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N Khan

Publications and source records attributed to N Khan.

At least 37 records · Page 2Linked to original sources
PubMed2005

The number of human peripheral blood CD4+ CD25high regulatory T cells increases with age.

Ageing is associated with evidence of immune deficiency and dysregulation. Key changes in the immune system with ageing include a progressive reduction in naive T cell output associated with thymic involution and peripheral expansion of oligoclonal memory T cells. These features are associated with evidence of impaired immune responsiveness both in vitro and in vivo, termed immune senescence. CD4+ CD25+ T cells have recently been recognized as mediators of peripheral immune regulation and play a role in the control of autoimmune and pathogen-specific immune responses. The significance of CD4+ CD25+ regulatory T cells in the context of immunosenescence is not known. We have investigated the number, phenotype and function of CD4+ CD25+ T cells in healthy volunteers over a wide age range. We demonstrate that the number of CD4+ CD25+ and CD4+ CD25high T cells in healthy volunteers increases with age. In both age groups CD4+ CD25+ T cells showed a phenotype consistent with that described for regulatory T cells. Further analysis of CD4+ CD25high T cells in young and elderly donors showed equivalent expression of intracellular CTLA-4 and surface expression of activation markers. In vitro, functional titration assays of CD4+ CD25high T cells demonstrated equivalent regulatory function in both young and elderly donors, with suppression of proliferation and cytokine production in response to polyclonal T cell stimulation. These observations demonstrate an increase in peripheral blood CD4+ CD25high regulatory T cells associated with ageing. The relevance of these expanded cells in relation to the immune senescence seen in the elderly as yet remains unclear.

Adult↗
PubMed2005

Tc-99m DTPA scintigraphy in soft tissue tumor.

Tc99m-DTPA scintigraphic study were done in Centre For Nuclear Medicine and Ultrasound (CNMU) Mymensingh presented with palpable soft tissue mass. All the patients referred to CNMU for ultrasonic evaluation of the mass. Taking proper consent form patient and we did the Tc-99m DTPA scanning of the masses. The study was carried out using Tc-99m DTPA in three phases dynamic, blood pool after 5 min, followed by a late scan after 2 hr. The uptake was categorized as consistently positive, initially positive but latter (progressively) negative, initially negative but latter (progressively) positive and consistently negative. Among our studied cases there were both benign and malignant lesion that were proved by histopathology after excisional biopsy. Two cases were inconclusive. Histologically proven lipoma showed no uptake of DTPA considered as consistently negative. Two cases of rhabdomyosarcoma showed consistently positive.

Adolescent↗
PubMed2004

Pseudorapidity distribution of charged particles in d+Au collisions at sqrt[sNN]=200 GeV.

The measured pseudorapidity distribution of primary charged particles in minimum-bias d+Au collisions at sqrt[s(NN)]=200 GeV is presented for the first time. This distribution falls off less rapidly in the gold direction as compared to the deuteron direction. The average value of the charged particle pseudorapidity density at midrapidity is |eta|< or =0.6)=9.4+/-0.7(syst) and the integrated primary charged particle multiplicity in the measured region is 82+/-6(syst). Estimates of the total charged particle production, based on extrapolations outside the measured pseudorapidity region, are also presented. The pseudorapidity distribution, normalized to the number of participants in d+Au collisions, is compared to those of Au+Au and p+(-)p systems at the same energy. The d+Au distribution is also compared to the predictions of the parton saturation model, as well as microscopic models.

Journal Article↗
PubMed2004

Seasonal variations in hospital admissions due to aneurysmal subarachnoid haemorrhage in the state of Zurich, Switzerland.

INTRODUCTION: In clinical practice, the occurrence of aneurysmal subarachnoid haemorrhage (SAH) often coincides with a particular season. Our objective was to examine seasonal variations in hospital admissions due to aneurysmal SAH. METHODS: The study population consisted of 489 patients with aneurysmal SAH who were admitted to the Department of Neurosurgery, University Hospital of Zurich, Switzerland, between 1st of January 1996 and 31st of December 2002. Statistical significance of seasonal variation was determined by applying Roger's r test. RESULTS: Statistically significant seasonal variation was only found among patients younger than 60 years, showing a first peak in spring and second lower peak in autumn (Roger's r=6.89, p<0.05). A borderline significance was found in men younger than 60 years (Roger's r=5.96, p=0.051). A trend was observed in patients presenting with Fisher grade 1-2 (Roger's r=5.70, p=0.058). CONCLUSIONS: Previous studies from different countries have shown significant seasonal variations, with the peak period for aneurysmal SAH differing widely. There appears to be some link between aneurysmal SAH and the season of the year or variations in weather conditions. Further investigations are desirable to evaluate which weather or climatic parameters correlate well with SAH.

