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H Gwirtsman

Publications and source records attributed to H Gwirtsman.

17 recordsLinked to original sources
PubMed2006

Covariate analysis of late-onset Alzheimer disease refines the chromosome 12 locus.

Alzheimer disease (AD) is a progressive neurodegenerative disorder of later life with a complex etiology and a strong genetic component. Several genomic screens have suggested that a region between chromosome 12p13 and 12q22 contains at least one additional locus underlying the susceptibility of AD. However, localization of this locus has been difficult. We performed a 5 cM microsatellite marker screen across 74 cM on chromosome 12 with 15 markers in 585 multiplex families consisting of 994 affected sibpairs and 213 other affected relative pairs. Analyses across the entire data set did not reveal significant evidence of linkage. However, suggestive linkage was observed in several subsets. In the 91 families where no affected individuals carry an ApoE varepsilon4 allele, an HLOD score of 1.55 was generated at D12S1042. We further examined the linkage data considering the proposed linkages to chromosome 9 (D9S741) and chromosome 10 (alpha-catenin gene). There was a modest (P=0.20) increase in the LOD score for D12S368 (MLOD=1.70) when using the D9S741 LOD scores as a covariate and a highly significant (P<0.001) increase in the MLOD score (4.19) for D12S1701 in autopsy-confirmed families (n=228) when using alpha-catenin LOD scores as a covariate. In both cases, families with no evidence of linkage to D9S741 or alpha-catenin demonstrated most of the evidence of linkage to chromosome 12, suggesting locus heterogeneity. Taken together, our data suggest that the 16 cM region between D12S1042 and D12S368 should be the subject of further detailed genomic efforts for the disease.

Age of Onset↗
PubMed1994

Steroid receptor-mediated modulation of CD4+CD62L+ cell homing. Implications for drug abusers.

Naive human T cells home to peripheral lymph nodes via the leukocyte endothelial cell adhesion molecule-1 (LECAM-1, l-selectin, CD62L, Leu8 antigen) they express. We enriched populations of CD4+CD62L+ cells (attachment of Leu8+ T cells to flasks coated with anti-mouse IgG (AIS); Leu8+ T cells, 82.3% pure (+/- 2.3%), enriched for CD4+ cells by incubation over flasks coated with anti-CD4 antibody--this 3-4-day procedure yields an 88 +/- 1.4% recovery. Cells were treated with dexamethasone in vitro for 24-48 h, and monitored by flow cytometry. We found severe toxicity by this steroid at high concentration (10(-6) M: 35% decrease in CD62L+ T cells, 22% drop specifically in CD4+CD62L+ cells), suggesting the onset of receptor-mediated apoptotic events. The toxicity was dose dependent (5% and 7% drop in CD62L+ T and CD4+CD62L+ cells, respectively, at 10(-9) M, the concentration found in plasma 10 h following the administration of 1 mg dexamethasone). One mg of dexamethasone given to normal subjects leads to a 15-20% decrease in circulating CD4+CD62L+ cells at 10 h. This tends to be correlated with a drop in the number of glucocorticoid cytosolic receptors. Thus, steroids seem to modulate CD4+CD62L+ cell homing by means of receptor-mediated mechanisms.

Adult↗
PubMed1992

The effect of anorexia nervosa and refeeding on growth hormone-binding protein, the insulin-like growth factors (IGFs), and the IGF-binding proteins.

We studied the relationship of serum insulin-like growth factor-I (IGF-I), IGF-II, the IGF-binding proteins IGFBP-1, IGFBP-2, and IGFBP-3, and GH-binding protein (GHBP; which is postulated to be derived from the extracellular portion of the GH receptor) in normal volunteers and patients with anorexia nervosa before and after a refeeding program. Serum GHBP, IGF-I, and IGFBP-3 were all significantly decreased in low weight patients with anorexia nervosa and returned to nearly normal levels with refeeding. Fasting serum GH and serum IGFBP-1 and IGFBP-2 were significantly increased in low weight patients with anorexia nervosa and also returned to nearly normal levels with refeeding. Serum IGF-II was 27% lower in the low weight group than in normal subjects, but this difference was not statistically significant. Both serum IGF-I and IGF-II were positively correlated with serum IGFBP-3 and negatively correlated with serum IGFBP-1 and IGFBP-2. These data are consistent with the hypothesis that nutritional deprivation alters the GH-IGF axis by down-regulation of the GH receptor or its postreceptor mechanisms, and that this effect is reversible with refeeding.

Adult↗
PubMed1991

High levels of thyrotropin-releasing hormone precursor peptide immunoreactivity and binding substance occur in human cerebrospinal fluid.

