Biomedical subjects

S M Gabriel

Publications and source records attributed to S M Gabriel.

At least 19 recordsLinked to original sources

PubMed1999

Patellar contact forces with and without patellar resurfacing in total knee arthroplasty.

Patellar contact forces were measured in 7 fresh-frozen cadaver knees during continuous flexion-extension cycling for the normal knee and after total knee arthroplasty without and with patellar resurfacing using 2 prosthesis systems with different designs for the femoral and patellar components. Analysis of variance with specimen as a repeated measure was used to examine the effect of contact surface. When compared to normal knees, total knee arthroplasty without patellar resurfacing resulted in no change in patellar contact forces. The magnitude of the inferosuperior patellar shear force increased significantly after patellar replacement with an oval, biconcave patellar component and increased further after replacement with an oval, domed patellar component. There were no significant changes in the mediolateral and anteroposterior contact force components after patellar replacement.

Arthroplasty, Replacement, Knee↗

PubMed1998

Postmortem studies in schizophrenia.

The past decade has seen renewed interest in the neuropathology of schizophrenia. The advent of new postmortem techniques and functional imaging, along with a greater understanding of the neuropsychology of schizophrenia, have provided many new clues to the nature of the underlying brain dysfunction in this disorder. There has also been a greater understanding of the presence of severe cognitive dysfunction among many elderly persons with schizophrenia. In this article, a series of investigations are described that seek to answer basic questions about the neuropathology of schizophrenia, in particular as it pertains to cognitive impairment. The first study describes neuropathological findings in 100 consecutively autopsied persons with schizophrenia, the majority of whom had had detailed antemortem assessments. Results from this first study prompted the conclusion that schizophrenia is not characterized by classical, histologically identifiable neuropathology. Moreover, most cases of dementia in schizophrenia are probably not the result of neuropathologically identifiable dementing illnesses. The next four studies examined chemical markers that are altered in Alzheimer's disease and some other dementing conditions and have also been suggested to be abnormal in schizophrenia: choline acetyltransferase, catecholamines and indolamines, neuropeptides, and synaptic proteins. Schizophrenia cases as a group did not show a cholinergic deficit; nor did they differ from elderly comparison cases with respect to cortical catecholamines and indolamines. Among the schizophrenia cases, however, cognitive impairment was negatively correlated with choline acetyltransferase activity. Those with cognitive impairment showed evidence of cortical noradrenergic and serotonergic deficits. Neuropeptide deficits were also present in schizophrenia, but their pattern differed from that seen in Alzheimer's disease. Increased synaptic protein activity was found in the cingulate cortex of persons with schizophrenia, and this activity was correlated with schizophrenia symptoms. From this second series of studies, it was concluded that some biological measures in schizophrenia may be related to cognitive impairment (e.g., cortical amines), whereas others may be related to diagnosis (e.g., neuropeptide deficits). In addition, synaptic organization may correlate with schizophrenia symptoms.

Aged↗

PubMed1998

Association of elevated alpha 1-antichymotrypsin with cognitive impairment in a prospective study of the very old.

OBJECTIVE: The authors investigated the relationships between concentrations of two acute-phase proteins, alpha 1-antichymotrypsin (ACT) and alpha 2-macroglobulin (MAC), and cognitive impairment in the very old. METHOD: Concentrations of ACT and MAC were determined in a prospective study using sera from medically stable elderly nursing home residents. Cognitive impairment was assessed with the Mini-Mental State. RESULTS: Concentrations of ACT were associated with greater cognitive impairment, as reflected by lower Mini-Mental State scores. This relationship did not exist for MAC. CONCLUSIONS: These data extend previous reports that patients with Alzheimer's disease have greater concentrations of ACT in their blood by demonstrating in a diagnostically diverse nursing home population a relationship between serum ACT and mental status. Elevated serum ACT in patients with compromised mental status may reflect a cerebral acute-phase response.

Acute-Phase Proteins↗

PubMed1997

Serotonin function in human subjects: intercorrelations among central 5-HT indices and aggressiveness.

