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Biomedical subjects

R Gleason

Publications and source records attributed to R Gleason.

At least 37 records · Page 2Linked to original sources

Effects of the lectin concanavalin-A on the regulation of second messengers and parathyroid hormone release by extracellular Ca2+ in bovine parathyroid cells.

The lectin Concanavalin-A (Con-A) binds to cell surface carbohydrate-containing moieties and modulates the function of a variety of glycoprotein receptors. Since extracellular calcium (Ca2+) may regulate parathyroid function by a receptor-like process, we examined the effects of Con-A on various aspects of Ca(2+)-regulated parathyroid function. We recently showed that Con-A significantly reduces the inhibitory effects of high Ca2+ on dopamine as well as isoproterenol- and forskolin-stimulated cAMP accumulation. In our present studies Con-A similarly reduced the inhibitory effect of 2.0 mM Ca2+ on PTH release from 60 +/- 6% to 40 +/- 6% and increased the set-point for Ca(2+)-regulated PTH release from 1.25 to 1.8 mM. This effect was dose dependent. Con-A also inhibited the Ca(2+)-stimulated accumulation of inositol phosphates by 50-60% in association with a marked reduction in the high Mg(2+)-evoked spike in cytosolic Ca2+ as well as a significant decrease in the sustained rise in cytosolic Ca2+ at 2-3 mM extracellular Ca2+. These data provide further evidence for a key role for cell surface carbohydrate-containing moieties in the mechanism through which parathyroid cells "sense" Ca2+ and, in turn, regulate PTH release, phosphoinositide turnover, and the release of intracellular Ca2+ stores. It is possible that the putative Ca2+ receptor is a glycoprotein or is closely associated with glycoproteins or other moieties containing alpha-methyl-D-glucoside or alpha-methyl-D-mannoside residues.

Animals↗

Occupational physician staffing in large US corporations.

Increased provision of occupational health services outside the workplace has been accompanied by signs of change in the quantity and structure of in-house corporate services. The occupational physician:employee ratios of the 25 largest US corporations were compared with each other, with the probable level of hazard as suggested by Bureau of Labor Statistics reports, and with both gross and per-capita measures of profitability. We infer that large corporations still employ a disproportionate share of available occupational health expertise. Oil and chemical companies employ the largest number of occupational physicians per capita; computer, electronics, and scientific equipment manufacturers employ the largest number of occupational physicians per capita relative to occupational illness/injury/lost workdays per capita. Tobacco companies employ the fewest occupational physicians by either measure. Corporate profitability explained more than half the variability for the one large within-sector comparison and appeared most related to employment practices for the most-successful and least-successful companies.

Industry↗

Selection of carbohydrate to protein ratio and correlations with weight gain and body fat in rats allowed three dietary choices.

In order to determine the spontaneous macronutrient choice of a normal rat population, we allowed growing animals to choose their food among three isocaloric diets: 5% protein - 40% carbohydrate; 45% protein - 40% carbohydrate and 5% protein - 70% carbohydrate, and we measured macronutrient intake, carbohydrate to protein (C/P) ratio and weight gain twice weekly during 9 weeks. At the end of the study, final body weight gain and fat accretion as well as brain serotonin content were measured. Protein consumption increased and fat intake decreased steadily during the assay (from 18.8 to 29 kcal% vs. 35.7 to 25.2 kcal%) whereas carbohydrate consumption remained constant (approx. 46 kcal%) ("carbohydrate homeostasis"), and as a consequence the C/P ratio dropped. There were great variations in total protein consumption between animals (13-32 kcal%) and an inverse relationship with fat intake because carbohydrate consumption was constant. Daily weight gain was negatively correlated with the corresponding C/P ratio, as were final weight gain and body fat content with the global C/P ratio characterizing the food choice of each rat. The concentrations of brain serotonin and 5-hydroxyindole acetic acid were rather uniform and did not show any correlations with any of the other variables. The percent food protein chosen by the animal determined the outcome of the trial at 9 weeks, i.e. food intake, weight gain and body fat accretion. In this experimental model, body fat accumulation is, therefore, directly linked to the protein content of the diet, inversely proportional to the fat level and not related to the carbohydrate content. Since the animals increase the proportion of protein in their food with age above basic nutritional requirements, it is postulated that the macronutrient choice of the rat is also determined by the need of the brain for a proper and balanced supply of neurotransmitter precursors adapted to the situation of each animal.

