Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

One of the hallmarks of Alzheimer pathology is extracellular deposition of beta-amyloid protein (BAP) which is derived from a larger glycoprotein called amyloid precursor protein (APP). Although APP has often been described as a surface membrane protein, such a localization has not previously been demonstrated at the light or electron microscopic level. We now report the results of immunoelectron microscopy using three specific antibodies against different synthetic fragments of APP. All three antibodies demonstrated a major localization to organelles such as the Golgi apparatus, endoplasmic reticulum and vesicular-like structures. A minor proportion of staining with all three was on selective postsynaptic membranes of asymmetrical synapses, whereas staining of presynaptic membranes was not observed. The morphological evidence suggests that one role of APP may be in association with the function of selective synapses.
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PMID:Localization of amyloid precursor protein in selective postsynaptic densities of rat cortical neurons. 128 May 22

A combination of medial temporal lobe atrophy, shown by computed tomography, and reduced blood flow in the parietotemporal cortex, shown by single photon emission tomography, was found in 86% (44/51) of patients with a clinical diagnosis of senile dementia of the Alzheimer type (SDAT). The same combination of changes was found in four out of 10 patients with other clinical types of dementia and in two out of 18 with no evidence of cognitive deficit. Of the 12 patients who died, 10 fulfilled histopathological criteria for Alzheimer's disease, nine of them having a clinical diagnosis of SDAT, and one a clinical diagnosis of multi-infarct dementia. All 10 patients with histopathologically diagnosed Alzheimer's disease had shown a combination of hippocampal atrophy and reduced parietotemporal blood flow in life. In 10 patients (nine with SDAT) out of 12 in whom the hippocampal atrophy was more noticeable on one side of the brain than on the other the parietotemporal perfusion deficit was also asymmetrical, being greater on the side showing more hippocampal atrophy. These results suggest that the combination of atrophy of the hippocampal formation and reduced blood flow in the parietotemporal region is a feature of dementia of the Alzheimer type and that the functional change in the parietotemporal region might be related to the loss of the projection neurons in the parahippocampal gyrus that innervate this region of the neocortex.
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PMID:Association of atrophy of the medial temporal lobe with reduced blood flow in the posterior parietotemporal cortex in patients with a clinical and pathological diagnosis of Alzheimer's disease. 156 78

A progressive disorder of relatively focal but asymmetric biposterior dysfunction is described in a 54 year old right handed male. Initial clinical features included letter-by-letter alexia, visual anomia, acalculia, mild agraphia, constructional apraxia, and visuospatial compromise. Serial testing demonstrated relentless deterioration with additional development of transcortical sensory aphasia, Gerstmann's tetrad, and severe visuoperceptual impairment. Amnesia was not an early clinical feature. Judgment, personality, insight, and awareness remained preserved throughout most of the clinical course. Extinction in the right visual field to bilateral stimulation was the sole neurological abnormality. Early CT was normal and late MRI showed asymmetrical bioccipitoparietal atrophy with greater involvement of the left hemisphere. Results from positron emission tomography (PET) showed bilaterally asymmetric (left greater than right) occipitotemporoparietal hypometabolism. The metabolic decrement was strikingly asymmetric with a 50% reduction in glucose consumption confined to the left occipital cortex. The picture of occipitotemporoparietal compromise verified by MRI, PET, and neurobehavioural testing would be unusual for such degenerative dementias as Alzheimer's (AD) and Pick's disease, although atypical AD with predominant occipital lobe involvement cannot be excluded. This case supports the concepts of posterior cortical dementia (PCD) as a clinically distinct entity and for the first time documents its corresponding metabolic deficit using PET.
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PMID:Posterior cortical dementia with alexia: neurobehavioural, MRI, and PET findings. 186 9

