PubMed Health⌕ Search

Biomedical subjects

S Khan

Publications and source records attributed to S Khan.

At least 19 recordsLinked to original sources
PubMed2001

Mutations of the protocadherin gene PCDH15 cause Usher syndrome type 1F.

Human chromosome 10q21-22 harbors USH1F in a region of conserved synteny to mouse chromosome 10. This region of mouse chromosome 10 contains Pcdh15, encoding a protocadherin gene that is mutated in ames waltzer and causes deafness and vestibular dysfunction. Here we report two mutations of protocadherin 15 (PCDH15) found in two families segregating Usher syndrome type 1F. A Northern blot probed with the PCDH15 cytoplasmic domain showed expression in the retina, consistent with its pathogenetic role in the retinitis pigmentosa associated with USH1F.

Aged↗
PubMed1997

Kenny-Caffey syndrome in six Bedouin sibships: autosomal recessive inheritance is confirmed.

We are reporting on 16 children, in 6 unrelated sibships, born to healthy, consanguineous parents of Bedouin ancestry. Eleven of them were assessed clinically. All presented with marked growth retardation, craniofacial anomalies, small hands and feet, hypocalcemia, hypoparathyroidism, radiological evidence of cortical thickening of long bones with medullary stenosis, and absent diploic space in the skull. There was a history of 6 affected sibs dying in infancy with hypocalcemic convulsions. All cases show absence of macrocephaly and early psychomotor retardation. The present cases confirm the presence of clinical variability and co firm autosomal recessive inheritance of Kenny-Caffey syndrome.

Abnormalities, Multiple↗
PubMed1997

Assessing emotional distress of women with breast cancer: a survey of surgical oncologists.

Studies to identify women with breast cancer who are at risk for psychosocial morbidity have identified several predictors, two of which are the focus of this study: 1) prior psychiatric history, and 2) poor initial emotional response to diagnosis. To examine current medical practice a survey was mailed to members of the Society of Surgical Oncology (response rate = 41.21%) asking how often they assess these two factors, reasons for not doing so, and asssessment methods. Results indicate that the majority rarely assess psychiatric history but frequently assess current emotional state, primarily using interview questions. Recommendations are presented to increase the likelihood of psychiatric assessment and enhance its value to the patient and physician.

Adult↗
PubMed1996

Cloning and expression of genes encoding lipid A biosynthesis from Haemophilus influenzae type b.

Genes similar to Escherichia coli lpx genes (encoding enzymes required for the biosynthesis of lipid A) have been cloned from Haemophilus influenzae type b using a hybridisation-based strategy. The derived amino acid sequences are highly homologous to their E. coli counterparts. The genes appear in the same order in both E. coli and H. influenzae, but the intergenic regions differ. H. influenzae lpxA and lpxB have been expressed in E. coli minicells and they encode proteins of the predicted sizes. Both H. influenzae lpxA and lpxB are able to complement temperature-sensitive mutants in the equivalent genes in E. coli. This provides evidence that the genetic manipulation of lpx genes to generate altered lipid A molecules may be possible.

Base Sequence↗
PubMed1996

FliN is a major structural protein of the C-ring in the Salmonella typhimurium flagellar basal body.

The Salmonella typhimurium FliN protein has been proposed to form a mutually interacting complex with FliG and FliM, the switch complex, that is required for flagellar morphogenesis and function. We have used affinity chromatography for purification of extended flagellar basal bodies sufficient for quantitative analysis of their protein composition. The belled, extended structure is predominantly comprised of the switch complex proteins; with FliN present in the most copies (111 +/- 13). This explains why single, missense fliN, fliG or fliM mutations, found in many non-motile strains, can alter the belled morphology. Cell lysates from these strains contained the wild-type complement of FliG, FliM and FliN; but the basal bodies lacked the outer, cytoplasmic(C)-ring of the bell and were separated by sedimentation from FliM and FliN. The amount of FliG present in basal bodies from wild-type and one such mutant, FliN100LP, was comparable. These data show that: (1) the mutations define a FliG and FliMFliN multiple contact interface important for motility. (2) FliG is responsible for the increased size of the membrane-embedded MS-ring complex of belled relative to acid-treated basal bodies. (3) FliN, together with FliM, account for most of the C-ring. As a major component of the C-ring, FliN is distinct from the other proteins implicated in axial flagellar protein export. Inner, cytoplasmic rod basal substructure, seen by negative-stain and quick-freeze replica electron microscopy, may gate such export. Lack of connectivity between the cytoplasmic rod and ring substructures places contacts between FliG and FliMFliN at the periphery of the basal body, proximal to the flagellar intramembrane ring particles. This topology is consistent with models where torque results from interaction of circumferential arrays of the switch complex proteins with the ring particles.

Bacterial Proteins↗
PubMed1996

Pollen specific expression of maize genes encoding actin depolymerizing factor-like proteins.

