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Biomedical subjects

A Bashir

Publications and source records attributed to A Bashir.

At least 37 records · Page 2Linked to original sources

Altering kinetic mechanism and enzyme stability by mutagenesis of the dimer interface of glutathione reductase.

In wild-type glutathione reductase from Escherichia coli residues Val421 and Ala422 are located in an alpha-helix in a densely packed and hydrophobic region of the dimer interface, with their side chains packed against those of residues Ala422' and Val421' in the second subunit. A series of mutant glutathione reductases was constructed in which the identities of the residues at positions 421 and 422 were changed. Mutations were designed so as to present like charges (mutants Val421-->Glu:Ala422-->Glu and Val421-->Lys:Ala422-->Lys) or opposite charges (mutant Val421-->Lys:Ala422-->Glu) across the dimer interface to assess the role of electrostatic interactions in dimer stability. A fourth mutant (Val421-->His:Ala422-->His) was also constructed to investigate the effects of introducing a potentially protonatable bulky side chain into a crowded region of the dimer interface. In all cases, an active dimeric enzyme was found to be assembled but each mutant protein was thermally destabilized. A detailed steady-state kinetic analysis indicated that each mutant enzyme no longer displayed the Ping Pong kinetic behaviour associated with the wild-type enzyme but exhibited what was best described as a random bireactant ternary complex mechanism. This leads, depending on the chosen substrate concentration, to apparent sigmoidal, hyperbolic or complex kinetic behaviour. These experiments, together with others reported previously, indicate that simple mutagenic changes in regions distant from the active site can lead to dramatic switches in steady-state kinetic mechanism.

Alanine↗

Severe mental retardation in 2 to 24-month-old children in Lahore, Pakistan: a prospective cohort study.

Severe mental retardation (developmental quotient (DQ) < 50) was investigated in 1303 children from 2 to 24 months of age, born during 1984-87 in four population groups representing different socio-economic levels in and around Lahore, Pakistan. The incidence per 1000 live births was 22 in the periurban slum, 9 in the urban slum, 7 in the village and 4 in the upper middle class group. The aetiology was prenatal in 79%, perinatal in 14% and untraceable in 7% of cases. Down's syndrome was the most common cause of severe mental retardation (36%). Impairments were studied at 2 years of age. Impairment of language was present in all, while locomotor dysfunction was seen in 89% of cases. Epilepsy and cerebral palsy were each present in 22% of cases. Mortality among these severely mentally retarded children was 36%.

Asphyxia Neonatorum↗

Flow cytometric DNA analysis of wheat-rye addition lines.

The nuclear DNA content of the 7 wheat-rye chromosome addition lines were determined by flow cytometry. The nuclear DNA content of each line was compared to the original wheat parental line. From this information, the amount of DNA per rye chromosome was calculated. The DNA per chromosome ranged from 0.8 picograms (pg) in chromosome 3R to 1.4 pg in chromosome 7R. Flow cytometry was proven to be a rapid and reliable technique for the evaluation of aneuploid plant populations. Flow cytometry has the potential to allow for more rapid screening of aneuploid and euploid cytological stocks than conventional cytogenetic techniques.

Aneuploidy↗

Sinapic acid esters from Polygala virgata.

Three sinapoyl glycosides have been isolated from the roots of Polygala virgata. The structures were established on the basis of UV, mass 1H and 13C NMR spectral data, including homonuclear and heteronuclear 2D shift correlation and selective INEPT experiments. alpha-D-(3-O-Sinapoyl)fructofuranosyl-alpha-D-(3-O-acetyl-6-O-s inapoyl)glucopyranoside and beta-D-(3,O-sinapoyl)fructofuranosyl-alpha-D-(4-O-acetyl-6-O-si napoyl)glucopyranoside are new natural products, whereas beta-D-(3-O-sinapoyl)fructofuranosyl-alpha-D-(6-O-sinapoyl) glucopyranoside has already been reported from other plants.

Carbohydrate Sequence↗

Glycosyl-phosphatidylinositol-anchored membrane proteins can be distinguished from transmembrane polypeptide-anchored proteins by differential solubilization and temperature-induced phase separation in Triton X-114.

