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Biomedical subjects

A Rehman

Publications and source records attributed to A Rehman.

At least 55 records · Page 3Linked to original sources
PubMed1997

Scavenging of hydroxyl radicals but not of peroxynitrite by inhibitors and substrates of nitric oxide synthases.

1. The nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) is widely used to study the role of NO. in physiological and pathological processes, including its role in the generation of the cytotoxic species peroxynitrite (ONOO-) and of reactive oxygen radicals such as hydroxyl (OH.). Often L-NAME is applied to tissues at mM concentrations. At such high concentrations, it might act as a free radical scavenger. A similar possibility might apply to the use of high levels of arginine to study the role of NO. in atherogenesis. 2. We therefore examined the rate of scavenging of OH. by L-NAME and found that L-NAME reacts more quickly with OH. than the established 'OH. scavenger' mannitol and the widely used 'OH. trap' salicylate. However, D-NAME can scavenge OH. at rates equal to L-NAME. Both L- and D-arginine were also good OH. scavengers, comparable in effectiveness to mannitol. 3. Neither L-NAME, D-NAME, L-arginine nor D-arginine was able to inhibit ONOO(-)-dependent nitration of tyrosine, suggesting that they are unlikely to be scavengers of ONOO(-)-derived nitrating species. 4. Neither L-NAME, D-NAME, L-arginine nor D-arginine was able to inhibit the inactivation of alpha 1-antiproteinase by ONOO-, suggesting that they cannot prevent direct oxidations by peroxynitrite. 5. We conclude that L-NAME has sufficient activity as an OH. scavenger to confound certain pharmacological experiments. However, this explanation of its biological effects can be ruled out if control experiments show that D-NAME has no effect and that L-arginine (also a free radical scavenger) antagonizes the action of L-NAME.

Dose-Response Relationship, Drug↗
PubMed1997

Clinicoepidemiological features of adult leukemias in Pakistan.

A total of 113 patients of leukemia, over 15 years of age, were seen in three different institutions from July, 1992 to June, 1994. There was an almost equal distribution of acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) (44 vs 43 cases respectively). Chronic lymphocytic leukemia (CLL) was the least common, accounting for 5% of all cases. Mean age in CLL was 59 years. Chronic myeloid leukemia (CML) was three times commoner than CLL with a younger age distribution (median age was 34 years). We conclude that the clinicoepidemiological features of adult leukemias differ considerably from that seen in the developed world. However, recruitment of patients needs to continue in order to define these features based on a larger patient population.

Acute Disease↗
PubMed1996

The consequences of replacing histidine 356 in isocitrate lyase from Escherichia coli.

Isocitrate lyase from Escherichia coli has been expressed in transformed E. coli JE10 cells lacking the isocitrate lyase (icl) gene. After directed mutagenesis of icl by the restriction-site elimination method, partially purified isocitrate lyase mutants in which His 356 has been converted to Lys, Arg, Gln, Asp, or Leu have been characterized after induction of transformed, induced JE10 cells. Values of kcat compared to those for wild-type (wt) enzyme (100) at 37 degrees C, pH 7.3, are 18, 1, <1, 0, and 0 for H356K, H356R, H356E, H356Q, and H356L mutant enzymes, respectively. Km values for the 1:1 Mg-isocitrate complex (in millimolar units) are: 0.13, wt; 0.11, H356K; and 0.63, H356R. Further chromatographic purification of isocitrate lyase yields highly purified wt, H356K, and H356R enzymes. The pH profile of the stability of isocitrate lyase, which has never been reported, showed that the H356R enzyme was unstable in the pH range investigated; the wt and H356R variant differed but each was sufficiently stable to study the pH dependence of catalysis. The log kcat/pH profiles for highly purified wt and H356K enzymes are roughly bell-shaped and have pKa and pKb values for dissociation of an ionizable group on the enzyme-substrate complex of <6.3 and 8.4 for wt and 5.9 and 7.9 for H356K enzymes. Plots of pKm vs pH were different for the wt and H356K variant. Values of pKa and pKb (derived from log kcat/Km plots vs pH) for the dissociation of an activity-related ionizable group on the variant were 5.3 and 7.6, whereas the analogous pKb value for the wt enzyme was 8.4. The data suggest that His 356 is an important functional residue in isocitrate lyase, perhaps in deprotonating isocitrate during catalytic cleavage.

