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Biomedical subjects

N Haque

Publications and source records attributed to N Haque.

At least 19 recordsLinked to original sources
PubMed2006

High-risk sexual behaviours among drug users in Pakistan: implications for prevention of STDs and HIV/AIDS.

Our objective was to describe HIV/STD risk behaviours and awareness among a community-based sample of drug users in Pakistan. Drug users contacted through street outreach by a non-governmental organization in Quetta, Peshawar and Rawalpindi underwent interviewer-administered questionnaires. Descriptive statistics were used to characterize sexual behaviours by city, marital status and the use of injection drugs. Logistic regression was used to identify correlates of ever having an STD. Of 608 drug users studied, all but one was male; median age was 32 years and 45% had no formal education. Half were married, of whom 25% were living with their wives. Sexual behaviours were reported as follows: 14% had sex with other males, 28% reported sex with males and females, 49% had paid money to have sex and only 10% had ever used condoms. One-fifth reported having had an STD and about 40% reported having suffered from either one or more STD-related symptoms. Only 41% had heard about HIV/AIDS, of whom 17% knew that HIV/AIDS could be transmitted through sexual contact. In conclusion, high-risk sexual behaviours are prevalent among male drug users in Pakistan, and awareness of transmission risks is low. These data attest to the urgent need for effective and specific interventions in Pakistan to prevent transmission of HIV and STDs among drug users and their sex partners (I J STD & AIDS 2004;15:601-7).

Journal Article↗
PubMed2004

Hyperphosphorylation-induced self assembly of murine tau: a comparison with human tau.

Alzheimer's disease-like neurofibrillary pathology is neither seen in rodents nor in transgenic animals expressing the disease causing mutant human APP or mutant human presenilins. Whether the absence of this pathology is due to inability of the murine tau to self assemble into filaments or due to some other factors is not understood. In this study, we compared recombinant murine and human taus in their ability to form filaments by AD-like hyperphosphorylation in vitro. Human and murine taus, 0N4R, were generated as recombinant proteins and phosphorylated with rat brain extract as a source of protein kinases. We found that murine tau could be hyperphosphorylated to similar stoichiometry and manner as human tau. Upon hyperphosphorylation, murine tau was able to self polymerize into bundles of paired helical filament- and straight filament-like morphology. The filaments obtained from self assembly of murine tau closely resembled those formed from identically treated human tau. Moreover, like human tau, 60-70% of murine tau aggregated on hyperphosphorylation.

Animals↗
PubMed2004

Clinical characteristics and outcomes of diabetic ketoacidosis in Pakistani adults with Type 2 diabetes mellitus.

AIMS: The aim of this study was to describe the clinical characteristics and outcomes of diabetic ketoacidosis (DKA) in Pakistani adult population with Type 2 diabetes mellitus. METHODS: We reviewed the medical records of all adult patients admitted with a diagnosis of DKA and Type 2 diabetes mellitus (DM) and followed their clinical course and outcome. Follow-up data were obtained by chart review or telephone contact where necessary. RESULTS: Fifty-seven patients fulfilled criteria for inclusion in the study. Their mean age was 48 +/- 7 years. The mean body mass index was 25.5 +/- 6.2 kg/m2. Forty-nine had a prior history of Type 2 DM but DKA was the initial presentation in 14%. Nine were on no treatment, 40 were using oral hypoglycaemic agents and eight were on insulin. A history of prior DKA was noted in eight patients. Infections were the most common precipitating factor (63%). There were 12 deaths. Follow-up after a period ranging between 12 and 43 months revealed that 30/45 patients remained on OHA without recurrence of DKA. CONCLUSION: This report highlights the need for the growing recognition of DKA occurring in adults with Type 2 DM in the South Asian population. Mortality rates are unacceptably high but the majority of survivors remain insulin independent.

Body Mass Index↗
PubMed2004

High-risk sexual behaviours among drug users in Pakistan: implications for prevention of STDs and HIV/AIDS.

Our objective was to describe HIV/STD risk behaviours and awareness among a community-based sample of drug users in Pakistan. Drug users contacted through street outreach by a non-governmental organization in Quetta, Peshawar and Rawalpindi underwent interviewer-administered questionnaires. Descriptive statistics were used to characterize sexual behaviours by city, marital status and the use of injection drugs. Logistic regression was used to identify correlates of ever having an STD. Of 608 drug users studied, all but one was male; median age was 32 years and 45% had no formal education. Half were married, of whom 25% were living with their wives. Sexual behaviours were reported as follows: 14% had sex with other males, 28% reported sex with both males and females, 49% had paid money to have sex and only 10% had ever used condoms. One-fifth reported having had an STD and about 40% reported having suffered from either one or more STD-related symptoms. Only 41% had heard about HIV/AIDS, of whom 17% knew that HIV/AIDS could be transmitted through sexual contact. In conclusion, high-risk sexual behaviours are prevalent among male drug users in Pakistan, and awareness of transmission risks is low. These data attest to the urgent need for effective and specific interventions in Pakistan to prevent transmission of HIV and STDs among drug users and their sex partners.

