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Biomedical subjects

S Misbah

Publications and source records attributed to S Misbah.

8 recordsLinked to original sources

Unusual case presentations associated with the CD45 C77G polymorphism.

CD45, the leucocyte common antigen, is a haematopoietic cell specific tyrosine phosphatase. Human polymorphic CD45 variants are associated with autoimmune and infectious diseases and alter the phenotype and function of lymphocytes, establishing CD45 as an important regulator of immune function. Here we report four patients with diverse diseases with unusual clinical features. All four have the C77G polymorphism of CD45 exon 4, which alters the splicing and CD45RA/CD45R0 phenotype of lymphocytes. We suggest that C77G may be a contributing factor in these unusual cases.

Abscess↗

Genomic species identification of Acinetobacter of clinical isolates by 16S rDNA sequencing.

INTRODUCTION: This study aims to identify Acinetobacter of clinical isolates from the University of Malaya Medical Centre (UMMC), Kuala Lumpur, to the species level by 16S rDNA sequencing. METHODS: 12 representative Acinetobacter isolates of the UMMC inpatients were randomly picked and used for the study. The 16S rDNA sequences were determined and phylogenetic relationships to all known Acinetobacter species were established. RESULTS: Based on the 16S rDNA sequences, all the UMMC isolates were identified as Acinetobacter baumannii. The isolates shared a common ancestral lineage with the prototypes Acinetobacter baumannii DSM30007 and DSM30008 with 99-100 percent sequence similarities. The isolates could be differentiated into two groups by a single nucleotide difference (thymine-cytosine) within the 16S rRNA sequence. Three different genotypes, 1, 3 and 4, were recognised using REP-PCR. CONCLUSION: The previously uncharacterised Acinetobacter isolates from the UMMC were identified by their 16S rDNA sequences as Acinetobacter baumannii. The isolates were distinguished into at least three different genotypes by REP-PCR genotyping. These findings confirmed for the first time the presence of Acinetobacter baumannii of different genotypes among patients at UMMC.

Acinetobacter baumannii↗

Antibiotic susceptibility and REP-PCR fingerprints of Acinetobacter spp. isolated from a hospital ten years apart.

The antibiotic susceptibility profiles and the repetitive extragenic palindromic sequence-based polymerase chain reaction (REP-PCR)-determined genotypes of 109 Acinetobacter strains collected from the University Malaya Medical Center (UMMC), Kuala Lumpur, Malaysia, in 1987 (N=21) and 1996-1998 (N=88) were established. Twelve antibiotic susceptibility profiles of antibiotics used at the UMMC were obtained. In descending order of effectiveness, imipenem, amikacin and ciprofloxacin were the most effective against the Acinetobacter strains. Compared with 1987 isolates, the isolates obtained in 1996-1998 had decreased susceptibility to these antibiotics and were tolerant to the antibiotics up to an MIC90 of > or =256 mg/L. REP-PCR DNA fingerprints of all the isolates revealed the presence of four Acinetobacter spp. lineages; 92% of all the isolates belonged to two dominant lineages (genotypes 1 and 4). Genotype 4 isolates predominant in 1987 showed increased resistance and antibiotic tolerance to imipenem, amikacin and ciprofloxacin compared with the 1996-1998 isolates. In contrast, genotype 1 isolates from 1996-1998 were mainly sensitive to these antibiotics. These findings demonstrate the presence of at least two independent Acinetobacter spp. lineages in the same hospital, and suggest the possibility that genotype 4 Acinetobacter spp. acquired the resistance phenotype in situ, whereas most of the genotype 1 isolates were probably introduced to the hospital in recent years.

Acinetobacter↗

Does 77C-->G in PTPRC modify autoimmune disorders linked to the major histocompatibility locus?

A 77G allele of the gene encoding CD45, also known as the protein tyrosine phosphatase receptor-type C gene (PTPRC), has been associated with multiple sclerosis (MS). Here we determine allele frequencies in large numbers of MS patients, primary immunodeficiencies linked to major histocompatibility complex (MHC) locus and over 1,000 controls to assess whether aberrant splicing of PTPRC caused by the 77C-->G polymorphism results in increased susceptibility to these diseases. Our results show no difference in the frequency of the 77G allele in patients and controls and thus do not support a causative role for the polymorphism in the development of disorders with a strong autoimmune component in etiology.

Animals↗

Intravenous immunoglobulin for ANCA-associated systemic vasculitis with persistent disease activity.

Intravenous immunoglobulin (IVIg) is a potential alternative treatment for anti-neutrophil cytoplasm antibody (ANCA)-associated systemic vasculitis (AASV) with less toxicity than conventional immunosuppressive agents. This randomized, placebo-controlled trial aimed to investigate the efficacy of a single course of IVIg (total dose 2 g/kg) in previously-treated AASV with persistent disease activity in whom there was an intention to escalate therapy. Vasculitic activity was monitored by the Birmingham vasculitis activity score (BVAS), C-reactive protein (CRP) and ANCA levels. Treatment response was defined as a reduction in BVAS of more than 50% after 3 months, and there was an intention to keep doses of concurrent immunosuppressive drugs unchanged during this period; follow-up continued to 12 months. Seventeen patients were randomized to receive IVIg and 17 to receive placebo. Treatment responses were found in 14/17 and 6/17 of the IVIg and placebo groups, respectively (p=0.015, OR 8.56, 95%CI 1.74-42.2). Following infusion of trial medication, greater falls in CRP were seen at 2 weeks (p=0.02) and 1 month (p=0.04) in the IVIg group. No differences were observed between ANCA levels or cumulative exposure to immunosuppressive drugs, and after 3 months there were no differences in CRP levels or disease activity between the IVIg and placebo groups. Seventeen adverse effects occurred after IVIg and six after placebo: they were mostly mild, although reversible rises in serum creatinine occurred in four from the IVIg group. A single course of IVIg reduced disease activity in persistent AASV, but this effect was not maintained beyond 3 months; mild, reversible side-effects following IVIg were frequent. IVIg is an alternative treatment for AASV with persistent disease activity after standard therapy.

Adult↗

Antibody responses to Haemophilus influenzae type b and Streptococcus pneumoniae vaccines in children with human immunodeficiency virus infection.

Antibody responses to Haemophilus influenzae type b (Hib) conjugate (ActHIB; Pasteur Merieux) and pneumococcal (Pneumovax II; Morson) vaccines were measured in 56 infected children (VI) and 44 uninfected children (U) older than 18 months of age, born to human immunodeficiency virus-positive mothers. Preimmunization, 21% U and 20% VI had protective concentrations of anti-Hib polysaccharide antibodies. Postimmunization, 100% U and 86% VI achieved protective titers (P = 0.008). The geometric mean increase in anti-Hib polysaccharide antibody was 7.6 (95% confidence interval, 3.5 to 16.3; P = 0.0001) times higher in U than in VI children after adjusting for age and ethnicity. Sixty-one percent U compared to 54% VI showed a 2-fold increase in antibody levels to at least one of the four pneumococcal vaccine serotypes (3, 6, 19, 23) measured (P = 0.4). For both vaccines there was a significant trend toward poorer responses in children with acquired immunodeficiency syndrome but no correlation with age adjusted CD4 counts. These data suggest that human immunodeficiency virus-infected children should be immunized with these polysaccharide vaccines early in the course of their disease.

Antibodies, Bacterial↗