Adult↗
PubMed2004

Aetiology of male urethritis in patients recruited from a population with a high HIV prevalence.

The aetiology of urethritis, the significance of potential pathogens and the relation of urethritis to HIV infection were determined in 335 men (cases) with and 100 men (controls) without urethral symptoms. Urethral swab specimens were tested for different organisms by PCR or by culture for Neisseria gonorrhoeae. The prevalence of N. gonorrhoeae and Chlamydia trachomatis was 52 and 16%, respectively. The potential pathogens: Mycoplasma genitalium, Ureaplasma urealyticum, Trichomonas vaginalis and herpes simplex virus (HSV), were present in 5, 36, 6 and 6% of the cases respectively. M. genitalium was the only potential pathogen associated with microscopic urethritis. After excluding gonococcal infections, U. urealyticum was more frequent in symptomatic patients, while the prevalence of T. vaginalis was similar among cases and controls. These results strongly suggest an a etiological role for M. genitalium in male urethritis, a possible role for U. urealyticum, but not for T. vaginalis. The control group, with 97% genital ulcer disease patients, was not suitable for the investigation of the role of HSV. The sero-prevalence of HIV was 45%. Current infections were not associated with HIV. However, a history of previous urethral discharge was associated with HIV in a multivariate analysis and supported the hypothesis that non-ulcerative sexually transmitted diseases facilitate HIV transmission.

Animals↗
PubMed2004

Study on prevention of two-stage skin carcinogenesis by Hibiscus rosa sinensis extract and the role of its chemical constituent, gentisic acid, in the inhibition of tumour promotion response and oxidative stress in mice.

We designed the present study to investigate the role of gentisic acid in the chemopreventive activity of Hibiscus rosa sinensis extract on 7,12-dimethyl benz(a)anthracene (DMBA)/croton oil-mediated carcinogenesis in mouse skin via 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced tumour promotion response and oxidative stress. Single topical application of DMBA followed by twice weekly applications of croton oil after one week for 20 weeks resulted in 100% incidence of tumours in animals in 15 weeks. However, application of H. rosa sinensis extract 30 minutes prior to the application of croton oil twice weekly for 20 weeks caused significant reduction in the number of tumours per mouse and the percentage of tumour-bearing mice. Also, the latency period for the appearance of the first tumour was delayed on H. rosa sinensis pretreatment. A single topical application of TPA caused significant depletion in reduced glutathione (GSH) content, activities of its metabolizing and antioxidant enzymes, while malondialdehyde (MDA) formation, H2O2 content, ornithine decarboxylase (ODC) activity and DNA synthesis were significantly increased. Interestingly, pretreatment of H. rosa sinensis extract (3.5 mg and 7 mg/kg body weight) and gentisic acid (2.0 microg and 4.0 microg/0.2 ml acetone per animal) restored the levels of GSH, and its metabolizing and antioxidant enzymes (P<0.05). There was also a statistically significant reduction in MDA formation and H2O2 content (P<0.05) at both doses. Although inhibition of ODC activity by gentisic acid was not dose-dependent, thymidine incorporation in DNA (P<0.05) was dose-dependently recovered by the plant extract and its chemical constituent. We therefore propose that gentisic acid has a role in the modulatory activity of H. rosa sinensis extract.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2004

Frontotemporal lobar degeneration and ubiquitin immunohistochemistry.

We set out to determine the frequency of the different pathologies underlying frontotemporal degeneration (FTD) in our brain bank series, by reviewing all cases of pathologically diagnosed FTD over the last 12 years. We identified and reviewed 29 cases of FTD and classified them using the most recent consensus criteria with further histological analysis of 6 initially unclassifiable cases. Detailed histological analysis of these 6 cases revealed variable numbers of ubiquitin-positive (tau and alpha-synuclein-negative) inclusions in 5 cases, consistent with the diagnosis of frontotemporal lobar degeneration with ubiquitin-only-immunoreactive neuronal changes (FTLD-U). As a consequence of the current re-evaluation, 18 (62%) of the 29 cases with FTD have underlying pathology consistent with FTLD-U. Therefore in our brain bank series of frontotemporal degeneration, most cases were non-tauopathies with FTLD-U accounting for 62% of all the diagnoses.

