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Biomedical subjects

J A Schlechte

Publications and source records attributed to J A Schlechte.

16 recordsLinked to original sources
PubMed1992

Intracranial dissemination of an ACTH secreting pituitary neoplasm--a case report and review of the literature.

A 52-year-old woman developed recurrent hypercortisolism 3 yr after successful surgical treatment of Cushing's disease. At postmortem, eosinophilic pituitary tissue showing positive ACTH immunohistochemical staining was present in the frontal lobe and cerebellum but there was no tumor in the sella. In the absence of a pituitary tumor, extrasellar ACTH producing tissue could arise from seeding of the cerebrospinal fluid with tumor cells at the time of operation or from an atypical pituitary carcinoma. In this report we review the mechanisms of intracranial dissemination of pituitary tissue and ACTH-secreting pituitary carcinomas, including parasellar invasion, meningeal seeding, and cerebrospinal and hematogenous spread.

Adenoma↗
PubMed1991

Prospective study of postpartum blues. Biologic and psychosocial factors.

Potential biologic and psychosocial causative factors for the postpartum blues were tested in a prospective study of 182 women followed up from the second trimester of pregnancy until postpartum week 9. Personal and family history of depression, depressive symptoms, stressful life events, and social adjustment were all assessed during the second trimester. Levels of progesterone, prolactin, estradiol, free and total estriol, and free and total cortisol were measured on several occasions during late pregnancy and early puerperium. Obstetric and child-care stressors and the postpartum blues were assessed after delivery. Predictors of the postpartum blues were personal and family history of depression, social adjustment, stressful life events, and levels of free and total estriol. Our results support the hypothesis that the postpartum blues is within the spectrum of affective disorders.

Adult↗
PubMed1991

Effects of chronic marijuana use on testosterone, luteinizing hormone, follicle stimulating hormone, prolactin and cortisol in men and women.

To investigate possible effects of chronic marijuana use on reproductive and stress hormones, we assayed testosterone, luteinizing hormone, follicle stimulating hormone, prolactin, and cortisol in 93 men and 56 women with a mean (+/- S.E.) age of 23.5 +/- 0.4 years. Hormone values were compared among groups of subjects stratified according to frequency of marijuana use (frequent, moderate and infrequent; N = 27, 18, and 30, respectively) and non-using controls (N = 74). Chronic marijuana use showed no significant effect on hormone concentrations in either men or women.

Adolescent↗
PubMed1991

Controlled prospective study of postpartum mood disorders: psychological, environmental, and hormonal variables.

Demographic, psychiatric, social, cognitive, and life stress variables were used to determine the etiology of depression in childbearing (CB; n = 182) and nonchildbearing (NCB; n = 179) women. Hormonal variables in postpartum depression were also evaluated. In the CB group predictors of depression diagnosis were previous depression, depression during pregnancy, and a Vulnerability (V) x Life Stress (LS) interaction; predictors of depressive symptomatology were previous depression, depressive symptoms during pregnancy, life events, and V x LS. Only estradiol was associated with postpartum depression diagnosis. In the NCB group V X LS was the only predictor of depression diagnosis; depressive symptoms during pregnancy and life events were predictors of depressive symptomatology. Previous findings about depression vulnerability were replicated. The significant V x LS interactions support the vulnerability-stress model of postpartum depression.

Adult↗
PubMed1990

Potentiation of glucocorticoid-induced cytolysis in sensitive human leukemic cells by an inhibitor of ADP-ribosylation.

