Biomedical subjects

N Ali

Publications and source records attributed to N Ali.

At least 73 records · Page 4Linked to original sources

PubMed1999

A case for comprehensive antenatal screening for blood group antibodies.

OBJECTIVES: To determine the frequency of various blood group antibodies responsible for haemolytic disease of the new born (HDN). DESIGN: A prospective study of all neonates and still born foetuses suspected to have haemolytic disease of the new born and their mothers. SUBJECTS: Neonates suspected to have HDN as per study criteria along with their mothers and mothers of still born foetuses with hydrops foetalis. METHODS: Pertinent serological tests, serum bilirubin estimation, haemoglobin estimation and reticulocyte count on neonate's blood samples and demonstration/titration of blood group specific antibodies in maternal blood samples. RESULTS: Six cases of HDN due to blood group antibodies were detected so far. Four were due to anti-D and all were of mild severity as per study criteria. Two cases were of severe haemolytic disease (hydrops foetalis). Both were due to anti Kell. Both women had history of previous blood transfusion and abortions. CONCLUSION: Comprehensive antibody screening should be performed during antenatal period in women who have received blood transfusion and/or have history of un-explained abortions.

Blood Group Incompatibility↗

PubMed1998

Complete sequence of the IncPbeta plasmid R751: implications for evolution and organisation of the IncP backbone.

The broad host range IncP plasmids are of particular interest because of their ability to promote gene spread between diverse bacterial species. To facilitate study of these plasmids we have compiled the complete sequence of the IncPbeta plasmid R751. Comparison with the sequence of the IncPalpha plasmids confirms the conservation of the IncP backbone of replication, conjugative transfer and stable inheritance functions between the two branches of this family. As in the IncPalpha genome the DNA of this backbone appears to have been enriched for the GCCG/CGGC motifs characteristic of the genome of organisms with a high G+C content, such as P. aeruginosa, suggesting that IncPbeta plasmids have been subjected during their evolution to similar mutational and selective forces as IncPalpha plasmids and may have evolved in pseudomonad hosts. The IncP genome is consistently interrupted by insertion of phenotypic markers and/or transposable elements between oriV and trfA and between the tra and trb operons. The R751 genome reveals a family of repeated sequences in these regions which may form the basis of a hot spot for insertion of foreign DNA. Sequence analysis of the cryptic transposon Tn4321 revealed that it is not a member of the Tn21 family as we had proposed previously from an inspection of its ends. Rather it is a composite transposon defined by inverted repeats of a 1347 bp IS element belonging to a recently discovered family which is distributed throughout the prokaryotes. The central unique region of Tn4321 encodes two predicted proteins, one of which is a regulatory protein while the other is presumably responsible for an as yet unidentified phenotype. The most striking feature of the IncPalpha plasmids, the global regulation of replication and transfer by the KorA and KorB proteins encoded in the central control operon, is conserved between the two plasmids although there appear to be significant differences in the specificity of repressor-operator interactions. The importance of these global regulatory circuits is emphasised by the observation that the operator sequences for KorB are highly conserved even in contexts where the surrounding region, either a protein coding or intergenic sequence, has diverged considerably. There appears to be no equivalent of the parABCDE region which in the IncPalpha plasmids provides multimer resolution, lethality to plasmid-free segregants and active partitioning functions. However, we found that the continuous sector from co-ordinate 0 to 9100 bp, encoding the co-regulated klc and kle operons as well as the central control region, could confer a high degree of segregational stability on a low copy number test vector. Thus R751 appears to exhibit very clearly what was first revealed by study of the IncPalpha plasmids, namely a fully functional co-ordinately regulated set of replication, transfer and stable inheritance functions.

Amino Acid Sequence↗

PubMed1998

Vasopressin-induced activation of protein kinase C in renal epithelial cells.

