Oxidants in cigarette smoke. Radicals, hydrogen peroxide, peroxynitrate, and peroxynitrite.
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Biomedical subjects
Publications and source records attributed to K Stone.
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Psychiatric admissions in Central Manchester of Europeans, Afro-Caribbeans, and Asians (within three age-bands) were studied over four years. Among the Afro-Caribbean group there were more single or unemployed persons than in either the Asian or European groups, which suggested greater socio-economic disadvantage. Rates for first admissions and readmissions among Afro-Caribbeans were greater; among Asians they were similar except for the 16-29-year age-group, who tended to have lower rates than Europeans. A higher proportion of Afro-Caribbeans and Asians were psychotic. In the Afro-Caribbean group, the raised rates of admission were largely attributable to increased rates of schizophrenia. The highest rate occurred in second-generation (UK-born) Afro-Caribbeans and was nine times that among Europeans. The police were more frequently involved in the admissions of Afro-Caribbeans compared with Europeans or Asians. Higher proportions of Afro-Caribbeans and Asians who were readmitted were detained under the Mental Health Act 1983, when compared with Europeans.
The pathophysiology of adhesion formation continues to be perplexing. A delicate balance appears to exist between those wound factors that would initiate the physiologic process of peritoneal wound healing and those factors necessary for the lysis of fibrin, a major component of adhesions. Research continues to elucidate the roles of leukotrienes, prostaglandins, protein kinase-C, and transforming growth factors in adhesiogenesis. The ability to enhance plasmin's fibrinolytic activity or to impede plasminogen activator inhibitor factor may have important clinical ramifications in adhesiolysis. Clinical studies continue to address the effectiveness of intraperitoneal additives (dextran, lactated Ringer's solution, heparin) and barriers to adhesion formation (Interceed, TC7, Johnson & Johnson, New Brunswick, NJ; Gore-Tex, polytetrafluoroethylene, Gore & Assoc, Flagstaff, AZ). Surgical technique with attention to hemostasis, minimal trauma, proper suture selection, and peritoneal irrigation continues to be the mainstay in adhesion prevention.
Insulin-stimulated glycogen synthase activity in human muscle is reduced in insulin-resistant subjects. Insulin regulation of human muscle glycogen synthase may require activation of a type-1 protein phosphatase (PP-1). We investigated the change of phosphorylase phosphatase and glycogen synthase activities in muscle biopsies obtained during a 2-h hyperinsulinemic euglycemic clamp in 12 insulin-sensitive (group S) and 8 insulin-resistant (group R) subjects. Fasting phosphorylase phosphatase activity was lower in group R than in group S, and did not increase significantly with insulin infusion in group R until 20 min. In group S, phosphorylase phosphatase was significantly stimulated by 10 min, remaining significantly higher than in group R at all time points. The insulin-mediated changes in phosphatase activities were not decreased by 3 nM okadaic acid but were completely inhibited by 1 microM okadaic acid, thereby verifying that insulin-stimulated phosphorylase phosphatase is accounted for by a PP-1. Subcellular fractionation demonstrated reduced fasting PP-1 activities in both the glycogen and cytosolic fractions of muscle obtained from subjects in group R compared to those in group S. These results suggest that insulin activation of PP-1 could contribute to the stimulation of glycogen synthase by this hormone in human muscle. Lower fasting PP-1 activity in cytosol and glycogen fractions plus lower insulin-stimulated PP-1 activity could explain, in part, reduced insulin-stimulated glycogen synthase in skeletal muscle of insulin-resistant subjects.
The pancreatic beta-cell hormone amylin acts in isolated rat skeletal muscle to decrease insulin-stimulated incorporation of glucose into glycogen. It also increases blood levels of lactate and glucose in fasted rats in vivo. However, it remained uncertain whether amylin exerts direct effects to stimulate muscle glycogenolysis. We now report that amylin caused a dose-dependent increase in activity of muscle glycogen phosphorylase in isolated rat soleus muscle by stimulating phosphorylase a. Insulin inhibited amylin-stimulated activation of phosphorylase. Effects of amylin to stimulate muscle glycogenolysis are consistent with observed effects of amylin in vivo and could be a major mechanism whereby amylin modulates carbohydrate metabolism.
