Biomedical subjects

J E Kleinman

Publications and source records attributed to J E Kleinman.

At least 109 records · Page 6Linked to original sources

PubMed1991

Differential diagnosis of choreiform tardive dyskinesia.

Orofacial dyskinesias and choreiform movements of limbs occur with moderate frequency among psychiatric patients. Abnormal involuntary movements are symptoms of a wide variety of neurological and medical disorders. For both therapeutic and medicolegal reasons, psychiatric patients should be thoroughly evaluated before being given the diagnosis of tardive dyskinesia. This review presents the differential diagnosis of disorders associated with orofacial and appendicular choreiform involuntary movements. In addition, this paper provides a guide to the clinical and laboratory evaluation of patients with these symptoms.

Athetosis↗

PubMed1991

The nucleus basalis of Meynert, senile plaques, and intellectual impairment in schizophrenia.

The large, hyperchromic, cholinergic neurons of the nucleus basalis of Meynert (nbM) and the presence of senile plaques were quantified in postmortem brain tissue from 10 intellectually impaired schizophrenic patients, seven intellectually intact schizophrenic patients, seven control subjects, and three patients with Alzheimer's disease. The two groups of schizophrenic patients did not show any significant differences when compared with the control group in nbM cell density or in plaque frequency. The Alzheimer's disease patients showed the expected decrease in nbM neuronal density and increase in plaques compared with the controls. The data suggest that compromised cognitive function in schizophrenia is not associated with diffuse neuropathology of the basal forebrain cholinergic system.

Acetylcholine↗

PubMed1991

PCP and sigma receptors in brain are not altered after repeated exposure to PCP in humans.

The psychotomimetic effects of phencyclidine (PCP) in humans can persist or reappear months after the drug has been eliminated, suggesting that PCP can induce long-term changes in the brain. The present study examined whether repeated exposure to PCP in a human drug-addicted population was accompanied by alterations in either PCP or sigma binding sites in their postmortem brains as compared to suicide controls. Saturation studies using [3H]TCP and [3H]haloperidol in the presence of spiperone to measure PCP and sigma sites, respectively, revealed no significant differences in the affinity or density of binding sites between these two clinical populations in a variety of brain areas examined. The results suggest that these brain binding sites remain unperturbed in humans despite multiple challenges with PCP. Delayed psychotic episodes following the use of PCP may be attributed to other neurochemical changes that are initiated by interactions of PCP with these two binding sites.

Adolescent↗

PubMed1991

The effect of amphetamine on regional cerebral blood flow during cognitive activation in schizophrenia.

To explore the role of monoamines on cerebral function during specific prefrontal cognitive activation, we conducted a double-blind placebo-controlled crossover study of the effects of 0.25 mg/kg oral dextroamphetamine on regional cerebral blood flow (rCBF) as determined by 133Xe dynamic single-photon emission-computed tomography (SPECT) during performance of the Wisconsin Card Sorting Test (WCST) and a sensorimotor control task. Ten patients with chronic schizophrenia who had been stabilized for at least 6 weeks on 0.4 mg/kg haloperidol participated. Amphetamine produced a modest, nonsignificant, task-independent, global reduction in rCBF. However, the effect of amphetamine on task-dependent activation of rCBF (i.e., WCST minus control task) was striking. Whereas on placebo no significant activation of rCBF was seen during the WCST compared with the control task, on amphetamine significant activation of the left dorsolateral prefrontal cortex (DLPFC) occurred (p = 0.0006). Both the mean number of correct responses and the mean conceptual level increased (p less than 0.05) with amphetamine relative to placebo. In addition, with amphetamine, but not with placebo, a significant correlation (p = -0.71; p less than 0.05) emerged between activation of DLPFC rCBF and performance of the WCST task. These findings are consistent with animal models in which mesocortical catecholaminergic activity modulates and enhances the signal-to-noise ratio of evoked cortical activity.

Adult↗

PubMed1990

Effect of ibotenic acid lesions of the medial prefrontal cortex on amphetamine-induced locomotion and regional brain catecholamine concentrations in the rat.

