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Biomedical subjects

M Singh

Publications and source records attributed to M Singh.

At least 775 records · Page 43Linked to original sources

Toxoplasmosis in Singapore.

The present paper reports research done in the following areas in the Parasitology Unit of the Department of Microbiology, National University of Singapore: determination of anti-Toxoplasma gondii antibodies in different IgG subclasses; immunoblot analysis of the antibody response to T. gondii and identification of key reactive epitopes; production and characterization of monoclonal antibodies to T. gondii; and the development of an IgM capture ELISA. IgG1 is the dominant subclass involved in the humoral response to T. gondii. IgG3 and IgG4 may be produced at low but significant levels. IgG2 production was not apparent. Immunoblot analysis of the positive sera revealed that the major antigens recognized by IgG and IgM antibodies were of MW 22, 35 and 67 kDa. Many of the bands observed in blots with positive sera were also present in blots with negative sera. The 22 kDa band was seen in majority of positive sera and was generally absent in negative sera. Anti-Toxoplasma sera also revealed IgA antibodies. Immunoblot analysis of the antigen revealed a 14 kDa band that reacted with all IgA positive sera. From a panel of monoclonals produced against T. gondii, one monoclonal, 5F3 (A) was selected for development of a monoclonal based IgM capture ELISA for detection of antibodies to 22 kDa and 41 kDa epitopes of T. gondii.

Animals↗

Current status of food-borne parasitic zoonoses in Singapore.

Parasitic infections adopt a rather low profile in the highly urbanized setting in Singapore. Very few food-borne parasitic infections are encountered. Apart from a few reports of infections with Clonorchis/Opisthorchis, Taenia spp. and hydatid disease, there are no other citations of such helminthic infections. Seroprevalence surveys have shown the presence of toxoplasmosis in local meat animals (sheep, pigs and cattle) and Toxoplasma strains have been isolated from the pig, tree shrew (Tupaia glis), slow loris (Nycticebus coucang) and guinea pigs. Human toxoplasmosis is prevalent in Singapore. Anti-Toxoplasma antibodies are found in the normal population as well as in clinical cases (cervical lymphadenopathy, ocular disease and congenital toxoplasmosis). Carcasses/organs from meat animals (sheep, pigs, cattle) slaughtered at local abattoirs were examined for parasites. The main parasites found were Ascaris suum, Dictyocaulus, Metastrongylus, Cysticercus ovis, Fasciola hepatica and Sarcocystis spp. Pigs were also examined for trichinosis and, thus far, these have all been negative.

Animals↗

Learning disability in rural primary school children.

In rural primary school children observed for two years, 12.97 per cent of those having IQ greater than or equal to 90 were found to have poor achievement in arithmetic test and teacher's assessment. These learning disabled children had impaired perceptual maturity and conceptual grasp as observed on MISIC (Indian modification of WISC), Bender Gestalt test and Piaget's test. On WISC Bannatyne categories learning disabled children scored highest in verbal conceptualization (similarities, vocabulary, comprehension), followed by spatial (picture completion, object assembly, block design) and sequencing (arithmetic, digit span, coding) abilities. These children on Bender Gestalt test made more errors particularly distortions (distortion of parts, incorrect number of dots, shape of design lost etc). They also showed delayed development on Piagetian tasks class inclusion, conservation (for length, substance, liquid and number) ordinal relation and one to one correspondence. These observations indicate impaired perceptual maturity, conception and information processing deficit.

Achievement↗

Intestinal malrotation in adults.

Intestinal malrotation presenting with abdominal problems are not common beyond the neonatal period. An adolescent or adult harboring this anomaly may suffer from delay in diagnosis and inappropriate treatment including surgery. We report three patients, aged 17, 31 and 50 years, with intestinal malrotation presenting as an appendicular problem (2) and chronic abdominal pain (1). The former mode of presentation has not been reported so far.

Abscess↗

A four year study on neonatal morbidity in a New Delhi hospital.

