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Biomedical subjects

S Gabriel

Publications and source records attributed to S Gabriel.

At least 19 recordsLinked to original sources
PubMed1996

Distal extremity swelling with pitting edema in polymyalgia rheumatica. Report on nineteen cases.

OBJECTIVE: To determine the frequency and clinical characteristics of diffuse distal extremity swelling with pitting edema occurring in polymyalgia rheumatica (PMR). METHODS: Clinical features and laboratory findings were recorded for all 245 residents of Olmsted County, Minnesota who developed PMR over a 22-year period (1970-1991). Those who exhibited > or = 1 episode of diffuse distal extremity edema with pitting were selected for this study, and were evaluated further. RESULTS: Thirteen women and 6 men in this incidence cohort of PMR had > or = 1 episode of distal extremity swelling with pitting edema. Giant cell arteritis was also identified in 5 patients. In 11 patients, the swelling and edema development concurrently with proximal PMR symptoms. In 2 patients, the distal swelling was the initial manifestation, and in 6 patients, the distal symptoms developed during relapses or recurrences of PMR. Both upper and lower extremities were affected, usually in a symmetric manner. Other peripheral manifestations were also common. The distal swelling and pitting edema responded promptly to corticosteroids, and slowly or incompletely to nonsteroidal anti-inflammatory drugs; a similar response was observed in the proximal symptoms. The distal swelling appeared to represent tenosynovitis and synovitis of regional structures. CONCLUSION: Distal extremity swelling with pitting edema represents a manifestation of PMR that has not been well described in previous studies. Awareness of this finding will help facilitate the proper diagnosis and institution of appropriate therapy for this disease.

Adrenal Cortex Hormones↗
PubMed1996

Effects of cholecystokinin on Y, X, and W cells in the dorsal lateral geniculate nucleus of rats.

The role of the cholecystokinergic input to the rat's dorsal lateral geniculate nucleus (dLGN) was studied by examining the effect of iontophoretically administered CCK-8S on the neuronal response to stimulation of the receptive field center. Peristimulus activity was recorded extracellularly from 108 neurons grouped according to the type of receptive field (OFF, ON, or ON-OFF) and classified with respect to their Y, X, or W properties by means of discriminant analysis. CCK affected the response to a center-sized spot of light in two thirds of the neurons investigated. The center response decreased in 50 of 73 CCK-sensitive neurons (69%), predominantly in Y OFF and X OFF center cells (17 of 19). In the remaining 23 cells the center response increased, most consistently (11 of 17) in W ON center cells. Center and surround responses were similarly influenced. Inhibitions and excitations induced by CCK-8S were reproducible, dose dependent, and receptor mediated. The CCKB antagonist PD 135158 reduced the CCK effects in 10 of 14 cells; the CCKA antagonist KL 1001 reduced the CCK effects in 17 of 36 cells. The CCK-induced inhibition was B-receptor specific in 4 of 8 cells, A-receptor specific in 2 of 8 cells, and partially mediated by each of the two types of receptor in the remaining 2 cells. Blocking by the CCKA antagonist was more frequently observed in W cells than in cells with Y or X characteristics. The data show that CCK modifies the activity of dLGN cells in a variable direction depending on the specific cell type (Y, X, W) and response pattern (OFF, ON). The effects of CCK are discussed in relation to proposed functions of the superior collicular input to the dLGN.

Animals↗
PubMed1996

Engineering, expression and renaturation of targeted TGF-beta fusion proteins.

