Search PubMed⌕ Search

Biomedical subjects

S Khan

Publications and source records attributed to S Khan.

At least 289 records · Page 16Linked to original sources
PubMed1995

Single cytoplasmic dynein molecule movements: characterization and comparison with kinesin.

Cytoplasmic dynein is a major microtubule motor for minus-end directed movements including retrograde axonal transport. To better understand the mechanism by which cytoplasmic dynein converts ATP energy into motility, we have analyzed the nanometer-level displacements of latex beads coated with low numbers of cytoplasmic dynein molecules. Cytoplasmic dynein-coated beads exhibited greater lateral movements among microtubule protofilaments (ave. 5.1 times/microns of displacement) compared with kinesin (ave. 0.9 times/micron). In addition, dynein moved rearward up to 100 nm over several hundred milliseconds, often in correlation with off-axis movements from one protofilament to another. We suggest that single molecules of cytoplasmic dynein move the beads because 1) there is a linear dependence of bead motility on dynein/bead ratio, 2) the binding of beads to microtubules studied by laser tweezers is best fit by a first-order Poisson, and 3) the run length histogram of dynein beads follows a first-order decay. At the cellular level, the greater disorder of cytoplasmic dynein movements may facilitate transport by decreasing the duration of collisions between kinesin and cytoplasmic dynein-powered vesicles.

Adenosine Triphosphate↗
PubMed1995

Pathogenesis-based treatment of recurring subareolar breast abscesses.

BACKGROUND: When a subareolar breast abscess (SBA) is incised and drained, an extraordinarily high frequency of recurrence is noted. METHODS: To develop a pathogenesis-based treatment plan, 24 women with a total of 84 abscesses were monitored. RESULTS: In nine women SBA was under the left areola, under the right, in 7 and in eight the SBA occurred either simultaneously or sequentially under both areolae. In 11 of 24 patients a chronic lactiferous duct fistula also existed. In four of 24 patients four SBAs were treated with antibiotics; alone; all recurred. In 16 of 24 patients initial treatment was incision and drainage plus antibiotics; all recurred. When the abscess plus the plugged lactiferous duct was excised, there were no recurrences; however, in four patients a new abscess in a different duct occurred, which was treated by en bloc resection of all subareolar ampullae, without further recurrence. Patients with a fistulous tract had the fistula, its feeding abscess, and its plugged lactiferous duct excised, without recurrence. In first time SBA the organism was usually staphylococcus; in recurrences mixed flora was isolated. Pathologic findings ranged from squamous metaplasia with keratinization of lactiferous ducts to chronic abscess. CONCLUSIONS: The cause of SBA is plugging of lactiferous duct within the nipple by keratin. To prevent recurrence the abscessed ampulla with its plugged proximal duct needs excision.

Abscess↗
PubMed1995

Selective use of segmental Doppler pressures and color duplex imaging in the localization of arterial occlusive disease of the lower extremity.

BACKGROUND: The purpose of this study was to compare the abilities of segmental Doppler pressures (SDP) and color duplex imaging (CDI) to localize arterial stenosis and to assess the ability of CDI to accurately categorize the severity of disease. METHODS: We analyzed 134 patients (268 limbs) who underwent all three tests; SDP, CDI, and arteriograms. Results of SDP and CDI were examined to determine their accuracy in localizing high grade (greater than 50%) stenosis at three levels; aortoiliac-common femoral artery (level I), superficial femoral artery (SFA; level II), and popliteal artery (level III). RESULTS: The sensitivity, specificity, positive and negative predictive values, and overall accuracy for SDP and CDI were as follows: level I, 63%, 88%, 81%, 75%, and 77%; 93%, 99%, 98%, 95%, and 96%, respectively (p < 0.01); level II, 51%, 99%, 99%, 57%, and 70%; 94%, 98%, 99%, 92%, and 96%, respectively (p < 0.01); level III, 55%, 92%, 60%, 90%, and 85%; 78%, 100%, 97%, 95%, and 95%, respectively (p < 0.01). Exact agreement was noted between the CDI and arteriogram in regard to the severity of disease in 88% of the limbs (1170 segments). The presence of SFA disease in patients with level I disease or aortoiliac-common femoral artery disease in patients with level II disease did not significantly alter the ability of SDP to localize the disease. The presence of diabetes significantly affected the accuracy of SDP in localizing SFA and popliteal artery stenosis. An analysis of SDP's ability to detect any segment as abnormal, as confirmed by arteriogram, revealed a sensitivity of 88%, specificity of 82%, positive predictive value of 96%, negative predictive value of 60%, and overall accuracy of 87%. The average cost was $149 for an SDP and $472 for a CDI. CONCLUSIONS: CDI is superior to SDP in localizing arterial stenosis at all levels. However, because SDP is cheaper it can be used initially if no surgical or endovascular intervention is planned.