Recent studies indicate that the actions of arginine vasopressin (AVP) and other agonists that stimulate electrogenic sodium transport in renal epithelial A6 cells are linked to a Ca(2+)-mobilizing signal transduction mechanism that involves generation of inositol trisphosphate. Since diacylglycerol is the other product in this pathway, studies were performed to determine the possible role of PKC in the stimulation of sodium transport. AVP induced a biphasic increase in diacylglycerol generation, characterized by an initial rapid rise and then a sustained elevation, and PKC activation, reflected by phosphorylation of a specific 80 kDa myristoylated alanine-rich PKC substrate (MARCKS). To determine the PKC isoform(s) involved in this process, immunoblot analysis was performed using antisera that recognize both classical PKC isoforms, XPKC-I and XPCK-II, cloned from Xenopus oocytes. The transcripts of both isoforms were expressed in the A6 cell. Since protein recognized by antisera was translocated from cytosol to the particulate fraction after exposure to AVP, one or both isoforms were activated in the A6 cell. Further studies showed that cyclohexyladenosine and insulin, additional agonists of sodium transport in A6 cells, also stimulated phosphorylation of MARCKS. These results argue that Ca(2+)-dependent PKC is involved in the action of AVP, and that of other agonists, which stimulate sodium transport.

Adenosine↗

PubMed1998

Formation of 8-oxodeoxyguanosine in brain DNA of rats exposed to acrylonitrile.

Acrylonitrile (ACN) produces tumors in rats, particularly gliomas of the brain, but tests for genotoxicity have yielded mixed results and no ACN-DNA adducts have been identified in the brain. To examine the possibility that ACN-related brain tumors were not a consequence of binding of ACN to brain DNA, experiments were conducted to investigate possible epigenetic mechanisms. Male Sprague-Dawley rats were exposed to 0, 3, 30, and 300 ppm ACN in drinking water for 21 days, a range that includes doses associated with brain tumorigenesis. In the 30 and 300 ppm ACN groups, 8-oxodeoxyguanosine (8-oxodG) levels were two fold greater than in the controls. Measures of glutathione levels, glutathione peroxidase and catalase were not significantly changed, but cyst(e)ine was somewhat increased. No changes were found in brain cytochrome oxidase activity, which indicates a lack of metabolic hypoxia. Also, no effects on thiobarbituric acid reactive substances were found, indicating a lack of lipid peroxidation. In an additional experiment, male Sprague-Dawley rats were exposed to 0 or 100 ppm ACN in drinking water for 94 days; interim sacrifices were conducted at 3, 10, and 31 days. Levels of brain nuclear DNA 8-oxodG were significantly increased in ACN-exposed rats compared with controls. Another group of animals were given weekly i.v. injections of 5 mg/kg methylnitrosurea and no increases in 8-oxodG were found. These studies suggest the possibility that ACN-induced tumors may be produced by a mode of action involving 8-oxodG. The formation of 8-oxodG is not understood, but does not appear to involve lipid peroxidation or disruption of antioxidant defenses.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed1998

Endothelial nitric oxide synthase exon 7 polymorphism, ischemic cerebrovascular disease, and carotid atheroma.

BACKGROUND AND PURPOSE: The role of endothelial nitric oxide synthase (eNOS) in normal physiology suggests that it could be a potential candidate gene for stroke. Reduced eNOS activity could mediate an increased stroke risk through hypertension or independent of hypertension through abnormal vasomotor responses, promoting atherogenesis, or increased platelet adhesion and aggregation. Recently, a common polymorphism in exon 7 of the eNOS gene (894G-->T) has been reported to be a strong risk factor for coronary artery disease. We determined whether it was also a risk factor for transient ischemic attack (TIA) and ischemic stroke and for carotid atheroma. METHODS: We studied 361 consecutive white patients presenting with ischemic stroke or TIA to a neurological cerebrovascular disease service and 236 normal white controls. In all patients CT and/or MR head imaging and high-resolution carotid duplex ultrasound were performed. The presence of the polymorphism (N/n) was determined by polymerase chain reaction and restriction with the enzyme BanII. RESULTS: There was no difference in the frequency of the NN genotype between patients and controls (13.0% versus 15.3%; P=0.44) or in N allele frequency (39% versus 37%; P=0.57). There was no association with genotype when only patients with stroke (excluding those with TIA) or when only individuals aged < or =65 years were considered. In contrast, there was a highly significant independent association between cerebrovascular disease and hypertension (odds ratio, 2.87; 95% CI, 2.0 to 4.15; P<0.00001), smoking (odds ratio, 2.58; 95% CI, 1.80 to 3.70; P<0.00001), and diabetes (odds ratio, 2.68; 95% CI, 1.38 to 5.24; P=0.004). There was no relationship between the polymorphism and any particular stroke subtype: large-vessel disease, for NN, 15 of 105 (14.3%); lacunar disease, 10 of 75 (13.3%); cardioembolic and unknown, 18 of 151 (11.9%); and tandem pathology, 4 of 30 (13.3%) (P=0.68, chi2). There was no difference in the mean degree of carotid stenosis between the 3 genotypes: NN, 31.1% (SD, 27.1); Nn, 30.1% (29.0); and nn, 31.2% (26.3) (P=0.9). There was no association between the NN genotype or the N allele and hypertension. CONCLUSIONS: We failed to find a relationship between this exon 7 polymorphism and ischemic cerebrovascular disease. In particular, it was not associated with stroke and TIA secondary to large-vessel atherosclerosis or with the degree of carotid stenosis in patients with cerebrovascular disease. It is unlikely that this particular polymorphism or any closely linked polymorphism is a major risk factor in the majority of white patients with stroke.

