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Biomedical subjects

S Khan

Publications and source records attributed to S Khan.

At least 253 records · Page 14Linked to original sources

Prospective randomized trial comparing sequential avulsion with stripping of the long saphenous vein.

Eighty patients with primary varicose veins of the long saphenous system were randomized to have the long saphenous vein removed either by stripping to below the knee or by sequential avulsion. There was no difference between the two methods in the time taken to remove the vein. There was significantly more pain after stripping during the week following operation (P < 0.001). Median pain score after stripping was 5, reducing to 3 at 1 week, compared with 2, reducing to 1, for sequential avulsion. Median area of bruising measured at 1 week was 160 (range 0-1800) cm2 for stripping and 56 (range 0-544) cm2 for sequential avulsion (P < 0.01). Sequential avulsion is less painful, reduces bruising and avoids a significant scar below the knee.

Activities of Daily Living↗

A precise method for the assessment of tibial ultrasound velocity.

We assessed a method for the measurement of ultrasound velocity in cortical bone of the human tibia using a probe designed to minimize the effects of surrounding soft tissues. Of four different measurement values, the maximum velocity (average of the five highest readings) gave the lowest errors of reproducibility in relation to the population variance (standardized coefficient of variation = 1.8%). The maximum velocity varied according to the tibial site measured and for practical reasons the mid-tibial site was chosen for further study. The short-term intra- and inter-observer reproducibilities (coefficients of variation) were 0.35% (n = 22) and 0.50% (n = 27) respectively. Long-term reproducibility over 4 months in 31 subjects was 0.68%. There was no significant difference in maximum ultrasound velocity between the dominant and nondominant tibia in 78 women (3764 +/- 209 vs 3763 +/- 199 m/s). Tibial ultrasound velocity was significantly higher in 73 premenopausal women (3999 +/- 102 m/s) than in 129 women referred for assessment of postmenopausal osteoporosis (3780 +/- 168 m/s), 26 women with steroid-induced osteoporosis (3790 +/- 188 m/s) and 4 women with hyperparathyroidism (3575 +/- 261 m/s). In premenopausal women, ultrasound velocity did not correlate significantly with age, height, weight or body mass index. In women with postmenopausal osteoporosis, ultrasound velocity decreased with age after the menopause (r = -0.47, p < 0.0001) and body weight exerted a weaker protective effect. The apparent annual decrease in velocity with age in postmenopausal osteoporosis (8.5 m/s) was comparable to the error of reproducibility. We conclude that the technique for measuring tibial ultrasound velocity is highly reproducible in relation to the distribution of values in the population and is sensitive to age- and osteoporosis-induced changes in bone. Further studies are required to examine its relationship to other indices of skeletal status to determine the biological and clinical relevance of the technique.

Adult↗

Comparison of supercritical fluid extraction and solvent extraction of twenty-two organochlorine pesticides from eggs.

The recoveries of twenty-two organochlorine pesticides spiked in egg samples were extracted by supercritical fluid extraction (SFE) using carbon dioxide and solvent extraction using acetonitrile were compared. The extracts were cleaned up with C18 and Florisil SPE columns. At 0.1 ppm spike level, the recoveries were 52 - 100% by SFE and 53 - 93% by solvent extraction. The limits of detection calculated at 0.01 ppm spike level were 0.072 - 0.006 ppm for SFE and 0.06 - 0.006 ppm for solvent extraction. Both methods show improvement in sample preparation time and solvent consumption from the existing Soxhlet extraction method.

Animals↗

N- and C-terminal substance P fragments modulate striatal dopamine outflow through a cholinergic link mediated by muscarinic receptors.