Adult↗
PubMed1995

Effect of contralateral severe stenosis or carotid occlusion on duplex criteria of ipsilateral stenoses: comparative study of various duplex parameters.

PURPOSE: This study compares the accuracy of various duplex parameters in grading ipsilateral carotid stenoses in patients with contralateral severe stenoses or occlusion. METHODS: Four duplex criteria were correlated to arteriography in 356 carotid arteries in blind fashion: (1) standard criteria: a peak systolic frequency (PSF) of the internal carotid artery (ICA) of > or = 4 kHz was used to diagnose > or = 50% stenosis; (2) new criteria: a PSF of the ICA of > or = 4.5 kHz was used; (3) Fujitani criteria: a PSF of the ICA of > 4.5 kHz and an end-diastolic frequency of < 5.0 kHz was used; (4) internal carotid/common carotid artery (ICA/CCA) PSF ratio of > or = 1.5 was used. RESULTS: The standard method overestimated 56 (16%) of 356 stenoses in contrast to 3% for the new method (p < 0.001), and this effect was most evident in the 50% to < 80% stenosis category (30%). The Fujitani method underestimated 97 (27%) of 356 stenoses, and the ICA/CCA ratio overestimated stenoses in 77 (22%) of 356. The overall exact correlation was 94%, 82%, 70%, and 75% for the new, standard, Fujitani, and ICA/CCA ratio, respectively. The kappa statistic and corresponding confidence intervals for the new method (kappa = 0.923, +/- 0.016) are significantly higher (p < 0.001) than those for the standard method (kappa = 0.760, +/- 0.027), the Fujitani method (kappa = 0.608, +/- 0.031), and the ICA/CCA ratio method (kappa = 0.642, +/- 0.051). The overall accuracy in diagnosing > or = 50% ipsilateral stenosis in the whole series was 85% for the standard method, 97% for the new method, 95% for the Fujitani method, and 81% for the ICA/CCA ratio. The new method was superior to the standard and ICA/CCA ratio methods (p < 0.001) and the Fujitani method (p = 0.024). CONCLUSIONS: The presence of significant contralateral stenosis (> or = 50%) can lead to overestimation of ipsilateral stenosis if the standard criteria are used; however, this problem can be avoided by using a PSF of the ICA of > or = 4.5 kHz for the diagnosis of > or = 50% stenosis.

Adult↗
PubMed1995

Cytochrome P450 peroxidase/peroxygenase mediated xenobiotic metabolic activation and cytotoxicity in isolated hepatocytes.

Cytochrome P450 (P450) can utilize organic hydroperoxides and peracids to support hydroxylation and dealkylation of various P450 substrates. However, the biological significance of this P450 peroxygenase/peroxidase activity in the bioactivation of xenobiotics in intact cells has not been demonstrated. We have shown that tert-butyl hydroperoxide (tBHP) markedly enhances 3-20-fold the cytotoxicity of various aromatic hydrocarbons and their phenolic metabolites. The tBHP-enhanced hepatocyte cytotoxicity of 4-nitroanisole (4-NA) and 4-hydroxyanisole (4-HA) was also accompanied by an increase in the hepatocyte O-demethylation of 4-NA and 4-HA up to 7.5- and 21-fold, respectively. Hepatocyte GSH conjugation by 4-HA was also markedly increased by tBHP. An LC/MS analysis of the GSH conjugates identified hydroquinone-GSH and 4-methoxy-catechol:GSH conjugates as the predominant adducts. Pretreatment of hepatocytes with P450 inhibitors, e.g., phenylimidazole, prevented tBHP-enhanced 4-HA metabolism, GSH depletion, and cytotoxicity. In conclusion, hydroperoxides can therefore be used by intact cells to support the bioactivation of xenobiotics through the P450 peroxidase/peroxygenase system.

Animals↗
PubMed1995

Molecular mechanisms of tirapazamine (SR 4233, Win 59075)-induced hepatocyte toxicity under low oxygen concentrations.

