Simultaneous time-varying systemic appearance of oral and hepatic glucose in adults monitored with stable isotopes.

The rates (and extent) of appearance of glucose in arterialized plasma from an oral glucose load and from liver (RaO, RaH) can be estimated in humans using radioisotopes, but estimates vary among laboratories. We investigated the use of stable isotopes and undertook 22 primed intravenous infusions of D-[6,6-2H2]glucose with an oral load including D-[13C6]glucose in healthy humans. The effective glucose pool volume (VS) had a lower limit of 230 ml/kg body weight (cf.

Splanchnic retention of intraduodenal and intrajejunal glucose in healthy adults.

Estimates of the spanchnic retention and appearance in the systemic circulation of orally administered glucose vary among laboratories even after recently identified sources of error have been accounted for [Livesey, G., P. D.

Defective pancreatic beta-cell glycolytic signaling in hepatocyte nuclear factor-1alpha-deficient mice.

Mutations in the hepatocyte nuclear factor-1alpha (HNF-1alpha) gene cause maturity onset diabetes of the young type 3, a form of type 2 diabetes mellitus. In mice lacking the HNF-1alpha gene, insulin secretion and intracellular calcium ([Ca2+]i) responses were impaired following stimulation with nutrient secretagogues such as glucose and glyceraldehyde but normal with non-nutrient stimuli such as potassium chloride. Patch clamp recordings revealed ATP-sensitive K+ currents (KATP) in beta-cells that were insensitive to suppression by glucose but normally sensitive to ATP.

Metabolizable energy of high non-starch polysaccharide-maintenance and weight-reducing diets in men: experimental appraisal of assessment systems.

We have examined the reliability of several food energy assessment systems for healthy men. The predictions of metabolizable energies were compared with determinations made in energy balance studies with three maintenance diets (12 MJ/d); one of the diets was moderate in non-starch polysaccharide (NSP; 2.1% of gross energy) and two were higher in NSP (3.

Characterization of a Ca2+ release-activated nonselective cation current regulating membrane potential and [Ca2+]i oscillations in transgenically derived beta-cells.

Although stimulation of insulin secretion by glucose is regulated by coupled oscillations of membrane potential and intracellular Ca2+ ([Ca2+]i), the membrane events regulating these oscillations are incompletely understood. In the presence of glucose and tetraethylammonium, transgenically derived beta-cells (betaTC3-neo) exhibit coupled voltage and [Ca2+]i oscillations strikingly similar to those observed in normal islets in response to glucose. Using these cells as a model system, we investigated the membrane conductance underlying these oscillations.

Defective insulin secretion in hepatocyte nuclear factor 1alpha-deficient mice.

Mutations in the gene for the transcription factor hepatocyte nuclear factor (HNF) 1alpha cause maturity-onset diabetes of the young (MODY) 3, a form of diabetes that results from defects in insulin secretion. Since the nature of these defects has not been defined, we compared insulin secretory function in heterozygous [HNF-1alpha (+/-)] or homozygous [HNF-1alpha (-/-)] mice with null mutations in the HNF-1alpha gene with their wild-type littermates [HNF-1alpha (+/+)]. Blood glucose concentrations were similar in HNF-1alpha (+/+) and (+/-) mice (7.

Apoptosis in insulin-secreting cells. Evidence for the role of intracellular Ca2+ stores and arachidonic acid metabolism.

This study investigated the role of intracellular free Ca2+ concentration ([Ca2+]i) in apoptosis in MIN6 cells, an insulin secreting cell line, and in mouse islets. Thapsigargin, an inhibitor of sarcoendoplasmic reticulum Ca2+-ATPases (SERCA), caused a time- and concentration-dependent decrease in the viability of MIN6 cells and an increase in DNA fragmentation and nuclear chromatin staining changes characteristic of apoptosis. Two structurally distinct SERCA inhibitors, cyclopiazonic acid and 2,5-di-[t-butyl]-1,4-hydroquinone also caused apoptosis, but agents that increased [Ca2+]i by other mechanisms did not induce apoptosis in MIN6 cells.

Elderly care. Early warning system.

In one area in Merseyside, primary care teams were only identifying elderly people with dementia in times of crisis, resulting in earlier than necessary residential or nursing home placements. Employing a social worker to work with primary care teams as a specialist care manager for this group has resulted in earlier and more appropriate care in the view of both carers and care workers. Following the appointment, interviews with 10 carers revealed that eight out of 10 patients were now receiving health and social care when nine out of 10 had previously received none.

Quality of life in schizophrenia: insight and subjective response to neuroleptics.

The relationship between quality of life, insight, and subjective response to neuroleptics was assessed in a selected group of clinically stable outpatients with schizophrenia. A significant portion of the variance in these individuals' quality of life was explained by a combination of protracted illness duration and the presence of a dysphoric response to neuroleptics. However, there was no significant relationship between quality of life and the level of insight these individuals had into the nature of their illness.

Design of a haptic stick interface as a pilot's assistant in a high turbulence task environment.

A study involving 8 Air Force pilots was conducted to examine the efficacy of a force-reflecting joystick to improve performance during a simulated landing task in wind turbulence. By adding certain force characteristics to a joystick, it was of interest to see if performance may change, different control effort may be utilized, and workload measures may be altered based on the joystick utilized. The main results show that certain performance measures significantly improved by having the force reflection condition on.

Cloning, expression, and chromosomal mapping of a novel human CC-chemokine receptor (CCR10) that displays high-affinity binding for MCP-1 and MCP-3.