The neonatal morbidity was studied in 7015 neonates born at the All India Institute of Medical Sciences Hospital, New Delhi. The incidence of low birth weight babies was 26.7 per cent; one seventh (13.5%) of the series were preterm (less than 37 wk), while 6.6 per cent were 'small-for-dates'. Birth asphyxia of varying severity developed in 5.9 per cent infants. Respiratory distress syndrome was diagnosed in 5.7 per 100 live-births; most being due to hyaline membrane disease (33.5%), which affected 14.1 per cent of preterm babies. Neonatal hyperbilirubinemia occurred in 5.9 per cent, most of whom were premature. In nearly one-fifth, the cause of jaundice could not be identified after detailed investigations. Minor bacterial infections (conjunctivitis, pyoderma, oral thrush, umbilical sepsis) were observed in 1.8 per cent while major infections (septicemia, meningitis, diarrhoea) in 3.0 per cent. The overall incidence of major malformations was 2.3 per cent. Reasons for low incidence of bacterial infections and common occurrence of hyaline membrane disease in premature infants, are highlighted.

Asphyxia Neonatorum↗

Perinatal & neonatal mortality in a hospital.

A total of 7109 consecutive births were studied over four years to assess perinatal and neonatal mortality. The extended perinatal mortality rate was 57 while conventional perinatal mortality rate (PNMR) was 41 per 1000 total births. Perinatal hypoxia (28.7%), immaturity (24.8%), congenital malformations (14.6%) and infections (5.6%) accounted for most perinatal deaths. The ranking of causes of neonatal deaths was immaturity, birth asphyxia, bacterial infections and congenital malformations. Neonatal mortality rate was 31 per 1000 live births and nearly 90 per cent mortality occurred in low birth weight (LBW) neonates. Hyaline membrane disease accounted for 13.4 per cent of early neonatal deaths. The case fatality rate among LBW babies and preterm babies was 10 per cent and 20 per cent respectively. There is a need to identify strategies to reduce the incidence of prematurity and LBW babies. Comprehensive antenatal coverage and adequate care followed by optimal management of infants at birth is likely to reduce PNMR and improve quality of life among the survivors.

Cause of Death↗

Neurodevelopmental outcome of asymptomatic & symptomatic babies with neonatal hypoglycaemia.

A total of 107 babies with hypoglycaemia were studied over a period of 15 months. Symptomatic hypoglycaemia was found in 43 while it was asymptomatic in the others. Asymptomatic hypoglycaemia occurred at a relatively earlier post-natal age (4.5 +/- 2.2 h), as compared to symptomatic hypoglycemia (18.5 +/- 5.4 h, P less than 0.001). The mean blood glucose in hypoglycaemic babies with seizures was found to be significantly lower (P less than 0.001) when compared to those with other features as well as asymptomatic ones. Hypoglycaemia lasted for a significantly longer duration in symptomatic babies as compared to those without symptoms (P less than 0.001). On neurodevelopment follow up the mental developmental index (MDI) and the psychomotor developmental index (PDI) of symptomatic babies with seizures were significantly lower (P less than 0.001) as compared to those with other features of hypoglycaemia as well as asymptomatic babies. The neurodevelopmental status of babies with symptoms other than seizures was also significantly poorer (P less than 0.001), when compared to asymptomatic hypoglycaemic babies. The duration of hypoglycaemia was directly related to the MDI (r = -0.74, y = 102.5 - 0.69x) and PDI (r = -0.81, y = 105.6 - 0.86x). This study indicates that there is a need to identify babies vulnerable to symptomatic hypoglycaemia more precisely.

Humans↗

Crystallization and preliminary X-ray studies of psophocarpin B1, a chymotrypsin inhibitor from winged bean seeds.

Psophocarpin B1 is a 20,000 Mr protein of winged bean (Psophocarpus tetragonolobus) seeds having chymotrypsin inhibitory activity. Single crystals of this protein suitable for X-ray crystallographic studies have been obtained by the vapour diffusion method using ammonium sulphate. The crystals are hexagonal, space group P6(4)22 or P6(2)22, cell dimensions a = b = 61 A, c = 210 A. They are stable to irradiation with X-rays and diffract to at least 2.6 A resolution.

Chromatography, DEAE-Cellulose↗

The diagnosis and prognosis of autosomal dominant polycystic kidney disease.

