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Biomedical subjects

D B Jarrett

Publications and source records attributed to D B Jarrett.

At least 55 records · Page 3Linked to original sources
PubMed1984

Effect of atropine on the diurnal PRL responses to TRH in normal subjects.

Prolactin (PRL) responses to TRH were investigated at 0900 and 1800 hr in six young healthy men under basal conditions and after atropine administration. TRH induced significantly higher PRL release during the evening administration compared to the morning. Atropine had no effect on basal PRL secretion. Unlike the reported influences of anticholinergic drugs on the diurnal PRL responses to other stimuli, atropine also had no effect on TRH-stimulated PRL release either in the morning or in the evening. These observations in part may be accounted for by the direct PRL-releasing effect of TRH (without neurotransmitter involvement).

Adult↗
PubMed1984

Relationship among selected neuroendocrine and sleep measures in patients with recurrent depression.

Relationships among cortisol, TSH, and EEG sleep variables were examined in a group of 23 outpatients with recurrent unipolar depression at initial assessment prior to treatment for an acute major depressive episode. Blunted TSH responses were found in 39% of the sample (criteria of less than or equal to 7 microU/ml); cortisol nadir of greater than 2.5 micrograms% was rated in 41% of the group; and a reduced REM latency (less than or equal to 60 min) was measured in 57% of the group. Although almost all patients demonstrated abnormalities in at least one major neuroendocrine or sleep category, this preliminary analysis failed to find significant associations among these multiple biologic variables. Further studies on this so-called lack of association in a larger group of recurrent depressives is indicated. At this point caution is urged in assuming that biologic measures will identify a homogeneous group of severely depressed patients.

Adult↗
PubMed1984

Effect of nocturnal intravenous cannulation upon sleep-EEG measures.

The effect of an indwelling intravenous cannula on sleep-EEG measures has not been extensively documented despite its relatively frequent use in a variety of clinical studies. When the sleep EEGs from 30 healthy subjects were critically examined, no changes in sleep architecture were found. However, there were significant differences in the distribution of sleep latency, maintenance, and efficiency, with many subjects showing a reduction in the latter two items on the night of cannulation. A decrease in sleep maintenance of greater than 7.5 on the night of cannulation has been used to operationally define an unsatisfactory cannulation study which accounted for 43% of our subjects. It was striking that this group could also be identified by having higher REM densities in each REM period on the previous two nights in the sleep laboratory. This was especially true for the second REM period on the second night when only three of those subjects with subsequent unsatisfactory studies had a REM density less than 0.9. When this criterion was applied to a new group of 19 subjects, 13 were correctly classified with respect to subsequent changes in sleep maintenance before the cannulation study was conducted. It therefore appears possible that REM-sleep measures can be used to predict which subjects will have disrupted sleep on a subsequent cannulation night. Since sleep disruption can significantly mask patterns of hormone secretion, it is essential to monitor the sleep-EEG during such studies.

Adolescent↗
PubMed1983

Reduced cortisol latency in depressive illness.

Depressed patients commonly have disturbances in their sleep and cortisol secretory patterns. When the sleep-related changes in plasma cortisol concentration were measured in 14 patients with a primary major depressive illness, they differed significantly from the changes measured in 14 age- and sex-matched healthy control subjects. The nadir of the nocturnal plasma cortisol concentration was significantly greater in the group of depressed patients, and the nocturnal increase in the plasma cortisol concentration occurred significantly closer to sleep onset in these patients. The circadian activity within the hypothalamic-pituitary-adrenal axis of these depressed patients showed a subtle but significantly disturbed temporal relationship to sleep onset. This reduced time between sleep onset and the nocturnal increase in cortisol secretion suggests a possible biologic correlate of a depressive illness that might be useful as an illness marker in depressed patients.

Adolescent↗
PubMed1983

Nighttime plasma cortisol secretion and EEG sleep--are they associated?