The neuronal dopamine transporter/uptake site can be covalently labeled with the photoaffinity probe 1-(2-[bis-(4-fluorophenyl) methoxy]ethyl)-4-[2-(4-azido-3-[125I]iodophenyl)ethyl]piperazine [( 125I]FAPP) and visualized following sodium dodecyl sulfate polyacrylamide gel electrophoresis and autoradiography. Upon photolysis, [125I]FAPP specifically incorporated into a polypeptide of apparent Mr = 62,000 in membranes from both the putamen and the caudate nucleus of control, Alzheimer's, schizophrenia, and Huntington's diseased brain, and following complete deglycosylation, migrated as an Mr approximately 48,000 polypeptide. In parkinsonian postmortem putamen, however, there was no detectable photoincorporation of [125I]FAPP into the ligand binding subunit of the dopamine transporter. [125I]FAPP did specifically label the Mr 62,000 polypeptide of parkinsonian caudate, although with efficiencies of 20-50% of control. The asymmetrical loss of the dopamine transporter in Parkinson's diseased striatum was confirmed in reversible receptor binding experiments using [3H]GBR-12935 (3H-labeled 1-[2-(diphenylmethoxy) ethyl]-4-(3-phenylpropyl)piperazine). In parkinsonian putamen, mazindol competitively inhibited the binding of [3H]GBR-12935 with an estimated affinity (Ki approximately 2,000 nM) 10 times lower than in controls (Ki approximately 30 nM), while the affinity of maxindol for [3H]GBR-12935 binding in the caudate was equal to that seen with controls (Ki approximately 50 nM). The proportion of [3H]GBR-12935 binding sites recognized by mazindol with high affinity in Parkinson's diseased caudate was, however, reduced by 50-80%.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The dopamine transporter is absent in parkinsonian putamen and reduced in the caudate nucleus. 198 18

In most Alzheimer patients brain atrophy seems to be symmetrical. Recent neuropsychological and brain imaging investigations suggest, however, that in some patients one hemisphere is more severely affected from the onset of symptoms. We have observed four Alzheimer patients with grossly asymmetrical cerebral atrophy at autopsy, in whom the topography of the most severe atrophy was consistent with the earliest clinical signs of focal brain damage. In the three patients who at onset had relevant language disorders, atrophy of the brain was more severe in the association areas surrounding the left sylvian fissure. In the fourth patient, who first complained of visuospatial troubles, the right, nondominant hemisphere was more affected. These clinical and pathological findings suggest that association areas of one hemisphere were involved quite early in the evolution of the disease, conceivably at the same time as the hippocampus and related limbic structures. In these patients, a morphometric analysis of cortical changes in homologous areas of the cortex (area 22) was carried out in order to investigate the effect of the evolution of the disease upon cortical changes. This analysis showed that the numerical densities of nerve cells and tangle-bearing neurons were lower on the more atrophied side and suggested that the severity of cortical atrophy might have affected the size, but not the density, of senile plaques.
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PMID:Asymmetrical cerebral atrophy in Alzheimer's disease. 205 78

Clinical records and EEGs of 114 consecutive patients with clinical diagnosis of Alzheimer's disease have been reviewed. The EEGs of 15 patients (13%) contained triphasic waves. Triphasic waves were always atypical as they occurred singularly or in short bursts, and/or they had occipital predominance, and/or they were bilateral but asymmetrical. Triphasic waves, in all but one patient were recorded in a state of complete alertness. No statistically significant differences were found between the triphasic waves group and the other one, with respect to age, age at onset, illness duration, presence of seizures. Myoclonus was more frequent in patients with triphasic waves (p less than 0.01). Triphasic waves patients had a higher degree of dementia (p less than 0.01), both in cases with rapidly evolving disease and in subjects with relatively slow clinical course.
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PMID:Triphasic waves in Alzheimer's disease. 208 90