BACKGROUND: Autosomal dominant polycystic kidney disease is usually caused by a mutant gene at the PKD1 locus on the short arm of chromosome 16, but in about 4 percent of families with the disorder it is caused by unknown mutations elsewhere in the genome. The natural course of the disease in both genetic forms is not well characterized. METHODS: We studied 17 families with autosomal dominant polycystic kidney disease to compare presymptomatic diagnosis by ultrasonography with diagnosis by genetic-linkage studies and to relate clinical variation of the disease to whether the PKD1 mutation was implicated. RESULTS: In 10 families the disorder was found to cosegregate with polymorphic DNA markers flanking the PKD1 locus, in 2 families it did not, and in 5 families linkage could not be determined. In the 10 families with the PKD1 mutation, 46 percent of the members less than 30 years old who had a 50 percent risk of inheriting a mutation had renal cysts, as compared with 11 percent of the members of the two families without linkage (P less than 0.001). In the PKD1 families, all 67 diagnoses made by ultrasonography were confirmed by determination of the genotype as inferred from linkage. Forty of 48 members (83 percent) less than 30 years old who inherited the PKD1 mutation had renal cysts. All 27 members 30 years old or older who inherited the mutation had renal cysts, suggesting that the probability of a false negative diagnosis did not exceed 0.13 in this age group (P less than 0.05). The mean (+/- SE) age at the onset of end-stage renal disease among members of the PKD1 families was 56.7 +/- 1.9 years, as compared with 69.4 +/- 1.7 years among members with cysts in the families without linkage (P = 0.0025). Hypertension and renal impairment were less frequent and occurred later in the families without the PKD1 mutation. CONCLUSIONS: At present, in most persons with a 50 percent risk of autosomal dominant polycystic kidney disease, imaging techniques are the only mode of reaching a diagnosis before symptoms appear. In such persons a negative ultrasonographic study during early adult life indicates that the likelihood of inheriting a PKD1 mutation is small. In the few who inherit a non-PKD1 mutation for polycystic kidney disease, renal failure is likely to occur relatively late in life.

Adult↗

HIV-1 regulator of virion expression (Rev) protein binds to an RNA stem-loop structure located within the Rev response element region.

HIV-1 Rev protein, purified from E. coli, binds specifically to an RNA transcript containing the 223 nucleotide long Rev response element (RRE) sequence. Rev binds to RRE in vitro with an apparent dissociation constant of 1 to 3 nM as determined by filter binding, gel mobility shift assays, or an immunoprecipitation assay using a monoclonal antibody specific for the Rev C-terminus. Antisense RRE sequences are bound by Rev with a 20-fold lower affinity than wild-type RRE sequences. The Rev-RRE complex forms even in the presence of a 10,000-fold molar excess of 16S rRNA, whereas formation of the low affinity antisense RRE-Rev complex is efficiently blocked by addition of excess 16S rRNA. A approximately 33 nucleotide fragment is protected from ribonuclease T1 digestion by the binding of Rev to RRE RNA, suggesting that Rev binds with high affinity to only a restricted region of the RRE. This protected fragment is unable to rebind Rev protein but has been mapped to a 71 nucleotide long Rev binding domain sequence that overlaps the protected fragment.

Amino Acid Sequence↗

HIV-1 tat protein stimulates transcription by binding to a U-rich bulge in the stem of the TAR RNA structure.

The HIV-1 trans-activator protein, tat, is an RNA binding protein with a high affinity for a U-rich bulge near the tip of the stem in the RNA stem-loop structure encoded by the trans-activation responsive region (TAR). A Scatchard analysis of tat binding has shown that the purified protein forms a one-to-one complex with HIV-1 TAR RNA with a dissociation constant of Kd = 12 nM. Deletion of the uridine residues in the bulge or substitution with guanine residues produced RNAs with a 6- to 8-fold lower affinity than wild-type TAR. Introduction of a point mutation expected to destabilize base pairing in nearby residues of the TAR stem-loop structure reduced tat binding 10-fold. In contrast, mutations that alter the sequence of the six nucleotide long loop at the tip of TAR RNA structure, and mutations which alter the sequence of the stem whilst preserving Watson-Crick base pairing, do not affect tat binding significantly. There is a direct correlation between the ability of tat to bind to TAR RNA and to activate HIV transcription. Viral LTRs carrying TAR sequences encoding any of the mutations known to produce transcripts which bind tat weakly, are not stimulated efficiently by tat in vivo.

Base Sequence↗

Giant subdural empyema in an infant. Sonographic observations.

A giant subdural empyema was found to be the cause of a large head in a two month old female child referred for cranial sonography. The sonographic features of the subdural empyema as illustrated by this case are: (1) The presence of an extra-axial space occupying lesion with mass effect. (2) Its fluid nature with mobile echogenic debris within. (3) Its large extent from frontal to occipital region, and (4) Its thick medial echogenic wall. A total of 250 ml of pus was evacuated from the empyema and the child was doing well on follow up at four months of age.

Empyema, Subdural↗