Adipose Tissue↗

Effects of fluoxetine or D-fenfluramine on serotonin release from, and levels in, rat frontal cortex.

Using in vivo microdialysis of frontal cortex in anesthetized rats, as well as analysis of frontal cortex homogenates, we examined the effects of chronic administration of fluoxetine (30 mg/kg, i.p.) or D-fenfluramine (7.5 mg/kg, i.p.), administered daily for 3 days, on serotonin and 5-HIAA levels a day later. Measurements were also taken after 3-, 7- , and 21-day recovery periods. Neither chronic fluoxetine nor D-fenfluramine changed basal serotonin release. Both treatments, however, transiently decreased the release of serotonin evoked by an acute dose of D-fenfluramine (10 mg/kg, i.p.). Release initially was completely suppressed in fluoxetine-pretreated animals but returned to normal by the 21st day of washout; following D-fenfluramine pretreatment, normal release was attained by the 7th day of washout. Both fluoxetine and D-fenfluramine transiently decreased 5-HIAA levels in the dialysates and tissues. Both drugs also caused prolonged changes in frontal cortex serotonin levels, D-fenfluramine lowering them but fluoxetine elevating them. These results suggest that, at comparable dosage levels relative to their ED50s, fluoxetine and D-fenfluramine cause comparable reversible effects on brain serotonin release. The drugs also cause prolonged but opposite changes in brain serotonin levels, probably reflecting differences in the extents to which they or their principal metabolites release serotonin and block its reuptake.

Animals↗

Preliminary trial of the effect of general practice based nutritional advice.

Despite formal recommendations for dietary change to reduce the incidence of ischaemic heart disease, the acceptability and effectiveness of the proposed diets have not been well investigated in population based studies. In this preliminary investigation of nutritional advice in a well population, subjects in one group practice were randomized to receive either dietary instruction or simple follow up without instruction. The dietary recommendations were well received, and a substantial proportion of subjects reported altering their diets in accordance with them. There were modest beneficial changes in plasma lipid levels among men. Thus, using general practice as an avenue for promoting dietary change is feasible, and may be effective among men.

Adult↗

d-Fenfluramine suppresses the increased calorie and carbohydrate intakes and improves the mood of women with premenstrual depression.

The ability of d-fenfluramine, a drug that releases brain serotonin and blocks its reuptake, to relieve premenstrual depression and excessive calorie and carbohydrate intakes was examined in 17 women with premenstrual syndrome. Subjects received d-fenfluramine (15 mg twice daily) or placebo, in random order, during the luteal phases of six menstrual cycles; ie, for three control and three treatment cycles each. Behavior was assessed with the Hamilton Rating Scale for Depression and its Addendum, and intakes of calories and nutrients were measured by allowing subjects unlimited access to isocaloric meal and snack foods rich in carbohydrates or protein. Pre-treatment follicular scores using the Hamilton Rating Scale for Depression and its Addendum were 2.0 +/- 0.5 and 0.5 +/- 0.5 (mean +/- SEM), respectively; corresponding luteal scores were 21.2 +/- 0.8 and 10.2 +/- 0.6 (P less than .0001). Luteal phase intakes of kilocalories, carbohydrates, and fats were also increased above follicular levels (P less than .01). d-Fenfluramine decreased premenstrual Hamilton Rating Scale for Depression and Addendum scores by 62% (P less than .001) and 60% (P less than .001), respectively; placebo reduced them by only 28% (P less than .02) and 30% (P less than .02). d-Fenfluramine also fully suppressed the premenstrual rise in kilocalorie, carbohydrate, and fat intakes (P less than .01).