In pollen development, a dramatic reorganization of the actin cytoskeleton takes place during the passage of the pollen grain into dormancy and on activation of pollen tube growth. A role for actin-binding proteins is implicated and we report here the identification of a small gene family in maize that encodes actin depolymerizing factor (ADF)-like proteins. The ADF group of proteins are believed to control actin polymerization and depolymerization in response to both intracellular and extracellular signals. Two of the maize genes ZmABP1 and ZmABP2 are expressed specifically in pollen and germinating pollen suggesting that the protein products may be involved in pollen actin reorganization. A third gene, ZmABP3, encodes a protein only 56% and 58% identical to ZmABP1 and ZmABP2, respectively, and its expression is suppressed in pollen and germinated pollen. The fundamental biochemical characteristics of the ZmABP proteins has been elucidated using bacterially expressed ZmABP3 protein. This has the ability to bind monomeric actin (G-actin) and filamentous actin (F-actin). Moreover, it decreases the viscosity of polymerized actin solutions consistent with an ability to depolymerize filaments. These biochemical characteristics, taken together with the sequence comparisons, support the inclusion of the ZmABP proteins in the ADF group.

Actin Depolymerizing Factors↗
PubMed1996

A melanoma cell line sensitive to expression of a fusion protein binding the retinoblastoma protein family pocket domain.

An established melanoma cell line (MM96L) was transfected with selectable plasmid constructs encoding either whole SV40 large T antigen, or beta-galactosidase fusions with the retinoblastoma protein (Rb)-binding region of SV40 large T antigen and a nonbinding mutant derivative of it. Both of the beta-galactosidase fusions also encoded the large T nuclear targeting signal. Transcription of inserted genes was regulated through a Zn+2-inducible metallothionein IA promoter, which provides tight but not absolute control of expression. Only the wild-type large T segment fusion was functionally active in the binding of Rb protein. Stable lines derived from primary transfectants with the expression plasmid encoding the mutant large T segment fusion showed a normal FACS scan profile, a normal growth rate, and (upon induction) high levels of nuclear staining for beta-galactosidase. However, cells transfected with the wild-type (Rb-binding) large T segment fusion grew slowly, with surviving clones assuming a predominantly tetraploid karyotype and relatively much lower levels of beta-galactosidase activity upon Zn+2 induction. The latter cells, but not those transfected with the corresponding non-Rb-binding fusion construct, also exhibited elevated cell death and apoptosis in response to the inducer Zn+2. These results implied that expression of an Rb-binding protein has deleterious effects on the melanoma cell line growth and may reflect a role for Rb of a related pocket protein in maintaining the differentiation state of these transformed cells.

Amino Acid Sequence↗
PubMed1996

Evidence for modulatory effects of substance P fragments (1-4) and (8-11) on endogenous dopamine outflow in rat striatal slices.

The effects of substance P-(1-4) and substance P-(8-11) on endogenous dopamine outflow in rat striatal slices were investigated. The dose-response curves (0.01 nM to 1 microM) were bell-shaped for both peptides, with significant increases in dopamine outflow at 0.1 and 1 nM. Dopamine overflow elicited by 1 nM substance P-(1-4) or substance P-(8-11) and 25 mM KCl was additive. Although substance P-(8-11) contains a truncated tachykinin sequence, the tachykinin NK1 receptor antagonist WIN 51,708 (17 beta-hydroxy-17 alpha-ethynyl-5 alpha-androstano[3,2-b]pyrimido[1,2- a]benzimidazole (2.5 nM) fully reversed its effect. The interaction between the antagonist and 1 nM substance P-(1-4) was statistically not significant. The data constitute the first evidence that the fragments substance P-(1-4) and substance P-(8-11) could exert central effects and suggest that they may play a role in neuromodulation in the basal ganglia.

Androstanes↗
PubMed1996

Intermediate filament protein domain interactions as revealed by two-hybrid screens.

All intermediate filament proteins possess three distinct domains: heads, rod and tail, and subdomains within the rod called helices 1A, 1B, 2A, and 2B. Subunit packing within a filament is a consequence of interactions among these domains. Several such interactions are known, but probably many more contribute to stabilizing filament structure. We examined a number of such potential interactions using the yeast two-hybrid system. Domains or subdomains of murine vimentin, a Type III intermediate filament protein, were fused with either the DNA-binding or trans-activating domain of GAL4, a transcription factor. Interaction between the vimentin domains/subdomains functionally reconstituted GAL4, thereby activating transcription of a GAL1-LacZ reporter gene. The oligomeric state at which the interactions took place, i.e. whether the domains/subdomains were dimeric or tetrameric as they interacted, was also determined. These studies revealed a number of interesting interactions, among which was a strong homotypic binding to helix 2B to form tetramers. They also demonstrated a lack of interaction among others expected to do so based on current structural models. From these results we deduced which of the candidates for interactions, suggested by current models, were true protein-protein interactions and which represented nearest-neighbors only. Thus, the A11 and A22 modes of molecular alignment identified by Steinert et al. (Steinert, P. M., Marekov, L. N., Fraser, R. D. B., and Parry, D. A. D. (1993) J. Mol. Biol. 230, 436-452) are probably true interactions, whereas the A12 and ACN modes may describe adjacent but non-interacting molecules.

Animals↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