3-Aminobenzamide, a general inhibitor of poly(ADP-ribose)polymerase, potentiated the triamcinolone acetonide-mediated growth inhibition and lysis of the glucocorticoid-sensitive CEM-C7 human leukemic cell line. This potentiation was dose-dependent with maximal response being detected at 3 mM 3-aminobenzamide, and was completely blocked by the glucocorticoid receptor antagonist RU 38486. Scatchard analysis of whole cell specific [3H]triamcinolone acetonide binding data did not reveal any effect of 3-aminobenzamide on either the number of intracellular receptor binding sites or their affinity for the agonist. Treatment of the ICR-27 cell line, which is a glucocorticoid resistant mutant isolated from CEM-C7, with 3-aminobenzamide did not restore triamcinolone acetonide sensitivity. Similarly, 3-aminobenzamide treatment of several other lymphoid cell lines (human HL60 and IM-9 and murine L1210 cells) which contain functional receptors but are not normally lysed by glucocorticoid agonists, failed to induce sensitivity to triamcinolone acetonide. Since treatment of sensitive lymphoid cells with glucocorticoid agonists results in DNA fragmentation prior to cell death, these data suggest that 3-aminobenzamide potentiates the cytolytic response of sensitive cells to glucocorticoid agonists by inhibiting DNA excision repair mechanisms.

Adenosine Diphosphate↗
PubMed1990

Factors influencing choice of academic or practice careers in radiology.

Factors, both personal and job-related in nature, that influence career choice among radiology residents are identified. Twenty-six third and fourth year radiology residents at two separate locations, and 17 age-matched and sex-matched internal medicine residents completed a 30-minutes interview and rated themselves on a series of job-related competencies. Data were collected on five groups of variables: demographic data, residency-related variables, factors that influence career choice, self-descriptions, and personal competencies. The results indicate that residents who choose academic careers and those who plan to have private practice careers differ substantially in their reasons for career choice. An academic career is chosen because of its atmosphere, emphasis on research and specialized techniques, and opportunity for teaching. In contrast, private practice careers are selected because of the autonomy they allow, the accompanying lifestyle, and financial reimbursement.

Career Choice↗
PubMed1987

The effect of glucocorticoids on corticosteroid binding globulin.

To evaluate the effect of glucocorticoids on corticosteroid binding globulin (CBG), we measured the binding capacity and binding affinity of cortisol for CBG in normal subjects, patients receiving glucocorticoids and patients with Cushing's syndrome. Normal subjects had a mean binding capacity of 3.8 (+/- SD 0.7) X 10(-7) mol/l and mean binding affinity of 1.96 +/- 0.48 X 10(-8) M. Patients with Cushing's syndrome had a 40% decrease in binding capacity (2.3 +/- 0.4 X 10(-7) mol/l) compared to control subjects and significantly lower mean binding capacity than patients receiving pharmacological (2.9 +/- 0.6 X 10(-7) mol/l) and physiological doses of glucocorticoids (3.4 +/- 0.6 X 10(-7) mol/l) (P = 0.05 one-way analysis of variance). Patients with endogenous cortisol excess also had significantly lower mean binding affinity (1.54 +/- 0.37 X 10(-8) M) than normal subjects and glucocorticoid treated subjects. These changes suggest that both endogenous and exogenous glucocorticoids can modulate circulating levels of CBG and may have important implications for patients receiving steroid therapy.

Adrenal Insufficiency↗
PubMed1987

Use of [3H]cortivazol to characterize glucocorticoid receptors in a dexamethasone-resistant human leukemic cell line.

ICR 27 is a mutant derived from the glucocorticoid-sensitive human leukemic cell line CEM C7 that has been characterized as glucocorticoid receptor negative based on its ability to specifically bind [3H]dexamethasone ([3H]DEX). We used the pyrazolosteroid [3H]cortivazol ([3H]CVZ) to determine whether ICR 27 cells actually contain glucocorticoid receptors and, if so, whether these receptors can mediate physiological effects. Scatchard analysis of the binding of [3H]CVZ to cytosol from ICR 27 cells was consistent with a single class of receptors of uniform affinity (0.7 nM). Cytosolic [3H]CVZ complexes had a sedimentation coefficient of 4.6S on linear sucrose gradients and eluted from DEAE-cellulose columns at a potassium phosphate concentration of 250 mM. CVZ also competed with [3H]DEX mesylate for binding to a 96,000 mol wt protein. Incubation of ICR 27 cells with CVZ caused 50% growth inhibition and 50% maximal induction of glutamine synthetase activity at concentrations of 20 and 35 nM, respectively. Elution profiles of [3H]CVZ complexes from DEAE-cellulose columns showed that complexes formed upon thermal activation were relatively unstable, and little or no increase in binding of [3H]CVZ-receptor complexes to DNA-cellulose was observed. Thus, [3H]CVZ identifies functional glucocorticoid receptors in a cell line previously described as DEX resistant. Although the binding of [3H]CVZ to activated receptors in vitro appears unstable, high concentrations of CVZ may facilitate stabilization of activated complexes that can mediate both anabolic and catabolic effects.