Adult↗
PubMed2004

Clinical features and outcome of surgery in 30 patients with acromegaly.

OBJECTIVE: To assess the surgical outcome of hypophysectomy in acromegalic patients, differences in response to surgery in micro and macroadenoma and the development of associated hormonal deficiency after surgery. METHODS: Retrospective analysis of charts of acromegalic patients who were operated upon at Aga Khan University Hospital, Karachi, was done. Information regarding presentation, laboratory data, radiological assessment, details of surgery and postoperative outcome was recorded. Surgical outcome was classified depending on the degree of disease control after surgery as biochemical cure, remission and treatment failure. RESULTS: Out of 30 patients, eighteen (60%) were males and 12 (40%) females with mean age at the time of diagnosis 35.6+/-10.4 years. The mean duration of symptoms was 3.2+/-2.4 years. Twenty-five patients had macroadenoma and five had microadenoma. Preoperative mean GH level was 42.4 ng/ml with range of 2.5 to 534 ng/ml. Following surgery, 13 had biochemical cure, 4 were in remission and 13 failed to respond. The outcome in microadenoma was better than in macroadenoma i.e. 100% vs. 32%. Preoperatively four patients had panhypopituitarism with additional six patients (20%) developing hypopituitarism postoperatively. CONCLUSION: Our study showed that acromegaly was seen at a much earlier age, outcome of surgery was comparable to other international studies and postoperative panhypopituitarism was seen in significant number of patients. The outcome in microadenoma was better than in macroadenoma but the number of patients seen with microadenoma was small.

Acromegaly↗
PubMed2003

Microtubule associated protein tau binds to double-stranded but not single-stranded DNA.

Tau, a major microtubule-associated protein of the neuron, which is known to promote the assembly of and to stabilize microtubules, has also been seen associated with chromatin in neuronal cell lines, but its role in this subcellular compartment is still unknown. In this study, the binding of tau to DNA was investigated using the electrophoretic mobility shift assay. Using polynucleotide as probe, we found that tau bound to double-stranded but not to single-stranded DNA. Formation of tau-polynucleotide complex was disrupted by alkaline pH and a high concentration of NaCl, but was not affected by dithiothreitol. Electron microscopy revealed that the protein associated with the nucleic acid in a necklacelike manner. DNA-cellulose chromatography and radioimmunodot-blot analyses showed that calf thymus histones VI-S, VII-S and VIII-S could replace both recombinant human brain tau352 (tau-23) and tau441 (tau-40) from DNA. Thus, tau appears to bind to DNA reversibly in the presence of histones.

Animals↗
PubMed2002

Pharmacological targets to inhibit Alzheimer neurofibrillary degeneration.

Neurofibrillary degeneration appears to be required for the clinical expression of Alzheimer disease (AD) and related tauopathies. Given the polyetiology of these diseases and the pivotal involvement of neurofibrillary degeneration in their pathogenesis, inhibition of this lesion offers a promising therapeutic target. Studies from our laboratories have shown that there is a protein phosphorylation/dephosphorylation imbalance and that the microtubule associated protein tau is abnormally hyperphosphorylated in the brain of patients with AD and in this form it is the major protein subunit of paired helical filaments/neurofibrillary tangles (PHF/NFT). The abnormal tau which is polymerized into PHF/NFT neither promotes or inhibits in vitro microtubule assembly. In contrast the cytosolic abnormally hyperphosphorylated tau from AD brain, the AD P-tau neither associates with tubulin nor promotes in vitro microtubule assembly but instead it sequesters normal tau, MAP1 and MAP2 and inhibits microtubule assembly. The AD P-tau readily self-assembles in vitro into tangles of PHF/straight filaments under physiological conditions of protein concentration, pH, ionic strength and reducing conditions and this self assembly requires the abnormal hyperphosphorylation of this protein. The activity of phosphoseryl/phosphothreonyl protein phosphatase (PP)-2A which regulates the phosphorylation of tau, is compromised in AD brain. Thus, modulation of the activities of protein phosphatase-2A and tau kinases and inhibition of the sequestration of normal MAPs by AD P-tau offer promising therapeutic opportunities to inhibit neurofibrillary degeneration and the diseases characterized by this lesion.

Aged↗
PubMed2001

Absolute measurements and theoretical calculations of photoionization cross sections along the isonuclear sequence of multiply charged barium ions.