We developed a method for estimating the mean and standard deviation of ratios of normal vertebral heights from a sample that includes people with and without vertebral fractures. This method assumes that the measurements in normal vertebrae have a Gaussian distribution and that, for any vertebral level, the prevalence of abnormal measurements is less than 10%. Under these assumptions, normal values for nonfractured vertebrae can be estimated from several statistical properties of Gaussian distributions. We applied these methods to the lateral spinal radiographs of 2992 women aged 65-70 years who were recruited from population-based listings. The estimated means and standard deviations for ratios of dimensions in nonfractured vertebrae were very similar to those based on studies of premenopausal women. Our method may be useful for defining normal values from large populations that include normal and abnormal women, does not require x-rays of normal premenopausal women, avoids the potential biases of defining normality based on qualitative judgment, and can be applied to other types of physical and biochemical measurements.
Malignant CD5 B cells obtained from patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) were analyzed for immunoglobulin variable gene usage, CD5 gene expression and autoantibody production. A statistically significant biased usage of the VH5, VH6 and VKIII immunoglobulin variable gene families was observed. It is important to point out that both VH5 and VH6 are extremely small families which are located at the 3' extremity of the immunoglobulin variable gene locus. We determined that the transcription of the CD5 gene in T cell malignancies, CLL, SLL and a selected group of EBV transformed lines was identical. Autoantibody production was studied in a panel of heterohybridomas obtained by the fusion of CLL cells with mouse myeloma line SP2/0. A large fraction of these heterohybridomas secrete autoantibodies; some were monospecific, some bispecific and some polyspecific.
Sulfonylureas are used in the treatment of non-insulin-dependent diabetes mellitus (NIDDM) largely because of their ability to enhance insulin secretion and possibly to potentiate insulin action. In this study, we investigated the effects of chronic glyburide treatment on glycogen synthase activity determined in skeletal muscle biopsies taken during euglycemic hyperinsulinemic clamps in nine Pima Indians with NIDDM. Insulin was infused at the rate of 40 mU/m2/min (low dose) followed by 400 mU/m2/min (high dose). Compared with the fasting value, the mean glycogen synthase activity assayed at low glucose-6-phosphate (G6P) concentration (active glycogen synthase) showed no significant changes during insulin infusion before glyburide treatment. After glyburide treatment, the mean active glycogen synthase increased by 39% (P less than .05) above the fasting value during the high-dose insulin infusion. Total glycogen synthase activity assayed at high G6P concentration did not change after glyburide treatment. Changes of insulin-stimulated active glycogen synthase associated with glyburide treatment correlated with changes in total body glucose disposal rates (r = .70, P less than .05) during euglycemic clamps. We conclude that glyburide treatment of subjects with NIDDM is associated with an increase in insulin action in vivo and concomitantly with improved insulin action on skeletal muscle glycogen synthase.
A systematic study of the relationship between empirically-derived diagnoses and symptom patterns is reported in a sample of 160 preadolescents and adolescents consecutively admitted to a psychiatric inpatient setting. Results show that the DSM-III diagnoses generated using the child version of the Diagnostic Interview Schedule for Children (DISC-C) were significantly associated with several factor analytically-derived symptom scales of the Achenbach and Edelbrock Youth Self-Report. The results included the finding of significant associations for conduct disorders with the delinquency scale, for affective disorders with the depressed scale, and for both affective and anxiety disorders with the broad-band internalizing scales. This study suggests implications about diagnostic categorizations and construct validity as well as implications for clinical evaluation.
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The Dartmouth COOP Project, a primary care research network, conducted a prospective study of patients presenting to 28 primary care practices with a chief complaint of fatigue. Data were gathered on fatigue status, associated systems, health status, and origin of fatigue. Fatigue patients were demographically similar to nonfatigue patients but had significantly worse physical and mental health at study intake. Sixty-three percent of physicians and 52% of patients rated fatigue origin as primarily physical (gamma = 0.48, P less than .05), but in 41% of cases, physicians indicated there was substantial interaction between physical and psychological factors. Only two factors--depression and anxiety--separated fatigue of physical origin from fatigue of psychological origin. Clinicians must thoughtfully evaluate fatigue's often multiple causes and communicate their understanding of those causes to the patient to gain support for a reasonable treatment regimen.
