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Biomedical subjects

K Iqbal

Publications and source records attributed to K Iqbal.

At least 199 records · Page 11Linked to original sources
PubMed1978

Juvenile Huntington chorea: clinical, ultrastructural, and biochemical studies.

A brain biopsy from a 20-year-old patient whose clinical course was marked by progressive dementia and chorea since age 10 years showed increased amounts of lipofuscin, abnormal mitochondria, and other organelles in cortical neurons, neurites, and astrocytes. Juvenile Huntington chorea was confirmed at autopsy. High levels of three histone-like proteins (molecular weight 10,000 to 16,000) in the microsomal fraction of purified neurons were found by SDS-polyacrylamide gel electrophoresis. Fatty acids were abnormal in white matter sphingomyelin. These ultrastructural and biochemical findings conformed to those established in adult Huntington chorea, thus strengthening the concept of a uniform pathologic process in adult and juvenile Huntington diseases in spite of some clinical and histologic differences.

Adolescent↗
PubMed1978

Huntington disease: normal lipid composition of purified neuronal perikarya and whole cortex.

This is the first report of the lipid composition of human neurons. Neuronoal perikarya were isolated from frozen samples of the cerebral cortex of persons with Huntington disease and two normal controls. These were analyzed for total lipid, individual lipids, and gangliosides. No differences were detected between diseased and normal cells. In addition, gray matter samples from the same patients, and one additional patient and control sample, were analyzed and found not to differ. Thus the ultrastructural abnormalities seen in cortical biopsies are not reflected in the concentration of the major lipid classes.

Cerebral Cortex↗
PubMed1977

Studies on the encephalitogenic effects of purified preparations of human and bovine oligodendrocytes.

Bulk-isolated human and bovine oligodendroglia, practically free from myelin, have been used in attempts to elicit an autoimmune response which has been compared with acute experimental allergic encephalomyelitis (EAE). For these experiments, a total of 20 Hartley guinea pigs, 33 Lewis rats and 16 rabbits have been studied. Animals were inoculated with a range of doses of purified preparations of both human and bovine oligodendroglial cells in complete Freund's adjuvant (CFA) and compared with others challenged with whole white matter in CFA. The latter animals all developed clinical and histological signs of experimental allergic encephalomyelitis (EAE) 2-3 weeks post-inoculation. In general, oligodendroglial cells were encephalitogenically less potent than white matter. Guinea pigs were the most susceptible to inoculations of oligodendroglia. In several given human oligodendroglia 14 days earlier, a paraparesis indistinguishable from conventional EAE was seen. Animals receiving bovine cells showed no clinical signs. Histologically, the CNS of afflicted guinea pigs displayed severe inflammation but, in contrast to conventional EAE in the same species, demyelination was rare in the small group of animals tested. After sensitization with oligodendroglia, rats displayed no clinical disease. Histologically, some given human cells had positive evidence of disease while bovine cells in others gave a mild response. Rabbits showed no clinical and very little histological disease. Although more extensive studies are needed to confirm the findings, from the animals studied it appears that (1) variation in response to inocula containing oligodendroglia exists among the species tested, (2) that human oligodendroglia are more potent immunologically than bovine cells, (3) that CNS lesions produced by these cells in guinea pigs, lack a strong demyelinative component and (4) a specific antigen might exist in oligodendrocytes which is distinct from myelin basic protein. The possible reasons underlying our findings are discussed.

Animals↗
PubMed1975

Chemical pathology of neurofibrils. Neurofibrillary tangles of Alzheimer's presenile-senile dementia.

A subcellular fraction enriched in twisted tubules was obtained by differential centrifugation of a homogenate of neurons isolated from areas of the brain with many neurofibrillary tangles from patients with Alzheimer's presenile-senile dementia. A unique protein (molecular weight 50,000 daltons) which does not co-migrate with either of the two tubulin monomers of the major neurofilament protein, both purified from human brain, was found in this subcellular fraction on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Similarly processed tissue from areas of the brain poor in neurofibrillary tangles contained low levels of this new protein. The new protein band could not be seen in control patients.

Alzheimer Disease↗
PubMed1970

Glutamine synthetase in muscle and kidney.

1. Glutamine synthetase activity has been determined in extracts of rat cardiac and skeletal muscle and kidney, after treatment to ensure that the rate of synthesis was proportional to time of incubation and to amount of extract added. The activity was measured by two methods, with hydroxylamine as substrate. 2. No activity was detected in rat heart extract by either method. The activity in skeletal muscle was of the order of 20mumol of glutamylhydroxamate synthesized/h per g of tissue under optimum conditions. The activity in kidney extracts was 180mumol/h per g of tissue when measured as ferric hydroxamate. 3. The activity in both skeletal-muscle and kidney extracts was inhibited by P(i). The inhibition is competitive for the muscle enzyme, with a K(i) of 12mm. For the kidney enzyme the inhibition is non-competitive, and less marked. Possible enzyme mechanisms that would lead to these types of inhibition are discussed. 4. Several observations are reported that suggest that the enzymes from muscle and kidney are not identical. 5. Growth hormone, either in vivo or in vitro, did not affect the measured glutamine synthetase activity of tissue extracts.