Cell Division↗
PubMed1987

Effect of the antiprogesterone RU-38486 on meningioma implanted into nude mice.

Meningiomas have been shown to have steroid-binding proteins. In vitro, estradiol, progesterone, and the antiestrogen tamoxifen stimulate tumor growth. However, incubation of tumor cells with an antiprogesterone agent results in tumor inhibition. In this investigation, a human meningioma was implanted subcutaneously in athymic nude mice. Two treatment groups were established, one receiving the antiprogesterone agent RU-38486 (10 mg/kg/day in suspension) and the other receiving only vehicle. After 3 months, the tumor growth index (defined as the tumor volume at 3 months divided by the initial tumor volume) was 0.25 +/- 0.46 (mean +/- standard deviation) in the group receiving antiprogesterone and was 1.54 +/- 0.58 in the control group (p = 0.041). Further investigation of the effect of antiprogestational agents on the growth and hormone-binding proteins of other meningiomas will better define the mechanism of their effects.

Animals↗
PubMed1986

A comparison of adrenal cortical function in patients with depressive illness and Cushing's disease.

We measured total and free plasma cortisol, 24-hour urinary cortisol excretion, and corticosteroid-binding globulin in 21 normal subjects, 25 patients with depressive illness, and 6 patients with Cushing's disease. Patients with depression had mean 24-hour plasma (8.3 +/- 2.7 micrograms/dl) and urinary (36 +/- 33.55 micrograms/g creatinine) cortisol levels that did not differ from those of normal subjects (6.6 +/- 1.7 microgram/dl; 24.6 +/- 15.4 micrograms/g creatinine), but were significantly lower than those of patients with Cushing's disease (14.4 +/- 2.4 micrograms/dl; 215 +/- 101 micrograms/g creatinine). Not all patients with depression had hypercortisolemia, and the 1-mg dexamethasone suppression test identified some of those with adrenal hyperfunction. 17 of 25 patients had normal 8 a.m. and/or 4 p.m. plasma cortisol after dexamethasone (suppressors), while 8 patients had values greater than 5 micrograms/dl (nonsuppressor). Suppressors had normal total 24-hour plasma and urinary cortisol, while nonsuppressors had levels that were in the range seen in Cushing's disease. Patients with depression showed the expected circadian variation in total and free cortisol, but nonsuppressors had elevated levels in evening and early a.m. hours when levels in normal subjects were low. Patients with Cushing's disease had elevated levels throughout the day. The mean binding capacity of corticosteroid-binding globulin was not different in normal and depressed subjects (23.9 +/- 3.2 vs. 22.2 +/- 3.4 micrograms/dl), but was significantly decreased in patients with Cushing's disease (15.7 +/- 3.5 micrograms/dl). Although total cortisol levels were similar, nonsuppressors had significantly lower mean 24-hour plasma free cortisol (1.01 +/- 0.27 microgram/dl) than patients with Cushing's disease (2.4 +/- 0.54 microgram/dl).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex Function Tests↗
PubMed1986

Long term follow-up of women with surgically treated prolactin-secreting pituitary tumors.