The present study investigated whether the modulatory effects of substance P and substance P fragments on striatal dopamine release involve a cholinergic link. Rat striatal slices were incubated with substance P, substance P(1-4), substance P(1-7), substance P(5-11) and substance P(8-11) in the absence or presence of various agents which modify cholinergic transmissions, and endogenous dopamine outflow was measured using high-performance liquid chromatography. The incubation of striatal slices with substance P and its N- and C-terminal fragments (1 nM) induced a significant overflow of endogenous dopamine. Neostigmine (150 nM) potentiated the effects of substance P and its fragments, whereas the incubation with hemicholinium-3 (50 microM) abolished the effects of the peptides on dopamine outflow. The acetylcholinesterase inhibitor and the inhibitor of choline uptake did not have intrinsic effects on dopamine outflow. The muscarinic antagonist atropine (1 microM) reversed completely the effects of substance P and its fragments, whereas the nicotinic antagonists dihydro-beta-erythroidine (0.5 microM) and pempidine (10 microM) were devoid of effects. None of the cholinergic antagonists modified dopamine outflow. The results suggest that substance P and several N- and C-terminal substance P fragments activate cholinergic neurons in striatal slices. The released acetylcholine induces an increased dopamine outflow, mediated by muscarinic receptors. These observations represent additional evidence which supports the functional interactions between substance P, acetylcholine and dopamine in the striatum. Furthermore, they show that substance P fragments may exert neuromodulatory effects through mechanisms similar to those underlying the effects of the parent peptide.

Animals↗

High performance liquid chromatographic determination of phenoxetol, methyl paraben, ethyl paraben, n-propyl paraben, iso-butyl paraben, n-butyl paraben and croconazole.HCl.

A high performance liquid chromatographic technique has been used to determine phenoxetol, methyl paraben, ethyl paraben, n-propyl paraben, iso-butyl paraben, n-butyl paraben and croconazole.HCl. The method developed involves isocratic, reversed phase chromatography. The range of quantitation was found to be 90-135.0 micrograms ml-1 for phenoxetol, 2.0-30.0 micrograms ml-1 for methyl paraben, 0.5-7.5 micrograms ml-1 for ethyl paraben, 0.3-4.5 micrograms ml-1 for n-propyl paraben, 0.3-4.5 micrograms ml-1 for iso-butyl paraben, 0.5-7.5 micrograms ml-1 for n-butyl paraben and 20.0-300 micrograms ml-1 for croconazole.HCl. Linear regression analysis of the data demonstrates the adequate performance of the method in terms of precision and accuracy.

Antifungal Agents↗

Comparison of electron beam computed tomography scanning and magnetic resonance imaging quantification of right ventricular mass: validation with autopsy weights.

RATIONALE AND OBJECTIVES: We compared, in the same human hearts, the ability of magnetic resonance (MR) imaging and electron beam computed tomography (CT) scanning to accurately quantify the free wall and septal components of right ventricular (RV) mass. METHODS: Eleven hearts extracted at autopsy were subjected to MR imaging and electron beam CT scanning in short-axis projections. Regression analyses of mass determinations obtained by manual planimetry MR imaging and electron beam CT scanning and autopsy weights were performed. RESULTS: RV free wall mass by both MR imaging (53.4 +/- 19.1 g) and electron beam CT scanning (53.9 +/- 20.4 g) correlated well with autopsy weight (57.7 +/- 20.2 g). Regression analysis showed a strong correlation for MR imaging (r = .88, slope = .88, standard error the estimate [SEE] = 7.2 g, p < .001) and electron beam CT scanning (r = .95, slope = .95, SEE = 6.6 g, p < .001). RV septal mass by MR imaging (10.8 +/- 3.5 g) and electron beam CT scanning (7.1 +/- 2.4 g) correlated less well with the autopsy weight (12.5 +/- 6.5 g). Regression analysis showed a fair correlation for MR imaging (r = .45, slope = .83, SEE = 2.05 g, p = .001) and a poor correlation for electron beam CT scanning (r = .46, slope = .17, SEE = 2.25 g, p = .57). CONCLUSION: Both MR imaging and electron beam CT scanning accurately predict RV free wall mass but have difficulty predicting the septal component. Because the septal component constitutes only a small proportion of the total RV mass, determinations of RV mass should be based solely on the free wall component.

