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Biomedical subjects

J Singh

Publications and source records attributed to J Singh.

At least 343 records · Page 19Linked to original sources

Epidemiology and transmission of V. cholerae O1 and V. cholerae O139 infections in Delhi in 1993.

In 1993, rectal swabs from clinically suspected cases of cholera admitted to the Infectious Diseases Hospital (IDH), Delhi were examined for Vibrio cholerae O1 and O139. Epidemiological data of 396 cholera cases were collected before the patients' discharge from IDH. Of the 1528 laboratory-confirmed cholera cases, 46% and 54% were caused by serotype O1 and O139 respectively. Both serotypes appeared and disappeared simultaneously, and peaked during the same time of the year. However, the two serotypes affected persons of different age groups; about 65% of the O1 cases occurred in children aged less than 10 years, whereas this age group accounted for 40% of the cases due to V. cholerae O139. Although there were some focal outbreaks due to serotype O139, both serotypes had almost similar geographical distributions. Important risk factors for transmission of cholera were almost equally prevalent in the majority of both types of cholera cases. Since the seasonality, geographical distribution, and risk factors for transmission were similar for both serotypes, the study indicates that the preventive and control measures are also likely to be similar. The study also shows that the emergence of V. cholerae O139 in 1993 did not affect the incidence, seasonality, and epidemiology of endemic V. cholerae O1 E1 Tor strains in Delhi.

Adolescent↗

Further observations on comparison of immunization coverage by lot quality assurance sampling and 30 cluster sampling.

Lot Quality Assurance Sampling (LQAS) and standard EPI methodology (30 cluster sampling) were used to evaluate immunization coverage in a Primary Health Center (PHC) where coverage levels were reported to be more than 85%. Of 27 sub-centers (lots) evaluated by LQAS, only 2 were accepted for child coverage, whereas none was accepted for tetanus toxoid (TT) coverage in mothers. LQAS data were combined to obtain an estimate of coverage in the entire population; 41% (95% CI 36-46) infants were immunized appropriately for their ages, while 42% (95% CI 37-47) of their mothers had received a second/ booster dose of TT. TT coverage in 149 contemporary mothers sampled in EPI survey was also 42% (95% CI 31-52). Although results by the two sampling methods were consistent with each other, a big gap was evident between reported coverage (in children as well as mothers) and survey results. LQAS was found to be operationally feasible, but it cost 40% more and required 2.5 times more time than the EPI survey. LQAS therefore, is not a good substitute for current EPI methodology to evaluate immunization coverage in a large administrative area. However, LQAS has potential as method to monitor health programs on a routine basis in small population sub-units, especially in areas with high and heterogeneously distributed immunization coverage.

Cluster Analysis↗

Immunity to diphtheria in women of childbearing age in Delhi in 1994: evidence of continued Corynebacterium diphtheriae circulation.

Blood samples from 171 full-term pregnant women (aged 18-38 years) of middle socioeconomic status from Delhi were tested for diphtheria antitoxins by indirect hemagglutination (IHA) test. History of primary immunization/clinical diphtheria during childhood was not ascertainable, but none had been revaccinated against diphtheria at any time. About 94% women had very high antitoxin titers (> or = 0.125 IU/ ml); none had antitoxin titer less than 0.015 IU/ml, the minimum protective level. The titers were uniformly high in all age groups. However, women having 2 or more children had significantly higher antitoxin titers than those having no or one child (p < 0.01). The results from this study and historical data on diphtheria in Delhi are compatible with continued transmission of C. diphtheriae in recent times in Delhi which is of sufficient magnitude to boost the antitoxin levels in adults, especially mothers having two or more children. The study highlights the need of increasing the immunization coverage with DPT among children to reduce the transmission of Corynebacterium diphtheriae.

Adolescent↗

Variant B human herpesvirus-6 associated febrile dermatosis with thrombocytopenia and encephalopathy in a liver transplant recipient.