This study reports the expression, purification, and renaturation of biologically active Transforming Growth Factor-beta 1 (TGF-beta 1) fusion proteins from Escherichia coli (E. coli). A prokaryotic expression vector was engineered to produce tripartite fusion proteins consisting of (i) a purification tag, (ii) a protease-sensitive linker/collagen binding domain, and (iii) a cDNA sequence encoding the active fragment of human TGF-beta 1. The expressed fusion proteins TGF-B1-F1 and TGF-B1-F2, located in inclusion bodies, were solubilized with 8 M urea and renatured using a glutathione redox-coupled system and protracted dialysis under several experimental conditions. The purification of the recombinant proteins was achieved by binding the His-tag of the fusion proteins on a Ni-NTA metal chelate column. The biological activity of the recombinant growth factor was demonstrated by its ability to inhibit mink lung (Mv1Lu) cell proliferation and/or to stimulate proliferation of NIH-3T3 mouse fibroblasts, where purified human platelet TGF-beta 1 served as a positive control. Purified TGF-B1-F1 and TGF-B1-F2 (collagen-binding) constructs exhibited anti-proliferative activities comparable to purified platelet TGF-beta 1, but at lower specific activities. Binding of the renatured TGF-B1-F2 fusion protein to collagen was demonstrated by stable binding on a collagen-conjugated Sephadex-G15 column. The high affinity binding was also demonstrated by the binding of 3H-collagen to the TGF-B1-F2 protein immobilized on a Ni-NTA column. The TGF-B1-F2 fusion protein bound to collagen coated surfaces with high affinity but exhibited comparatively lower biological activity than the fusion protein in solution, suggesting a potentially latent configuration. Taken together, these results demonstrate that biologically active TGF-beta 1 fusion proteins can be recovered from transformed bacteria by oxidative refolding; thus, providing a means for its high-yield production, purification, and renaturation from microorganisms. Furthermore, these results support the concept that auxiliary domains may be used to modulate and/or target TGF-beta 1 for specific applications.

3T3 Cells↗
PubMed1995

Diurnal neuroendocrine and autonomic function in acute and remitted depressed male patients.

This study evaluated diurnal data gathered hourly (1000 to 1800 hours) in males during acute depression and during remission of depression and in age-range/gender-matched normal controls. Mean, peak, variability, and time-course of the noradrenergic metabolite, plasma 3-methoxy, 4-hydroxyphenylglycol [MHPG]), plasma cortisol, and autonomic (mean arterial blood pressure [MAP] and heart rate) variables were examined. Compared to controls, acutely depressed, but not remitted depressed, patients had 1) an earlier plasma MHPG peak, 2) a greater intragroup variability of plasma MHPG, 3) a higher plasma cortisol concentration, 4) a lower MAP, and 5) tended to increase MAP more slowly than did the normal controls. The time course of diurnal heart rate also differed in acutely depressed patients from controls: acutely depressed patients started higher and converged by midday to normal levels. These diurnal data lend limited support to the dysregulation hypotheses of depression that suggest normal circadian rhythmicities are altered or disrupted in acute depression and that peripheral manifestations of central dysregulation normalize in remission of depression.

Adult↗
PubMed1995

Neurochemical correlates of dementia severity in Alzheimer's disease: relative importance of the cholinergic deficits.

Cholinergic markers, neuropeptides, and amines and their metabolites were sampled from identical specimens across 10 neocortical regions in a large sample of Alzheimer's disease (AD) cases and controls. Levels of choline acetyltransferase, acetylcholinesterase, somatostatin, corticotropin-releasing factor, serotonin, and 5-hydroxyindoleacetic acid were significantly reduced in AD versus controls. After data reduction, the most descriptive neurochemical indices were used to examine the relationship of neurochemical measures and dementia severity within the AD sample, controlling for age effects. Dementia severity ratings were based on antemortem assessments (46.9% of AD sample) and postmortem chart review (53.1% of the AD sample). Choline acetyltransferase activity was highly correlated with clinical dementia ratings across the neocortex of the AD cases. Somatostatin and corticotropin-releasing factor levels were correlated with dementia severity only when control cases were included in the analyses. None of the amines, their metabolites, or the neuropeptides quantified related significantly to dementia severity in the AD cohort. These data (a) confirm the strong association of cholinergic deficits with functional impairment in AD and show that this association is independent of age and (b) suggest that of all the neurochemical species quantified, the cholinergic indices may be unique in their association with dementia severity.