Aged↗
PubMed2004

Comparison of the OptiMAL rapid antigen test with field microscopy for the detection of Plasmodium vivax and P. falciparum: considerations for the application of the rapid test in Afghanistan.

To establish the sensitivity and specificity of a batch of 'OptiMAL 48' rapid antigen tests procured by the World Health Organization in Afghanistan, a sample was tested, in parallel with routine, microscopical diagnosis, at basic health units (BHU) within Afghan refugee camps in Pakistan. The results of both methods of field diagnosis were compared with those of cross-checking microscopy at a reference laboratory, which were taken as the 'gold standard'. Out of 499 patients examined, 36% were diagnosed as malaria cases by field microscopy and 34% by the rapid test. For the OptiMAL 48 test, cross-checking of the corresponding smears at the reference laboratory gave a sensitivity of 79.3% and a specificity of 99.7% for Plasmodium falciparum and corresponding values of 86.1% and 98.7% for P. vivax infections. The performance of the field microscopy was better, with a sensitivity and specificity of 85.2% and 99.7% for P. falciparum, and 90.4% and 98.7% for P. vivax, respectively. These results show that the performance of OptiMAL 48 is adequate for acute- and post-emergency situations when the alternative is just clinical diagnosis. However, in the developing health system of Afghanistan, the main focus should be on the expansion of the existing network for microscopical diagnosis and quality control, to meet the needs of a stable situation. Rapid antigen tests are more suited to investigations of outbreaks in remote situations, where health services are deficient or absent.

Afghanistan↗
PubMed2003

Moyamoya disease and Moyamoya syndrome: experience in Europe; choice of revascularisation procedures.

OBJECTIVES: To present our clinical experience in terms of disease presentation and choice of revascularisation procedure in our first group of 23 European Moyamoya angiopathy (disease and syndrome) patients. METHOD AND PATIENT SELECTION: Twenty three patients were diagnosed and treated from 1997-2001 in our neurosurgical department. All patients underwent preoperative angiography, colour Doppler examination, cranial MRI and/or CT scans, HMPAO-SPECT or H(2)(15)O PET (baseline and Diamox challenge) scans. Nineteen patients presented with child-juvenile Moyamoya angiopathy with an average age at presentation of 8 years (range 1-17 years), in 4 patients adult Moyamoya was diagnosed with a mean age at presentation of 34 years (range 23-40 years). RESULTS: In all but one patient bilateral affection was present at the time of diagnosis. All patients underwent direct and/or additional indirect revascularisation procedures. Twenty-one patients underwent bilateral revascularisation procedures. In two patients a unilateral procedure was performed. A direct STA-MCA bypass (superficial temporal artery branch - middle cerebral artery branch anastomosis) was performed in all patients. Additional direct STA-ACA bypass (STA - anterior cerebral artery branch anastomosis) was performed in 10 patients. Indirect arteriosynangiosis using the occipital artery was performed in the posterior cerebral artery (PCA) territory in 3 patients. The frontal branch of the STA was used for arteriosynangiosis in the frontal region in another 2 patients. Indirect frontal durasynangiosis was performed in 14 patients. The number and location of multiple revascularisation procedures was determined according to the angiographic findings as well as the site of decreased perfusion reserves seen on H(2)(15)O PET. A one stage revascularisation procedure was performed in 7 patients. Fourteen patients underwent two stage procedures. Following operation no complications were encountered in all but one adult patient who died postoperatively due to a massive middle cerebral artery infarct on the nonoperated side. CONCLUSIONS: As territorial hemodynamic disorder seems to be a characteristic in Moyamoya disease and/or syndrome, judging from our experience with European patients in our series, and several reports hitherto, treatment with multiple revascularisation procedures is considered to be justified.

Adolescent↗
PubMed2003

Centrality dependence of charged-hadron transverse-momentum spectra in d+Au collisions at sqrt[s(NN)]=200 GeV.

We have measured transverse momentum distributions of charged hadrons produced in d+Au collisions at sqrt[s(NN)]=200 GeV. The spectra were obtained for transverse momenta 0.25<p(T)<6.0 GeV/c, in a pseudorapidity range of 0.2<eta<1.4 in the deuteron direction. The evolution of the spectra with collision centrality is presented in comparison to p+pmacr; collisions at the same collision energy. With increasing centrality, the yield at high transverse momenta increases more rapidly than the overall particle density, leading to a strong modification of the spectral shape. This change in spectral shape is qualitatively different from observations in Au+Au collisions at the same energy. The results provide important information for discriminating between different models for the suppression of high-p(T) hadrons observed in Au+Au collisions.