Three central indices of serotonin (5-HT) system activity in human subjects were examined to: (a) estimate intercorrelations among 5-HT indices and (b) compare correlations of these indices with a measure of assaultiveness (Buss-Durkee 'Assault') in personality-disordered individuals. Cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA) concentration and prolactin responses to m-chlorophenylpiperazine (m-CPP) m-CPP (PRL[m-CPP]) and fenfluramine (PRL[FEN]), served as indices of pre-, post- and 'net'-synaptic central 5-HT activity, respectively. PRL[D,L-FEN] responses were inversely related to CSF 5-HIAA concentration and positively correlated with PRL[m-CPP] responses. Both PRL[D,L-FEN] and PRL[m-CPP] response data correlated equally, and inversely, with BD Buss-Durkee Assault when the same subjects were examined. Basal CSF 5-HIAA concentration did not correlate with Buss-Durkee 'Assault'. PRL responses to challenge probes which involve activation of 5-HT post-synaptic receptors may correlate better than a basal measure of pre-synaptic 5-HT function with a tendency to assaultive behavior in non-criminally aggressive personality-disordered individuals.

Adult↗

PubMed1997

Increased concentrations of presynaptic proteins in the cingulate cortex of subjects with schizophrenia.

BACKGROUND: Cytoarchitectural and neurochemical studies demonstrate disorganization in the cerebral cortex in schizophrenia, which perhaps underlies the severe behavioral disturbances of the disease. This neuronal disarray should be accompanied by synaptic abnormalities. As such, presynaptic proteins have proved valuable indexes of synaptic density and their concentrations have correlated markedly with synaptic loss. Our study sought to determine whether abnormalities exist in the concentrations of presynaptic proteins in the postmortem cerebral cortex of subjects with schizophrenia. METHODS: Presynaptic protein immunoreactivities were assessed in 4 different cerebrocortical regions derived from 16 elderly controls, 19 elderly subjects with schizophrenia, and 24 subjects with Alzheimer's disease. Tissues were assayed with the monoclonal antibodies EP10 and SP4, which recognize synaptophysin, and the monoclonal antibodies SP6 and SP14, which detect syntaxin and synaptosomal-associated protein-25-kd immunoreactivities, respectively. RESULTS: In subjects with schizophrenia relative to controls, presynaptic proteins were increased in the cingulate cortex, but were unchanged in the temporal, frontal, and parietal cortices. In contrast, when cases with Alzheimer's disease were compared with controls, presynaptic proteins were decreased in the frontal, temporal, and parietal samples. CONCLUSIONS: These findings reveal changes in the synaptic organization of the cingulate cortex in schizophrenia relative to other areas examined. These changes are distinct from the deficits in presynaptic proteins observed in Alzheimer's disease.

Alzheimer Disease↗

PubMed1996

Hormonal responses to meta-chlorophenylpiperazine (m-CPP) are undiminished by acute m-CPP pretreatment.

Two challenges with meta-chlorophenylpiperazine (m-CPP, 0.5 mg/kg, p.o.) were performed in healthy volunteers to test the short-term stability of hormonal responses. Challenges were performed in an identical fashion and were conducted on sequential days. Circulating m-CPP plasma levels, as well as prolactin and cortisol responses to m-CPP, were correspondingly similar in magnitude on the 2 days. These data suggest that both prolactin and cortisol responses to single oral administrations of m-CPP are stable over at least a 24-h period.

Administration, Oral↗

PubMed1996

Neuropeptide deficits in schizophrenia vs. Alzheimer's disease cerebral cortex.

Neuropeptide concentrations were determined in the postmortem cerebral cortex from 19 cognitive-impaired schizophrenics, 4 normal elderly subjects, 4 multi-infarct dementia (MID) cases, and 13 Alzheimer's disease (AD) patients. Only AD patients met criteria for AD. The normal elderly and MID cases were combined into one control group. Somatostatin concentrations were reduced in both schizophrenia and AD. Neuropeptide Y concentrations were reduced only in schizophrenia, and corticotropin-releasing hormone concentrations were primarily reduced in AD. Concentrations of vasoactive intestinal polypeptide and cholecystokinin also were reduced in schizophrenia, although not as profoundly as somatostatin or neuropeptide Y. In AD, cholecystokinin and vasoactive intestinal peptide were unchanged. Neuropeptide deficits in schizophrenics were more pronounced in the temporal and frontal lobes than in the occipital lobe. The mechanisms underlying these deficits in schizophrenia and AD are likely distinct. In schizophrenia, a common neural element, perhaps the cerebral cortical gaba-aminobutyric acid (GABA)-containing neuron, may underlie these deficits.

Aged↗

PubMed1996

In vivo knee kinematics derived using an inverse perspective technique.

