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M R Islam

Publications and source records attributed to M R Islam.

At least 37 records · Page 2Linked to original sources
PubMed1996

beta-Glucuronidase P408S, P415L mutations: evidence that both mutations combine to produce an MPS VII allele in certain Mexican patients.

Mucopolysaccharidosis type VII (MPS VII, Sly syndrome) is an autosomal recessively inherited lysosomal storage disease caused by a deficiency in beta-glucuronidase. We identified and studied a novel allele containing two C-to-T transitions resulting in P408S and P415L alterations, which is present in homozygous state in one Mexican patient and in heterozygous state in another. None of the previous reports describing mutations in the MPS VII gene include Mexican patients. Expression of either of the mutations individually showed only modest effects on the properties of the enzyme. However, expression of the doubly mutant allele resulted in markedly reduced activity and rapid degradation in an early biosynthetic compartment.

Animals↗
PubMed1996

Molecular analysis of patients with beta-glucuronidase deficiency presenting as hydrops fetalis or as early mucopolysaccharidosis VII.

Although not all mucopolysaccharidosis type VII (MPS VII) neonates present with hydrops fetalis or with related symptoms, hydrops fetalis is a common form of presentation of this mucopolysaccharidosis. We used reverse-transcription-PCR-SSCP and direct sequencing to screen for mutations in the human beta-glucuronidase cDNA of 17 MPS VII patients with severe presentation of the disease. Mutations resulting in an unstable mRNA were detected in genomic DNA with direct sequencing of the PCR-amplified beta-glucuronidase exons. We found extensive genetic heterogeneity in MPS VII alleles: in addition to 6 or 12 previously reported mutations (L176F, R216W, R357X, R382C, W507X, and W627C), we detected 14 undescribed mutations in the beta-glucuronidase coding region that produce MPS VII alleles (G136R, E150K, S312X, Y320S, Y320C, H351Y, R382H, R374C, R435P, R477W, G572D, Y508C, K606N and 1900 delta GA). The mutations in hydropic fetuses were widely scattered in the beta-glucuronidase gene. Analysis of three polymorphic sites of the mutant alleles (1766T/C, 1972C/T and a new 1091+27C/G polymorphism) allowed exclusion of identity by descent for some recurrent mutations. Three of four mutations introducing a premature translation stop codon were found to affect mRNA abundance and/or structure. Expression studies provided evidence for the causal relationship between each of the mutations found in MPS VII alleles and the enzyme deficiency, in that all mutations identified exhibited markedly reduced enzyme activity expressed in COS7 cells following transfection with the mutant cDNA.

Adult↗
PubMed1995

A pseudodeficiency allele (D152N) of the human beta-glucuronidase gene.

We present evidence that a 480G-->A transition in the coding region of the beta-glucuronidase gene, which results in an aspartic-acid-to-asparagine substitution at amino acid position 152 (D152N), produces a pseudodeficiency allele (GUSBp) that leads to greatly reduced levels of beta-glucuronidase activity without apparent deleterious consequences. The 480G-->A mutation was found initially in the pseudodeficient mother of a child with mucopolysaccharidosis VII (MPSVII), but it was not on her disease-causing allele, which carried the L176F mutation. The 480G-->A change was also present in an unrelated individual with another MPSVII allele who had unusually low beta-glucuronidase activity, but whose clinical symptoms were probably unrelated to beta-glucuronidase deficiency. This individual also had an R357X mutation, probably on his second allele. We screened 100 unrelated normal individuals for the 480G-->A mutation with a PCR method and detected one carrier. Reduced beta-glucuronidase activity following transfection of COS cells with the D152N cDNA supported the causal relationship between the D152N allele and pseudodeficiency. The mutation reduced the fraction of expressed enzyme that was secreted. Pulse-chase experiments indicated that the reduced activity in COS cells was due to accelerated intracellular turnover of the D152N enzyme. They also suggested that a potential glycosylation site created by the mutation is utilized in approximately 50% of the enzyme expressed.

Alleles↗
PubMed1995

Effect of antimicrobial (nalidixic acid) therapy in shigellosis and predictive values of outcome variables in patients susceptible or resistant to it.