Adenosine Triphosphate↗
PubMedDate not supplied

Mechanism of neurofibrillary degeneration in Alzheimer's disease.

Neurofibrillary degeneration associated with the formation of intraneuronal neurofibrillary tangles of paired helical filaments (PHF) and 2.1 nm tau filaments is one of the most characteristic brain lesions of Alzheimer's disease. The major polypeptides of PHF are the microtubule associated protein tau. tau in PHF is present in abnormally phosphorylated forms. In addition to the PHF, the abnormal tau is present in soluble non-PHF form in the Alzheimer's disease brain. The level of tau in Alzheimer's disease neocortex is severalfold higher than in aged control brain, and this increase is in the form of the abnormally phosphorylated protein. The abnormally phosphorylated tau does not promote the assembly of tubulin into microtubules in vitro, and it inhibits the normal tau-stimulated microtubule assembly. After in vitro dephosphorylation both PHF and non-PHF abnormal tau stimulate the assembly of tubulin into microtubules. The activities of phosphoseryl/phosphothreonyl protein phosphatase 2A and nonreceptor phosphotyrosyl phosphatase(s) are decreased in AD brain. It is suggested that 1. A defect(s) in the protein phosphorylation/dephosphorylation system is one of the early events in the neurofibrillary pathology in AD; 2. A decrease in protein phosphatase activities, at least in part, allows the hyperphosphorylation of tau; and 3. Abnormal phosphorylation and polymerization of tau into PHF most probably lead to a breakdown of the microtubule system and consequently to neuronal degeneration.

Alzheimer Disease↗
PubMedDate not supplied

Immunoreactivity of neuronal lipofuscin with monoclonal antibodies to the amyloid beta-protein.

Monoclonal antibodies generated against a synthetic peptide corresponding to amino acids 1 to 24 of cerebrovascular amyloid beta-protein do not only stain amyloidotic blood vessels and the amyloid deposits of the (senile) neuritic plaques, but also the neuronal pigment lipofuscin. Staining of lipofuscin is observed in both cerebral and cerebellar cortices, subcortical nuclei as well as the brain stem, and is identical in Alzheimer and normal control brain. Western blots of a lipofuscin enriched fraction show an anti-beta-protein reactive polypeptide migrating at approximately 31 kDa position on SDS-polyacrylamide gel electrophoresis. These results suggest that this polypeptide is associated with lipofuscin and is most likely derived from the predicted amyloid precursor protein. This implicates that, unlike in Alzheimer's disease where this protein is also processed extraneuronally in a manner to release an amyloid fiber forming fragment, the end point of its processing in the nerve cell seems to accumulate on a lipopigment characteristic for normal aging.

Adolescent↗
PubMedDate not supplied

Cytoskeletal protein pathology and the formation of beta-amyloid fibers in Alzheimer's disease.

Discovery of the abnormally phosphorylated tau in paired helical filaments, its accumulation preceding the formation of the tangles and the in vitro microtubule assembly defect suggest that an abnormality in the protein phosphorylation/dephosphorylation system is involved in the pathogenesis of Alzheimer cytoskeletal pathology. The levels of mRNA for the beta-amyloid precursor protein (beta APP) in the brain suggest that only a small deficiency in the processing of the precursor would be sufficient to account for the accumulation of beta-amyloid in Alzheimer brain. Identification of reticuloendothelial system cells responsible for the production/processing of beta-amyloid will help to elucidate the pathogenesis of the brain amyloidosis. The disproportionate accumulation of paired helical filaments and amyloid within the same affected brain and from disease to disease raises the possibility of different etiologies for each of these lesions coexisting in Alzheimer's disease.

Alzheimer Disease↗
PubMedDate not supplied

A silver impregnation method for labeling both Alzheimer paired helical filaments and their polypeptides separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis.

The Gallyas silver impregnation which is specific to neurofibrillary changes of paired helical filaments (PHF) and 15 nm straight filaments, was adapted to stain polypeptides separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Both PHF and tau polypeptides were readily and consistently stained by the Gallyas stain. This technique stained PHF greater than tau greater than high-molecular-weight microtubule-associated polypeptides (MAPS). Tubulin was stained only weakly. Neurofilament triplet, ubiquitin, bovine serum albumin and histones were unstained. The staining of PHF and tau polypeptides by Gallyas silver stain is consistent with the presence of tau in PHF.

Alzheimer Disease↗