Adult↗

A randomized, placebo-controlled, double-blind study evaluating the efficacy of leuprolide acetate depot in the treatment of uterine leiomyomata.

Thirty-eight premenopausal women with uterine leiomyomata were enrolled in a randomized, double-blind, placebo-controlled study evaluating the efficacy of depot leuprolide acetate (LA), a gonadotropin-releasing hormone agonist, in decreasing uterine volume. Eighteen women received intramuscular (IM) depot LA 3.75 mg every 4 weeks for 24 weeks (group A); 20 women received IM placebo with the same injection schedule (group B). Group A patients had a mean reduction in pretreatment uterine volume from 505 +/- 93 cu cm (mean +/- standard error of the mean) to 305 +/- 57 cu cm after 12 weeks (P less than 0.05 versus pretreatment) and 307 +/- 57 cu cm after 24 weeks of therapy (P less than 0.05 versus therapy (P less than 0.05 versus pretreatment). At 3 months after cessation of therapy, the mean uterine volume in group A had increased to 446 +/- 92 cu cm (P less than 0.05 versus week 24). Group B patients had no significant change in uterine volume over the 24-week treatment period. These results suggest that depot LA therapy may significantly decrease uterine volume in patients with leiomyomata, but that regrowth of uterine size occurs shortly after cessation of therapy.

Adult↗

Protein-restricted diets in diabetic nephropathy.

Low-protein diets in nondiabetic renal failure may slow the progressive loss of renal function in some patients, but few studies have detailed the nutritional consequences of these diets in patients with diabetic nephropathy. We studied 7 patients with insulin-dependent diabetes mellitus and chronic renal insufficiency [mean +/- SEM creatinine clearance (S, U): 28.3 +/- 6.5 ml/min (0.47 +/- 0.11 ml/s x 1.73/A)] for 15 weeks who were prescribed a diet of 0.6 g protein/kg ideal body weight. Midarm muscle circumference (24.1 +/- 1.8 at onset vs. 24.5 +/- 1.5 cm at completion), triceps skinfold thickness (21.6 +/- 3.1 vs. 21.0 +/- 1.5 mm), body weight (71.8 +/- 4.1 vs. 71.2 +/- 4.6 kg), and serum albumin [3.0 +/- 0.1 vs. 3.2 +/- 0.1 g/dl (30 +/- 1 vs. 32 +/- 1 g/l)] remained stable. Based on urinary nitrogen excretion, diet diaries overestimated the degree of dietary protein restriction; there was good adherence to the diet as evidenced by a reduction in urinary urea nitrogen (average 32%). Blood glucose control was maintained despite increased carbohydrate intake. On average, creatinine clearance did not change significantly, but proteinuria diminished slightly (1.8 +/- 0.2 vs. 1.5 +/- 0.6 g/day). These results indicate that 0.6 g/kg/day protein diets did not cause protein depletion in insulin-dependent diabetic patients. Longer-term studies are indicated to assess more fully the efficacy of these dietary regimens in reducing proteinuria or benefiting diabetic nephropathy.

Adult↗

Red blood cell lithium-sodium countertransport in non-modulating essential hypertension.

Abnormalities in erythrocyte Li-Na countertransport have been reported in hypertensive subjects, and the available evidence favors familial aggregation and striking heritability of this marker. It is uncertain, however, whether the abnormalities are associated with hypertension per se or whether they may be concentrated in a particular subset of hypertensive subjects. In the present study, maximal rates of Li-Na countertransport were measured in red blood cells of 82 white subjects, including 37 normotensive subjects and 45 normal- or high-renin hypertensive subjects previously classified as non-modulators (n = 21) or modulators (n = 24). Mean countertransport activity was significantly higher in non-modulators compared with normally modulating hypertensive or normotensive subjects (0.475 +/- 0.044 vs. 0.309 +/- 0.028 or 0.249 +/- 0.012 mmol/l cell x hr, respectively, p less than 0.001). Modulators did not differ significantly from normotensive subjects with regard to mean countertransport activity. Red blood cell sodium pump and Na-K-Cl cotransport were not significantly different in modulating and non-modulating hypertensive subjects. These relations remained unchanged after adjusting for age, body weight, and plasma cholesterol levels by analysis of covariance. A countertransport value exceeding 0.50 mmol/l cell x hr occurred in 40% of the non-modulators but in only one of the other subjects. In contrast , while one half of the modulators and normotensive subjects had a countertransport value less than 0.235 mmol/l cell x hr, none of the non-modulators did. Thus, elevated countertransport appears to aggregate in the non-modulating subset of essential hypertensive subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Antiporters↗