Human herpesvirus 6 (HHV-6) is a recently discovered virus the pathogenicity of which in solid organ transplant recipients has not been defined. We describe a unique febrile syndrome due to disseminated invasive variant B HHV-6 infection in a liver transplant recipient with evidence of direct tissue invasion by the virus. Acute febrile illness characterized by life-threatening thrombocytopenia, progressive encephalopathy and skin rash developed in association with invasive HHV-6 infection in a liver transplant recipient. HHV-6 was isolated from the patient's peripheral blood in cell culture; variant B HHV-6 DNA was detected in the patient's peripheral blood mononuclear cells (PBMC) at a concentration greater than 1000 virus genomes per 10(6) PBMC. A bone marrow biopsy was also positive for HHV-6, documenting direct tissue invasion. Intravenous ganciclovir for three weeks led to a prompt clinical response. Although larger studies are warranted, our case suggests that HHV-6 should be considered in the diagnostic evaluation of patients with fever, cytopenia, and encephalopathy, particularly since HHV-6 is susceptible to ganciclovir and foscarnet.

Adult↗

Lipoprotein receptor 'CK'--dependent signalling in human platelets.

The study addressed to understand whether or not lipoproteins at low concentrations could modulate Receptor-'C' dependent platelet signalling revealed that LDL, like exogenous cholesterol, had the capacity to initiate PLD-dependent platelet signalling in a dose dependent fashion and this effect was inhibited in presence of HDL; cAMP; DTT; Zn++ and butanol whereas cGMP had no effect upon this PLD-dependent signalling. Further Receptor 'C' from platelet in the purified-form displayed LDL-or cholesterol-dependent autophosphorylation at the tyrosine residues and this Receptor-'C' tyrosine kinase (Receptor-Ck) activity contributed to the observed LDL-or cholesterol -dependent PLD activity in human platelets. Based upon these results coupled with earlier results, an attempt was made to define the lipoprotein-dependent platelet signalling pathway.

Adenosine Triphosphate↗

Structural studies on the PH domains of Db1, Sos1, IRS-1, and beta ARK1 and their differential binding to G beta gamma subunits.

Pleckstrin homology (PH) domains are approximately 110 amino acid residues in length and are structurally conserved in a number of intracellular signaling proteins. A role for these domains has been postulated for beta ARK, which binds to G beta gamma subunits. We have quantified the binding of individual (His)6-tag PH domains of human Db1, human Sos1, rat IRS-1, human beta ARK, and human beta ARK with an extra 33-residue C-terminal extension (beta ARK + C) to G beta gamma subunits. Our in vitro binding studies show that all of the PH domains (apart from Sos1), bind G beta gamma subunits in a dose-dependent manner, but beta ARK + C binds 4 times as much G beta gamma at saturation as the others. The IRS-1 PH domain has a similar half-maximal concentration of G beta gamma binding (18 nM) to beta ARK + C (30 nM), suggesting that the IRS-1 PH domain has sufficient determinants for G beta gamma binding. The beta ARK PH domain alone has a half-maximal value of 45 nM but a drastically reduced extent of G beta gamma binding, suggesting that both the PH domain and the C-terminal 33 residues are necessary for maximal binding. Db1 has a half-maximum concentration of G beta gamma binding of 45 nM and a maximal extent of binding similar to that of beta ARK, but it is difficult to demonstrate saturable binding of G beta gamma to Sos1. Since it was previously predicted that the C-terminal PH domain of Pleckstrin [Tyers, M., et al. (1988) Nature 333, 470-473] contains a potential calcium binding site, we have tested the different PH domains for calcium binding. Only the PH domain of Db1 bound 45Ca2+ with a Kd of 10 microM. CD spectroscopy of the purified recombinant PH domains indicated that they are predominantly beta-sheet structures.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Dysfibrinogenemia: a case with thrombosis (fibrinogen Richfield) and an overview of the clinical and laboratory spectrum.