Sixty-four subjects having implanted and nonimplanted knees were studied using fluoroscopic videos. Each subject, flexing in the sagittal plane, performed successive deep knee bends under fluoroscopic surveillance. Femorotibial contact in the sagittal plane was then determined using image matching and discrete digitization. At full extension, the mean contact point of the normal and posterior stabilized implanted femurs was anterior to the tibial midpoint in the sagittal plane. The average position was 6.49 mm (+3 - +13 mm) for the normal knees and 0.30 mm (0 - +4 mm) for the posterior stabilized knees. The implanted posterior cruciate retaining and anterior cruciate ligament deficient knees differed from the other knee types. Their average initial contact was posterior. The average contact at full extension for the posterior cruciate retaining and anterior cruciate ligament deficient knees was -5.13 mm (-2 - -8 mm) and -5.45 mm (-2 - -14 mm), respectively. The femur of the normal knee contacts the tibia anterior to the midpoint in the sagittal plane in full extension and translates posteriorly during flexion. The femur of the posterior stabilized knee contacts the tibia anteriorly, slightly less than the normal knee, and rolls back posteriorly during flexion similar to normal knees. The femurs of the posterior cruciate retaining and anterior cruciate ligament deficient knees contact the tibia posterior in extension, but translate anteriorly during midflexion in a substantial number of cases, which is kinematically opposite of the normal knees. The abnormal anterior femoral translation observed in the posterior cruciate retaining knees may be a factor in the premature polyethylene wear seen in retrieval studies.

Adult↗

PubMed1995

Alterations in cerebral cortical galanin concentrations following neurotransmitter-specific subcortical lesions in the rat.

Galanin is associated with multiple projection neurons, and its immunoreactivity in the cerebral cortex may be derived from diverse sources. We investigated the effects of subcortical lesions on cerebral cortical galanin concentrations. Lesions of the anterior noradrenergic bundle (ANB) comparably reduced cerebral cortical galanin and norepinephrine (NE) concentrations. The effects of the ANB lesions on galanin were immediate and became most pronounced 1 week later. Extensive unilateral lesions of the nucleus basalis of Meynert (NBM) decreased galanin concentrations, although not as markedly as after ANB lesions. The NBM lesions had no additional effect in the presence of an ANB lesion. Decreases in cerebral cortical galanin concentrations depended upon the extent and the duration of the NBM lesion and were not as pronounced as the decreases in markers of cholinergic activity. Acute treatments with physostigmine, which inhibit cerebral cortical AChE, had no effect on galanin concentrations. The depletion of galanin following an NBM lesion was most pronounced within hours of the insult, while the depletion of ChAT following the same lesions required several days to develop. Cortical concentrations of galanin and 5-HT increased 1 hr after dorsal raphe nucleus (DRN) lesions and then decreased 7 d later. Six weeks later, galanin concentrations recovered in the cerebral cortex despite the continued depletion of 5-HT. These studies suggest that a substantial portion of cerebral cortical galanin may derive from noradrenergic neurons and may be modulated by cortically-projecting ACh and 5-HT neurons.

Animals↗

PubMed1994

Intracerebroventricular injection of dibutyryl cyclic adenosine 3',5'-monophosphate increases hypothalamic levels of neuropeptide Y.

This investigation examined in vivo the relationship between the nucleotide cAMP and hypothalamic levels of two peptides, neuropeptide Y (NPY) and galanin (GAL), which are known to potentiate feeding behavior. In brain-cannulated rats, third ventricular injections of N6,2'-O-dibutyryl cyclic adenosine 3',5'-monophosphate ((Bu)2cAMP, 25 micrograms), compared to saline, caused a significant increase in NPY levels in the arcuate nucleus (ARC) and medial parvocellular portion of the paraventricular nucleus (mPVN), while having no impact in other hypothalamic areas. These site-specific changes in NPY occurred in the absence of any alteration in circulating levels of insulin, corticosterone, aldosterone or glucose, or of changes in hypothalamic levels of GAL. These findings implicate cAMP as having regulatory functions within specific hypothalamic NPY-synthesizing neurons, projecting from the ARC to the mPVN, that are believed to be involved in energy homeostasis.

Aldosterone↗

PubMed1994

Hypothalamic galanin-like immunoreactivity and its gene expression in relation to circulating corticosterone.