Treatment of kidney microvillar membranes with the non-ionic detergent Triton X-114 at 0 degrees C, followed by low-speed centrifugation, generated a detergent-insoluble pellet and a detergent-soluble supernatant. The supernatant was further fractionated by phase separation at 30 degrees C into a detergent-rich phase and a detergent-depleted or aqueous phase. Those ectoenzymes with a covalently attached glycosyl-phosphatidylinositol (G-PI) membrane anchor were recovered predominantly (greater than 73%) in the detergent-insoluble pellet. In contrast, those ectoenzymes anchored by a single membrane-spanning polypeptide were recovered predominantly (greater than 62%) in the detergent-rich phase. Removal of the hydrophobic membrane-anchoring domain from either class of ectoenzyme resulted in the proteins being recovered predominantly (greater than 70%) in the aqueous phase. This technique was also applied to other membrane types, including pig and human erythrocyte ghosts, where, in both cases, the G-PI-anchored acetylcholinesterase partitioned predominantly (greater than 69%) into the detergent-insoluble pellet. When the microvillar membranes were subjected only to differential solubilization with Triton X-114 at 0 degrees C, the G-PI-anchored ectoenzymes were recovered predominantly (greater than 63%) in the detergent-insoluble pellet, whereas the transmembrane-polypeptide-anchored ectoenzymes were recovered predominantly (greater than 95%) in the detergent-solubilized supernatant. Thus differential solubilization and temperature-induced phase separation in Triton X-114 distinguished between G-PI-anchored membrane proteins, transmembrane-polypeptide-anchored proteins and soluble, hydrophilic proteins. This technique may be more useful and reliable than susceptibility to release by phospholipases as a means of identifying a G-PI anchor on an unpurified membrane protein.

Animals↗

Flavonol glycosides from Monnina sylvatica.

A new kaempferol triglycoside and three known kaempferol glycosides, among them two apiosides, have been isolated from the aerial parts of Monnina sylvatica. The structures were established on the basis of acid and enzymatic hydrolysis and spectral data (UV, 1H and 13CNMR, NOE difference measurements, D/CI and FAB-MS) of the isolates and of some derivatives. The triglycoside kaempferol 3-O-beta-D-glucosyl-(1----2)-O-[alpha-L-rhamnosyl(1----6)]-beta-D- galactoside is a new natural product. The configuration of the apiosyl moiety in kaempferol 3-O-beta-D-apiosyl(1----2)-beta-D-galactoside and kaempferol 3-O-beta-D-apiosyl(1----2)-O-[alpha-L-rhamnosyl(1----6)]- beta-D-galactoside was established through NOE difference measurements on the peracetate.

Carbohydrate Sequence↗

Cannabis psychosis following bhang ingestion.

The purpose of this preliminary investigation is to systematically characterize the signs and symptoms of cannabis psychosis in individuals who presented for psychiatric treatment in Pakistan after ingestion of bhang; a beverage containing cannabis. In order to control for the behavioral effects of cannabis alone, symptoms produced by bhang ingestion among non-patients consuming the same beverage were compared with those symptoms found among psychotic patients. Patients differed from controls in that a higher proportion of patients were found to be chronic users of bhang, and had a past history of psychotic episodes. Presenting symptoms of bhang-induced psychosis found in patients included grandiosity, excitement, hostility, uncooperativeness, disorientation, hallucinatory behavior and unusual thought content. Neuroleptic treatment successfully attenuated psychotic symptoms within five days of the initiation of the episode. The presenting symptoms of bhang-induced psychosis are consistent with a brief mania-like disorder with paranoid psychotic features, and cognitive dysfunction. Several etiologic hypotheses are proposed.

Administration, Oral↗

Quick responses save mothers' lives.

The maternal mortality rate in the city of Faisalabad, Pakistan, has been reduced to a level significantly below the national average. How this has been achieved is explained below.

Emergency Medical Services↗

Genetic variation on chromosome 16 is associated with abdominal aortic aneurysm.

1. There is a familial tendency to abdominal aortic aneurysms. We have followed up a previous report of a weak association between the haptoglobin 2-1 phenotype and aortic aneurysm and investigated polymorphisms of the haptoglobin gene and neighbouring cholesterol ester transfer protein gene on the long arm of chromosome 16 in patients with atherosclerotic abdominal aortic aneurysm, patients with stenosing aortic atherosclerosis and healthy control subjects. The protein polymorphism of haptoglobin results from variant alpha-chains, alpha 1 and alpha 2, the phenotype nomenclature describing the two alpha-chains. We have also investigated whether the different haptoglobin phenotypes influence the degradation of aortic connective tissue. 2. The frequency of the haptoglobin alpha 1 allele was increased in patients with aneurysms compared with healthy control subjects (0.51 versus 0.35, P less than 0.05). Patients homozygous for the alpha 2 allele had the highest mean age at aneurysm resection. The frequency of a rare polymorphism at the cholesterol ester transfer protein locus was also increased in aneurysm patients (0.15 versus 0.05 in control subjects, P less than 0.01). These two genetic markers appear to act independently. Haptoglobins containing an alpha 1-chain accelerated two- to four-fold the degradation by elastases of aortic elastin in vitro. 3. Genetic variation in the haptoglobin and cholesterol ester transfer protein genes appears to influence dilatation of the abdominal aorta. Variation at the haptoglobin locus could have a direct effect on the degradation of elastin in atherosclerotic aorta, whereas variation at the cholesterol ester transfer protein locus could affect lipid metabolism and promote atherosclerosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