Previously we showed that tirapazamine (SR 4233, Win 59075) is cytotoxic towards hepatocytes under conditions of hypoxia but not in 10% or 95% oxygen and that bioreduction by DT-diaphorase or cytochrome P450 is not a major pathway. In the present study, we report that tirapazamine is highly cytotoxic to isolated rat hepatocytes maintained under 1% oxygen and the molecular cytotoxic mechanism has been elucidated. Cytotoxicity was prevented by the cytochrome P450 2E1 inhibitors phenyl imidazole, isoniazid, isopropanol or ethanol, suggesting that cytochrome P450 2E1 catalysed tirapazamine reductive bioactivation. By contrast, dicoumarol, a DT-diaphorase inhibitor, markedly increased tirapazamine-induced cytotoxicity. Cytotoxicity was also inhibited in normal but not DT-diaphorase-inactivated hepatocytes by increasing cellular NADH levels with lactate or ethanol or the mitochondrial respiratory inhibitors. Evidence that oxygen activation contributed to cytotoxicity was that glutathione oxidation occurred well before cytotoxicity ensued and that tirapazamine was more cytotoxic towards catalase- or glutathione reductase-inactivated hepatocytes. Furthermore, polyphenolic antioxidants such as quercetin, caffeic acid or purpurogallin, the radical trap Tempol or the iron chelator desferrioxamine prevented tirapazamine-mediated cytotoxicity. However, the antioxidants diphenylphenylenediamine, butylated hydroxyanisole or butylated hydroxytoluene did not prevent cytotoxicity and malonaldehyde formation was not increased, suggesting that lipid peroxidation was not important. The above results suggest that DT-diaphorase detoxifies tirapazamine whereas reduced cytochrome P450 reduces tirapazamine to a nitrogen oxide anion radical which forms cytotoxic reactive oxygen species as a result of redox cycling.

Animals↗
PubMed1995

Vasodilatory state of decompensated cirrhosis: relation to hepatic dysfunction, ascites, and vasoactive substances.

The objective of this study was to determine the relations between the hallmark circulatory finding of decompensated cirrhosis, a reduced systemic vascular resistance (SVR), and the indices of hepatic decompensation, the accumulation of ascites, and the concentrations of various vasoactive substances. At a university-affiliated teaching hospital, eighteen hospitalized patients with cirrhosis and 18 age- and sex-matched healthy subjects were used. This was a case-control study. Measurements included cardiac dimensions and indices derived from echocardiograms and Doppler studies, abdominal ultrasound estimates of ascites, indices of hepatic function, and various serum (S) and urinary (U) substances. Results showed that cirrhotics had increased left atrial and left ventricular dimensions, left ventricular mass, heart rate, cardiac output (CO), transvalvular velocities, and a decreased SVR. SVR was related to hepatic dysfunction, as reflected by an abnormal prothrombin time ratio (r = -0.64, p = 0.006), and also related to overall severity of liver disease as estimated by the Child-Pugh score (r = -0.53, p = 0.044). Although cirrhotics with ascites generally had a reduced SVR, estimates of ascites were directly related to SVR (r = 0.57, p = 0.03) and inversely related to CO (r = -0.53, p = 0.04). Concentrations of S and U digoxin-like immunoreactive substance (DLIS) were also increased, but the concentrations of S glucagon and estradiol were not elevated. The accumulations of S and U DLIS, S glucagon, and S estradiol were all related to hepatic dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Vaginal rhabdomyosarcoma in a patient with Noonan syndrome.

This is the first report of a Noonan syndrome patient who has had a vaginal rhabdomyosarcoma. Recent reports of Noonan syndrome patients with leukaemia have prompted speculation that there may be a slightly increased malignancy risk associated with this syndrome.

DNA Mutational Analysis↗
PubMed1995

Multiphasic disseminated encephalomyelitis presenting as alternating hemiplegia.

Two cases of alternating hemiparesis are reported, one in a black Sudanese woman, the other in a Saudi man, who had two episodes of alternating hemiparesis separated in time by six and three years respectively. Based on the typical appearance of the MRI and the results of brain biopsy, the diagnosis of multiphasic disseminated encephalomyelitis was made rather than that of multiple sclerosis. This entity is also differentiated from recurrent disseminated encephalomyelitis, where the relapses are symptomatically stereotyped although the appearance of the MRI is similar and in which new lesions do not occur. Because of the unusual appearance of these MRI lesions, brain biopsy is often performed but recognising their relevance should obviate that need.

