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N Khan

Publications and source records attributed to N Khan.

At least 19 recordsLinked to original sources
PubMed2016

Characterization of a novel adeno-associated viral vector with preferential oligodendrocyte tropism.

No adeno-associated virus (AAV) capsid has been described in the literature to exhibit a primary oligodendrocyte tropism when a constitutive promoter drives gene expression, which is a significant barrier for efficient in vivo oligodendrocyte gene transfer. The vast majority of AAV vectors, such as AAV1, 2, 5, 6, 8 or 9, exhibit a dominant neuronal tropism in the central nervous system. However, a novel AAV capsid (Olig001) generated using capsid shuffling and directed evolution was recovered after rat intravenous delivery and subsequent capsid clone rescue, which exhibited a >95% tropism for striatal oligodendrocytes after rat intracranial infusion where a constitutive promoter drove gene expression. Olig001 contains a chimeric mixture of AAV1, 2, 6, 8 and 9, but unlike these parental serotypes after intravenous administration Olig001 has very low affinity for peripheral organs, especially the liver. Furthermore, in mixed glial cell cultures, Olig001 exhibits a 9-fold greater binding when compared with AAV8. This novel oligodendrocyte-preferring AAV vector exhibits characteristics that are a marked departure from previously described AAV serotypes.

Animals↗
PubMed2006

IL-7R alpha versus CCR7 and CD45 as markers of virus-specific CD8+ T cell differentiation: contrasting pictures in blood and tonsillar lymphoid tissue.

In humans, circulating CD8(+) memory T cells to a nonpersistent virus (influenza) lie within CCR7(+)CD45RA(-) central memory, whereas memory to Epstein-Barr virus (EBV) latent, EBV lytic, and cytomegalovirus (CMV) antigens are progressively larger in size and are more biased toward CCR7(-)CD45RA(-) effector memory and CCR7(-)CD45RA(+) terminally differentiated compartments. We found that these populations are also distinguished by progressively lower expression of the interleukin-7 receptor (IL-7R alpha) and by lower IL-7 responsiveness; indeed, percentage IL-7R alpha -positive values showed a tight inverse correlation with population size. However, these relationships among size, differentiation phenotype, and IL-7R alpha status in blood did not hold in tonsillar tissue. In tonsil tissue, although EBV reactivities outnumbered their CMV and influenza counterparts, the distinct CCR7/CD45 isoform signatures of the different virus-specific populations were retained. Moreover, all detectable reactivities showed high levels of IL-7R alpha expression. As a discriminator between different virus-specific populations, IL-7R alpha therefore appears to be more susceptible to tissue location than the classical CCR7/CD45 markers.

CD8-Positive T-Lymphocytes↗
PubMed2006

Influence of different anesthetics on skin oxygenation studied by electron paramagnetic resonance in vivo.

The effects of two general anesthetics on skin oxygenation in mice are evaluated by electron paramagnetic resonance oximetry. Up to now no data on the effects of different anesthetics on skin oxygenation could be found. In this study animals were anesthetized with ketamine/xylazine or isoflurane, and partial pressure of oxygen (pO(2)) in the skin, heart rate and hemoglobin oxygen saturation were followed as a function of time and inhaled oxygen concentration. The skin pO(2) significantly increased continuously for about 60 min in mice anesthetized with isoflurane and remained constant after that. During ketamine/xylazine anesthesia, the pO(2) in the skin only slightly decreased. The skin pO(2) increased with higher inspired oxygen concentrations for both anesthetics groups. When breathing 21% oxygen, mice anesthetized with isoflurane had two-fold higher pO(2) in the skin compared to mice anesthetized with ketamine/xylazine. The heart rate was significantly lower in animals anesthetized with ketamine/xylazine, while hemoglobin saturation was almost the same in both groups at all inhaled oxygen concentrations. These results show that the type of anesthesia is an important parameter that needs to be considered in experiments where skin pO(2) is followed.

Anesthetics, Combined↗
PubMed2006

Biologic control ability of plant growth-promoting Paenibacillus lentimorbus NRRL B-30488 isolated from milk.