Journal Article↗
PubMed2003

Preliminary evaluation of nanoscale biogenic magnetite in Alzheimer's disease brain tissue.

Elevated iron levels are associated with many types of neurodegenerative disease, such as Alzheimer's, Parkinson's and Huntington's diseases. However, these elevated iron levels do not necessarily correlate with elevated levels of the iron storage or transport proteins, ferritin and transferrin. As such, little is known about the form of this excess iron. It has recently been proposed that some of the excess iron in neurodegenerative tissue may be in the form of the magnetic iron oxide magnetite (Fe(3)O(4)). We demonstrate, for the first time to our knowledge, using highly sensitive superconducting quantum interference device (SQUID) magnetometry, that the concentrations of magnetite are found to be significantly higher in three samples of Alzheimer's disease tissue than in three age- and sex-matched controls. These results have implications, not only for disease progression, but also for possible early diagnosis.

Aged↗
PubMed2003

Significance of the fragmentation region in ultrarelativistic heavy-ion collisions.

We present measurements of the pseudorapidity distribution of primary charged particles produced in Au+Au collisions at three energies, sqrt[s(NN)]=19.6, 130, and 200 GeV, for a range of collision centrali-ties. The distribution narrows for more central collisions and excess particles are produced at high pseudorapidity in peripheral collisions. For a given centrality, however, the distributions are found to scale with energy according to the "limiting fragmentation" hypothesis. The universal fragmentation region described by this scaling grows in pseudorapidity with increasing collision energy, extending well away from the beam rapidity and covering more than half of the pseudorapidity range over which particles are produced. This approach to a universal limiting curve appears to be a dominant feature of the pseudorapidity distribution and therefore of the total particle production in these collisions.

Journal Article↗
PubMed2003

Human cytomegalovirus-associated periodontitis in renal transplant patients.

BACKGROUND: Human cytomegalovirus (HCMV) infection is associated with renal transplant failure. Periodontal pockets may be reservoirs for HCMV replication. OBJECTIVES: This study was done to determine active HCMV replication in saliva and gingival crevicular fluid of renal transplant patients affected by periodontitis. METHODS: HCMV pp67-mRNA amplification was analyzed in oral fluids of 38 transplant recipients at 6 months' posttransplantation. Patients received antiviral therapy until 3 months' posttransplantation. The HCMV-positive cell line VR-977 was the positive control, and oral fluids from healthy volunteers served as the negative control. Periodontitis was diagnosed by clinical examination. Serum HCMV IgG and IgM were analyzed to differentiate recent and latent infection. RESULTS: Prevalence of gingival overgrowth was 68.4%. HCMV gene transcripts were detected in the saliva of 21% and the gingival crevicular fluid of 18% of patients. All patients (100%) with HCMV pp67-mRNA detected in saliva demonstrated clinical manifestations of viral infection, as did 86% of patients with HCMV pp67-mRNA detected in the gingival crevicular fluid. Serum IgM was positive in 7.9% of patients and IgG in 65.8%; however, associations with active mRNA replication were not statistically significant. CONCLUSIONS: Renal transplant patients affected by periodontitis are at risk of viral replication within the periodontal tissues despite antiviral therapy. This study suggests that use of HCMV pp67-mRNA detection in saliva and gingival crevicular fluid provides markers of active viral infection, and evidence for a link between HCMV-associated periodontitis and renal transplant complications.

Adult↗
PubMed2003

Specific sites in the Beta Interaction Domain of a schistosome Ca2+ channel beta subunit are key to its role in sensitivity to the anti-schistosomal drug praziquantel.