A thyrotropin-releasing hormone (TRH) precursor peptide, pGlu-His-Pro-Gly (TRH-Gly) and related peptides were measured in human cerebrospinal fluid (CSF) with a TRH-Gly radiommunoassay and the levels of immunoreactivity (IR) were found to be 136- to 352-fold higher than the corresponding levels of TRH-IR. TRH-IR levels in CSF are elevated during the active phase of multiple sclerosis (MS). We have used this TRH-Gly RIA to determine whether this TRH precursor peptide is also elevated in CSF from MS and Alzheimer's (ALZ) disease patients in comparison with the corresponding levels in non-central nervous system disease (control) patients. A highly significant increase in TRH-Gly-IR was observed in MS and ALZ CSF samples compared to control CSF. Cation exchange and exclusion chromatography of extracts of mixtures of CSF and synthetic TRH-Gly revealed two peaks of TRH-Gly-IR. One cochromatographed with synthetic TRH-Gly and the other was attributable to the formation of a complex between TRH-Gly and a binding substance originating in CSF. Corresponding studies with extracts of mixtures of CSF and synthetic TRH revealed no evidence for TRH binding with any component of CSF. Reverse-phase high-pressure liquid chromatography of pooled extracts of normal CSF revealed that about a third of the total TRH-Gly-IR coeluted with synthetic TRH-Gly. The half-time for in vitro metabolism of synthetic TRH-Gly in fresh CSF was 5 times longer than for synthetic TRH at 37 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

Alzheimer Disease↗
PubMed1990

Altered cerebrospinal fluid neuropeptide Y and peptide YY immunoreactivity in anorexia and bulimia nervosa.

The related central nervous system peptides neuropeptide Y and peptide YY have been found to be among the most potent endogenous stimulants of feeding behavior. We measured these neuropeptides in cerebrospinal fluid to determine whether they contributed to the pathophysiologic characteristics of anorexia and bulimia nervosa. Cerebrospinal fluid neuropeptide Y concentrations were significantly elevated in underweight anorectic patients and in many of the anorectic patients studied at intervals after weight restoration. These levels normalized in long-term weight-restored anorectic patients who had a return of normal menstrual cycles. Increased neuropeptide Y activity may contribute to several characteristic disturbances in anorexia, including menstrual dysregulation. Cerebrospinal fluid peptide YY concentrations were significantly elevated in normal-weight bulimic patients abstinent from pathological eating behavior for a month compared with themselves when actively bingeing and vomiting or compared with healthy volunteers. Increased peptide YY activity may contribute to a drive to overfeed in normal-weight bulimic patients.

Adult↗
PubMed1988

Cerebrospinal fluid peptide YY immunoreactivity in eating disorders.

Peptide YY (PYY), a recently discovered peptide, is a potent stimulant of eating behavior in rats. We developed a radioimmunoassay for PYY and measured cerebrospinal fluid (CSF) levels in subjects with anorexia nervosa, bulimia and matched normal controls. Bulimics who had abstained from bingeing for 30 days showed a dramatic increase in CSF PYY levels compared to normal values (p less than 0.001) or their own values when actively bingeing (p less than 0.01, paired t test). No differences were seen for anorexia nervosa. These results suggest that bulimic behavior may correct a central nervous system abnormality in PYY.

Adolescent↗
PubMed1986

Abnormal hypothalamic-pituitary-adrenal function in anorexia nervosa. Pathophysiologic mechanisms in underweight and weight-corrected patients.

To study the pathophysiology of hypercortisolism in patients with anorexia nervosa, we examined plasma ACTH and cortisol responses to ovine corticotropin-releasing hormone before and after correction of weight loss. We also studied patients with bulimia whose weight was normal, since this disorder has been suspected to be a variant of anorexia nervosa. Before their weight loss was corrected, the anorexic patients had marked hypercortisolism but normal basal plasma ACTH. The hypercortisolism was associated with a marked reduction in the plasma ACTH response to corticotropin-releasing hormone. When these patients were studied three to four weeks after their body weight had been restored to normal, the hypercortisolism had resolved but the abnormal response to corticotropin-releasing hormone remained unchanged. On the other hand, at least six months after correction of weight loss their responses were normal. The bulimic patients whose weight was normal also had a normal response to corticotropin-releasing hormone. We conclude that in underweight anorexics, the pituitary responds appropriately to corticotropin-releasing hormone, being restrained in its response by the elevated levels of cortisol. This suggests that hypercortisolism in anorexics reflects a defect at or above the hypothalamus. The return to eucortisolism soon after correction of the weight loss indicates resolution of this central defect despite persistence of abnormalities in adrenal function.

Adrenocorticotropic Hormone↗
PubMed1986

Cognitive processing in anorexia nervosa. A disturbance in automatic information processing.