The neuropeptide galanin (GAL), which exists in dense concentrations within the hypothalamus, has physiological actions which are neuroendocrine in nature. In light of evidence showing GAL to alter the release of the adrenal steroid, corticosterone (CORT), a possible effect of this steroid on GAL gene expression and peptide production in discrete hypothalamic and brainstem sites was investigated. Using radioimmunoassay and in situ hybridization techniques, this peptide was examined in rats that had received SHAM surgery, adrenalectomy (ADX) and ADX+CORT replacement. The results showed a clear, site-specific change in GAL in relation to circulating CORT. A loss of CORT after ADX caused a dramatic decline in GAL peptide and mRNA levels in the arcuate nucleus and peptide levels in the median eminence, with no change occurring in other hypothalamic areas. In the brainstem, a similar change was detected in the dorsal raphe nucleus but not the locus coeruleus. The GAL peptide and mRNA levels in these specific brain areas of ADX rats was restored by CORT replacement, which had no impact on GAL in other brain sites. These findings demonstrate that CORT's impact on brain GAL is highly site specific, possibly determined by local concentrations of steroid receptors.

Adrenal Glands↗

PubMed1994

Diurnal rhythm of galanin-like immunoreactivity in the paraventricular and suprachiasmatic nuclei and other hypothalamic areas.

The peptide galanin (GAL), when injected into the rat hypothalamus, is known to stimulate feeding behavior and affect the secretion of various hormones, including insulin and the adrenal steroid, corticosterone. To determine whether endogenous peptide levels shift in relation to natural rhythms of feeding and circulating hormone levels, rats were sacrificed at different times of the light/dark cycle, and their GAL levels were measured, via radioimmunoassay, in medial hypothalamic dissections and micropunched hypothalamic areas. The results suggest the existence of two distinct diurnal rhythms for hypothalamic GAL. One rhythm, detected exclusively in the area of the SCN, is characterized by bimodal peaks of GAL, threefold higher than basal peptide levels, around the onset of the dark and light periods. The second rhythm shows a single peak of GAL towards the middle of the nocturnal feeding cycle, specifically between the third and sixth hour. This latter rhythm is evident in the dorsal region of the medial hypothalamus, localized specifically to the lateral portion of the PVN. Moreover, it is inversely related to circulating insulin but unrelated to the adrenal steroids, suggesting a possible association between this pancreatic hormone and GAL in the PVN.

Aldosterone↗

PubMed1994

The stability of plasma growth hormone and MHPG responses to repeated clonidine challenge in normal males.

Clonidine is a centrally acting alpha 2-adrenergic agonist used in many psychiatric studies to assess adrenergic functioning. The short- and long-term stability of plasma growth hormone (GH) and plasma 3-methoxy-4-hydroxy phenylglycol (MHPG) responses to clonidine (2 micrograms/kg IV) over a 60-min period were assessed in subsets of 13 male normal controls on 2 consecutive days (Study A; n = 11) and on 2 days separated by several months (Study B; n = 11). In Study A, no significant differences between consecutive days were found in either baseline plasma GH or MHPG or their responses to clonidine. The 60 minute plasma GH responses between consecutive days were highly correlated (r = 0.75, n = II, p < .001), while the 60 min plasma MHPG responses were not. In Study B, no significant differences in baseline plasma GH or MHPG, or their responses to clonidine challenge, were found between the 2 test days. However, neither the plasma GH responses nor the plasma MHPG responses to clonidine at 60 min correlated significantly between the 2 study days separated by several months. Both in Study-A and in Study B, 8 of 11 subjects had a stable GH response to clonidine across both study days when defined dichotomously (blunted < 4 ng/ml; otherwise, not blunted). These results suggest that the plasma GH response and plasma MHPG response to clonidine are unaffected by repeat clonidine challenge separated by 24 h, and that the plasma GH response to clonidine may be more stable over time than the plasma MHPG response to clonidine.

Adrenergic alpha-Agonists↗

PubMed1994

Galanin-like immunoreactivity is increased in the postmortem cerebral cortex from patients with Alzheimer's disease.

Galanin is a peptide that is associated with cholinergic neurons of the basal forebrain, and, thus, of interest for the neuropathology of Alzheimer's disease. In the present study, human galanin-like immunoreactivity was measured in postmortem human cerebral cortical tissues by using a homologous radioimmunoassay. In an initial study, six cerebral cortical regions were evaluated from nine elderly controls, 13 neuropathologically verified Alzheimer's disease patients, and 19 elderly schizophrenics. A significant 65% increase in galanin was found in frontal cortex Brodmann area 8 of Alzheimer's disease patients compared with controls. In contrast, cerebral cortical tissues from elderly schizophrenics were not different from those from elderly controls in any region. In a second study, 10 cerebral cortical regions were evaluated from 50 neuropathologically verified Alzheimer's disease patients and nine elderly controls. Concentrations of galanin were increased significantly 26-61% in six of 10 cerebral cortical regions examined (Brodmann areas F8, F44, T20, T21, T36, and P22). Purification of brain extracts by size-exclusion Sephadex G-50 chromatography revealed that human galanin-like immunoreactivity eluted in two peaks of different molecular weights. These studies reveal increased concentrations of galanin in the cerebral cortex of Alzheimer's disease, similar to previous findings in basal forebrain tissue. Because galanin inhibits cholinergic neurotransmission, these findings may have important implications in the understanding of Alzheimer's disease neuropathology and associated cognitive deficits.