Fibrinogen Richfield exemplifies a dysfibrinogen associated with a life-long thrombotic tendency. The evaluation of this novel case indicates that, like similar thrombotic dysfibrinogenemias, the abnormal protein polymerizes abnormally and demonstrates impaired clot dissolution. A survey of other cases of dysfibrinogenemia indicates that the relatively common abnormalities of Fibrinopeptide A release are generally asymptomatic or associated with bleeding, polymerization abnormalities are likely to be asymptomatic or associated with thrombosis (or occasionally bleeding), and complex abnormalities or additional, independent hemostatic defects are rather common. Thrombin and Reptilase clotting times are not helpful in distinguishing between the subsets, but clinical history, fibrinopeptide release, and polymerization studies may be useful. Abnormalities of fibrinogen function tend to correlate with changes in molecular domains related to binding and hydrolysis.

Afibrinogenemia↗

Differentiation of peptide molecular recognition by phospholipase C gamma-1 Src homology-2 domain and a mutant Tyr phosphatase PTP1bC215S.

Activated epidermal growth factor receptor (EGFR) undergoes autophosphorylation on several cytoplasmic tyrosine residues, which may then associate with the src homology-2 (SH2) domains of effector proteins such as phospholipase C gamma-1 (PLC gamma-1). Specific phosphotyrosine (pTyr)-modified EGFR fragment peptides can inhibit this intermolecular binding between activated EGFR and a tandem amino- and carboxy-terminal (N/C) SH2 protein construct derived from PLC gamma-1. In this study, we further explored the molecular recognition of phosphorylated EGFR988-998 (Asp-Ala-Asp-Glu-pTyr-Leu-Ile-Pro-Gln-Gln-Gly, I) by PLC gamma-1 N/C SH2 in terms of singular Ala substitutions for amino acid residues N- and C-terminal to the pTyr (P site) of phosphopeptide I. Comparison of the extent to which these phosphopeptides inhibited binding of PLC gamma-1 N/C SH2 to activated EGFR showed the critical importance of amino acid side chains at positions P+2 (Ile994), P+3 (Pro995), and P+4 (Gln996). Relative to phosphopeptide I, multiple Ala substitution throughout the N-terminal sequence, N-terminal sequence, N-terminal truncation, or dephosphorylation of pTyr each resulted in significantly decreased binding to PLC gamma-1 N/C SH2. These structure-activity results were analyzed by molecular modeling studies of the predicted binding of phosphopeptide I to each the N- and C-terminal SH2 domains of PLC gamma-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Characterization of a low-temperature-induced cDNA from winter Brassica napus encoding the 70 kDa subunit of tonoplast ATPase.

A cDNA clone, pBN59, was isolated by differential screening of a cDNA library of winter Brassica napus during cold acclimation. Nucleotide sequence of BN59 was found to be homologous to that encoding the 70 kDa subunit of the vacuolar H(+)-ATPase in plants. Transcripts hybridizing to BN59 accumulated during exposure to low temperatures and to the exogenous application of abscisic acid (ABA). Western blot analyses also indicated an increase in the 70 kDa subunit during cold acclimation. The accumulation of an endomembrane H(+)-ATPase is consistent with the observation of osmotic adjustment, increases in endogenous ABA and the proliferation of endomembranes during cold acclimation.

Abscisic Acid↗

Herpes simplex virus recombination vectors designed to allow insertion of modified promoters into transcriptionally "neutral" segments of the viral genome.

The use of recombinant viruses has been essential in investigation of the biology of herpes simplex virus (HSV). In this communication we describe a number of viral recombination vectors that we have generated for use in promoter structure/function analysis within the context of the HSV-1 genome. We have utilized two regions of the HSV genome that contain genes nonessential for replication in cultured cells--the glycoprotein C (gC or UL44) locus in the UL of the genome and the area encompassing the promoter and 5' portion of the latency associated transcript (LAT) within the RL factual influence on promoters due to the site of insertion. Two different kinetic promoters were analyzed, those controlling expression of the gamma UL 38 and the beta dUTPase genes, in both loci. All constructs tested displayed reporter gene mRNA expression with expected kinetics, and we conclude that there are no neighboring cryptic promoter elements that could interfere with expression studies using the vectors described.