Since the initial rise in plasma cortisol during sleep usually occurs near the second period of rapid eye movement (REM) sleep, a more precise association between the initial cortisol rise and electroencephalographic (EEG) sleep was examined in 22 normal control subjects. Our results indicate that the length of the total non-REM sleep period between the first and second REM period including awake time was significantly correlated to the cortisol rise time. However, the timing of the initial cortisol rise was not significantly related to the overall plasma cortisol levels during the night. But the second non-REM sleep period (minus awake time) is inversely related to overall cortisol levels during the night.

Adolescent↗
PubMed1983

REM latency in depression: is there one best definition?

The concurrent validity of different definitions of REM latency has been tested by comparing the ability of each definition to discriminate between primary depressives (outpatients and inpatients) and normal controls. In outpatients the percentage of cases correctly identified ranged from 62.5% to 70.8%; in inpatients, from 64.6% to 70.8%. REM latency definitions with the least stringent sleep-onset criteria yielded the lowest specificity. In contrast, the range of sensitivities yielded by different definitions was narrower and not clearly affected by sleep-onset criterion or exclusion/inclusion of wakefulness between sleep onset and first REM period. Furthermore, different definitions of REM latency correlated equally well (p less than 0.01) with Hamilton depression ratings. The shorter REM latencies in both outpatients and inpatients were associated with a later time of NREM sleep onset than in controls, rather than with an earlier REM sleep-onset time.

Adult↗
PubMed1978

Direct demonstration that receptor crosslinking or aggregation is important in insulin action.

Exposure of adipocytes to antibodies to the insulin receptor results in a blockade of (125)I-labeled insulin binding, stimulation of glucose oxidation, and many more insulin-like effects. Allowing for differences in purity, antireceptor antibody is equipotent with insulin on a molar basis. Both the bivalent F(ab')(2) and monovalent Fab' fragments of the antireceptor antibody are fully active in inhibiting (125)I-labeled insulin binding. Bivalent F(ab')(2) also retains its insulin-like effects. In contrast, the monovalent Fab' loses almost all ability to stimulate glucose oxidation and acts as a competitive antagonist of insulin-stimulated glucose oxidation. Addition of anti-F(ab')(2) antisera, which crosslink the Fab'-receptor complexes, results in a restoration of the insulin-like activity of the antibody. Similarly, when cells are exposed to submaximal doses of insulin, addition of anti-insulin antibodies at low concentration enhances the biological activity of insulin. These data suggest that receptor occupancy by ligand is not sufficient for signal generation and that the insulin-like effects of antireceptor antibody (and perhaps insulin itself) require receptor aggregation or clustering. This aggregation, however, appears to be independent of microfilaments or microtubules because the insulin-like effects of antireceptor antibody, and in fact, of insulin itself, are unaffected by agents that are known to disrupt these structures.

Adipose Tissue↗
PubMed1977

Adenosine 3'5' cyclic monophosphate metabolism in patients with severe depressive illness.

The daily excretion of adenosine 3'5' cyclic monophosphate (c-AMP) in a group of 19 patients with a severe depressive illness was found to be significantly decreased when compared with that from a group of euthymic patients being treated for other disorders in the same ward. The daily excretion of the depressed patients increased during the period of treatment and recovery from the illness. Treatment with a tricyclic antidepressant caused a greater increase than electroconvulsive treatment (ECT). There was no difference between the mean plasma c-AMP concentration of the depressed and euthymic groups. The mean CSF-c-AMP concentration was not different from the mean plasma c-AMP concentration in 12 patients with severe depression. There was no direct correlation between the CSF and plasma concentrations within patients. It was concluded that there may be a reversible disturbance in the renal metabolism of c-AMP in patients with severe depression.

Adult↗
PubMed1977

Autoantibodies to the insulin receptor. Effect on the insulin-receptor interaction in IM-9 lymphocytes.