Aged↗
PubMed1994

Very slow oscillations of activity in geniculate neurones of urethane-anaesthetized rats.

The spontaneous activity of neurones of the dorsal lateral geniculate nucleus (dLGN) in urethane-anaesthetized rats was examined for the presence of very slow oscillatory activity. Fifty-four of the 86 dLGN neurones (63%) recorded extracellularly displayed oscillatory activity in the 0.02-0.03 Hz range. Similar very slow oscillations were observed in the ventral part of the LGN and the nucleus lateralis posterior (LP), but not in the hippocampus. Diffuse light stimuli dampened or blocked these oscillations in 23 of the 29 neurones tested. In a second group of experiments (iontophoretic studies) the very slow oscillatory activity was efficiently blocked by N-methyl-D-aspartate.

Action Potentials↗
PubMed1994

Effects of ipsapirone in healthy subjects: a dose-response study.

A dose-response study of ipsapirone (IPS), a 5HT1a partial agonist, was conducted in healthy male subjects. IPS was administered in doses of 5, 10 and 20 mg PO in a placebo-controlled, double-blind design to 15 subjects on 4 test days separated by at least 3 days. Oral temperature, ACTH, cortisol, prolactin, blood pressure, pulse rate and behavioral variables were assessed every 30 min for 3 h after administration of tablets (at 10:00 A.M.). IPS at 20 mg significantly decreased temperature and increased cortisol levels. Although IPS increased ACTH levels at 20 mg, this effect was variable and not significant. IPS did not affect prolactin levels nor did it have any behavioral effects. Although 20 mg IPS decreased blood pressure and pulse rate in one subject, overall it had no significant effect on these parameters. IPS at 20 mg PO appears a useful probe to test 5HT1a function when temperature and cortisol are used as response variables. These results replicate earlier studies on the effect of IPS in healthy human subjects.

Adrenocorticotropic Hormone↗
PubMed1993

Serotonin function and treatment response to clozapine in schizophrenic patients.

OBJECTIVE: Clozapine is the only compound proven to be effective in the 20% of schizophrenic patients refractory to treatment with conventional neuroleptics. Although its mechanism of action has not been elucidated, clozapine appears, in contrast to most conventional neuroleptics, to be a potent serotonin (5-HT) antagonist. This study hypothesized that 5-HT function is increased in patients who benefit from clozapine treatment relative to patients who fail to improve on it. METHOD: The 5-HT receptor agonist m-chlorophenylpiperazine (MCPP) was used as a probe to examine 5-HT function. MCPP (0.35 mg/kg p.o.) was administered in a placebo-controlled design after a 3-week drug-free period to 19 schizophrenic patients. ACTH, prolactin, body temperature, behavior, and MCPP blood level were measured. Patients were then treated with a conventional neuroleptic, and, having failed to respond to it, were treated with clozapine for 5 weeks (up to 600 mg/day). RESULTS: Patients who responded to clozapine had significantly higher ACTH responses to MCPP during the drug-free state than the patients who failed to benefit from clozapine. Moreover, the degree of improvement with clozapine, particularly the improvement in psychotic symptoms, was strongly correlated with the magnitude of MCPP-induced ACTH release. Other MCPP-induced responses and MCPP blood level were similar for the two groups and did not correlate with the degree of symptomatic improvement with clozapine. CONCLUSIONS: Results of this study suggest that MCPP-induced ACTH release, and by inference 5-HT receptor function, may be increased in patients who benefit from treatment with clozapine relative to patients who fail to improve on this drug.

Adrenocorticotropic Hormone↗
PubMed1993

A reliability study of SLEDAI: a disease activity index for systemic lupus erythematosus.