Alzheimer Disease↗

PubMed1994

Lack of association between cortisol hypersecretion and nonsuppression on the DST in patients with Alzheimer's disease.

Among 23 patients with Alzheimer's disease, 11 (48%) exhibited cortisol hypersecretion (> or = 11.8 micrograms/dl) and nine (39%) displayed cortisol nonsuppression on the dexamethasone suppression test. Only four patients exhibited both neuroendocrine abnormalities, demonstrating a lack of association between these two neuroendocrine disturbances of over 50%. Twenty-two of the 23 patients were studied for 4 1/2 years, and 14 died during that period. Six of the eight surviving patients exhibited cortisol hypersecretion without cortisol nonsuppression.

Aged↗

PubMed1993

The cortisol response to clonidine in acute and remitted depressed men.

To assess the relationship between the hypothalamo-pituitary-adrenal (HPA) axis and the noradrenergic system in patients with major depression, 26 normal controls, 32 acutely depressed patients, and 21 patients with remitted depression, all men, were administered intravenous clonidine (2 micrograms/kg) or placebo. Acute, but not remitted, depressed patients had a greater plasma cortisol baseline than did normal controls (t = 2.0, p < 0.03). Only acutely depressed patients had a greater decrease in plasma cortisol in response to clonidine than to placebo (t = 2.5, p < 0.02). Statistically controlling for both diurnal variation and baseline cortisol, acute, but not remitted, depressed patients had a greater decrease in plasma cortisol in response to clonidine than did the controls (analysis of covariance: F[1,35] = 4.26, p < 0.05). These results support a state-dependent noradrenergic-HPA axis regulatory disturbance in depressed patients, suggesting that clonidine inhibits the elevated plasma cortisol in acute depression but not the normal concentrations observed in remitted depression or healthy controls.

Adult↗

PubMed1993

Estrogen stimulation of galanin gene expression and galanin-like immunoreactivity in the rat and its blockade by the estrogen antagonist keoxifene (LY156758).

Rat galanin (rGAL) gene expression is stimulated potently by 17 beta-estradiol in the anterior pituitary. Neuroendocrine tissue extracts of were purified by chromatography and analyzed for rGAL-like (-LI) immunoreactivity. Greater than 90% of rGAL-LI eluted at the same position as the synthetic rGAL standard in untreated anterior pituitary, median eminence and neurointermediate lobe tissues. Additional immunoreactive forms were detected in the hypothalamus, anterior pituitary and MtT/W15 adenoma tissues, particularly after 17 beta-estradiol treatment. We examined rGAL and its encoding mRNA in the anterior pituitary of immature female rats after the injection of pregnant mare serum gonadotropin (PMSG). One and two days after PMSG injection, serum 17 beta-estradiol increased 3-fold and 4-fold, respectively. This resulted in a surge of endogenous gonadotropin 2 days after PMSG. At this time, rGAL-encoding mRNA was increased 40-fold over controls. Three days after PMSG, there was a 6-fold increase in anterior pituitary and a 41% increase in plasma rGAL-LI concentrations. Plasma 17 beta-estradiol one day after injection of PMSG and the consequent anterior pituitary rGAL-LI concentrations 2 days later were positively correlated. This stimulation of rGAL and its encoding mRNA by PMSG was inhibited by treatment with the estrogen antagonist keoxifene (LY156758).

Adenoma↗

PubMed1993

Widespread deficits in somatostatin but not neuropeptide Y concentrations in Alzheimer's disease cerebral cortex.

Somatostatin-like immunoreactivity (SLI) and neuropeptide Y-like immunoreactivity (NPYLI) were measured in the cerebral cortex of 49 patients with Alzheimer's disease (AD), and 9 elderly controls. Concentrations of SLI were lower in AD patients relative to controls in 9 of 10 cortical regions. In contrast, no significant differences in NPYLI concentrations between the two groups were observed in any of 10 regions. These studies suggest a dissociation between SLI deficits and NPYLI concentrations in the postmortem cerebral cortex of AD patients. The apparent sparing of NPYLI-containing neurons suggests that neuropeptide Y may be located within a separate group of neurons compared to somatostatin.

Aged↗