Amino Acid Sequence↗
PubMed1996

Inhibition by CTLA4Ig of experimental allergic encephalomyelitis.

B7-1 and B7-2 are well characterized costimulatory ligands on Ag presentation cells for the CD28 and CTLA4 receptors on T cells. The fusion protein CTLA4Ig can block this interaction and prevent specific T cell activation. The development of fatal CD4+ T cell-mediated experimental allergic encephalomyelitis (EAE) in susceptible female Lewis rats was optimized by immunization with 20 mg of guinea pig spinal cord homogenate in CFA on day 0 with three doses of 1 microgram pertussis toxin given i.v. on days 0, 3, and 7. This immunization regimen uniformly resulted in the development of severe clinical neurologic signs of EAE with 100% mortality by day 17 postimmunization. Treatment with 0.5 mg/dose of rhCTLA4-Ig on days - 2, 0, 3, 6, 9, 12, 15 and 18 significantly decreased the incidence, delayed the onset, and reduced the severity of clinical EAE (p = 0.0002 vs control by the Mann-Whitney U test) enough to completely prevent fatal EAE, whereas treatment with control human IgG had no effect. Histologically, perivascular neutrophilic infiltrates were also dramatically decreased in the spinal cords of animals treated with CTLA4 but not in those treated with control human IgG. The proliferative response to encephalitogenic Ags (guinea pig myelin basic protein and proteolipid protein) by lymph node cells from animals immunized with guinea pig spinal cord 10 days before was also significantly suppressed in vitro by CTLA4Ig (1 microg/ml). However, the protective effect of CTLA4Ig could be completely prevented by the daily i.p. administration, from day 0 to 10, of exogenous human rIL-2 (180,000 IU). These results indicate a critical requirement of the costimulatory B7/CD28 pathway early in the development of CD4+ T cell-mediated EAE in the rat.

Abatacept↗
PubMed1996

Diabetes in pregnancy in Pakistani women: prevalence and complications in an indigenous south Asian community.

The aim of this study was to determine the prevalence and complications as well as to correlate maternal and fetal outcome with glycaemic control, in a community of Pakistani women. This was a retrospective study of 6830 deliveries over a 5-year period in a tertiary care hospital in Karachi. Either a 75 g glucose tolerance test or a screening 50 g glucose challenge was administered depending on risk factors for Gestational Diabetes Mellitus (GDM). Case records of deliveries during this period were analysed for presence of GDM or pre-existing diabetes; glycaemic control and complications were ascertained for those with diabetes. During this period 267 (3.9%) of the 6380 deliveries were identified as diabetic pregnancies. Of these 223 (3.3%) had GDM and 44 (0.6%) women had pre-existing diabetes mellitus. Overall maternal complications were high; pre-eclampsia (19%), polyhydramnios (4.6%), and threatened abortion (3.4%). Fetal complications of macrosomia (13.1%), intrauterine growth retardation (7.1%), intrauterine deaths (5.3%) were noted. Complications were higher in poorly controlled groups. We conclude that the prevalence of GDM in Pakistani women in our study was comparable to their Western counterparts but complication rates were higher, possibly due to poorer glycaemic control.

Adult↗
PubMed1996

Long-term survival of rat to mouse cardiac xenografts with prolonged blockade of CD28-B7 interaction combined with peritransplant T-cell depletion.

