospective study, recalled information, obtained initially by a telephone interview, was compared with recorded information provided by a 4-week diary. Recalled and recorded data were compared using Kappa indices. Subsequently, children were assigned to three diagnostic groups: constipation, solitary encopresis and a rest group. Based on these diagnoses, the first two groups were allocated for laxative treatment. Analysis of recalled and recorded data was performed in 46 children (5-14 years). Most defaecation parameters showed fair agreement, only limited agreement occurred for frequency of soiling episodes. Identical clinical groups using the two methods were obtained in 63% of the children. Particularly, the assessment of large amounts of stool and the number of soiling episodes were responsible for the shift in the diagnostic groups. A total of 83% children were correctly allocated for treatment using recalled data.     

Impact of a pharmacist-based consult service on nutritional rehabilitation of nonambulatory patients with severe developmental disabilities

A pharmacist consult service was developed to evaluate the appropriateness of enteral feeding through a permanent ostomy in 24 nonambulatory patients with severe developmental disabilities. Several problems with enteral nutrition were identified. Policies to improve them were instituted, and several educational presentations were made. Pharmacists' actions were implemented, including assessment of energy needs by indirect calorimetry and rearrangement of enteral feeding schedules to achieve optimal nutrition support and pharmacotherapy administration. By the fourth month of the consult service, body weight in these patients increased from 101 +/- 6% of baseline to 109 +/- 7% (p<0.05). Weight continued to increase through the seventh month of the consult service to 116 +/- 12% of baseline (p<0.0001). Measured resting energy expenditure for the group was 889 +/- 170 kcal/day compared with the predicted 1055 +/- 163 kcal/day.     

Insulin sensitivity index, acute insulin response, and glucose effectiveness in a population-based sample of 380 young healthy Caucasians. Analysis of the impact of gender, body fat, physical fitness, and life-style factors

BACKGROUND: Insulin sensitivity and insulin secretion are traits that are both genetically and environmentally determined. AIM: The aim of this study was to describe the distribution of the insulin sensitivity index (Si), the acute insulin response, and glucose effectiveness (Sg) in young healthy Caucasians and to estimate the relative impact of anthropometric and environmental determinants on these variables. METHODS: The material included 380 unrelated Caucasian subjects (18-32 yr) with measurement of Si, Sg and insulin secretion during a combined intravenous glucose (0.3 grams/kg body weight) and tolbutamide (3 mg/kg body weight) tolerance test. RESULTS: The distributions of Si and acute insulin response were skewed to the right, whereas the distribution of Sg was Gaussian distributed. Sg was 15% higher in women compared with men (P < 0.001). Waist circumference, body mass index, maximal aerobic capacity, and women's use of oral contraceptives were the most important determinants of Si. Approximately one-third of the variation of Si could be explained by these factors. Compared with individuals in the upper four-fifths of the distribution of Si, subjects with Si in the lowest fifth had higher waist circumference, higher blood pressure, lower VO2max, and lower glucose tolerance and fasting dyslipidemia and dysfibrinolysis. Only 10% of the variation in acute insulin response could be explained by measured determinants. CONCLUSION: Estimates of body fat, maximal aerobic capacity, and women's use of oral contraceptives explain about one-third of the variation in Si in a population-based sample of young healthy Caucasians.