Anorexia nervosa patients were found to perform as well or better than control subjects on cognitive tasks that both require considerable cognitive effort and 'direct' the subject to the information that will be tested, but do more poorly than controls on tests that assess automatic or incidental processing of information. The implications of this particular pattern of cognitive alterations for theories concerning the etiology of anorexia nervosa are discussed.

Adult↗
PubMed1986

Cortisol response to dexamethasone in women with premenstrual syndrome.

There were no significant differences in post-dexamethasone cortisol between the follicular and luteal phase of the menstrual cycle in both women with premenstrual syndrome (PMS) and control subjects tested on these two occasions. Within each menstrual cycle phase, there were also no differences in post-dexamethasone cortisol between the two groups. In a second group of control subjects tested on a single occasion, post-dexamethasone cortisol values were higher when subjects were tested in the middle 2 weeks of the menstrual cycle compared with the first and last weeks of the cycle. This phenomenon, possibly due to estrogen effects, suggests that post-dexamethasone cortisol should be assessed weekly in women with PMS to determine whether they also manifest this normally observed menstrual cycle phase-related pattern, or whether it is absent, reflecting a reproductive endocrine abnormality in this patient group.

Adult↗
PubMed1984

Pharmacologic treatment of eating disorders.

Increased research focusing on the eating disorders has put the clinician on firmer ground when choosing appropriate psychopharmacologic treatments. Recent studies of patients with bulimia demonstrate that treatment with antidepressant medications may substantially reduce symptoms of bingeing and vomiting. The efficacy of pharmacologic approaches to anorexia nervosa is more uncertain, in part because of the limited availability of long-term follow-up studies. The judicious use of appetite suppressant medications, as reviewed in the text, is helpful for mild to moderate obesity. In treating these disorders, the clinician needs to integrate medication treatment with psychotherapeutic and behavioral treatment approaches.

Anorexia Nervosa↗
PubMed1984

Comparative cardiac effects of maprotiline and doxepin in elderly depressed patients.

In a double-blind study, 49 elderly patients with primary major depression, with or without cardiovascular disease, were treated with maprotiline or doxepin. Holter monitors, 12-lead ECGs, and orthostatic blood pressure measurements were used. Maprotiline was associated with decreased PVCs in patients with a "high" baseline rate, while doxepin was associated with increased PVCs in this group. There were no significant differences in orthostatic blood pressure changes between treatment and nontreatment phases or between the two drugs. Small but significant increases in heart rate and prolonged PR interval were noted with both drugs. QRS interval was prolonged by maprotiline but decreased by doxepin. Neither drug produced untoward effects in patients with stable angina or an old myocardial infarction. Maprotiline may have an antiarrhythmic effect which could be beneficial in the treatment of depression with concomitant PVCs. Conversely, doxepin may be more appropriate for depressed patients with heart block or intracardiac conduction delays. Further research is necessary to confirm these suggestions.

Aged↗
PubMed1984

Dexamethasone suppression test and treatment response.

The dexamethasone suppression test (DST) is frequently used to predict response to antidepressant therapy or to noradrenergic vs. serotonergic antidepressants. In a study of 173 inpatients and outpatients, the DST was not found to be predictive of response to antidepressant treatment for all depressed patients or of treatment response in a subgroup of melancholic patients (N = 86). Response of DST suppressors and nonsuppressors to antidepressants stratified by neurotransmitter specificity was not found to differ.

Adolescent↗
PubMed1984

Dexamethasone suppression test and Axis I diagnoses of inpatients with DSM-III borderline personality disorder.

To determine the relationship of Axis I diagnoses to the DSM-III diagnosis of borderline personality disorder, 100 consecutive admissions to an inpatient service were studied. Of the 27 patients labeled borderline, 14 were given an Axis I diagnosis of major depression (unipolar) compared with 8 of 73 nonborderlines; 73% (19 of 26) of all borderlines tested but only 46% (18 of 39) of nonborderlines had a positive DST (p less than .05). Few borderline patients received concomitant nonaffective diagnoses, and even fewer were given bipolar or schizoaffective diagnoses.

Adolescent↗
PubMed1982

The overnight dexamethasone suppression test: clinical and theoretical review.

The overnight dexamethasone suppression test (DST) has emerged as a useful clinical test in identifying a proportion of patients with primary affective disorder. This test may also be helpful in predicting response to tricyclic antidepressants, MAO inhibitors, and/or electroconvulsive therapy. This review summarized the recent clinical studies on the DST.

Antidepressive Agents, Tricyclic↗
PubMed1981

The dexamethasone suppression test and response to methylphenidate in depression.

The authors studied 19 inpatients with major depressive episode or schizoaffective disorder, depressed type, and compared their response to the dexamethasone suppression test (DST) with their response to the methylphenidate stimulation test. They found a significant negative correlation between responses to DST and to methylphenidate.

Depressive Disorder↗