Photoionization of multiply charged ions of the Ba isonuclear sequence up to Ba6+ has been studied in a beam-beam experiment. A very strong increase in the resonance structures was observed when moving from Ba2+ to Ba6+. Absolute values of the photoionization cross sections were measured for Ba2+ and Ba3+ ions. The interpretation of the results is provided using theoretical multiconfiguration Dirac-Fock and relativistic random phase approximation calculations, showing that the collapse of the nf orbitals occurs for Ba4+.

Journal Article↗
PubMed2001

Dynamical relativistic effects in photoionization: spin-orbit-resolved angular distributions of xenon 4d photoelectrons near the Cooper minimum.

Two decades ago, it was predicted [Y. S. Kim et al., Phys. Rev. Lett. 46, 1326 (1981)] that relativistic effects should alter the dynamics of the photoionization process in the vicinity of Cooper minima. The present experimental and theoretical study of the angular distributions of Xe 4d(3/2) and 4d(5/2) photoelectrons demonstrates this effect for the first time. The results clearly imply that relativistic effects are likely to be important for intermediate- Z atoms at most energies.

Journal Article↗
PubMed2001

Evaluation of Acetaminophen tablets by control test.

Various pharmacopoeial and non-pharmacopoeial control test applied to Acetaminophen tablets were used to evaluate for the uniformity of weight, diameter, thickness, medicaments, hardness and friability. The tests were intended to check the compliance of the prepared tablets with the accepted specifications.

Journal Article↗
PubMed2000

Mechanism of neurofibrillary degeneration and pharmacologic therapeutic approach.

Neurofibrillary degeneration is a key histopathological brain lesion of Alzheimer disease (AD) and related neurodegenerative disorders such as frontotemporal dementia and Parkinsonism linked to chromosome 17 (FTDP-17), commonly referred to as tauopathies. Microtubule associated protein (MAP) tau, which is a major MAP of a normal mature neuron is abnormally hyperphosphorylated in tauopathies and is the major protein subunit of paired helical filaments (PHF)/straight filaments (SF) which accumulate in the soma (as neurofibrillary tangles) and dystrophic neurites (as neuropil threads and as dystrophic neurites surrounding the beta-amyloid core in neuritic plaques in AD) of the affected neurons. Unlike normal tau which stimulates assembly and stabilizes microtubules, the abnormally hyperphosphorylated tau inhibits assembly and disrupts microtubules. The abnormally hyperphosphorylated tau competes with tubulin/microtubules in associating with normal tau, MAP1 and MAP2. This sequestration of normal MAPs by the abnormal tau results in the breakdown of the microtubules. The association of the abnormal tau with normal tau and not with MAP1 or MAP2 results in the formation of tangles of tau filaments. All these toxic properties of the abnormally hyperphosphorylated tau are eliminated by its enzymatic dephosphorylation. Activities of phosphoseryl/phosphothreonyl protein phosphatases (PP)-2A and PP-1 which can dephosphorylate the abnormal tau to a normal-like state are compromised in AD brain. Dephosphorylation by PP-2A and PP-2B and to a lesser extent by PP-1 restores the normal microtubule assembly promoting activity in AD P-tau in vitro. Neurofibrillary tangles of PHF isolated from AD brain are also dissociated on in vitro dephosphorylation with PP-2A, and the tau released by this treatment can stimulate microtubule assembly. Thus, it appears that the abnormal hyperphosphorylation of tau leads to neurodegeneration through breakdown of the microtubule network and that the abnormal tau on association with normal tau forms neurofibrillary tangles of tau filaments i.e. PHF/SF. Increase in tau phosphatase activity is a promising approach to inhibit neurofibrillary degeneration and thereby the diseases characterized by this lesion.

Alzheimer Disease↗
PubMed2000

Auditory evoked potentials to spectro-temporal modulation of complex tones in normal subjects and patients with severe brain injury.

In order to assess higher auditory processing capabilities, long-latency auditory evoked potentials (AEPs) were recorded to synthesized musical instrument tones in 22 post-comatose patients with severe brain injury causing variably attenuated behavioural responsiveness. On the basis of normative studies, three different types of spectro-temporal modulation were employed. When a continuous 'clarinet' tone changes pitch once every few seconds, N1/P2 potentials are evoked at latencies of approximately 90 and 180 ms, respectively. Their distribution in the fronto-central region is consistent with generators in the supratemporal cortex of both hemispheres. When the pitch is modulated at a much faster rate ( approximately 16 changes/s), responses to each change are virtually abolished but potentials with similar distribution are still elicited by changing the timbre (e.g. 'clarinet' to 'oboe') every few seconds. These responses appear to represent the cortical processes concerned with spectral pattern analysis and the grouping of frequency components to form sound 'objects'. Following a period of 16/s oscillation between two pitches, a more anteriorly distributed negativity is evoked on resumption of a steady pitch. Various lines of evidence suggest that this is probably equivalent to the 'mismatch negativity' (MMN), reflecting a pre-perceptual, memory-based process for detection of change in spectro-temporal sound patterns. This method requires no off-line subtraction of AEPs evoked by the onset of a tone, and the MMN is produced rapidly and robustly with considerably larger amplitude (usually >5 microV) than that to discontinuous pure tones. In the brain-injured patients, the presence of AEPs to two or more complex tone stimuli (in the combined assessment of two authors who were 'blind' to the clinical and behavioural data) was significantly associated with the demonstrable possession of discriminative hearing (the ability to respond differentially to verbal commands, in the assessment of a further author who was blind to the AEP findings). Behavioural and electrophysiological findings were in accordance in 18/22 patients, but no AEPs could be recorded in two patients who had clear behavioural evidence of discriminative hearing. The absence of long-latency AEPs should not, therefore, be considered indicative of complete functional deafness. Conversely, AEPs were substantially preserved in two patients without behavioural evidence of discriminative hearing. Although not necessarily indicative of conscious 'awareness', such AEP preservation might help to identify sentient patients who are prevented by severe motor disability from communicating their perception.