To determine the influence of intrinsic medial prefrontal cortex (MPFC) neurons on regional brain catecholamine turnover, dopamine (DA) and its metabolites were assayed in several brain areas 14 and 28 days after bilateral ibotenic acid (IA) lesions of the MPFC in the rat. The locomotor response to D-amphetamine was also assessed. On the 14th postoperative day levels of DA, homovanillic acid concentrations and 3,4-dihydroxyphenylacetic acid were elevated in the anterior striatum of IA-lesioned animals. Spontaneous and amphetamine-induced locomotion were also increased. These changes disappeared by the 28th postoperative day. It is concluded that destruction of the efferents of the MPFC induces transient increases in DA turnover within the medial striatum and transiently increases spontaneous and amphetamine-induced locomotion.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1990

The neuropathology of schizophrenia: a critical assessment of research methodologies.

Modern neuropathology has been the recipient of several high-powered quantitative analytical techniques. If properly applied, these techniques provide experimental results with high inter-rater reliability and scientific validity. However, inadvertent methodological problems can be the cause of some of the conflicting results in the schizophrenia research literature. In the present article, we discuss some of the inconsistencies reported in the recent literature and provide suggestions for improving tissue retrieval, selection of anatomical levels, neuronal counts, and neuronometry. We emphasize the importance of shrinkage correction for individual brains and suggest caution in the interpretation of immunocytochemistry and computerized image analysis studies.

Brain↗

PubMed1990

A postmortem quantitative study of iron in the globus pallidus of schizophrenic patients.

Several postmortem studies have reported the presence and probable overabundance of basal ganglia mineralization in schizophrenic patients. In order to study this problem in a quantitative fashion we analyzed the mineral content of the globus pallidus in 9 schizophrenic patients and 10 age-matched controls with a Loats computer image analysis system. No significant differences were noted between schizophrenic patients and controls in regard to gender, age, or mineral content of the globus pallidus. The mean content of iron per internal segment of globus pallidus was greater in schizophrenic patients, but the large variation and small number of patients in our sample may have accounted for the negative findings.

Adult↗

PubMed1990

The hippocampus and parahippocampus in schizophrenia, suicide, and control brains.

Recent postmortem studies in schizophrenia have shown abnormalities in medial temporal lobe structures, including the hippocampus and parahippocampus. We tried to replicate previous studies and to explore the specificity of this finding to schizophrenia. The anterior hippocampus and parahippocampal cortex were evaluated for area and shape in postmortem tissue from 12 schizophrenic, 17 nonschizophrenic suicide, and 10 nonpsychiatric control brains. No significant differences were found in hippocampal area, but the parahippocampal cortex was significantly smaller in the schizophrenic group than in the control group. When parahippocampi from right and left sides were analyzed separately, both the suicide and schizophrenic groups had smaller parahippocampi on the right side than did the controls [corrected]. The suicide group exhibited greater parahippocampal areas in the left than in the right tissue samples within the group, while such a difference did not exist in the schizophrenic or control groups. This study demonstrated changes in temporal lobe structures in both schizophrenic and nonschizophrenic suicide groups.

Adult↗

PubMed1990

Characterization of Na(+)-Ca2+ exchange activity in plasma membrane vesicles from postmortem human brain.

Procedures were developed for measurement of Na+/Ca2+ exchange in resealed plasma membrane vesicles from postmortem human brain. The vesicle preparation method permits use of stored frozen tissue with minimal processing required prior to freezing. Vesicles prepared in this manner transport Ca2+ in the presence of a Na+ gradient. The kinetic characteristics of the Na+/Ca2+ exchange process were determined in membrane vesicles isolated from hippocampus and cortex. The Kact for Ca2+ was estimated to be 32 microM for hippocampal and 17 microM for cortical tissue. The maximal rate of Ca2+ uptake (Vmax) was 3.5 nmol/mg protein/15 sec and 3.3 nmol/mg protein/15 sec for hippocampal and cortical tissue, respectively. Exchange activity was dependent on the Na+ gradient, and was optimal in the high pH range. Therefore, membranes in which Na(+)-dependent Ca2+ transport activity is preserved can be isolated from postmortem human brain and could be used to determine the influence of pathological conditions on this transport system.

Brain↗

PubMed1990

Glutamate receptor changes in brain synaptic membranes from human alcoholics.