A plant growth-promoting Paenibacillus lentimorbus NRRL B-30488 (B-30488) was isolated from cows' milk. Bacterial colonization and growth responses of different plant species after inoculation with B-30488 were evaluated in a controlled environment and in microplot assays. Survival and colonization of B-30488 in the phytosphere of plants and soil was monitored using a chromosomally located rifampicin-marked mutant B-30488 (B-30488R). The strain showed variable ability to invade plants. The interaction between B-30488R and Fusarium oxysporum f. sp. ciceri was studied by scanning electron microscopy. Chitinase and beta-1,3-glucanase enzymes were produced when B-30488R was grown in the presence of colloidal chitin as sole carbon source. Deliberate dilution of B-30488R with field soil offers a reliable process for decreasing the cost of bacterial inoculants in developing countries. Seed treatment of chickpea demonstrated significantly (P = 0.05) greater seedling mortality in nonbacterized compared with bacterized seedlings. Bacterization significantly (P = 0.05) improved seed germination, plant height, number of pods/plant(-1), and seed dry weight.

Animals↗
PubMed2006

Energy dependence of directed flow over a wide range of pseudorapidity in Au + Au collisions at the BNL Relativistic Heavy Ion Collider.

We report on measurements of directed flow as a function of pseudorapidity in Au + Au collisions at energies of square root of SNN = 19.6, 62.4, 130 and 200 GeV as measured by the PHOBOS detector at the BNL Relativistic Heavy Ion Collider. These results are particularly valuable because of the extensive, continuous pseudorapidity coverage of the PHOBOS detector. There is no significant indication of structure near midrapidity and the data surprisingly exhibit extended longitudinal scaling similar to that seen for elliptic flow and charged particle pseudorapidity density.

Journal Article↗
PubMed2006

Comparison of extent of tau pathology in patients with frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17), frontotemporal lobar degeneration with Pick bodies and early onset Alzheimer's disease.

In order to gain insight into the pathogenesis of frontotemporal lobar degeneration (FTLD), the mean tau load in frontal cortex was compared in 34 patients with frontotemporal dementia linked to chromosome 17 (FTDP-17) with 12 different mutations in the tau gene (MAPT), 11 patients with sporadic FTLD with Pick bodies and 25 patients with early onset Alzheimer's disease (EOAD). Tau load was determined, as percentage of tissue occupied by stained product, by image analysis of immunohistochemically stained sections using the phospho-dependent antibodies AT8, AT100 and AT180. With AT8 and AT180 antibodies, the amount of tau was significantly (P < 0.001 in each instance) less than that in EOAD for both FTDP-17 (8.5% and 10.0% respectively) and sporadic FTLD with Pick bodies (16.1% and 10.0% respectively). With AT100, the amount of tau detected in FTDP-17 was 54% (P < 0.001) of that detected in EOAD, but no tau was detected in sporadic FTLD with Pick bodies using this particular antibody. The amount of insoluble tau deposited within the brain in FTDP-17 did not depend in any systematic way upon where the MAPT mutation was topographically located within the gene, or on the physiological or structural change generated by the mutation, regardless of which anti-tau antibody was used. Not only does the amount of tau deposited in the brain differ between the three disorders, but the pattern of phosphorylation of tau also varies according to disease. These findings raise important questions relating to the role of aggregated tau in neurodegeneration - whether this represents an adaptive response which promotes the survival of neurones, or whether it is a detrimental change that directly, or indirectly, brings about the demize of the affected cell.

Adult↗
PubMed2006

Prolonged deterioration of endothelial dysfunction in response to postprandial lipaemia is attenuated by vitamin C in Type 2 diabetes.