We observed the clinical features and results of simple laboratory tests on stools of 33 children with bacteriologically proven shigellosis to identify features that could be used to assess the effectiveness of antimicrobial therapy. Persistence of fever (rectal temperature > 37.8 degrees C), abdominal pain/tenderness and anorexia on days 3 and 5 were significantly more common (P < 0.001) among children who received an antimicrobial to which the infecting Shigella was resistant. Similarly, a significantly higher number of children treated with an ineffective antimicrobial had faecal leucocytes of > 50/high power microscopic field (HPF), erythrocytes of > 50/HPF and macrophages of > 5/HPF on study day 5. The best predictors of ineffective antimicrobial therapy on days 3 and 5 of treatment were fever, presence of blood by naked eye examination of stool, and minimum change in stool frequencies. These observations suggest that by careful follow-up of clinical features and simple laboratory tests, such as stool microscopic examinations, it is possible to identify patients unlikely to respond to initial therapy by 72 hours permitting the start of alternative antimicrobial treatment. This may be of great help where stool culture and sensitivity facilities for Shigella spp. are not available.

Abdominal Pain↗
PubMed1994

Plant resistance to rusts and mildews: genetic control and possible mechanisms.

Genes in plants that confer race-specific resistance to rusts and mildews are widely exploited in agriculture and can prevent huge losses at little cost. However, nothing is known of the molecular basis of their action. Genetic studies, together with observations of responses at the ultrastructural level, can provide broad insights into how resistance is achieved, which may help in cloning resistance genes.

Alleles↗
PubMed1994

Double-blind comparison of oral gentamicin and nalidixic acid in the treatment of acute shigellosis in children.

To compare the efficacy of oral gentamicin with nalidixic acid in the treatment of acute shigellosis, we studied, in a double blind-trial, 79 comparable children with bloody diarrhoea of less than 72 h duration. Of them Shigella spp. were isolated in 71 patients. Patients were randomly assigned to receive either gentamicin 30 mg/kg/day or nalidixic acid 60 mg/kg/day, both given orally in four equal doses for 5 days. Stool frequency differed significantly between the groups from day two until completion of the study. Treatment failure was observed in 14 (42 per cent) patients receiving oral gentamicin compared to none of those with nalidixic acid-sensitive strains of Shigella spp. (P = 0.0002). Although all the shigella isolates were sensitive to gentamicin in vitro, 19 (58 per cent) patients on gentamicin therapy failed to eliminate shigella organisms from stool, compared to none in the nalidixic acid treated group infected with nalidixic acid-sensitive Shigella spp. (P < 0.001). One patient in each group had a bacteriological relapse. We conclude that gentamicin given orally was therapeutically ineffective in the treatment of acute shigellosis.

Acute Disease↗
PubMed1994

Comparison of pivmecillinam and nalidixic acid in the treatment of acute shigellosis in children.

The efficacy of oral pivmecillinam was compared with nalidixic acid in the treatment of acute shigellosis in children 1-8 years of age. In a double-blind trial we studied 80 comparable children with bloody diarrhoea of less than 3 days' duration. Shigella spp. was isolated in 71 children. Patients were randomly assigned to receive either pivmecillinam, 50 mg/kg.day, or nalidixic acid, 60 mg/kg.day, both given orally for 5 days. The stool frequency decreased progressively in both treatment groups. Nalidixic acid failed to eradicate Shigella species in 10 patients, compared with three in the pivmecillinam group (p = 0.04). Similarly, clinical failure was observed in 11 of 37 patients receiving nalidixic acid and in 2 of 26 patients infected with nalidixic acid-susceptible strains as against none in the group receiving pivmecillinam. The results suggest that pivmecillinam given orally was, in fact, more effective than nalidixic acid in the treatment of acute shigellosis in children, particularly when the resistant strains are taken into account.

Acute Disease↗
PubMed1993

C-terminal processing of human beta-glucuronidase. The propeptide is required for full expression of catalytic activity, intracellular retention, and proper phosphorylation.

beta-Glucuronidase undergoes proteolytic C-terminal processing during or after its transport to lysosomes or endosomes. We determined the C-terminal processing site for human placental beta-glucuronidase to be the peptide bond between Thr633-Arg634. To evaluate the role of the 18-amino acid peptide removed in C-terminal processing, we changed the codon for Arg634 to a stop codon by site-directed mutagenesis and studied expression of the truncated mutant enzyme in COS-7 cells. An increased fraction of newly synthesized enzyme from R634Stop cDNA was secreted. Pulse-chase experiments provided no evidence for increased degradation of the intracellular R634Stop enzyme. The total amount of catalytic activity expressed from the R634Stop mutant cDNA was only half that seen with the wild type cDNA, and the Kcat of the mutant enzyme was 52% that of wild type enzyme. These results indicate that the C-terminal propeptide in the precursor is important for beta-glucuronidase to achieve maximal activity. The truncated enzyme formed hybrid tetramers in cotransfection experiments with the cDNA for rat beta-glucuronidase. There appeared to be no decrease in stability of the R634Stop enzyme, since chaotropic agents, heat treatment, and pH had similar effects on the mutant and the wild type enzymes. The uptake rate of the truncated mutant (R634Stop) enzyme by beta-glucuronidase-deficient human fibroblast cells was only 55-60% that of the wild type enzyme. Binding to the immobilized cation-independent mannose-6-phosphate receptor and measurement of the 32P-labeled phosphorylated oligosaccharides revealed that the truncated mutant enzyme was 32-34% less phosphorylated and appeared to contain proportionately more covered phosphate groups than the wild type enzyme. These results suggest that the propeptide influences the accessibility to both processing enzymes that produce the mannose-6-phosphate recognition marker on beta-glucuronidase.