The serum of some patients with insulin-resistant "diabetes" contains antibodies that bind to and block the cell membrane receptors for insulin. In this report, we have characterized the effects of the antireceptor antibodies on the interaction of (125)I-insulin with its receptor on the human lymphoblastoid cell line IM-9. Up to 95% of specific insulin binding can be inhibited by pretreatment of the cells with these immunoglobulins. The onset of the inhibitory effect is time- and temperature-dependent, and the effect is reversed extremely slowly if the cells are suspended in a large excess of antibody-free buffer. These features of antibody binding can be easily distinguished from those for insulin binding to its receptor. The inhibitory effect of the antibodies can be reversed by exposure of the cells to conditions known to elute surface immunoglobulins. The three antireceptor sera studied appear to alter the insulin-receptor interaction in different ways. Two antisera markedly reduce receptor affinity through combined effects on the insulin association and dissociation rates, and, additionally, have smaller effects on available receptor number. A third antiserum primarily affects available receptor number and has little effect on receptor affinity. All three antisera inhibit the capacity of insulin to promote negatively cooperative site-site interactions among insulin receptors. The data suggest that these autoantibodies to the insulin receptor bind to different determinants on the receptor and may therefore be useful as unique probes of insulin receptor structure and function.

Allosteric Regulation↗
PubMed1977

Effects of autoantibodies to the insulin receptor on isolated adipocytes. Studies of insulin binding and insulin action.

Autoantibodies to the insulin receptor have been detected in the sera of several patients with the Type B syndrome of insulin resistance and acanthosis nigricans. In this study we have used three of these sera (B-1, B-2, and B-3) as probes of the insulin receptor in isolated rat adipocytes. Preincubation of adipocytes with each of the three sera resulted in an inhibition of subsequent [(125)I]insulin binding. 50% inhibition of binding occurred with serum dilutions of 1:5 to 1:7,500. As in our previous studies with other tissues, Scatchard analysis of the insulin-binding data was curvilinear consistent with negative cooperativity. Computer analysis suggested that in each case the inhibition of binding was due to a decrease in receptor affinity rather than a change in available receptor number. In addition to the effects on insulin binding, adipocytes pretreated with antireceptor sera also showed alterations in biological responses. All three sera produced some stimulation of basal glucose oxidation. With serum B-3, maximal stimulation of glucose oxidation occurred at a serum concentration that inhibited binding by only 10-15%, whereas with serum B-2 the dilution curves for inhibition of binding and stimulation of glucose oxidation were superimposable. Serum B-1 behaved as a partial agonist; that is, it inhibited binding more effectively than it stimulated glucose oxidation. Cells pretreated with this serum in a concentration which inhibited binding by 80% also showed a five-fold shift to the right in the dose response of insulin-stimulated glucose oxidation, whereas spermine-stimulated glucose oxidation was unaffected. Serum B-2, which contained the highest titer of antireceptor antibodies, also stimulated 2-deoxy-glucose transport, as well as glucose incorporation into lipid and glycogen. Both the ability of the serum to inhibit binding and stimulate glucose utilization were enriched in purified immunoglobulin fractions and retained in the F(ab')(2) fragment of the IgG. In addition, the bioactivity was blocked by antihuman IgG but not by anti-insulin antibodies. Enzymatic digestion of adipocytes with trypsin resulted in a complete loss of insulin-stimulated bioactivity of serum B-3, but had only minor effects on the glucose oxidation produced by serum B-1 or B-2.These data suggest that the antibodies present in these three sera bind to different determinants on the insulin receptor. Thus, these antibodies may be useful probes of receptor structure and function.

Acanthosis Nigricans↗
PubMed1976

Direct method for detection and characterization of cell surface receptors for insulin by means of 125I-labeled autoantibodies against the insulin receptor.