Brains from human alcoholics and non-alcoholics were obtained shortly after death. The hippocampus was dissected, homogenized, and processed for the isolation of a synaptic membrane-enriched fraction and the study of L-[3H]glutamic acid and 3-((+-)-2-carboxypiperazin-4-yl)-[1,2(3H)propyl-1-phosphonic acid ([3H]CPP) binding sites. The pharmacological characteristics of L-[3H]glutamic acid binding to synaptic membranes isolated from hippocampus corresponded to the labeling of a mixture of N-methyl-D-aspartate (NMDA), kainate and quisqualic acid receptor sites. Synaptic membranes prepared from the hippocampus of individuals classified as alcoholics had significantly higher density of glutamate binding sites than identically prepared membranes from non-alcoholic individuals. In addition, there was a clear definition of a population of L-glutamate binding sites (approx. 10% of total) in the membranes from alcoholics that had a higher affinity for the ligand than the major set of sites labeled in membranes from both alcoholics and non-alcoholics. Neither the age of the individuals at the time of death nor the time that elapsed between death and processing of brain tissue were significant factors in determining either recovery of purified synaptic membranes from brain homogenates or L-[3H]glutamate binding to synaptic membranes. In order to determine whether some of the changes in L-[3H]glutamic acid binding were due to alterations in binding at the NMDA receptor subtype, we also measured binding of [3H]CPP to extensively washed crude synaptosomal membranes. Membranes from brains of alcoholics had higher affinity (3-fold) for [3H]CPP but lower binding capacity (3-fold) when compared with those of non-alcoholics.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcoholism↗

PubMed1990

Astrocytosis in the molecular layer of the dentate gyrus: a study in Alzheimer's disease and schizophrenia.

Recently, several authors have claimed prominent abnormalities in the entorhinal cortex of both patients with Alzheimer's disease (AD) and schizophrenia. The entorhinal cortex is the origin of the perforant pathway, a major input to granule cells of the dentate gyrus of the hippocampus. The present study explored the possibility of a lesion in the entorhinal cortex of both AD and schizophrenic patients by quantitating astrocytic markers within the terminal fields of the perforant pathway. An increase in fibrillary astrocytes was found in half (3/6) of the AD patients while none of the schizophrenic (n = 6) or control (n = 7) brains exhibited gliosis. Since the redistribution and hyperplasia of astrocytes within the molecular layer of the partially deafferented dentate gyrus depend on the chronicity of the entorhinal lesion, the abnormalities observed in AD patients are consistent with the progressive course of the illness. Furthermore, the presence of gliosis in the subiculum of three out of six AD patients suggested pathology secondary to projections from the entorhinal region, amygdala, or prepyriform cortex. The absence of similar changes in schizophrenic patients does not disprove previous claims of entorhinal pathology but suggests that the lesion, if it exists, is either static in nature or occurred long before death.

Adult↗

PubMed1990

Neuropathological findings in a suspected case of childhood schizophrenia.

The ventral tegmental area (VTA) is the major dopaminergic (DA) center responsible for the innervation of the prefrontal cortex, nucleus accumbens, and entorhinal region. These areas have been causally implicated in schizophrenia. Thus, the existence of brainstem pathology could explain many of the previously reported findings in schizophrenic (SC) patients. The authors focus on uncovering brainstem abnormalities in schizophrenia by studying the autopsied material of a patient having an early onset of symptomatology. The patient was evaluated at the age of 10 years for manneristic behavior, a speech disorder, and violence. Prominent auditory hallucinations became apparent years later. His mental status and ability for self-care steadily deteriorated until he succumbed to pneumonia at age 22. Microscopic examination of the brain showed central chromatolysis of neurons and mild gliosis in a restricted distribution of the brainstem and thalamus. Cell loss and cytoarchitectural disruption were evident in the frontal lobes, prepyriform cortex, and entorhinal region. The neuropathological changes were interpreted as a chronic derangement in the function of neurons of the rostral brainstem tegmental area and medial thalamus with secondary involvement of their terminal projection sites.

Adolescent↗

PubMed1990

Quantitative shape analysis of the temporal and prefrontal lobes of schizophrenic patients: a magnetic resonance image study.

