Sleep deprivation by the "flower pot" technique and spatial reference memory.

This study investigated whether paradoxical, or rapid eye movement (REM), sleep deprivation (SD) affected spatial memory. SD was induced in male Wistar rats by housing them on small platforms over water. They fell into the water if they lost muscle tone.

Expression of interleukin-7 receptor by lineage-negative human bone marrow progenitors with enhanced lymphoid proliferative potential and B-lineage differentiation capacity.

Relatively little is known about the relationship of lymphoid-associated gene expression to the proliferation and differentiation potential of early human bone marrow lymphoid progenitors. Surface expression of interleukin-7 (IL-7) receptor-alpha (IL-7R alpha), a component of the high-affinity receptor for the lymphoid precursor growth factor IL-7, defined a CD34+ progenitor subset lacking the CD19+ pro-B phenotype but demonstrating markedly enhanced lymphoid clonogenic capacity and the ability to differentiate into pro-B cells in short-term culture. These progenitors expressed mRNA for the lymphoid-associated genes Ig beta, RAG-1, and PAX-5, and were uniformly TdT-positive (TdT+).

CRF receptor antagonist attenuates immobilization stress-induced norepinephrine release in the prefrontal cortex in rats.

Neuroanatomical, neurophysiological, and behavioral studies suggest that brain stem nucleus locus coeruleus (LC) plays an important role in stress response. The present study was designed to clarify, whether infusion of CRF antagonist, alpha hCRF, into LC could attenuate or block stress-induced changes in norepinephrine (NE) concentrations in microdialysates collected from the medial prefrontal cortex (PFM). Rats were implanted with a bilateral cannulae assembly aimed in the LC and a microdialysis probe (4 mm active membrane length) into the LC.

Corticotropin-releasing factor receptor antagonist infused into the locus coeruleus attenuates immobilization stress-induced defensive withdrawal in rats.

It has been proposed that corticotropin-releasing factor (CRF) released during stress in the region of the locus coeruleus (LC) induces changes in behavior that are typical indices of anxiety. The experiments tested the ability of a CRF antagonist, alpha hCRF9-41, to attenuate stress-induced defensive withdrawal in rats. 1 microgram of alpha hCRF in 300 nl was infused bilaterally in the LC of rats 10 min prior to 30 min immobilization.

Medicating the obese patient.

The acceptance of medication as a legitimate adjunct to diet and behavior modification in the treatment for obesity is an emerging phenomenon spurred by advances in understanding the biologic basis of body weight regulation and by the demonstration of safe and effective chronic maintenance of weight loss using a pharmacobehavioral approach. The decision to medicate for obesity depends on good clinical judgment based on such considerations as body mass index; body composition; body fat dissociation; age; sex; and comorbid conditions, such as diabetes and hypertension. Several nonadrenergic agents and a serotonergic agent have FDA-approved indications for weight loss.

A double-blind randomized placebo-controlled trial of sibutramine.

Sibutramine is a beta-phenethylamine which blocks reuptake of norepinephrine and serotonin. In this clinical study, a group of 173 patients were randomized to treatment with sibutramine at doses of 1, 5, 10, 15, 20 or 30 mg/d and were compared with placebo in a 24-week double-blind trial. There was a dose-dependent reduction in body weight, with doses of 10, 15, 20 and 30 mg being significantly greater than placebo.

Sibutramine: a novel new agent for obesity treatment.

Sibutramine is a novel new pharmacologic agent which is a specific reuptake inhibitor for norepinephrine and serotonin. Preclinical data show that sibutramine and its two metabolites reduce food intake of animals eating either high or low carbohydrate diets and of obese Zucker rats. An 8-week clinical trial showed a dose-dependent decrease on body weight.

Association of body mass with dietary restraint and disinhibition.

The relationship of disinhibition and dietary restraint with body mass was studied in a sample of 293 women. Results suggested that higher body mass was associated with an interaction of disinhibition and dietary restraint. The association of disinhibition with higher body mass was moderated by increased dietary restraint.

Regulation of human B cell lymphopoiesis by adhesion molecules and cytokines.

Recent advances in the ability to culture normal human B cell precursors have emphasized the supportive relationship between these cells and stromal cells in the bone marrow microenvironment. It is now possible to examine the role of adhesion molecules and cytokines in the regulation of different stages of human lymphopoiesis using these culture systems. Direct cell-cell adhesion mediated by the integrin adhesion molecule VLA-4 plays a critical role in supporting stromal dependent proliferation of human B cell precursors.

The association of body weight, dietary intake, and energy expenditure with dietary restraint and disinhibition.

The hypotheses that dieting and/or overeating are associated with adiposity, eating disturbances, and lowered energy expenditure were tested in this study. A sample of 44 premenopausal women scoring high and low on measures of dietary restraint and disinhibition of dietary control, as measured by the Three Factor Eating Questionnaire, was studied. A 2 x 2 factorial design was employed (High/Low restraint x High/Low Disinhibition).