BACKGROUND: The hCTLA4Ig/mCTLA4Ig fusion protein of the extracellular domain of human/mouse CTLA4 and the Fc portion of the human/mouse immunoglobulin G1 block the CD28/B7 costimulatory T-cell activation pathway. We evaluated the effect of prolonged B7-CD28 blockade, T-cell depletion, or both on rat to mouse cardiac xenografts. METHODS: C57BL/6 (H-2b) mice receiving infant Wistar Furth (RT1u) rat cardiac xenografts were treated with anti-CD4 (GK1.5) and anti-CD8 (2.43) monoclonal antibodies (mAb; 0.2 mg intravenous each) on days -2 and 0, hCTLA4Ig or mCTLA4Ig every other day from day 0 until day 14 and then twice a week until day 50 or day 100, or both. Changes in cellular reactivity were assayed by mixed lymphocyte culture and cell-mediated cytotoxicity and the development of cytotoxic antibodies was serially measured after transplantation. RESULTS: Either human CTLA4Ig or murine CTLA4Ig alone led to significant prolongation of rat to mouse cardiac xenografts (median survival time [MST], 22 or 26 days, respectively [p = 0.008], versus control). hCTLA4Ig given for 50 days in combination with two doses of anti-CD4/CD8 monoclonal antibodies further prolonged graft survival (MST, 61 days; p versus control < 0.0001). In this combination, when hCTLA4Ig was continued until day 100, the graft survival was further prolonged (MST, 119 days). mCTLA4Ig for 100 days plus anti-CD4/CD8 similarly prolonged rat xenograft survival (MST, 94 days). However, all cardiac xenografts eventually failed, primarily from humoral rejection. Cytotoxic antibody titers rose rapidly only in animals rejecting a graft, and suppressed cell-mediated immunity had completely recovered in rejecting recipients. CONCLUSIONS: Blockage of the CD28-B7 costimulatory interaction can inhibit both humoral and cell-mediated immune responses and result in the prolonged acceptance of rat to mouse cardiac xenografts. Longer administration of CTLA4Ig and anti-CD4/CD8 monoclonal antibodies further prolongs but does not achieve indefinite survival of rat cardiac xenografts.

Abatacept↗
PubMed1995

Clinical characteristics of adult asthmatics requiring intubation.

Fifty eight admissions for 52 adult asthmatics who required intubation were reviewed for the years of 1988-1995 to examine factors related to specific clinical patterns and profile the course of these patients. Of the 56 admissions where patients were intubated for respiratory failure and/or cyanosis, 5 were associated with significant complications of mechanical ventilation/intubation (pneumothorax, subcutaneous emphysema, aspiration pneumonia, and laryngeal edema) and there were no fatalities. Patients > or = 35 years of age had significantly more profound respiratory acidosis in initial arterial blood gases (pH = 7.14 versus 7.23, p = 0.03). In contrast, patients with a history of drug abuse or psychiatric disorders had lower mean pCO2 (p < = 0.01). The overall mean length of intubation was 17.6 hours, while the overall mean hospital stay was 6.6 days. Longer intubation times were associated with the occurrence of major complications, female gender, and hospital administration of ipratropium. Hospital stay was correlated with length of intubation, later month of admission, and earlier year of admission. Common precipitating factors noted for first admissions were upper respiratory infections (61%), followed by allergy or smoke exposure (13%), compliance related problems (12%), and drug abuse/inhalation (6%). Inhaled anti-inflammatory drugs, oral steroids or either were taken at the time of admission by 35%, 35% and 65% of the patients, respectively. There was an even distribution of patients with respect to medical insurance coverage type, admissions per season or year, ethnicity, marital status, and gender. We conclude that severe asthma resulting in respiratory failure is common despite the frequent use of anti-inflammatory asthma medications. Mechanical ventilatory support can be administered safely in the majority of these patients and should be considered early in acute asthma.

Adult↗
PubMed1994

Rabbit IgG cross-reacts with Alzheimer neurofibrillary tangles.

Biochemical studies have demonstrated that the paired helical filaments (PHF) of Alzheimer neurofibrillary tangles are mostly made up of tau and to a lesser degree of ubiquitin and other proteins. In addition, immunocytochemical labeling of tangles with antibodies to various other neuronal proteins has been shown previously. We report here the labeling of the locations of PHF, i.e., Alzheimer neurofibrillary tangles, neuropil threads and plaque neurites in tissue sections with a goat antiserum to rabbit IgG (GAR-T). The labeling is comparable in strength and distribution to that of tau and ubiquitin antibodies. The PHF-staining antibodies could be removed by absorption with native rabbit IgG but not with human IgG, IgG-depleted rabbit serum, rabbit IgG heavy chains or light chains eluted from nitrocellulose membranes. Furthermore, the PHF reactivity was obliterated by absorption with brain homogenate and a fraction enriched in soluble abnormally phosphorylated tau, but not with purified bovine tau or SDS-washed preparations of the relatively insoluble population of PHF. On immunoblots of both normal human tau and Alzheimer abnormally phosphorylated tau-enriched preparations, GAR-T labeled a set of three to five polypeptides in the tau region. Some of these polypeptides co-migrated with the tau bands. These results indicate (i) that PHF in Alzheimer's disease brain cross-react with a structural epitope/s present on native rabbit IgG, and (ii) that the cross-reactivity with PHF is probably due to tau.