In a recent quantitative neuroimaging study, the authors reported significant reduction in the gray matter volume of both temporal lobes of schizophrenic (SC) patients. In order to better elucidate the nature of this finding (i.e., diffuse vs. focal), we analyzed the shape of the temporal lobes of 17 SC patients and an equal number of age-sex matched controls. Our shape analysis was able to discriminate between a significant number of SC and control patients based on the Fourier harmonic amplitudes of both the middle and posterior levels of the temporal lobes. These results are consistent with bilateral focal or multifocal distortions of the temporal lobes of SC patients. A similar shape analysis of the prefrontal lobes showed no significant conformational differences between the groups. The basis of this quantitative shape analysis (the Fourier expansion series) and the method by which it can be applied are explained in detail.

Atrophy↗

PubMed1989

Monoclonal antibodies to study the brain in schizophrenia.

Twelve monoclonal antibodies were developed which show selective reactivity with brain tissue homogenates from 4 patients with schizophrenia compared to 4 normal controls. Certain antibodies were more reactive with tissue from cases with schizophrenia, others with control tissue. Patterns of reactivity also depended on brain region tested. Differences in reactivity generally ranged from 2- to as much as 8-fold. This panel of monoclonal antibodies may be useful to investigate the pathophysiology of schizophrenia.

Adult↗

PubMed1989

A quantitative investigation of hippocampal pyramidal cell size, shape, and variability of orientation in schizophrenia.

Hippocampal abnormalities have been described in patients with schizophrenia, with disarray of pyramidal cells being one of the more intriguing findings. Controversy exists regarding whether disarray is present in the brains from schizophrenics in the Yakovlev collection at the Armed Forces Institute of Pathology, Washington, DC. We examined for disarray the CA1 region of the midhippocampus of 17 schizophrenics and 32 controls from this collection using computerized determination of neuronal angle and directional statistical analysis of the variability of neuronal angle. Neuronal area and shape were also assessed. We found no differences between patients and controls in these measures. Possible methodological reasons for the discrepancy between our and others' findings are discussed, as well as directions for further research into possible pathological study of the hippocampus and related structures in schizophrenia.

Anthropometry↗

PubMed1989

Axonal counts of the corpus callosum of schizophrenic patients.

This study attempted to identify microscopic correlates to the structural abnormalities reported in the corpus callosum of schizophrenic patients. Sections of the genu, body, and splenium of the corpus callosum were taken from formalin-fixed brains of deceased patients with schizophrenia and nonschizophrenic control subjects. Photomicrographs of stained tissue were projected, and nerve fibers were counted. There were no significant differences (p greater than 0.4) in axonal counts between schizophrenic and control patients for any of the sites sampled. Our results suggest that morphometric abnormalities of the corpus callosum of schizophrenic patients, if present, are not the consequence of a primary process within this structure.

Adult↗

PubMed1988

GABA concentrations in forebrain areas of suicide victims.

Concentrations of GABA and seven other amino acids, including the neurotransmitters or neuromodulators taurine, glycine, aspartate, and glutamate, were determined in postmortem brain samples from suicide victims and normal controls. The five brain areas (caudate nucleus, nucleus accumbens, frontal cortex, amygdala, and hypothalamus) contained very similar concentrations of the amino acids in both groups. The only significant difference between the groups was a low glutamine concentration in the hypothalamus of suicide victims. Even when the data were adjusted for differences in tryptophan concentration, a putative biochemical index for agonal and postmortem changes of brain tissue, no new differences emerged in the concentrations of neuroactive amino acids between suicide victims and control subjects.

Adolescent↗

PubMed1988

Intracerebral inoculation of experimental animals with brain tissue from patients with schizophrenia. Failure to observe consistent or specific behavioral and neuropathological effects.

To test the possibility that some cases of schizophrenia result from infection with a transmissible slow viral agent, 57 experimental animals (six chimpanzees, 12 Old World monkeys, 17 New World monkeys, and 22 guinea pigs) were inoculated intracerebrally with brain tissue from ten patients and followed up for six years. Behavioral comparisons with control animals revealed no consistent behavioral differences. Histological, immunohistochemical, and morphometric examination of brains of animals that died revealed no specific neuropathological abnormalities. These findings do not support a role for a virus-induced slow infection in the pathogenesis of schizophrenia but must be weighed against methodological limitations in animal susceptibility, disease communicability, and assay sensitivity.

Adult↗