Attempts to draw a line of genetic demarcation between schizophrenic and affective illnesses have failed. It must be assumed that these diseases are genetically related. A postmortem study has demonstrated that enlargement of the temporal horn of the lateral ventricle in schizophrenia but not in Alzheimer-type dementia is selective to the left side of the brain. This suggest that the gene for psychosis is the 'cerebral dominance gene', the factor that determines the asymmetrical development of the human brain. That the psychosis gene is located in the pseudoautosomal region of the sex chromosomes is consistent with observations that sibling pairs with schizophrenia are more often than would be expected of the same sex and share alleles of a polymorphic marker at the short-arm telomeres of the X and Y chromosomes above chance expectation. That the cerebral dominance gene also is pseudoautosomal is suggested by the pattern of verbal and performance deficits associated with sex-chromosome aneuploidies. The psychoses may thus represent aberrations of a late evolutionary development underlying the recent and rapid increase in brain weight in the transition from Australopithecus through Homo habilis and Homo erectus to Homo sapiens.
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PMID:The continuum of psychosis and its genetic origins. The sixty-fifth Maudsley lecture. 227 27

Regional cerebral blood flow (rCBF) was determined by single photon emission CT (SPECT) with N-isopropyl-p-[123I]iodoamphetamine in 22 patients with clinically diagnosed senile dementia of Alzheimer type (SDAT) and in 18 age matched controls. We calculated asymmetry indices (AIs) of rCBF for matched right-left regions of interest. rCBF of parietal lobe in SDAT patients was significantly most laterally asymmetrical, but the least in occipital lobe. Lateral asymmetry of rCBF in SDAT patients correlated with asymmetry of language and visuospatial functions; decreased rCBF in the left parietal lobe was associated with language dysfunction, and that in the right parietal lobe, with visuospatial dysfunction. Furthermore cerebellar AIs correlated negatively with those of the cerebral hemisphere and lower frontal region in SDAT patients. The results demonstrate that rCBF measurement by 123I-IMP SPECT is useful to detect lateral asymmetry in reduction of rCBF in SDAT.
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PMID:[Asymmetry of cerebral blood flow in patients with senile dementia of Alzheimer type by SPECT using I-123 IMP]. 229 Feb 11

Seventy-one EEGs (0.49%) of 53 patients, out of 14,458 recordings, contained triphasic waves: twenty-nine were patients with metabolic encephalopathies and 24 were demented patients (16 of these had a presumptive diagnosis of Alzheimer's disease and the other eight of mult-infarct dementia). Demented subjects with metabolic disorders are included in the metabolic encephalopathies group. In all of the cases of Alzheimer's disease, triphasic waves were atypical: in 14 they occurred singly or in short bursts, in 10 they had occipital predominance and in 2 they were bilateral but asymmetrical. In 5 cases, triphasic waves were associated with myoclonus and in 2 of them they occurred in long runs with a pseudo-periodic pattern. In these cases the distinction from Creutzfeldt-Jakob disease was based on neuropathologic findings.
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PMID:[Triphasic waves in dementia syndromes]. 261 26

Because of its binding to specific cerebral amine receptor sites 123I-N-isopropyl-amphetamine (IMP) tracer activity can be used as a measure for the regional cerebral blood flow (rCBF) in the human brain. In 21 psychiatric in-patients an IMP perfusion study was performed using a rotating gamma camera system. The findings at single photon emission computed tomography (SPECT) were compared with different clinical parameters including conventional transmission computed tomography. In SPECT, two different patterns of decrease in IMP uptake could be identified. In patients with a history of cerebrovascular disease SPECT showed asymmetrical, multifocal microcirculatory defects without preference for either hemisphere. In patients with suggested Alzheimer type dementia the perfusion deficits involved the gray and white matter of the parieto-occipital lobes in a bilaterally symmetrical mode with variable extension. Thus, by using IMP-SPECT, it was possible to define the underlying pathologic condition in dementia.
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PMID:123I-N-isopropyl-amphetamine single photon emission computed tomography as a brain imaging technique in dementia. 298 May 27


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