SLEDAI, a disease activity index for systemic lupus erythematosus (SLE) has been validated against other such indices and its reliability has been shown by specialists in SLE. To assess its reliability among less experienced clinicians, we conducted a reliability study with 3 rheumatology trainees and 9 patients with SLE according to a Latin square design. SLEDAI easily distinguished between patients (p = 0.0009), and physician variability was not statistically significant (p = 0.27). Inter and intraobserver agreement were 78.7 and 98.0%, respectively. SLEDAI was thus shown to be a reliable instrument among less experienced observers for the assessment of disease activity in SLE.

Education, Medical, Graduate↗
PubMed1992

Effect of m-chlorophenylpiperazine on plasma homovanillic acid concentrations in healthy subjects.

In view of the abundant anatomical and functional interactions between serotonin and dopamine systems, this study examined the effect of the serotonin agonist, m-chlorophenylpiperazine (mCPP) on plasma concentrations of the dopamine metabolite, homovanillic acid. Plasma prolactin levels, body temperature, and mCPP blood level were also measured. mCPP (0.35 mg/kg) and placebo were administered orally to 10 healthy men in a randomized double-blind design. Variables were measured for 210 min after administration of capsules. mCPP raised prolactin and temperature as compared to placebo, but did not affect plasma homovanillic acid concentrations. Results suggest that mCPP does not alter dopamine function.

Administration, Oral↗
PubMed1992

Nocturnal growth hormone secretion in schizophrenic patients and healthy subjects.

Plasma growth hormone concentrations were measured at hourly intervals between 10 p.m. and 8 a.m. the next morning in 15 drug-free chronic schizophrenic male inpatients and 14 healthy males. Growth hormone secretion was significantly lower in the patients as compared with the controls. Growth hormone release peaked around 1 a.m. in the controls, but a growth hormone peak was absent in the patient group. Increased dopamine activity, increased serotonin activity, or both could explain the absence of a nocturnal growth hormone surge in the schizophrenic patients.

Adult↗
PubMed1992

Serotonin function in schizophrenia: effects of meta-chlorophenylpiperazine in schizophrenic patients and healthy subjects.

This study examined serotonin (5-hydroxytryptamine; 5HT) receptor responsivity in 22 chronic schizophrenic patients and 17 healthy control subjects. The 5HT agonist meta-chlorophenylpiperazine (MCPP) was used as a probe of serotonergic function. MCPP (0.35 mg/kg) or placebo was administered orally after a 3-week drug-free period in a randomized double-blind design. Hormonal (adrenocorticotropic hormone and prolactin), temperature, and behavioral responses and MCPP blood levels were assessed for 210 minutes after administration of the capsules. The schizophrenic patients had blunted temperature responses compared with those of the healthy control subjects: MCPP raised body temperature in the control subjects, but not in the patients. Behavioral responses also differed in the two groups: MCPP increased the total Brief Psychiatric Rating Scale (BPRS) score in the control subjects and tended to decrease it in the patients. In patients, MCPP decreased the BPRS psychosis subscore. Hormonal responses did not differ significantly in the two groups. These findings suggest that further exploration of 5HT function in schizophrenia is warranted.

Adrenocorticotropic Hormone↗
PubMed1992

Agitation and postdexamethasone cortisol levels in Alzheimer's disease.

The clinical correlates of hypothalamic-pituitary-adrenal (HPA) functioning were examined in 29 patients with probable Alzheimer's disease. The 8:00 a.m. postdexamethasone cortisol levels of these patients were highly correlated with higher agitation scores but not with the degree of depressed mood or memory impairment. The possible neural basis for the association between hypercortisolism and behavioral disturbance in Alzheimer's disease warrants further exploration and replication.

Alzheimer Disease↗
PubMed1992

[An analysis of the organization, profile of the clientele and pathologies managed in the urology division of the Public Assistance-Hospital of Paris. A 15-day cross-sectional survey of 10 services].

A cross-sectional study was carried out in ten urology departments over a two-week period. Three categories of data were collected concerning socio-economic status and epidemiological profiles and management of the patients. The results are presented with comparative analysis of performance of the clinics, and the epidemiological data are analysed with reference to the inpatient case mix.

Aged↗