Aged↗
PubMed1991

Quantitation of solid-phase immunoassays using a fibre-optic reflectance spectrophotometer.

A reflectance measuring instrument (fibre-optic spectrometer linked to a personal computer) which will quantitate the results of immunoassays that result in the deposition of a coloured chromophore on a membrane or other similar solid phase (SP) is described and the reflectance spectra of some chromophores which are commonly produced or used in SP immunoassays are presented. The instrument has been used in conjunction with silver-enhanced SP-immunogold capture assays to determine the concentrations in serum of IgG and of IgM rheumatoid factor (RF) and the results have been compared with those obtained by rate nephelometry and latex agglutination assays, respectively. It is concluded that fibre-optic reflectance photometry is an accurate and useful means of quantitating SP immunoassays in which coloured chromophores are produced and that the results obtained from such immunoassays are comparable to those given by established procedures.

Agglutination Tests↗
PubMed1989

Specificity of the interaction of furfural with DNA.

Furfural or 2-furaldehyde is a dietary mutagen and is present in various frequently consumed food products. The alkaline unwinding assay and protection of cleavage sites from the action of various restriction enzymes was used to study the interaction of furfural with DNA. Alkaline unwinding experiments showed the formation of an increasing number of strand breaks in duplex DNA both with increasing furfural concentration and with time of reaction. Treatment of lambda phage DNA with furfural protected cleavage with restriction endonucleases DraI and SspI but not with ApaI, BssHII and SacII. These results indicate that under the conditions used furfural reacts exclusively with AT base pairs. A minimum of 3-4 consecutive AT base pairs are required for this reaction. This was determined by the use of several restriction enzymes whose hexanucleotide recognition sequences contain subsets of AT base pairs.

Base Sequence↗
PubMed1987

Retinal arterial macroaneurysms: a retrospective study of 40 patients.

We studied 40 patients with a total of 44 retinal arterial macroaneurysms. All patients were followed up for at least six months. Macroaneurysms (MAs) have variable clinical presentations and are still frequently misdiagnosed before fluorescein angiography. Haemorrhagic MAs were most frequently misdiagnosed (75%), and had a sudden onset with a relatively poor visual outcome. Patients with these MAs had higher systolic blood pressures and significantly fewer associated retinal vein occlusions (p less than 0.05) than other types of MA. Exudative MAs caused a gradual onset of symptoms, were frequently associated with retinal vein occlusions, and were the most frequent indication for laser treatment. Only one of 10 quiescent MAs subsequently developed significant exudation or haemorrhage. We confirm the association of MAs with retinal and systemic vascular disease. In addition we found that MA patients had a significantly higher blood packed cell volume (haematocrit) than controls (p less than 0.05). Laser treatment significantly shortened the duration of MA patency (p = 0.006).

Aged↗
PubMed1984

Effects of prolonged poisoning by Russell's viper venom on blood coagulation, platelets and fibrinolysis.

The effects of Russell's viper venom on blood coagulation, platelets and the fibrinolytic enzyme system were studied in rabbits after injecting repeated doses of 0.05 MLD of the venom. Thrombocytopenia was the earliest change to appear. It was followed by rise in serum fibrinogen degradation products and prolongation of prothrombin time, activated partial thromboplastin time and thrombin time indicating a progressive consumption coagulopathy and activation of fibrinolysis. Red blood cell morphology was unchanged during the first three weeks; whereas the fragmentation appeared after the fourth week and it increased in severity with further envenomations, i.e. when chronic DIC was established.

Animals↗
PubMed1982

Comparison of isolation methods of urinary organic acids by high-performance liquid chromatography.

Four methods for extracting organic acids from human urine prior to analysis by high-performance liquid chromatography (HPLC) were compared. The methods were manual solvent extraction with ethyl acetate and diethyl ether, continuous solvent extraction, anion exchange with pyridinium acetate as the eluting solvent and anion exchange with hydrochloric acid as the eluting solvent. All four methods produced samples that could be analyzed by reversed-phase HPLC, but the continuous solvent extraction and anion exchange with pyridinium acetate methods gave the best reproducibilities (approximately 6% relative standard deviations). Pretreatment of the urine with barium hydroxide and hydroxylamine hydrochloride prior to anion exchange did not markedly alter the HPLC profiles.

Adult↗