BACKGROUND: Endothelial dysfunction (ED) has been described in Type 2 diabetes (T2DM). We have described previously a diminution of flow-mediated arterial dilatation and, by implication, further ED in T2DM in response to postprandial lipaemia (PPL) at 4 h. This is possibly mediated by oxidative stress/alteration of the nitric oxide (NO) pathway. T2DM subjects tend to exhibit both exaggerated and prolonged PPL. We therefore studied the relationship of PPL to the duration of ED in T2DM subjects and oxidative stress with or without the antioxidant, vitamin C. METHODS: Twenty subjects with T2DM with moderate glycaemic control (mean HbA1c 8.4%) were studied. After an overnight fast, all subjects consumed a standard fat meal. Endothelial function (EF), lipid profiles, and venous free radicals were measured in the fasting, peak lipaemic phase (4 h) and postprandially to 8 h. The study was repeated in a double-blinded manner with placebo, vitamin C (1 g) therapy for 2 days prior to re-testing and with the fat meal. Oxidative stress was assessed by lipid-derived free radicals in plasma, ex vivo by electron paramagnetic resonance spectroscopy (EPR) and by markers of lipid peroxidation (TBARS). Endothelial function was assessed by flow-mediated vasodilatation (FMD) of the brachial artery. RESULTS: There was a significant decrease in endothelial function in response to PPL from baseline (B) 1.3 +/- 1.3% to 4 h 0.22 +/- 1.1% (P < 0.05) and 8 h 0.7 +/- 0.9% (P < 0.05) (mean +/- sem). The endothelial dysfunction seen was attenuated at each time point with vitamin C. Baseline EF with vitamin C changed from (fasting) 3.8 +/- 0.9-2.8 +/- 0.8 (at 4 h) and 2.9 +/- 1.3 (at 8 h) in response to PPL. Vitamin C attenuated postprandial (PP) oxidative stress significantly only at the 4-h time point [301.1 +/- 118 (B) to 224.7 +/- 72 P < 0.05] and not at 8 h 301.1 +/- 118 (B) to 260 +/- 183 (P = NS). There were no changes with placebo treatment in any variable. PPL was associated with a PP rise in TG levels (in mmol/l) from (B) 1.8 +/- 1 to 2.7 +/- 1 at 4 h and 1.95 +/- 1.2 at 8 h (P = 0.0002 and 0.33, respectively). CONCLUSION: PPL is associated with prolonged endothelial dysfunction for at least 8 h after a fatty meal. Vitamin C treatment improves endothelial dysfunction at all time points and attenuates PPL-induced oxidative stress. This highlights the importance of low-fat meals in T2DM and suggests a role for vitamin C therapy to improve endothelial function during meal ingestion.

Administration, Oral↗
PubMed2006

Influence of diabetes on manifestations and treatment outcome of pulmonary TB patients.

OBJECTIVE: To understand the influence of diabetes on the clinical and bacteriological aspects and treatment outcome of pulmonary tuberculosis (PTB) patients. SETTING AND DESIGN: Records of 692 consecutive smear-positive PTB patients admitted to a referral hospital in Riyadh, Saudi Arabia, were reviewed retrospectively. The characteristics of 187 patients with diabetes mellitus (PTB-DM group) were compared to 505 patients without DM (PTB group). RESULTS: In the PTB-DM group, 65.2% of the patients had numerous acid-fast bacilli (AFB) on sputum smear examination compared to 54.1% in the control group (P = 0.008). Among new cases, PTB-DM patients had a lower prevalence of resistance to any anti-tuberculosis drug (6.4% vs. 16.0%, P = 0.007) and achieved higher sputum conversion rates at the end of 3 months of treatment (98.9% vs. 94.7%, P = 0.013). Favourable outcomes (cured/treatment completed), failure, death and default were comparable in both groups (P = 0.7005). CONCLUSIONS: PTB-DM patients have a higher pre-treatment bacillary load, a lower prevalence of anti-tuberculosis drug resistance and achieve slightly higher sputum conversion by the end of 3 months of treatment compared to non-diabetic patients. The association of diabetes does not alter the final treatment outcome among PTB patients.

Adolescent↗
PubMed2005

Distal posterior inferior cerebellar artery aneurysms: clinical characteristics and surgical management.

BACKGROUND: Aneurysms located on the distal posterior inferior cerebellar artery (PICA) are rare, and their underlying clinical features and surgical management are poorly understood. We report our series of 16 patients with 18 distal PICA aneurysms. METHOD: All patients with distal PICA aneurysms were treated between March 1996 and August 2004. We excluded all PICA aneurysms that involved the vertebral artery. Patients were analysed in the light of their clinical profiles, radiological studies, intraoperative findings and outcomes. All patients underwent non-enhanced and contrast enhanced CT scans followed by 4-vessel cerebral angiography on admission. The hemorrhagic patterns on initial CT scans were assessed using the Fisher Grading Score. The outcomes were documented using the Glasgow Outcome Scale at time of discharge and at three or twelve months follow-up. FINDINGS: The series included 6 men and 10 women. Massive intraventricular haemorrhage was found in 13 patients with proven CT subarachnoid haemorrhage, one patient revealed SAH without intraventricular components, one presented with only intraventricular blood in the occipital horns and 3 aneurysms were found incidentally without presence of blood. Fourteen aneurysms were saccular and four were fusiform. Nine cases were associated with another cerebrovascular lesion. A lateral transcondylar or a median suboccipital approach was used to secure the aneurysms in 15 patients, either by direct clipping (14 lesions) or vessel sacrifice (3 lesions). One aneurysm was treated by an endovascular approach. At long-term follow up, an excellent or good outcome was achieved in 75% of cases. One patient died due to pre-existing cardiopulmonary complications. CONCLUSIONS: Most of our cases of ruptured distal PICA aneurysms presented with haematocephalus. These were frequently associated with another vascular abnormality and 22% were fusiform or multilobulated. These specific features require special management strategies entailing an appropriate surgical approach to the aneurysm, clipping method, haematoma removal, ventricular drainage and when suitable choice of endovascular interventions.