Treatment of seasonal depression with d-fenfluramine.

Eighteen patients with seasonal affective disorder (SAD) participated in a double-blind, placebo-controlled crossover study in 1986-1987. Each received, in random order, d-fenfluramine (15 mg p.o. twice daily)-a serotonin-releasing drug previously shown to suppress carbohydrate craving-or a placebo; these were given for 4 weeks separated by a 2-week washout period. Symptoms were assessed by means of clinical interviews and the Hamilton Rating Scale for Depression (HAM-D) with a special SAD addendum (AAD). Patients were also weighed. Depression scores (mean +/- SE) were identical before treatment with drug (20.9 +/- 1.3, HAM-D; 13.3 +/- 0.8, AAD) or placebo (21.4 +/- 1.2, HAM-D: 13.2 +/- 0.6, AAD). During placebo treatment, mean HAM-D scores declined by 22% (p less than .02) and AAD scores by 9% (p greater than .2). During d-fenfluramine treatment, HAM-D scores fell by 71% (p less than .001) and AAD scores by 73% (p less than .001). Thirteen (72%) of the patients demonstrated complete reversal of their abnormal test scores while taking d-fenfluramine. The group as a whole lost weight (mean = 1.2 kg) while receiving d-fenfluramine (p less than .033) but not when taking placebo. A second study, conducted in 1987-1988 with nine subjects who had previously responded to d-fenfluramine, showed that the drug remains effective for the full 3-month annual period of symptoms. These results indicate that d-fenfluramine may be useful in treating SAD and suggest that serotonin is involved in both SAD's affective and appetitive symptoms.

Adult↗

Dietary carbohydrate, a Big Mac, and insulin requirements in type I diabetes.

Using the artificial beta-cell (Biostator), we determined the insulin requirements in five nonobese type I (insulin-dependent) diabetic subjects who received isocaloric 40 and 60% mixed-carbohydrate diets in a crossover randomized fashion for 4 days, each day consisting of four equal meals. This was followed on day 5 by a "Big Mac Attack" lunch consisting of a Big Mac, french fries, and milk shake. Insulin requirements to maintain normoglycemia were calculated for each 24-h period and for the 2 h after each meal. The mean 24-h insulin requirements to maintain normoglycemia was greater for the 60% carbohydrate diet than the 40% diet. Although the four meals were of equal size, in all patients the insulin required to cover breakfast greater than lunch greater than dinner greater than or equal to snack. Expressed as milliunits per kilocalorie, the amount of insulin to cover breakfast was greater for the 60% (P less than .05) than the 40% carbohydrate diet and greater for breakfast than the other meals (P less than .01). Insulin requirements for the Big Mac (43% carbohydrate) were 58% greater than for the 40% carbohydrate diet, even after correction for caloric differences. In summary, 1) increasing dietary carbohydrate from 40 to 60% results in an increased insulin requirement for meals only; 2) insulin requirements are greater in the morning than in the evening, even when meal size is constant; and 3) very large meals with high fat and carbohydrate content result in a major increase in insulin requirement. These data indicate that diet has an important impact on insulin requirements in diabetes.

Adult↗

Pancreatic alpha cell response to alanine during and after normal and diabetic pregnancies.