Autoantibodies directed against the cell surface receptors for insulin are found in some patients with extreme insulin resistance. These antibodies specifically inhibit the binding of insulin to its receptor. A purified IgG fraction from one patient's plasma was labeled with 125I. The 125I-labeled antireceptor antibody, which initially represented about 0.3% of the total 125I-IgG, was enriched by selective adsorption and subsequent elution from cells rich in insulin receptors. The 125I-antireceptor antibody bound to cells and the binding was inhibited by whole plasma and purified IgG from this patient, as well as whole plasma from another patient with autoantibodies to the insulin receptor. Insulins that differed 300-fold in biological potency and affinity inhibited binding of 125I-antireceptor antibody in direct proportion to their ability to bind to the insulin receptor. The binding of 125I-antireceptor antibody was closely correlated with the binding of 125I-insulin over a wide range of receptor concentrations on different cell types. Experimentally induced reduction of the insulin receptor concentration was associated with parallel decreases in the binding of 125I-antireceptor antibody and 125I-insulin. The preparation of 125I-antireceptor antibody with a high specific activity by cytoadsorption and elution has provided a sensitive method for the detection of receptors and autoantibodies to cell surface components.

Antigen-Antibody Reactions↗
PubMed1976

Characterization of antibodies to the insulin receptor: a cause of insulin-resistant diabetes in man.

We have characterized the circulating inhibitor of insulin receptor binding found in several patients with a new syndrome of extreme insulin resistance. The inhibitor is an immunoglobulin by multiple criteria, including precipitation by 33% ammonium sulfate, migration on G-200 Sephadex gel filtration and DEAE chromatography, and immuno-precipitation with specific anti-human immuno-globulins. Although predominantly IgG, some activity is found in the IgM fraction of the immunoglobulins in one patient. The inhibitory immunoglobulins reacted with antisera to both kappa and lambda light chain determinants and are therefore polyclonal. In addition, activity is retained in the F(ab')2 fraction of pepsin-digested IgG. Evidence suggests that these antibodies are directed at determinants on or near the insulin receptor, and that they are responsible for the observed clinical insulin resistance.

Antibodies↗
PubMed1976

The immunology of the insulin receptor.

We have detected and characterized anti-insulin-receptor autoantibodies which circulate in several patients with insulin resistance diabetes. These antibodies are predominantly IgG and are polyclonal. They inhibit insulin binding to its receptor on a variety of tissues from widely separated species. Antibodies obtained from different patients appear to bind to different determinants on the receptor and alter receptor function in several ways. Some anti-receptor antibodies are capable of stimulating insulin-like effects on target tissues, while others block insulin-stimulated effects. Direct labeling of anti-receptor antibody with 125I permits use of these antibodies as an assay and probe of insulin receptors.

Adipose Tissue↗
PubMed1975

Corticosteroids in brain tissue.

Total corticosteroid concentrations were determined in the plasma and brains of five species: mouse, rat, cat, monkey and man. Corticosteroid concentrations were measured also in the livers of mice, rats and monkeys. Competitive protein binding techniques were validated and used for the tissue corticosteroid assays. In each species the brain corticosteroid value was less than the total plasma corticosteroid level but greater than the presumed unbound fraction of plasma corticosteroids. A clear circadian variation of brain corticosteroid values was found in mice, together with a rapid elevation of the tissue levels in response to stress. Reduction of both plasma and tissue corticosteroid concentrations was observed after adrenalectomy and in response to dexamethasone treatment of mice. Between 24 and 48 h post morten, mouse brain corticosteroid values decreased greatly. In cat, monkey and human brains all regions examined contained approximately equal amounts of corticosteroids. In particular, brain areas which are not involved in pituitary-adrenocortical regulation contained large amounts of corticosteroids.

Adrenal Glands↗
PubMedDate not supplied

Sleep-related growth hormone secretion is persistently suppressed in women with recurrent depression: a preliminary longitudinal analysis.

Growth hormone secretion was monitored during sleep in a group of 43 women with recurrent major depression who were participating in a 3-year maintenance therapy program. Patients were studied before acute treatment, after complete remission, and at 3-month intervals during maintenance treatment and the data generated were compared to those obtained in a control group of 14 age-matched healthy women studied once under identical conditions. When compared to the control group, the depressed patients secreted significantly less growth hormone before treatment. This reduction in growth hormone secretion, which was confined to the first half of the sleep period, persisted across the length of the maintenance study regardless of whether the subjects completed three years of therapy or experienced a recurrence.

Adult↗