Animals↗

The source and action of histamine in the isolated guinea-pig gallbladder.

We have investigated the effects of histamine on motility of the gallbladder and characterized the receptor types involved. Histamine and the histamine H1-receptor agonist, 2-thiazolylethylamine (2-TEA) contracted the isolated guinea-pig gallbladder strip in a dose dependent manner. The contractile response to histamine was shifted to the right by the H1-receptor antagonist, mepyramine. In pre-contracted gallbladder strips, the H2-receptor agonist dimaprit reduced the tension generated in a dose dependent fashion. The histamine H2-receptor antagonist, ranitidine shifted the histamine concentration effect curve to the left and attenuated the dose dependent relaxations elicited at high concentrations. The histamine H3-receptor agonist, (R)-alpha-methylhistamine (RMHA) elicited dose dependent contraction of the tissue which was significantly inhibited in the presence of mepyramine. The effects of electrical field stimulation (EFS) on the strips were not significantly altered by the presence of RMHA (10(-10) - 10(-7) M) indicating little pre-synaptic H3 activity in this tissue. Histamine immunoreactivity (IR) was detected in gallbladder whole mount preparations of the mucosa and the muscularis/serosa. The histamine IR appeared cell bound in cells of varying morphological characteristics but no IR was detected in nerve fibres or cell bodies (ganglia). Alcian blue staining was consistent with the distribution of histamine IR cells as mast cells. The results indicate that histamine is distributed in the guinea-pig gallbladder and it can regulate contractile activity via activation of H1 and H2 but not H3 receptors.

Animals↗

An outbreak of bacillary haemoglobinuria in sheep in India.

An outbreak of bacillary haemoglobinuria was recorded in 60 out of 110 sheep in Ludhiana, Punjab, India. The condition was clinically characterised by fever, haemoglobinuria, constipation, weakness of hind quarters followed by recumbency, respiratory distress and death in 16 sheep. Haematological studies revealed moderate to severe degrees of anaemia associated with leucocytosis. Plasma gamma-glutamyl transferase, alkaline phosphatase and creatinine phosphokinase activities were significantly higher in haemoglobinuric sheep. Babesiosis and copper poisoning were ruled out on stained blood film examination and from blood mineral profiles, respectively. Post-mortem examination of affected sheep revealed no gross changes. Pure cultures of Clostridium haemolyticum isolated from heart blood, liver, kidney and spleen of freshly killed sheep confirmed the disease. Parenteral administration of procaine penicillin was effective in the treatment of affected sheep.

Animals↗

Purification and properties of four monocot lectins from the family Araceae.

Four new monocot lectins from the tubers of araceous plants, namely, Arisaema consanguineum Schott (ACA), A. curvatum Kunth (ACmA) and Sauromatum guttatum Schott (SGA) from the tribe Areae, and Gonatanthus pumilus D. Don (GPA) from the tribe Colocasieae have been purified by affinity chromatography on asialofetuin-linked amino activated silica beads. These lectins possess similar physicochemical and biological properties. All the lectins gave a single peak on HPLC size exclusion and cation exchange columns, and a single band on PAGE, (pH 4.5). In SDS-PAGE, all the lectins gave a single band corresponding to a subunit of M(r) 1,3000. All the lectins yielded multiple peaks on anion-exchange column, multiple bands on non-denatured PAGE (pH 8.3) and a family of bands on isoelectric focusing. The lectins agglutinate rabbit, rat and sheep red blood cells (RBCs) but are inactive towards human ABO erythrocytes. The haemagglutination activity of these lectins is inhibited by asialofetuin only, while simple sugars/derivatives including chitin, porcine mucin and fetuin did not react. In serological studies against rabbit anti-SGA serum, all four lectins produced immunoprecipitin lines. The lectins within each tribe were identical but the lectins belonging to the tribe Areae were only partially identical to the lectins from the tribe Colocasieae.

ABO Blood-Group System↗