Aged↗

PubMed1998

Isotype profiles of Leishmania donovani-infected BALB/c mice: preferential stimulation of IgG2a/b by liposome-associated promastigote antigens.

Leishmaniasis presents a complex spectrum of diseases and immunological manifestations depending upon both the species of the microorganism and the host it infects. BALB/c mice, which are homozygous for Lsh(s) on chromosome 1, are genetically susceptible to the visceralizing species of Leishmania. Infection of these mice with an Indian strain of Leishmania donovani showed a steady rise in the level of parasite burden in both the liver and the spleen to 24 wk. To investigate the immune responses determining the course of infection, we studied the relative levels of specific IgG, IgM, and IgA antibodies, and IgG isotypes, in the sera of diseased and protectively immunized mice at different periods of infection. IgG1 and IgG2a were stimulated in the control, infected, and immunized mice after parasite challenge. However, an early induction of IgG1 in the normal infected mice and stimulation of IgG2a and IgG2b isotypes prior to parasite challenge in liposome-antigen-immunized mice suggest that the elicitation of a particular subset of CD4+ T cells at the onset of disease may be responsible for either progression or resolution of infection.

Animals↗

PubMed1997

Identification and characterization of MARCKS in Xenopus laevis.

MARCKS proteins are widely distributed in mammalian cells and subserve an important role as probes in the examination of signal transduction processes because they are specific endogenous phosphoreceptors for activated protein kinase C. Experiments were performed to determine whether MARCKS proteins are present in amphibia and to show their usefulness as substrates for stimulated PKC activation, using cultured renal epithelial cells (A6) derived from Xenopus laevis as an experimental model.

Animals↗

PubMed1997

The La antigen binds 5' noncoding region of the hepatitis C virus RNA in the context of the initiator AUG codon and stimulates internal ribosome entry site-mediated translation.

Translation initiation of the hepatitis C virus (HCV) RNA genome occurs through an internal ribosome entry site in a cap-independent manner. Here, we have examined the interaction between La antigen and the HCV 5' noncoding region (5'NCR). In this analysis, competitor RNAs derived from HCV 5'NCR carrying deletions and a point mutation were used to identify the site(s) of La antigen binding during UV cross-linking assay. These studies suggest that La antigen recognizes the intact HCV 5'NCR structure. Further, these interactions occurred in the context of the initiator AUG. The latter view is supported by an analysis in which mutants of the HCV 5'NCR RNA with deletion or substitution in the initiator AUG codon failed to compete for La antigen binding to the wild-type 5'NCR. The evidence for the interaction between liver cell-derived La antigen and the HCV 5'NCR is provided by immunoprecipitation of a UV cross-linked species from the S100 fraction of Huh7 cell lysates. The functional relevance of this interaction was demonstrated by the stimulation of the HCV internal ribosome entry site-mediated translation in the presence of La protein. These results suggest an important functional role of La protein in the regulation of internal initiation of translation of the HCV RNA genome.

Autoantigens↗

PubMed1997

Research on the schizont cell culture vaccine against Theileria annulata infection in Xinjiang, China.