Adult↗
PubMed2005

Energy dependence of elliptic flow over a large pseudorapidity range in Au+Au collisions at the BNL relativistic heavy ion collider.

This Letter describes the measurement of the energy dependence of elliptic flow for charged particles in Au+Au collisions using the PHOBOS detector at the Relativistic Heavy Ion Collider. Data taken at collision energies of square root of s(NN)=19.6, 62.4, 130, and 200 GeV are shown over a wide range in pseudorapidity. These results, when plotted as a function of eta(')=|eta|-y(beam), scale with approximate linearity throughout eta('), implying no sharp changes in the dynamics of particle production as a function of pseudorapidity or increasing beam energy.

Journal Article↗
PubMed2005

Centrality dependence of charged hadron transverse momentum spectra in Au+Au collisions from sqrt[s(NN)]=62.4 to 200 GeV.

We have measured transverse momentum distributions of charged hadrons produced in Au+Au collisions at sqrt[s(NN)]=62.4 GeV. The spectra are presented for transverse momenta 0.25<p(T)<4.5 GeV/c, in a pseudorapidity range of 0.2<eta<1.4. The nuclear modification factor R(AA) is calculated relative to p+p data at the same collision energy as a function of collision centrality. For 2<p(T)<4.5 GeV/c, R(AA) is found to be significantly larger than in Au+Au collisions at sqrt[s(NN)]= 130 and 200 GeV. In contrast to the large change in R(AA), we observe a very similar centrality evolution of the p(T) spectra at sqrt[s(NN)]=62.4 and 200 GeV. The dynamical origin of this surprising factorization of energy and centrality dependence of particle production in heavy-ion collisions remains to be understood.

Journal Article↗
PubMed2005

EPR spectrometer for clinical applications.

This article describes an EPR spectrometer specifically designed and constructed for EPR spectroscopy in humans. The spectrometer is based on a permanent magnet, suitable for measurements at 1200 MHz. The magnet has a full 50 cm gap between the poles, which facilitates accurate and comfortable placement of the subject for the EPR measurement at any location on the human body. The bridge includes features to facilitate clinical operations, including an indicator for phasing of the reference arm and a 2 level RF amplifier. Resonators with holders for each type and site of measurement have been developed that comfortably position the resonator and the patient and prevent artifacts due to motion. The initial applications for which the spectrometer has been designed are for oximetry using loops on the surface, oximetry using implanted resonators for measuring deep sites, and measurements in the teeth for determination of exposures to clinically significant doses of ionizing radiation.

Electron Spin Resonance Spectroscopy↗
PubMed2005

Three cases of AVM at eloquent areas finally treated with conventional microsurgical method.

Three special cases of AVM finally treated with conventional microsurgical method are presented. Two cases of medium sized AVMs were located at the central region, one of them was primarily treated with Gamma-knife followed by endovascular embolization having been complicated with growing cyst formation followed ultimately by microsurgical removal. The AVM of another case was embolized three times, followed by removal of the residual nidus under awake surgery. The third AVM located at the hypothalamus in the vicinity of the optic nerve was considered unsuitable for embolization and Gamma-knife therapy, and therefore removed by microsurgery using special approaches after a trial of embolization. In terms of microsurgical removal, preoperative embolization, embolization material, awake surgery and selection of special approaches are discussed.

Adult↗
PubMed2005

Moyamoya angiopathy in Europe.