To examine the long term effectiveness of transsphenoidal microsurgery for patients with PRL-secreting pituitary tumors, we studied 54 women at yearly intervals after transsphenoidal surgery. Five years after surgery, 19 women (35%) had normal serum PRL concentrations, and 23 (43%) had persistent hyperprolactinemia. Hyperprolactinemia recurred in 12 of 31 patients (39%) who had normal PRL concentration 6 weeks after surgery. None of the patients with recurrent hyperprolactinemia had radiographic evidence of tumor regrowth, and only 3 of 12 had amenorrhea. A serum PRL level below 6 ng/ml 6 weeks after surgery occurred more frequently in cured patients than in those who had a recurrence. PRL responses to TRH were normal in cured patients 1 and 5 yr after surgery and abnormal in those who had recurrent hyperprolactinemia. The PRL responses to chlorpromazine- and insulin-induced hypoglycemia were blunted in patients with normal as well as elevated PRL levels. Patients with recurrent, as well as those with persistent, hyperprolactinemia had no nocturnal rise in serum PRL 5 yr after surgery. The 39% recurrence rate of hyperprolactinemia and persistent abnormalities in pituitary-hypothalamic regulation of PRL secretion after transsphenoidal surgery raise important questions about the choice of primary therapy for patients with PRL-secreting tumors.

Adenoma↗
PubMed1985

Lymphocyte glucocorticoid receptor binding in depressed patients with hypercortisolemia.

Despite elevated levels of serum and urinary cortisol, patients with depressive illness manifest none of the clinical stigmata of glucocorticoid excess. This hypercortisolemia in the absence of clinical effects suggests a state of hormone resistance and could be mediated by alterations in the glucocorticoid receptor. Earlier studies have shown that small doses of glucocorticoids cause a decrease in glucocorticoid receptor binding in normal human lymphocytes. White cells from depressed patients with significant hypercortisolemia would be expected to show a similar change in receptor concentration if peripheral tissues are adequately exposed to and sensitive to the hormone. In this study we compared the binding of [3H]dexamethasone to lymphocytes from normal subjects and depressed patients with hypercortisolemia. Lymphocytes from normal subjects had a mean receptor concentration of 10.2 +/- 0.66 fm/10(6) cells (S.E.M.) and a dissociation constant of 4.8 +/- 0.47 nM. Lymphocytes from depressed patients with abnormal 0800 h serum cortisol after dexamethasone had a mean receptor concentration of 8.8 +/- 0.75 fm/10(6) cells, which was not significantly different from that in lymphocytes from normal subjects or from depressed subjects with normal post-dexamethasone cortisol levels (9.4 +/- 0.95 fm/10(6) cells). Lymphocytes from depressed patients with elevated urinary free cortisol excretion (UFC) also had normal receptor concentration and binding affinity for dexamethasone. The lack of a change in lymphocyte glucocorticoid receptor concentration in the presence of cortisol excess suggests the possibility that hypercortisolemia in depressive illness represents a state of peripheral glucocorticoid resistance.

Adult↗
PubMed1985

[3H]cortivazol: a unique high affinity ligand for the glucocorticoid receptor.