Theileria annulata infection (TAI) is one of the most serious diseases of cattle in Xinjiang Autonomous Region of Uigur Minority Nationality. It has been recorded in 14 prefectures, except the Tulufan Prefecture, but the enzootic areas are mainly distributed around the Zhunger Basin and Talim Basin. According to the records collected in the ten years before vaccination with the schizont cell culture vaccine was carried out, the average incidence rate of TAI in enzootic areas was 7.22% and the mortality rate was 24%. The milk production of cattle suffering from TAI was sharply decreased, and there were usually abortions in pregnant cows. The incidence rate and mortality rate were greater in high grade cattle, so TAI was a constraint to improving cattle breeds. To control this disease effectively in Xinjiang, researchers at the Xinjiang Academy of Animal Science began to study the schizont cell culture vaccine in 1972. In 1977 an immortalised cell line was achieved from a primary cell culture starting with white blood cells from cattle suffering from acute TAI caused by an artificial tick bite. The cell culture medium mainly consisted of calf serum, lactalbumin-hydrolysate, Eagles' medium DMEM and three antibiotics. As a vaccine, the above cells were mixed with preserving medium containing gelatin. This paper describes the experiments on the immunological properties of the vaccine carried out in subsequent years. Up to 1996, vaccine doses for 1,186,150 cattle have been produced and sold. This vaccine has had a critical effect on the control of TAI in Xinjiang. Owing to the sharp decrease in the incidence rate and mortality rate of TAI after cattle were vaccinated, the annual economic benefit of the vaccine is at least 1,620,000 yuan.

Animals↗

PubMed1997

Identification of hibernating myocardium: comparative accuracy of myocardial contrast echocardiography, rest-redistribution thallium-201 tomography and dobutamine echocardiography.

OBJECTIVES: We sought to evaluate the comparative accuracy of myocardial contrast echocardiography (MCE), quantitative rest-redistribution thallium-201 (Tl-201) tomography and low and high dose (up to 40 microg/kg body weight per min) dobutamine echocardiography (DE) in identifying myocardial hibernation. BACKGROUND: Myocardial contrast echocardiography can assess myocardial perfusion and may therefore be useful in predicting myocardial hibernation. However, its accuracy in comparison to myocardial perfusion scintigraphy and to that of high dose DE remains to be investigated. METHODS: Eighteen patients (aged [+/- SD] 57 +/- 10 years) with stable coronary artery disease and ventricular dysfunction underwent the above three modalities before coronary revascularization. Myocardial contrast echocardiography was achieved with intracoronary Albunex. Rest echocardiographic and Tl-201 studies were repeated > or = 6 weeks after revascularization. RESULTS: Of 109 revascularized segments with severe dysfunction, 46 (42%) improved. Left ventricular ejection fraction increased from 38 +/- 14% to 45 +/- 13% at follow-up (p = 0.003). Rest Tl-201 uptake and the ratio of peak contrast intensity of dysfunctional to normal segments with MCE were higher (p < 0.01) in segments that recovered function compared with those that did not. Myocardial contrast echocardiography, thallium scintigraphy and any contractile reserve during DE had a similar sensitivity (89% to 91%) with a lower specificity (43% to 66%) for recovery of function. A biphasic response during DE was the most specific (83%) and the least sensitive (68%) (p < 0.01). The best concordance with MCE was Tl-201 (80%, kappa 0.57). Changes in ejection fraction after revascularization related significantly to the number of viable dysfunctional segments by all modalities (r = 0.54 to 0.65). CONCLUSIONS: In myocardial hibernation, methods evaluating rest perfusion (MCE, Tl-201) or any contractile reserve have a similar high sensitivity but a low specificity for predicting recovery of function. A limited contractile reserve (biphasic response) increases the specificity of DE. Importantly, the three techniques identified all patients who had significant improvement in global ventricular function.

Aged↗

PubMed1997

Hemispheric lateralization of perception and memory for emotional verbal stimuli in normal individuals.

The purposes of this study were to extend the literature on lateralization of perception of emotional verbal stimuli in normal individuals, including a test of both the right hemisphere and valence models, and to investigate predictions from these models regarding lateralization of memory for emotional verbal stimuli in normal individuals, an area that, to our knowledge, has not been investigated. Seventy-nine undergraduates were presented lateralized positive, negative, and neutral English words and nonwords. Participants were then asked to freely recall the presented words and, after a 20-min delay, to recognize the words. Recognition memory data provided strong support for the valence model. In addition, free-recall and perception data provided partial support for this model. The literature on the lateralization of processing emotional verbal and nonverbal material is discussed.