Over the past 6 years we at the Neurosurgery Department in Zürich have had the opportunity to manage increasing numbers of patients, especially children, with Moyamoya angiopathy. With increasing awareness of presence of this angiopathy in Europe the number of referrals from all across Europe is constantly on the increase. We have also been able to readdress the presence of the entity of Moyamoya angiopathy i.e. both the Moyamoya disease and the Moyamoya syndrome in the European population. Thorough presurgical workup is mandatory for evaluation of surgical candidates for the type of effective revascularisation procedure and therefore for their successful management. Apart from scrutinizing the routine yet indispensable presenting symptomatology with clinical examination of the patients, our preoperative diagnostic workup mainly consists of a 6 vessel cerebral angiography, cerebral perfusion studies with HMPAO-SPECT and H(2)15O-PET examinations and transcranial Doppler. Longterm follow-up of these patients is indispensable and of great interest to us in terms of etiology and progression of the disease process as well as the choice of effective revascularisation procedure especially in our European population.

Anastomosis, Surgical↗
PubMed2005

Conventional microsurgical treatment of paraclinoid aneurysms: state of the art with the use of the selective extradural anterior clinoidectomy SEAC.

Surgical treatment of paraclinoid aneurysms is considered to be difficult due to their complicated anatomical location in the vicinity of important neural, vascular and bony structures. We present our clinical experience of the past 10 years of conventional microsurgical treatment of 81 paraclinoid aneurysms in 75 patients with the use of selective extradural anterior clinoidectomy SEAC and discuss the method of therapy option by reviewing recent reports on results of endovascular coiling method and the combination of these with conventional microsurgical therapy. The favorable surgical results with the use of SEAC and no recurrence of the treated aneurysm after clipping procedure in our series indicate that direct surgery can still be a standard technique for paraclinoid aneurysms in view of the fact that the endovascular aneurysm coiling methods are still associated with a considerable percentage of incomplete occlusion and present the problem of coil packing.

Blood Vessel Prosthesis↗
PubMed2005

Basilar bifurcation aneurysms. Lessons learnt from 40 consecutive cases.

Basilar bifurcation aneurysms are lately treated frequently with endovascular technique. Microsurgical clipping occlusion technique has, however, still its solid position because of its completeness. This standard technique is required often due to unfeasibility and/or incompleteness at the time of application of the endovascular technique for aneurysms of this location. The authors suggest following strategies and tactics for safe and secure occlusion of aneurysms of this location: pterional approach, selective extradural anterior clinoidectomy SEAC, no transection of the posterior communicating artery, isolation of perforating arteries at the time of neck clipping with oxycellulose and combination of the use of fenestrated clip and conventional clip (especially for aneurysms projected posteriorly), controlled hypotension (systolic pressure of around 100 mmHg), temporary clipping (trapping) procedures of usually less than 15 min. All these are aimed for prevention of intraoperative premature rupture, and of injury of perforating arteries and for complete occlusion of aneurysms in the narrow depth of the operative field.

Adult↗
PubMed2005

Inhibition of two stage renal carcinogenesis, oxidative damage and hyperproliferative response by Nigella sativa.

In an earlier communication we reported that Nigella sativa suppresses potassium bromate-induced renal oxidative damage. In the present study, we report the chemopreventive effect of Nigella sativa against ferric nitrilotriacetate (Fe-NTA)-induced renal oxidative stress, hyperproliferative response and renal carcinogenesis. Fe-NTA (9 mg Fe/kg body weight, intraperitoneally) enhances renal lipid peroxidation, xanthine oxidase, gamma-glutamyl transpeptidase and hydrogen peroxide (H2O2) generation with reduction in renal glutathione content, antioxidant enzymes and phase II metabolizing enzymes. It also caused increase in blood urea nitrogen, serum creatinine, ornithine decarboxylase (ODC) activity and thymidine [H] incorporation into renal DNA. It also enhanced DEN (N-diethylnitrosamine)-initiated renal carcinogenesis by increasing the percentage incidence of tumours. Treatment of rats orally with Nigella sativa (50 and 100 mg/kg body weight) resulted in significant decrease in gamma-glutamyl transpeptidase, lipid peroxidation, xanthine oxidase, H2O2 generation, blood urea nitrogen, serum creatinine, renal ODC activity, DNA synthesis (P<0.001) and incidence of tumours. Renal glutathione content (P<0.01), glutathione-metabolizing enzymes (P<0.001) and antioxidant enzymes were also recovered to significant levels (P<0.001). Thus, our data suggest that Nigella sativa is a potent chemopreventive agent and suppresses Fe-NTA-induced oxidative stress, hyperproliferative response and renal carcinogenesis in Wistar rats.

Animals↗