Adult↗
PubMed1995

Oxidized low-density lipoproteins facilitate leukocyte adhesion to aortic intima without affecting endothelium-dependent relaxation. Role of P-selectin.

Inflammatory cell deposition in atherosclerotic blood vessels has been thought to relate to loss of endothelium-derived nitric oxide (NO). To examine whether cell deposition correlates temporally with the loss of NO activity, rat aortic rings were incubated with buffer, native LDL (n-LDL), oxidized LDL (ox-LDL), or the endothelium-derived relaxing factor synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) for 2 hours, and vascular contractile response to norepinephrine and relaxant response to acetylcholine, thrombin, and calcium ionophore A23,187 were examined. Thereafter, the rings were exposed to biotin-fluorescein isothiocyanate-labeled fluorescent or unlabeled leukocytes for 30 minutes. Cell adhesion was quantitated by fluorescent microscopy as well as by scanning electron microscopy. Incubation with n-LDL or ox-LDL did not affect either the contractile or the relaxant response of rings. However, leukocyte adhesion increased markedly in all ox-LDL-treated rings but not in those treated with n-LDL. Thus, leukocyte adhesion occurred independent of NO activity. In keeping with this concept, pretreatment of rings with the NO precursor L-arginine failed to influence leukocyte adhesion to rings incubated with ox-LDL. Treatment of rings with L-NAME also resulted in adhesion of a large number of leukocytes. Furthermore, all rings treated with ox-LDL or L-NAME demonstrated marked expression of P-selectin leukocyte adhesion molecules, determined by immunohistochemistry. Pretreatment of rings with the P-selectin blocking antibody PB1.3 markedly decreased deposition of leukocytes in rings exposed to ox-LDL.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Inhaled nitric oxide used as a bridge to heart-lung transplantation in a patient with end-stage pulmonary hypertension.

We describe a 40-yr-old woman who received inhaled nitric oxide (NO) as a therapeutic bridge to heart-lung transplantation for end-stage primary pulmonary hypertension. After 10 yr of increasing disability, the patient presented in October 1993 with severe dyspnea, right ventricular angina, and syncope. As predicted by a prior vasodilator trial, prostacyclin produced as initial favorable clinical and hemodynamic response. With the recurrence of severe symptoms and hemodynamic compromise, inhaled NO was successfully tried at 40 ppm, initially via a face mask and later via a transtracheal Scoop catheter. The patient was "bridged" to heart-lung transplant after 68 d of therapy (mean dose of NO, 50.4 +/- 23 ppm). The explanted lungs revealed no evidence of significant NO toxicity, and the explanted heart was successfully transplanted into another patient. Inhalation of NO via a transtracheal catheter is a useful and practical treatment of refractory pulmonary hypertension. The limits of NO therapy in terms of duration and dosage have not been determined.

Administration, Inhalation↗
PubMed1995

Anomaly of the facial nerve and cochlear implantation.

The incidence of preoperative damage to the facial nerve in cochlear implantation is very low. The course of the facial nerve is not routinely evaluated preoperatively, but variations in its course can restrict access to the round window and impede implantation. In 5 of 42 operations, direct visualization of the round window was not possible. In 1 patient there was an obvious congenital bifurcation. Successful implantation was made possible by mobilizing the nerve.

Adult↗
PubMed1995

Conserved machinery of the bacterial flagellar motor.

Novel periplasmic and cytoplasmic structural modules of the bases of bacterial flagella have been observed in situ and isolated using new biochemical protocols. Flagellar rotation may depend upon interactions of these modules with the intramembrane particle rings, a ubiquitous feature of flagellar bases necessary for torque generation. The outer membrane-associated basal disk of the Wolinella succinogenes polar flagellum has architecture well suited for interaction with the ring particles. However, antibody against the main W. succinogenes basal disk protein did not cross-react with flagella-enriched fractions from Salmonella typhimurium and Bacillus firmus; nor have such structures been observed in these species thus far. Antibodies against two S. typhimurium proteins, FliG and FliM, known to be involved in motor function and part of the cytoplasmic module in this species cross-reacted with flagella-enriched fractions from both W. succinogenes and B. firmus. In addition, flagellar cytoplasmic structure could be isolated from B. firmus. The basal disk may anchor the flagellar motor to the cell wall in some polar bacteria, but this does not seem to be a unique strategy. In contrast, the data indicate that the cytoplasmic module is conserved.

Antigens, Bacterial↗