Adult↗

PubMed1997

High salt and solvent induced Z-conformation in native calf thymus DNA.

The Z-DNA forming potentiality of native calf thymus DNA using spectrophotometric measurements and diethyl pyrocarbonate reactivity have been investigated. The Z value was evaluated from absorbance ratio for B- and Z-DNA and compared with the values obtained for native DNA. The results suggest that native DNA undergoes B- to Z-/Z-analogous transition to an extent of 20 per cent under constraint conditions. Possible Z-DNA formation was also characterized by hyper-reactivity of native DNA towards diethyl pyrocarbonate in aqueous solvent. The thermal melting profile of native and modified DNA and nuclease S1 digestibility data, in addition, reflects B- to Z-/Z-analogous transition in native DNA.

Animals↗

PubMed1997

The effect of repeated-dose activated charcoal on the pharmacokinetics of sodium valproate in healthy volunteers.

AIMS: We investigated the effects of repeated-dose charcoal administered several hours after sodium valproate on the pharmacokinetics of a single dose of the drug in healthy volunteers. METHODS: The pharmacokinetics of sodium valproate were studied in seven healthy volunteers after administration of a syrup (300 mg) on two occasions, one of which was followed by administration of repeated doses of oral charcoal starting 4 h after the drug up to 32 h (total dose 80 g). RESULTS: Valproate was rapidly absorbed with maximum concentrations 1 h after administration. The area under the plasma concentration-time curve to 48 h (AUC (0.48 h)) was 408 +/- 114.5 (s.d.) mg l-1 h in the control phase and 398 +/- 108.6 mg l-1 h after charcoal and the t1/2 elimination was 20 +/- 6.8 h in the control phase, and 22 +/- 9.2 h after charcoal (NS). CONCLUSIONS: Repeated-dose activated charcoal does not appear to enhance the rate of elimination of sodium valproate after therapeutic doses of the drug and any beneficial effect of charcoal in overdose may be to prevent absorption of valproate still present in the gut.

Adult↗

PubMed1997

Adjuvanticity and protective immunity elicited by Leishmania donovani antigens encapsulated in positively charged liposomes.

In the search for a leishmaniasis vaccine, extensive studies of cutaneous leishmaniasis have been carried out. Investigations in this regard with the visceral form are limited. As an initial step in the identification of the protective molecules, leishmanial antigens extracted from the membranes of Leishmania donovani promastigotes, alone or in association with liposomes, were evaluated for their immunogenicity and ability to elicit a protective immune response against challenge infection. Intraperitoneal immunization of hamsters and BALB/c mice with the leishmanial antigens conferred protection against infection with the virulent promastigotes. Encapsulation in positively charged liposomes significantly enhanced the protective efficacy of these antigens. The splenic parasite burden of hamsters was reduced by 97% after 6 months of infection. BALB/c mice exhibited 87 and 81.3% protection in the liver and spleen, respectively, after 4 months of infection. These protected animals elicited profound delayed-type hypersensitivity and increased levels of Leishmania-specific immunoglobulin G (IgG) antibodies. Protection in mice also coincided with elevated levels of IgM and IgA antibodies, which decreased with disease progression in the control-infected animals. Although both IgG1 and IgG2a antibodies were present in the sera of infected mice, IgG1 appeared to be the predominant isotype, suggesting a preferential induction of the Th2 type of immune response over that of Th1. Effective stimulation of all the IgG isotypes, particularly IgG2a, after immunization with liposome encapsulated antigens seems to be responsible for the significant levels of resistance against the disease. Taken together, these data indicate a potential for the liposomal antigens as a vaccine which could trigger both humoral and cell-mediated immune responses.

Animals↗

PubMed1997

A common polymorphism in the methylenetetrahydrofolate reductase gene, homocysteine, and ischemic cerebrovascular disease.