A Scottish record linkage study of risk factors in medical history and dementia outcome in hospital patients.

The relative risk (RR) of acquiring a hospital diagnosis of dementia was estimated in 101,104 patients (1 in 25 fraction) randomly selected from total admissions to Scottish general hospitals between 1968 and 1977. The patients were allocated to putative at-risk groups according to main diagnosis at time of index admission, and RR of dementia (ICD 9,290) was contrasted between ten risk groups and a reference group. Record linkage was used to reduce admission episodes to individual cases, to link general and psychiatric Scottish Morbidity Records (SMR 1 and SMR 4), to identify subsequent admission diagnoses of dementia, and to establish person-years-at-risk for each case by linking to the Registrar General's mortality file.

CD34+ progenitor cell isolation from blood and marrow: a comparison of techniques for small-scale selection.

The isolation and characterization of primitive hematopoietic cells and their purification in sufficient numbers is important in clinical and research marrow transplantation settings. As systems for large-scale isolation and amplification of such cells are developed, they may assume importance in transplantation, treatment of marrow failure and for gene therapy applications. Such cells have been isolated by numerous techniques and in this work, small-scale isolation of CD34+ cells by two immunoadsorption purification methods is compared with isolation by flow cytometry.

Cytokine regulation of early human lymphopoiesis.

An in vitro culture system in which bone marrow-derived fibroblast-like cells support the growth of TdT+ colonies derived from CD34+/CD10- human bone marrow progenitor cells has recently been described. The regulatory role of cytokines during early B lineage commitment was investigated using this culture system. Expression of IL-7, a cytokine that induces proliferation of B cell precursors, was detectable in the adherent layer by PCR and bioassay.

Sodium bromide acts as a contrast material on DEXA scanning.

Subjects undergoing a series of procedures to determine body composition, including dual-energy x-ray absorptiometry (DEXA) scanning and extracellular water volume determination by bromide dilution, demonstrated abnormal DEXA scans in some cases. Oral doses of sodium bromide in the stomach were detected on total body DEXA scanning as contrast material. The physical principles that cause bromide to be imaged in a manner similar to calcium by the DEXA scanner are discussed so that other investigators may be aware of this potential pitfall in body composition analysis.

Age-specific hospital incidence rates in dementia. A record linkage study of first-admission rates to Scottish hospitals (1968-1987).

A random sample (n = 101,104) was taken from total general hospital admissions to Scottish hospitals (1:25 fraction) during the period 1968-1977. Record linkage was used to connect general hospital and psychiatric hospital morbidity records (SMR 1 and SMR 4). Patients with a subsequent admission with dementia (principal diagnosis ICD 9,290) were identified from the general hospital sample on follow-up.

Subpopulations of bone marrow fibroblasts support VLA-4-mediated migration of B-cell precursors.

Proliferation of normal human lymphoid progenitors in culture is dependent on interaction with bone marrow-derived fibroblast-like cells (BM-FB). To investigate possible heterogeneity in this lymphoid-supportive microenvironment, we studied the interaction of a human B-precursor cell line (NALM-6) with BM-FB. NALM-6 cells associate with BM-FB by either adhesion or migration underneath the fibroblast.

Adherence of normal and neoplastic human B cell precursors to the bone marrow microenvironment.

The early development of B lineage cells occurs in the bone marrow in close association with fibroblast-like accessory cells. The integrin VLA-4 is preferentially expressed by B cell precursors and mediates adhesion of B cell precursors to bone marrow derived fibroblasts (BM-FB), which express a VLA-4 counter/receptor, VCAM-1. The functional importance of this adhesion interaction is suggested by the inhibition by anti-VLA-4 antibody of in vitro proliferation of B cell progenitor colonies grown with a BM-FB adherent layer.

Expression of integrins and examination of their adhesive function in normal and leukemic hematopoietic cells.

Adhesion of hematopoietic progenitor cells to marrow-derived adherent cells has been noted for erythroid, myeloid, and lymphoid precursors. In this report, we have characterized very late antigen (VLA) integrin expression on normal CD34+ marrow progenitors, on leukemic cell lines, and on blasts from patients with acute myelogenous or monocytic leukemias. CD34+ progenitor cells expressed the integrin beta 1 chain (CD29), VLA-4 alpha (CD49d), and VLA-5 alpha (CD49e).

Molecular mechanisms of human melanocyte attachment to fibronectin.

In this report we show that fetal and neonatal melanocyte attachment to fibronectin (FN) is inhibited by antibodies to the beta 1 integrin subunit, suggesting a role for these molecules in melanocyte attachment to FN. The VLA-5 integrin was shown to be the predominant receptor for fetal melanocyte attachment to FN, in contrast with neonatal melanocytes in which the very late antigen (VLA)-5, VLA-3, and alpha v integrins each contributed to melanocyte attachment to FN. Peptides containing the arginyl-glycyl-aspartyl-serine (RGDS) sequence inhibited fetal and neonatal melanocyte attachment to FN by a maximum of 48% and 85%, respectively.