Autopsy↗

The involvement of cytochrome P450 peroxidase in the metabolic bioactivation of cumene hydroperoxide by isolated rat hepatocytes.

Organic hydroperoxides are believed to be primarily detoxified in cells by the GSH peroxidase/GSSG reductase system and activated to cytotoxic radical species by non-heme iron. However, organic hydroperoxides seem to be bioactivated by cytochrome P450 (P450) in isolated hepatocytes as various P450 (particularly P450 2E1) inhibitors inhibited cumene hydroperoxide (CumOOH) metabolism and attenuated subsequent cytotoxic effects including antimycin A-resistant respiration, lipid peroxidation, iron mobilization, ATP depletion, and cell membrane disruption. CumOOH metabolism was also faster in P450 1A-induced hepatocytes and was inhibited by the P450 1A inhibitor alpha-naphthoflavone. The ferric chelator deferoxamine also prevented cytotoxicity even after CumOOH had been metabolized but had no effect on CumOOH metabolism. This emphasizes the toxicological significance of the iron released following hydroperoxide metabolic activation by cytochrome P450. The radical trap, 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO), had no effect on CumOOH metabolism but prevented CumOOH-induced antimycin A-resistant respiration, lipid peroxidation, iron mobilization, and loss of membrane integrity. These results suggest that CumOOH is metabolically activated by some P450 enzymes (e.g., P450 2E1) in hepatocytes to form reactive radical metabolites or oxidants that cause lipid peroxidation and cytotoxicity.

Animals↗

The involvement of cytochrome P4502E1 in 2-bromoethanol-induced hepatocyte cytotoxicity.

The cytotoxicity of 2-bromoethanol towards hepatocytes isolated from rats was concentration-dependent (EC(50)100 mu M, 2 hr). Bromoacetaldehyde was more toxic (EC(50)60 mu M, 2 hr) and bromoacetic acid was less toxic (EC(50)150 mu M, 2 hr). Glutathione (GSH) depletion occurred before cytotoxicity ensued and GSH depleted hepatocytes were more susceptible to 2-bromoethanol. Lipid peroxidation increased steadily 1 hr after 2-bromoethanol addition and antioxidants, iron chelators or hypoxia prevented 2-bromoethanol induced lipid peroxidation and cell lysis. Alcohol dehydrogenase inhibitors, methyl pyrazole or dimethyl sulfoxide only partly prevented 2-bromoethanol induced GSH depletion, lipid peroxidation and cytotoxicity. However, cytochrome P4502E1 (CYP2E1) inhibitors/substrates were more effective at preventing 2-bromoethanol-induced GSH depletion, lipid peroxidation and cytotoxicity suggesting that 2-bromoethanol is mostly metabolically activated by CYP2E1. Also, hepatocytes isolated from CYP2E1 induced rats were more susceptible to 2-bromoethanol and hepatocytes isolated from rats pretreated with carbon disulfide to inactivate CYP2E1 were more resistant to 2-bromoethanol treatment. Formation of S-(formylmethyl)glutathione during 2-bromoethanol metabolism by microsomal mixed function oxidase in the presence of GSH was also prevented by cytochrome P4502E1 inhibitors/substrates or by Anti-Rat CYP2E1. Furthermore, aldehyde dehydrogenase inhibitors-cyanamide or chloral hydrate increased 2-bromoethanol dependent hepatocyte susceptibility. This suggests that 2-bromoethanol is preferably metabolised by CYP2E1 dependent monoxygenase to form 2-bromoacetaldehyde which causes cell lysis as a result of GSH depletion and lipid peroxidation.

1-Propanol↗

The role of estradiol, progesterone, and transforming growth factor on human endometrioma cell culture.