A sample of 163 children and adolescents, consecutively admitted to a large, private psychiatric teaching hospital, was interviewed using the child version of the Diagnostic Interview Schedule for Children (DISC-C). Patients, ages 12 to 16, were interviewed during the first month of admission. Kappa coefficients were obtained from cross-tabulated frequencies of DISC and clinician diagnoses. Agreement between clinical and DISC diagnoses was generally poor across diagnostic categories. In general, when algorithms of a higher threshold were used, the percentage of patients in a particular diagnostic group was closer to the percentage diagnosed by the clinician. Discussion focuses on factors that may contribute to the discrepancy between number and type of diagnoses that the DISC yields compared to those made by the clinicians.
A retrospective study of 92 patients admitted with mania, aged over 65 years of age, found that 26% had no prior history of affective illness; 30% had previously only experienced depression, and half of these had at least three episodes of depression before the first manic illness. Patients with a family history of affective disorders had a significantly earlier age of onset of illness. There was evidence of cerebral organic impairment in 24% of the patients, and this group had a significantly later age of onset of illness. Prognosis was good, with only 8% still in hospital at six months. Half of the patients were started on lithium prophylaxis, but this did not significantly alter the number of readmissions. A quarter of those started on lithium developed evidence of lithium toxicity.
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A sample of new patients attending an ATU was followed up for 6 months. All those who had completed at least 3 months of treatment were asked about the kinds of treatment they had received and their views about the usefulness of the various treatment options available (as were staff). Treatment outcome was assessed in terms of drinking behaviour and patient ratings of the severity of their drinking problem. The survey showed considerable variation in the intensity of treatment received; overall the cohort reduced their alcohol consumption substantially (particularly those who received more intensive treatment) and believed their drinking problem to be much less serious. Patient (and staff) views of the various treatment options are presented and discussed. Although staff and patients differed substantially in their views both groups showed little support for the involvement of relatives in treatment.
We measured total body insulin-mediated glucose uptake, carbohydrate oxidation, storage (nonoxidative disposal), muscle glycogen synthase activity, and muscle glucose 6-phosphate (G-6-P) content in response to five levels of insulinemia (means 16, 52, 152, 573, and 5,550 microU/ml) in 16 male glucose-tolerant volunteers. Insulin dissociation constants (KDs) for disposal, storage, and synthase activity (but not for oxidation) are coincident, suggesting that storage via glycogen synthesis could be a major determinant of glucose disposal. Increases in glucose disposal were associated with decreases in muscle G-6-P concentration. These data suggest that the principal control over carbohydrate disposal is exerted after G-6-P. The coincidence of insulin sensitivities for disposal, storage, and synthase activity suggest that storage via glycogen synthesis could be a major determinant of glucose disposal.
Insulin-mediated glycogen synthase activity in skeletal muscle correlates with the rate of insulin-mediated glycogen deposition and is reduced in human subjects with insulin resistance. To assess the role of glycogen synthase phosphatase as a possible mediator of reduced glycogen synthase activity, we studied 30 Southwestern American Indians with a broad range of insulin action in vivo. Percutaneous biopsies of the vastus lateralis muscle were performed before and during a 440-min euglycemic clamp at plasma insulin concentrations of 89 +/- 5 and 1,470 +/- 49 microU/ml (mean +/- SEM); simultaneous glucose oxidation was determined by indirect calorimetry. After insulin stimulation, glycogen synthase activity was correlated with the total and nonoxidative glucose disposal at both low (r = 0.73, P less than 0.0001; r = 0.68, P less than 0.0001) and high (r = 0.75, P less than 0.0001; r = 0.74, P less than 0.0001) plasma insulin concentrations. Fasting muscle glycogen synthase phosphatase activity was correlated with both total and nonoxidative glucose disposal rates at the low (r = 0.48, P less than 0.005; r = 0.41, P less than 0.05) and high (r = 0.47, P less than 0.05; r = 0.43, P less than 0.05) plasma insulin concentrations. In addition, fasting glycogen synthase phosphatase activity was correlated with glycogen synthase activity after low- (r = 0.47, P less than 0.05) and high- (r = 0.50, P less than 0.01) dose insulin stimulations. These data suggest that the decreased insulin-stimulated glucose disposal and reduced glycogen synthase activation observed in insulin resistance could be secondary to a low fasting glycogen synthase phosphatase activity.
Two previously unreported cell lines of human renal cell carcinoma are presented. TK-10 and TK-164 have each been in culture for over 4 years. The epithelial nature of both cell lines has been documented by light and electron microscopy. The cells in each line contain a Y chromosome, have specific marker chromosomes, and a distinct flow cytometric histogram. Both lines grow in agar, albeit not in athymic mice.