Amino Acid Sequence↗
PubMed1993

Models of crossed categorization and intergroup relations.

Two studies explored 6 models of crossed categorization. In Experiment 1, Muslims (majority) and Hindus (minority) in Bangladesh evaluated 1 of 4 target groups created by crossing religion (Hindu or Muslim) and nationality (Bangladeshi or Indian) and then rated the target group's perceived variability. Experiment 2 was an extension of the research, including new measures. Both studies showed additive effects of religion and nationality, as predicted by 3 models, a strong effect of category dominance for religion, and out-group homogeneity only when the religious in-group was the dominant and majority group in its country. Experiment 2 also showed a significant relationship between discrimination based on religion and self-esteem and marginal support for the hierarchical ordering model. When and how specific models of crossed categorization might operate in different intergroup contexts are discussed.

Adult↗
PubMed1993

Effect of FK506 on the development of diabetes in BB rats in comparison with that of cyclosporin.

FK506, a agent extracted from a streptomyces, has more potent immunosuppressive properties compared with cyclosporin in vitro. We compared the preventive effect of FK506 on the development of diabetes mellitus with that of cyclosporin in BB rats, which are regarded as a useful model of insulin-dependent diabetes mellitus. BB rats aged 30 days were treated intramuscularly with FK506 (0.1 mg/kg/day and 0.32 mg/kg/day) or with cyclosporin (10 mg/kg, alternate days) until 150 days of age. Diabetes developed in 2 (10.5%) of 19 rats treated with the lower dose of FK506 and none of 20 rats with the higher dose of FK506; on the other hand, 1 (5.3%) of 19 rats treated with cyclosporin developed diabetes. In contrast, 9 (36.0%) of 25 control rats became diabetic. The cumulative incidence of diabetes mellitus in the group treated with FK506 (0.32 mg/kg) showed a decrease similar to or more than that of the cyclosporin-treated group. Histological examination showed that FK506 and cyclosporin prevented the reduction in the average size of islets and in the area of beta cells. The analysis of lymphocyte subsets proved the decrease of W3/25: OX8 ratio in both FK506- and cyclosporin-treated groups. These data suggest that the administration of FK506 might be a more useful tool for preventing the development of insulin-dependent diabetes mellitus.

Aging↗
PubMed1991

Direct enantiomeric high performance liquid chromatographic separation of aminoglutethimide and its major metabolite on a series of Chiralcel OD and Chiralcel OJ columns and its application to biological fluids.

A direct, isocratic, sensitive and precise liquid chromatographic method is presented for the enantiomeric separation of aminoglutethimide (AG) and its acetylated metabolite (AcAG) using cellulose tris-3,5-dimethyl phenyl carbamate (Chiralcel OD) and cellulose tris(4-methylphenyl benzoate) ester (Chiralcel OJ) columns in series. The enantiomeric elution order is determined by separate chromatography of the racemate AG and racemate AcAG and of their separate enantiomers under similar conditions. This method has been used to determine and identify the enantiomers of AG and AcAG in the urine sample collected from a metastatic breast cancer patient after administration of AG for 24 h. Large amounts of (+)-R-AG are excreted unchanged in the urine together with smaller quantities of (+)-R-AcAG, while most of the (-)-S-AG is metabolically converted into (-)-S-AcAG.

Aminoglutethimide↗
PubMed1991

Efficacy of a single dose of furazolidone for treatment of cholera in children.