The present study demonstrates several aspects of endometrioma cells in culture, namely, 1) cell growth, proliferation, and morphology, 2) effect of cell culture on estrogen and progesterone receptor concentration, 3) effect of estradiol, progesterone, and transforming growth factor. The tissue sample was obtained from ovarian endometriomas that were removed via laparotomy or laparoscopy. The tissue sample was digested with collagenase. After washing, the tissue was cultured in endothelial cell culture medium. Cell count was done by flow cytometry. Receptor study was done by immunohistochemistry. The results demonstrated the growth and proliferation of endometrioma cell in culture medium. Electron microscopy showed stroma-like cells. The cells lost their estrogen and progesterone receptors. Estradiol and progesterone added to these cultures did not affect the rate of growth and proliferation of the cells. Transforming growth factor significantly increased the rate of growth and proliferation of these cells.

Cell Division↗

FliG and FliM distribution in the Salmonella typhimurium cell and flagellar basal bodies.

Salmonella typhimurium FliG and FliM are two of three proteins known to be necessary for flagellar morphogenesis as well as energization and switching of flagellar rotation. We have determined FliG and FliM levels in cellular fractions and in extended flagellar basal bodies, using antibodies raised against the purified proteins. Both proteins were found predominantly in the detergent-solubilized particulate fraction containing flagellar structures. Basal flagellar fragments could be separated from partially constructed basal bodies by gel filtration chromatography. FliG and FliM were present in an approximately equimolar ration in all gel-filtered fractions. FliG and FliM copy numbers, estimated relative to that of the hook protein from the early fractions containing long, basal, flagellar fragments, were (means +/- standard errors) 41 +/- 10 and 37 +/- 13 per flagellum, respectively. Extended structures were present in the earliest identifiable basal bodies. Immunoelectron microscopy and immunoblot gel analysis suggested that the FliG and, to a less certain degree, the FliM contents of these structures were the same as those for the complete basal bodies. These facts are consistent with the postulate that FliG and FliM affect flagellar morphogenesis as part of the extended basal structure, formation of which is necessary for assembly of more-distal components of the flagellum. The determined stoichiometries will provide important constraints to modelling energization and switching of flagellar rotation.

Bacterial Proteins↗

Adult coeliac disease and cigarette smoking.

BACKGROUND: Genetic predisposition and gliadin exposure are known to be crucial factors in the development of coeliac disease. Circumstantial evidence suggests that other unidentified environmental factors may also be of pathogenetic importance. AIM: To define the relation between cigarette smoking and the risk of development of symptomatic adult onset coeliac disease. SUBJECTS: Eighty six recently diagnosed adult coeliac disease patients and 172 controls matched for age and sex. METHOD: Matched case control study, using a simple questionnaire to determine smoking history, and in particular smoking status at the time of diagnosis of coeliac disease. RESULTS: At the time of diagnosis, the proportion of current smokers was 7% in the coeliac group, and 32.6% in the control group, giving a matched odds ratio of 0.15 (95% confidence intervals 0.06, 0.38). The difference could not be accounted for by social class, nor by coeliac patients giving up smoking after the onset of symptoms as most non-smokers in the coeliac group had never smoked. CONCLUSION: Cigarette smoking, or a factor closely linked to it, seems to exert a major protective effect against the development of symptomatic adult onset coeliac disease. The implication is that gliadin exposure is not the only important environmental factor involved in the pathogenesis of this condition.

Adolescent↗

Sequential insulin degradation in cultured fetal hepatocytes in relation to chloroquine-dependent events.

Insulin cellular degradation was studied in cultured 18-day-old fetal rat hepatocytes in the presence and absence of insulin degradation inhibitors that decrease the glycogenic response to insulin. After cell incubation with 3 nM [125I]A14 or -B26 insulin, hormone degradation products associated with cells or present in the medium were analyzed by high-performance liquid chromatography. Within cells, four components containing intact [125I]A14 insulin A-chain and part of the B-chain (A1-A4, according to increasing retention times) were found together with two [125I]B26 insulin B-chain COOH-terminal fragments (B1 and B2). Medium degradation intermediates comprised B1 and B2 but not A1-A4. Cellular insulin fragments A3 and B2 exhibited a maximal transient accumulation after 2 min, whereas the others increased progressively to plateau after 10 min. Chloroquine inhibited the formation of A1, A2, and B1 by 70-80%, whereas that of A3, A4, and B2 was not significantly affected. N-ethylmaleimide and bacitracin, two inhibitors of insulin-degrading enzyme (IDE), decreased the formation of chloroquine-dependent cellular peptides. Thus cell-associated insulin degradation implied primarily two cleavages in B-chain near the COOH-terminus, the one sensitive to chloroquine and IDE inhibitors occurring after endosomal segregation of insulin and its receptor.