BACKGROUND AND PURPOSE: A common polymorphism (T/t) in the gene encoding the methylenetetrahydrofolate reductase (MTHFR) enzyme has been associated with elevated serum homocysteine, itself a risk factor for stroke. Some studies have reported an association with ischemic heart disease, but no published studies have examined its relationship with stroke. METHODS: We determined the TT genotype frequency and T allele frequency in 345 patients with ischemic cerebrovascular disease (CVD) and 161 control subjects. In a subgroup we also determined serum homocysteine and folate concentrations. RESULTS: In the patient group there was a significant relationship between TT genotype and homocysteine concentration after we controlled for other risk factors. Controlling for serum folate weakened this relationship, and folate itself was independently related to serum homocysteine. There was no difference between patients and control subjects in either TT genotype frequency (10.7% versus 13.7%; P = .34) or T allele frequency (0.68 versus 0.67; P = .67). There was no association when analysis was limited to individuals deficient in folate (serum folate < 25th centile) or to younger individuals (< 65 years). There was no association between TT genotype and any stroke subtype or with degree of carotid stenosis. CONCLUSIONS: In patients with CVD we confirmed a relationship between the MTHFR genotype and serum homocysteine concentration and an interaction with serum folate concentration. We found no association between CVD and genotype. However, the interaction with serum folate suggests that the genotype could still be a risk factor in populations with a low folic acid intake.

Aged↗

PubMed1997

HTLV-I seroprevalence in the Sultanate of Oman.

2329 subjects (blood donors and patients) from various areas of the Sultanate of Oman were investigated for the presence of HTLV-I antibody by as enzyme immunoassay (EIA) method. 10 subjects (0.4%), including 9/1586 blood donors (0.6%) and 1/165 patients with sexually transmitted diseases (0.6%), were found to be EIA seropositive with a regional variation in seroprevalence of 0-14%. 6/9 EIA seropositive samples from blood donors yielded 'indeterminate' results on Western immunoblot analysis (WBA). A much larger survey with additional confirmatory assays such as a radioimmunoprecipitation assay (RIPA), should provide a more conclusive picture of the prevalence of this retroviral infection in the Sultanate.

Blood Donors↗

PubMed1997

Protection of mice against visceral leishmaniasis by immunization with promastigote antigen incorporated in liposomes.

Leishmanial antigens (LAg) were used as a vaccine against Leishmania donovani, the causative agent of visceral leishmaniasis. BALB/c mice, immunized intraperitoneally with 20 micrograms of the antigen in phosphate-buffered saline (PBS) or entrapped in liposomes, were infected intravenously with 2 x 10(7) L. donovani promastigotes. Mice immunized with PBS and empty liposomes showed similar levels of parasite burdens in the liver and spleen. Injection of the antigen alone or entrapped in liposomes, followed with infection, induced significant levels of protection against the disease. After 2 and 4 mo of infection, mice immunized with free antigen induced 7.4% and 50.7% reduction in the liver parasite burden, respectively, compared to control (PBS) mice. With antigen encapsulated in liposome, the liver parasite burden was further reduced by 30.4% and 73% at 2 and 4 mo by infection, respectively. Splenic parasite burden was very low at 2 mo of infection. At 4 mo, the parasite level was reduced by 54.2% with free antigen and 69.3% with antigen entrapped in liposomes. Whereas the protection induced by the free antigen is mainly cell mediated, stimulation of an antibody response together with a strong delayed-type hypersensitivity may be responsible for the better protection with liposomal antigen.

Animals↗

PubMed1997

Tachykinergic neurotransmission is enhanced in small intestinal circular muscle in a rabbit model of inflammation.

Previous electrophysiological studies have shown that tachykinin-mediated excitatory junction potentials are enhanced in a ricin model of inflammatory bowel disease. The present study extends these findings by investigating the contractile response to stimulation of noncholinergic nerves and tachykinin agonists. According to rank order potencies, the rabbit ileal circular muscle was neurokinin (NK)1 preferring, and the response to these agonists was down-regulated by acetylcholine and up-regulated by nitric oxide. In ricin-treated tissue, cholinergic and nitridergic modulation was lost; in the presence of atropine and N-nitro-L-arginine methyl ester, or tetrodotoxin, the response to NK1 and NK2 agonists was enhanced. The noncholinergic response to nerve stimulation was predominantly mediated by NK1 receptors, and the enhanced response of ricin-treated tissue to NK1 agonists probably contributes to the increased response to electrical field stimulation observed under these conditions. Increased tachykinin response and loss of control of this response by acetylcholine and nitric oxide are likely to have profound effects on intestinal motility and could contribute to some of the symptomology of inflammatory bowel disease.

Acetylcholine↗