Acoustic Stimulation↗
PubMed2000

Dissolution rate studies on Acetaminophen tablets.

The effect of disintegrants on the dissolution rate of Acetaminophen tablets at different hardness has been investigated. It was determined that the dissolution rate is influenced by disintegrants as well as hardness for all formulations except in tablets containing Veegum as the disintegrant.

Journal Article↗
PubMed1999

Regulation of expression, phosphorylation and biological activity of tau during differentiation in SY5Y cells.

Tau, one of the best characterized microtubule-associated proteins (MAPs), is a phosphoprotein, the biological activity of which is regulated by its degree of phosphorylation. The objective of the present study was to evaluate the regulation, phosphorylation and the biological activity of tau during differentiation. On differentiation, the tau/tubulin ratio increased about 3-fold regardless whether cells were optimally differentiated with retinoic acid and aphidicolin or with retinoic acid alone which does not inhibit proliferation. The phosphorylation at the Tau-1 (Ser-195/Ser-198/Ser-199/Ser-202) and PHF-1 (Ser-396/Ser-404) sites was increased, mostly in the retinoic acid treated cells, whereas phosphorylation of tau at the 12E8 (Ser-262/Ser-356) epitope was decreased in both groups by approximately 60%. Phosphorylation at the 12E8 site is thought to be one of the most prominent factors affecting the biological activity of tau. However, the microtubule binding activity of tau increased only slightly upon differentiation. Furthermore, a large part of the tau that bound to taxol-stabilized microtubules was phosphorylated at all three sites indicating that these sites are not major sites determining the biological activity of tau. These data show that differentiation of SY5Y cells results in increased tau levels rather than dephosphorylation of tau to meet the additional need in tau's biological activity.

Cell Differentiation↗
PubMed1999

Corticospinal function in severe brain injury assessed using magnetic stimulation of the motor cortex in man.

We have assessed corticospinal function in 19 post-coma patients severely brain-injured by anoxia or physical trauma. Eleven patients were unresponsive (Category 1) and eight demonstrated minimal, non-verbal responses to simple commands (Category 2). Motor evoked potentials (MEPs) could be elicited in hand and leg muscles in nine Category 1 and all eight Category 2 patients in response to transcranial magnetic stimulation (TMS). In comparison with normal subjects, threshold to TMS was significantly elevated in Category 1 but not in Category 2. Central conduction times were within the normal range except for two patients (one in each category) in whom they were prolonged. The variability in MEP amplitude to constant TMS was not significantly different from normal in either category. The size of MEPs recorded simultaneously in different hand muscles were correlated in all three groups. The presence of H-reflexes in hand muscles was associated with an absence of MEPs or a high threshold to TMS. Variability of MEPs was substantially greater than that of H-reflexes. We conclude that brain injury of a severity that may preclude consciousness and voluntary movement does not invariably predicate a non-functional motor cortex and corticospinal system.

Adult↗
PubMed1999

Growth from spores of nonproteolytic Clostridium botulinum in heat-treated vegetable juice.

Unheated spores of nonproteolytic Clostridium botulinum were able to lead to growth in sterile deoxygenated turnip, spring green, helda bean, broccoli, or potato juice, although the probability of growth was low and the time to growth was longer than the time to growth in culture media. With all five vegetable juices tested, the probability of growth increased when spores were inoculated into the juice and then heated for 2 min in a water bath at 80 degrees C. The probability of growth was greater in bean or broccoli juice than in culture media following 10 min of heat treatment in these media. Growth was prevented by heat treatment of spores in vegetable juices or culture media at 80 degrees C for 100 min. We show for the first time that adding heat-treated vegetable juice to culture media can increase the number of heat-damaged spores of C. botulinum that can lead to colony formation.

Beverages↗