Cortivazol (CVZ) and deacylcortivazol (DAC) are pyrazolosteroids with potent glucocorticoid activity. In previous work we showed that DAC is 40-fold more potent than dexamethasone (DEX) in lysing leukemic lymphoblasts. To assess the interaction between these atypical steroids and the glucocorticoid receptor, we examined the binding of [3H]CVZ to cytosol from glucocorticoid-sensitive and -resistant variants of the human leukemic cell line CEM C7. In glucocorticoid-sensitive cells [3H]CVZ causes a 2-fold induction of glutamine synthetase and binds to a protein in the 4.6 S region of high salt sucrose gradients. On DEAE-cellulose chromatography, [3H]CVZ-receptor complexes show a shift from high (0.25 M KP) to low salt (0.09 M KP) eluting forms upon activation. CVZ competes for a 97,000-dalton protein labeled by [3H]dexamethasone mesylate. Scatchard analysis of the binding of [3H]CVZ in glucocorticoid-sensitive cells revealed a curvilinear plot which resolved into high (0.4 nM) and low (11 nM) affinity components. The receptor concentration of the low affinity site (0.30 pmol/mg protein) was approximately twice that of the high affinity site (0.14 pmol/mg protein). Dissociation experiments with dilution and/or excess unlabeled CVZ supported the presence of independent sites. In contrast, the binding of [3H]DEX to C7 cytosol revealed a single class of binding sites (Kd = 1.9 nM; receptor concentration, 0.46 pmol/mg protein). Examination of the binding of [3H]CVZ using 10(-5) M DEX as the competing ligand showed that DEX binds only to the low affinity site detected by [3H]CVZ. In cytosol from a glucocorticoid-resistant cell line with virtually no [3H]DEX binding, [3H]CVZ detected a single high affinity binding site that was similar in dissociation constant (0.8 nM) and receptor concentration (0.13 pmol/mg protein) to the high affinity site detected in the glucocorticoid-sensitive cell line C7.

Binding, Competitive↗
PubMed1985

Plasma free cortisol in depressive illness--a review of findings and clinical implications.

Measurements of a variety of parameters of biologically active cortisol indicate that a small number of patients with depressive illness have significantly elevated levels of unbound plasma cortisol. Abnormalities in corticosteroid binding globulin do not account for the hypercortisolemia, and elevated urinary levels of free cortisol confirm the data obtained for plasma free cortisol. Direct measurements of free cortisol suggest that the absence of physical effects of cortisol in patients with depression is related to the very mild elevation in plasma levels of free cortisol in these patients and that high levels are not sustained throughout the day as they are in patients with pathologic glucocorticoid excess. The apparent discrepancy between elevated total cortisol levels and the mild elevation of unbound plasma cortisol is best explained by the generous binding capacity of corticosteroid binding globulin. Total cortisol levels of greater than 25 micrograms/dl are necessary to saturate the binding sites of corticosteroid binding globulin. Only then can free cortisol be detected in plasma. Although these studies suggest that unbound plasma cortisol is elevated, whether these levels represent biologically active cortisol in other tissue sites as well, particularly the central nervous system, is still unclear. It is well accepted that discrete binding sites for cortisol and dexamethasone occur in hypothalamic and pituitary tissue, but the mechanism of glucocorticoid regulation of these binding sites has not been elucidated. Cortisol levels in cerebrospinal fluid correspond closely to plasma levels of unbound cortisol. Ruf and Steiner have shown that corticosteroid responsive neurons are present in the periventricular gray matter of the third ventricle, where other investigators have identified active ependymal transport mechanisms for cortisol.(ABSTRACT TRUNCATED AT 250 WORDS)

Depressive Disorder↗
PubMed1984

Dissociation of plasma cortisol and ACTH responses to dexamethasone in healthy subjects.

We examined the plasma cortisol and ACTH concentrations after graded doses of dexamethasone in a group of young, healthy adults. The decrease in cortisol was uniform in all subjects, and in 8 subjects there was a high degree of correspondence with the plasma ACTH concentration. The remaining 5 subjects had no change in plasma ACTH concentration during dexamethasone administration. All subjects had an expected diurnal change in cortisol on 2 pretreatment days and there was a corresponding diurnal change in ACTH for those subjects who had associated ACTH and cortisol responses after dexamethasone, while those with dissociated ACTH and cortisol after dexamethasone had no diurnal ACTH pattern. These findings were consistent with the 24-hour pattern of ACTH and cortisol before and after 1.0 mg of dexamethasone in 2 of the same subjects. These results are further evidence for ACTH independent regulation of adrenal function and indicate that pituitary-adrenal regulation in man is more complex than the traditional model of ACTH-cortisol feedback would predict.

Adrenocorticotropic Hormone↗