Animals↗

Unrelated donor bone marrow transplantation for Fanconi anemia.

Patients with Fanconi anemia (FA) commonly develop bone marrow failure, which may evolve to myelodysplasia or acute myeloid leukemia (AML). Treatment of these patients is complicated by their marked hypersensitivity to DNA cross-linking agents. In this report we describe the results of allogeneic unrelated donor bone marrow transplantation in seven FA patients, using a low-dose cyclophosphamide (40 mg/kg) and TBI (400-450 cGy) conditioning regimen. Two patients had bone marrow failure with normal chromosomes and no dysplasia prior to transplant. The remaining five had clonal chromosomal abnormalities. One patient had refractory anemia with excess blasts in transformation and two had early AML with 20 and 25% blasts, respectively. Two patients died early (before day 28) without hematological evidence of engraftment, one of veno-occlusive disease and one of infection (fungal). Four of the remaining five patients achieved sustained engraftment after the first marrow infusion; one patient had secondary graft failure requiring repeat marrow infusion but subsequently achieved engraftment. Of five evaluable patients, three had mild (grades I-II) acute GVHD and two had grade IV GVHD, which was fatal in both cases. Two of three evaluable surviving patients have chronic GVHD controlled with immunosuppression. Three patients survive 9 months to 3 years post-unrelated donor BMT: two who had early leukemia and one with severe aplasia at the time of transplant. These data indicate that unrelated donor BMT can be performed successfully in FA patients using cyclophosphamide 40 mg/kg and TBI 400 to 450 cGy, even after evolution to early leukemia. However, significant problems with both GVHD and engraftment remain. Future studies will evaluate the role of T cell depletion in improving the results of unrelated donor marrow transplantation in FA patients.

Adolescent↗

Protein kinase C inhibitor, chelerythrine, potentiates the adrenaline-mediated aggregation of human platelets through calcium influx.

The role of protein kinase C (PKC) using its selective inhibitor, chelerythrine, in agonist mediated platelet aggregation was studied. Chelerythrine had no effect on the aggregation induced by adrenaline, PAF, collagen and ADP at the maximum doses of these agonists. However, it potentiated the aggregatory response of low doses of adrenaline (0.4-1 microM). Such an effect was blocked by Ca(++)-channel blockers, verapamil and diltiazem indicating the likely involvement of Ca++ influx in the platelet aggregation during the cascade.

Adrenergic alpha-Agonists↗

HLA frequencies in Pakistani population groups.

HLA Antigen A, B and DR frequencies were determined in 912 subjects who were prospective donors and recipients for renal transplantation. Of the 912, 305 were Sindhi, 248 Punjabi, 315 Urdu and 44 Pushto speaking. HLA A1, A2, A11 and A19 were common in all these groups. A3 was more frequent in Pushto, A9 (24) in Punjabi, A10 (26) in Sindhi and A28 in Urdu-speaking group. HLA B5 (51) and B40 (60) were common in all, while B8 in Sindhi and Punjabi, B35 in Sindhi, Urdu and Pushto and B27 in Punjabi and Urdu speaking individuals. HLA-DR3 and DR2 (15) were common in all groups. DR6 (13) in Sindhi, Urdu and Pushto and DR6 (14) in Punjabi, DR5 (11) in Urdu, Punjabi and Pushto speaking subjects. Overall, Pakistani frequencies showed linkage to Caucasians and Orientals. This paper describes differences in frequencies in various population groups within Pakistan which may have relevance in factors where HLA system plays a crucial role.

Asian People↗