Pancreatic alpha cell response to oral alanine was assessed in the third trimester of pregnancy and in the puerperium in 16 insulin-dependent diabetic and 7 normal pegnant women. Insulin response was also measured in the nondiabetic subjects. The nondiabetic subjects had higher basal glucagon and insulin levels as well as a greater response to oral alanine stimulation at 34 weeks' gestation than at 6 weeks post partum. In addition, basal levels of both hormones remained low at a time remote from pregnancy (9 months post partum), indicating both hyperinsulinemia and hyperglucagonemia in the postabsorptive state in normal human pregnancy. The secretory response of glucagon and insulin or oral alanine was blunted at 6 weeks post partum in the nondiabetic subjects. This suggests that the late puerperium may not be an appropriate "nonpregnant control period" for metabolic studies. During pregnancy, basal and stimulated glucagon levels were not significantly different in diabetic and normal women. Despite higher concentrations of blood glucose in diabetic women, basal and stimulated glucagon secretion was equivalent in the 2 groups. No pegnancy-induced increment in glucagon secretion was evident in insulin-treated diabetic subjects. Thus hyperglucagonemia does not contribute to the increased requirements for insulin during pregnancy in these women.

Administration, Oral↗

Clinical features as diagnostic guides in obstructive sleep apnea.

Obstructive sleep apnea (OSA) may induce psychiatric problems, but clinical risk factors do not reliably predict laboratory-verified OSA. Therefore, OSA diagnosis requires laboratory sleep monitoring. To find additional clinical features that would sharpen indications for sleep monitoring, we applied univariate analyses to clinical data for 137 OSA patients seen in a psychiatry sleep clinic. A symptomatology questionnaire was obtained from 101 of these patients: 71 had morning and 86 had afternoon vigilance tests, and all had upper-airway evaluation and polysomnography. Cigarette consumption but no other clinical features differed among OSA severity groups and total sleep period groups; upper-airway findings differed among vigilance groups. Multidiscriminant clinical predictor terms categorized several patients with severe OSA into less severe OSA categories. Clinical features did not accurately predict OSA. OSA will continue to be identified primarily by sleep laboratory testing. A two-phase laboratory routine, reserving full laboratory testing for patients with negative results on initial, less expensive screening tests, might conserve resources.

Adult↗

Electron paramagnetic resonance studies of gamma-irradiated corn.

Gamma-irradiated corn samples in the range 0.1-2.0 kGy dose range were studied by the EPR technique. The signal consists of one structureless line with a width of 0.82 +/- 0.02 mT and a g-factor of 2.004 +/- 0.002. The intensity of this line shows a linear dependence in this dose range. The corn samples were ground prior to irradiation. Before grinding the samples did not show any EPR signal. After grinding they present a free radical EPR line with the same characteristics as that produced by the gamma rays. The stability of these centers as a function of the temperature and time after irradiation was investigated. Analysis of these results suggest the presence of only one type of radical produced by both the mechanical and irradiation processes.

Electron Spin Resonance Spectroscopy↗

[An in vitro study of the mechanism by which captopril attenuates myocardial reperfusion damage].

The purpose of this study was to establish the molecular mechanism whereby captopril prevents the formation of active oxygen species, since many studies have provided evidence that postischemic myocardial dysfunction is mediated, at least in part, by the generation of these agents. Results indicate that captopril is a potent inhibitor of certain reactions mediated by O2-. However, this interference of captopril was not understood as an scavenging activity against the free radicals generated. The data could be explained by considering a direct interaction of captopril with the metal ions present that catalyse the formation of O2-. This mechanism could be of biological relevance.

Animals↗

Electron paramagnetic resonance of the mitochondrial respiratory chain in the presence of phenazine methosulfate.

The EPR spectra of phenazine methosulfate (PMS) generated under different conditions, as reduction or excitation with light were studied. In addition, results show the EPR spectra of reduced-submitochondrial particles and reduced-submitochondrial particles in the presence of PMS. Combined systems of this last type have been repeatedly utilized in EPR studies. This work proves that such systems give rise to characteristic signals around g = 2, which behaviour reflects the presence of particular prosthetic groups of the respiratory chain combined with the reduced dye. The consequences of these findings are discussed.

Animals↗