Praziquantel, the drug of choice against schistosomiasis, disrupts calcium (Ca2+) homeostasis in schistosomes via an unknown mechanism. Voltage-gated Ca2+ channels are heteromultimeric transmembrane protein complexes that contribute to impulse propagation and also regulate intracellular Ca2+ levels. Beta subunits modulate the properties of the pore-forming alpha1 subunit of high voltage-activated Ca2+ channels. Unlike other Ca2+ channel beta subunits, which have current stimulatory effects, a beta subunit subtype found in S. mansoni (SmbetaA) and S. japonicum (Sjbeta) dramatically reduces current levels when co-expressed with Ca2+ channel alpha1 subunits in Xenopus oocytes. It also confers praziquantel sensitivity to the mammalian Cav2.3 alpha1 subunit. The Beta Interaction Domains (BIDs) of SmbetaA and Sjbeta lack 2 conserved serines that each constitute a consensus site for protein kinase C (PKC) phosphorylation. Here, we use site-directed mutagenesis of schistosome beta subunits to show that these unique functional properties are correlated with the absence of these consensus PKC sites in the BID. Furthermore, a second schistosome beta subunit subtype contains both serines in the BID, enhances currents through alpha1 subunits, and does not confer praziquantel sensitivity. Thus, phosphorylation sites in the BID may play important roles in defining the modulatory properties and pharmacological sensitivities of schistosome Ca2+ channel beta subunits.

Amino Acid Sequence↗
PubMed2003

Effects of insulin lispro and chronic vitamin C therapy on postprandial lipaemia, oxidative stress and endothelial function in patients with type 2 diabetes mellitus.

BACKGROUND: Insulin therapy may influence cardiovascular disease (CVD) and lipid metabolism in type 2 diabetes (T2D). Exaggerated postprandial lipaemia (PPL) is a feature of diabetic dyslipidaemia affecting CVD via enhanced oxidative stress (OS) and endothelial dysfunction. We assessed endothelial function and OS during PPL following insulin and vitamin C. Twenty (17 M) T2D patients were studied (mean Hba1c 8.4%) at baseline, following 6 weeks of insulin lispro (0.2 Iu kg-1) and vitamin C 1-g daily. Eight-h lipid and glucose profiles were measured following a fatty meal. Endothelial function (flow-mediated vasodilatation: FMD) and OS were measured at fasting, 4 h and 8 h. MATERIALS AND METHODS: Glucose, body mass index, and total and LDL cholesterol remained unchanged. FMD improved. Placebo group: fasting, 1.1 +/- 1.2 to 4.2 +/- 1.1% (P < 0.001); 4-h, 0.3 +/- 1.2 to 3.1 +/- 0.9% (P < 0.01); 8-h, 0.7 +/- 1.1 to 3.76 +/- 1.1% (P < 0.001). Vitamin C group: fasting, 0.9 +/- 1.1 to 6.1 +/- 1.3% (P < 0.001); 4-h, 0.7 +/- 1.5 to 4.9 +/- 2.1% (P < 0.001); 8-h, 0.8 +/- 0.9 to 5.8 +/- 0.6% (P < 0.01). Post-prandial lipaemia was attenuated: TG area-under-curve (mmol L-1 8 h-1), 52.6 +/- 11 to 39.1 +/- 12.5 (placebo group), P < 0.02; and 56.9 +/- 8 to 40.1 +/- 10.3 (vitamin C group), P < 0.02. Oxidative stress was reduced, with greater changes in the vitamin C group. CONCLUSION: Insulin may thus exert vascular benefits in T2D, by modifying fasting and postprandial lipid metabolism resulting in reduced OS and improved EF. Vitamin C therapy may augment the vascular benefits of insulin in T2D through additional effects on OS and EF.

Adult↗
PubMed2003

Pathological inclusion bodies in tauopathies contain distinct complements of tau with three or four microtubule-binding repeat domains as demonstrated by new specific monoclonal antibodies.

Pathological inclusions containing fibrillar aggregates of hyperphosphorylated tau protein are a characteristic feature in the tauopathies, which include Alzheimer's disease, frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17), progressive supranuclear palsy, corticobasal degeneration and Pick's disease. Tau isoform composition and cellular and regional distribution as well as morphology of these inclusions vary in each disorder. Recently, several pathological missense and exon 10 splice-donor site mutations of the tau gene were identified in FTDP-17. Exon 10 codes for the second of four microtubule-binding repeat domains. The splice-site mutations result in increased inclusion of exon 10 which causes a relative increase in tau isoforms containing four microtubule-binding repeat domains over those containing three repeat domains. This could be a central aetiological mechanism in FTDP-17 and, perhaps, other related tauopathies. We have investigated changes in the ratio and distribution of three-repeat and four-repeat tau in the different tauopathies as a basis of the phenotypic range of these disorders and the selective vulnerability of different subsets of neurones. In this study, we have developed two monoclonal antibodies, RD3 and RD4 that effectively distinguish these closely related tau isoforms. These new isoform-specific antibodies are useful tools for analysing tau isoform expression and distribution as well as pathological changes in the human brain.

Animals↗