Chemokines mediate their chemotactic, proinflammatory effects by binding to and activating a variety of specific receptors belonging to the G protein-coupled superfamily of seven-transmembrane serpentine receptors. We report the cloning, chromosomal localization, expression, and ligand binding of a novel CC chemokine receptor, CCR10. CCR10 is expressed primarily in placenta and fetal liver, and binds two of the CC chemokines, monocyte chemoattractant protein (MCP)-1 and MCP-3, with highest affinity.

Sequential changes of auditory processing during target detection: motor responding versus mental counting.

Brain potentials evoked to non-targets in an auditory target detection task changed in amplitude, duration, polarity, and scalp topography as a function of position in the stimulus sequence relative to the target. (1) A negative prestimulus readiness like-potential, or RP, the poststimulus N100, and a late slow wave to non-targets immediately after the target were reduced in amplitude compared to non-targets immediately before the target. The amplitudes of these potentials after the target then increased in size as a linear function of the number of non-targets in the sequence.

Sorting of MHC class II molecules and the associated invariant chain (Ii) in polarized MDCK cells.

Epithelial cells have been found to express MHC class II molecules in vivo and are able to perform class II-restricted antigen presentation. The precise intracellular localization of these molecules in epithelial cells has been a matter of debate. We have analyzed the polarized targeting of human MHC class II molecules and the associated invariant chain (Ii) in stably transfected MDCK cells.

Expression and function of pancreatic beta-cell delayed rectifier K+ channels. Role in stimulus-secretion coupling.

Voltage-dependent delayed rectifier K+ channels regulate aspects of both stimulus-secretion and excitation-contraction coupling, but assigning specific roles to these channels has proved problematic. Using transgenically derived insulinoma cells (betaTC3-neo) and beta-cells purified from rodent pancreatic islets of Langerhans, we studied the expression and role of delayed rectifiers in glucose-stimulated insulin secretion. Using reverse-transcription polymerase chain reaction methods to amplify all known candidate delayed rectifier transcripts, the expression of the K+ channel gene Kv2.

Is the rat a suitable model for humans on studies of cereal digestion?

Objectives: To compare the extent of starch digestion from barley flake and flour in humans and rat. Is the rat a useful model?

Design: Four healthy male ileostomy volunteers consumed, in random order, flapjacks containing flaked barley on one occasion and barley flour on another. Ileostomy fluid was collected for analysis of starch and nonstrach polysaccharide (NSP) hourly for 12 h.

Guidelines for producing patient information literature.

This article provides practical information on developing patient information literature. The step-by-step approach provided by the authors should be of use to nurses who are currently involved in producing such literature or who are looking at ways of effectively disseminating information to patients on specific topics.

Quality of life in schizophrenia: relationship to sociodemographic factors, symptomatology and tardive dyskinesia.

The influence of sociodemographic, clinical and treatment factors on the quality of life of patients with schizophrenia has yet to be fully defined. We evaluated the quality of life of patients with schizophrenia who were attending a catchment area rehabilitation centre, in order to establish its clinical correlates. These patients had a poor to moderate quality of life which was inversely related to negative symptom severity, illness duration, the cumulative length of previous hospitalization and patient age.

Circadian patterns of total 24-h hydrogen and methane excretion in humans ingesting nonstarch polysaccharide (NSP) diets and the implications for indirect calorimetric and D2 18O methodologies.

Objectives: To quantify the relationship between substrate fermentation and total 24-h H2 and CH4 excretion on mixed diets and to assess errors incurred in the calculation of energy expenditure and fuel selection by the exclusion of these gases from standard calculations.

Design And Subjects: Twelve healthy, lean men were studied over two consecutive dietary periods of 3 weeks. Measurements of total H2 and CH4 excretion were made during 24h within a whole body calorimeter.

Microglia are not exclusively associated with plaque-rich regions of the dentate gyrus in Alzheimer's disease.

The functional significance of microglia found in neuritic plaques in Alzheimer's disease (AD) remains a source of controversy. In the present study, we explored the anatomic relationships between microglia and neuritic plaques in order to determine the potential role of microglia in plaque formation. We chose to study the molecular layer of the hippocampal dentate gyrus, a brain region where plaques have a strong tendency to line up parallel to the adjacent granule cell layer.

NIDDM is associated with loss of pancreatic beta-cell L-type Ca2+ channel activity.

Development of non-insulin-dependent diabetes mellitus (NIDDM) is associated with defects in glucose-stimulated insulin secretion. We have investigated Zucker diabetic fatty rats (ZDF), an animal model of NIDDM, and found that, compared with control islets, the expression of mRNA encoding C- and D-isoforms of alpha 1-subunits of beta-cell L-type voltage-dependent Ca2+ channels (VDCC) was significantly reduced in islets isolated from ZDF rats. This correlated with a substantial reduction of L-type Ca2+ currents (ICa) in ZDF beta-cells.

A preliminary report on the effect of a psychosocial and educative rehabilitation programme on quality of life and symptomatology in schizophrenia.

Individuals with schizophrenia who participated in a psychosocial and educative rehabilitation programme showed a 46% improvement in quality of life in the absence of any significant change in symptom severity. In contrast, there was no significant change in quality of life for individuals who continued with supportive rehabilitation. Our preliminary findings highlight the 'quality of life' benefits of psychosocial and educative rehabilitation for individuals with schizophrenia who are clinically stable and living in the community.