To test the efficacy and safety of furazolidone given as a single dose for childhood cholera, a randomized double-blind placebo-controlled trial was carried out among 118 culture-positive dehydrated children with diarrhea. Patients were randomly assigned to one of four groups to receive medication orally in liquid suspension: furazolidone at 7 mg/kg/day once, furazolidone at 7 mg/kg/day divided into four doses for 3 days, placebo once, or placebo for 3 days. After 12 patients with furazolidone-resistant infections were excluded from the analysis of efficacy, it was determined that both groups treated with furazolidone showed significantly higher rates of bacteriologic success (stool cultures negative for Vibrio cholerae on days 2 to 4 after start of therapy) and clinical success (cessation of diarrhea within 72 h after start of therapy) than corresponding placebo groups (P less than 0.001). There were no significant differences between responses to the 3-day and single-dose regimens of furazolidone, but there was a trend toward better clinical responses in patients who received furazolidone for 3 days. No patient treated with furazolidone dropped out because of side effects. These results indicate that furazolidone, given as either a single dose or divided doses for 3 days, is effective treatment for childhood cholera.

Adolescent↗
PubMed1991

Complete amino acid sequence of luffin-b, a ribosome-inactivating protein from sponge gourd (Luffa cylindrica) seeds.

The complete amino acid sequence of luffin-b has been determined. All the twenty-seven tryptic peptides were isolated by reverse-phase HPLC from the tryptic digests of intact luffin-b and one of its CNBr fragments (CB4), and sequenced using the DABITC/PITC double coupling method. The overlap of these peptides was achieved by analyzing the CNBr fragments and their chymotryptic peptides. Luffin-b consists of 250 amino acid residues with a relative molecular mass of 27,275 Da. Investigation for glycosylation sites indicated that Asn at positions 2, 78, and 85 might carry sugars. Sequence comparison with luffin-a showed that amino acid substitution occurred in 55 positions. Luffin-b contains three glycosylation sites instead of the six sites in luffin-a, of which two were found to be conserved.

Amino Acid Sequence↗
PubMed1991

N-acetyl-D-glucosamine-asparagine structure in ribosome-inactivating proteins from the seeds of Luffa cylindrica and Phytolacca americana.

Glycosylation-site-containing peptides were isolated from the proteolytic digests of luffin-a, luffin-b, PAP-S and CNBr-fragments of PAP-S by reverse-phase HPLC, and their amino acid compositions and sequences were analyzed. Six peptides were obtained from luffin-a, and three each from luffin-b and PAP-S. All of these peptides were negative toward the phenol-H2SO4 reaction and gave only N-acetyl-D-glucosamine in gas chromatography after methanolysis and reacetylation. Amounts of N-acetyl-D-glucosamine in these peptides were determined as D-glucosamine to be approximately one mol per peptide by an amino acid analyzer after HCl hydrolysis. Based on these results we concluded that Asn residues at positions of 28, 33, 77, 84, 206, and 227 in luffin-a, of 2, 78, and 85 in luffin-b, and of 10, 44, and 255 in PAP-S were glycosylated with only GlcNAc, and contained one residue per site.

Acetylglucosamine↗
PubMed1990

Direct separation and optimization of timolol enantiomers on a cellulose tris-3,5-dimethylphenylcarbamate high-performance liquid chromatographic chiral stationary phase.

A high-performance liquid chromatographic method was developed for the direct resolution and optimization of the separation of timolol enantiomers. The method involves the use of a cellulose tris-3,5-dimethylphenylcarbamate chiral stationary phase (OD-Chiralcel) column. The effects of concentration of 2-propanol, various aliphatic alcohols and diethylamine in the mobile phase and column temperature on the retention and enantioselectivity of timolol enantiomers were studied. The maximum resolution factor obtained was 4.00 when using the solvent system hexane-2-propanol (95:5) containing 0.4% (v/v) diethylamine at 5 degrees C.

1-Propanol↗
PubMed1990

Isocratic high-performance liquid chromatographic resolution of glutethimide enantiomers and their 4-hydroxyglutethimide metabolites using cellulose tribenzoate chiral stationary phase.

Glutethimide (2-ethyl-2-phenylglutarimide) enantiomers and their corresponding 4-hydroxyglutethimide metabolites (RS and RR) are separated using newly developed commercially available cellulose tris(4-methylphenyl benzoate) ester (Chiralcel OJ) chiral stationary phase and hexane-ethanol or hexane-2-propanol as the mobile phase. The effects of ethanol or 2-propanol concentration in the mobile phase and of column temperature on retention and enantioselectivity of glutethimide enantiomers are also demonstrated. Maximum resolutions of 14.23 and 7.09 are obtained for glutethimide and their 4-hydroxyglutethimide metabolites, respectively, with hexane-ethanol (60:40) at 23 degrees C and a flow rate of 1 mL/min.

Chromatography, High Pressure Liquid↗