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Biomedical subjects

G Bhardwaj

Publications and source records attributed to G Bhardwaj.

17 recordsLinked to original sources
PubMed2001

Sonic hedgehog induces the proliferation of primitive human hematopoietic cells via BMP regulation.

A pool of stem cells that arise from the mesoderm during embryogenesis initiates hematopoiesis. However, factors that regulate the expansion of blood stem cells are poorly understood. We show here that cytokine-induced proliferation of primitive human hematopoietic cells could be inhibited with antibodies to hedgehog (Hh). Conversely, Sonic hedgehog (Shh) treatment induced the expansion of pluripotent human hematopoietic repopulating cells detected in immunodeficient mice. Noggin, a specific inhibitor of bone morphogenetic protein 4 (BMP-4), was capable of inhibiting Shh-induced proliferation in a similar manner to anti-Hh; however, anti-Hh had no effect on BMP-4-induced proliferation. Our study shows that Shh functions as a regulator of primitive hematopoietic cells via mechanisms that are dependent on downstream BMP signals.

Base Sequence↗
PubMed1998

Cardiac arrhythmias in aluminium phosphide poisoning studied by on continuous holter and cardioscopic monitoring.

Variable incidences of cardiac arrhythmias (based on isolated 12 lead ECG records) have been reported in patients of aluminium phosphide (ALP) poisoning. We did continuous holter and cardioscopic monitoring in ICU in 30 patients of acute ALP poisoning. Supraventricular and ventricular ectopics were recorded in each and every patient. Life threatening ventricular tachycardia was recorded in 40% cases and ventricular fibrillation in 23.3% cases. Supraventricular tachycardia and atrial flutter/fibrillation occurred in 46.7% and 20% patients, respectively. ST-T changes simulating myocardial ischaemia were also present in all patients (S-T depression in 90%, S-T elevation in 10%). One-third of the patients developed variable degrees of heart block, IV amiodarone/xylocard could revert dangerous ventricular arrhythmias to sinus rhythm in 4 cases. Toxic myocarditis produced by phosphine seems to be responsible for the development of these arrhythmias.

Adolescent↗
PubMed1993

Localization of a novel multidrug resistance-associated gene in the HT1080/DR4 and H69AR human tumor cell lines.

Two doxorubicin-selected human tumor cell lines, H69AR and HT1080/DR4, display a multidrug resistance phenotype but do not overexpress P-glycoprotein. Recently, a 6.5-kilobase mRNA encoding a novel member of the ATP-binding cassette superfamily of transport proteins, designated multidrug resistance-associated protein (MRP), has been identified in the H69AR cell line. In the present study, the levels of MRP mRNA were found to be 14-fold higher in HT1080/DR4 cells relative to sensitive HT1080 cells. Southern blotting indicates that gene amplification contributes to the overexpression of MRP in HT1080/DR4 cells. Using a 4-kilobase MRP complementary DNA probe, MRP genes were localized to 2-5 chromosomes bearing homogeneously staining regions and to multiple double minute chromosomes in H69AR cells. Resistant H69AR cells also contained a new der(16) with a structural aberration affecting 16p13.1, the normal cellular locus of the MRP gene. The MRP probe hybridized to two small homogeneously staining regions (hsr) in HT1080/DR4 cells including hsr(7)(p12p15). MRP localization was restricted to the normal cellular locus, 16p13.1, in the parental H69 and HT1080 cells and the drug-sensitive H69PR revertant cells. Our data provide combined evidence that amplification of the MRP gene is associated with the expression of drug resistance in selected solid tumor cell lines.

Carcinoma, Small Cell↗
PubMed1992

Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line.

The doxorubicin-selected lung cancer cell line H69AR is resistant to many chemotherapeutic agents. However, like most tumor samples from individuals with this disease, it does not overexpress P-glycoprotein, a transmembrane transport protein that is dependent on adenosine triphosphate (ATP) and is associated with multidrug resistance. Complementary DNA (cDNA) clones corresponding to messenger RNAs (mRNAs) overexpressed in H69AR cells were isolated. One cDNA hybridized to an mRNA of 7.8 to 8.2 kilobases that was 100- to 200-fold more expressed in H69AR cells relative to drug-sensitive parental H69 cells. Overexpression was associated with amplification of the cognate gene located on chromosome 16 at band p13.1. Reversion to drug sensitivity was associated with loss of gene amplification and a marked decrease in mRNA expression. The mRNA encodes a member of the ATP-binding cassette transmembrane transporter superfamily.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

Elevated expression of annexin II (lipocortin II, p36) in a multidrug resistant small cell lung cancer cell line.

The doxorubicin-selected multidrug resistant small cell lung cancer cell line, H69AR, is cross-resistant to the Vinca alkaloids and epipodophyllotoxins, but does not overexpress P-glycoprotein, a 170 kDa plasma membrane efflux pump usually associated with this type of resistance. Monoclonal antibodies were raised against the H69AR cell line and one of these, MAb 3.186, recognises a peptide epitope on a 36 kDa phosphorylated protein that is membrane associated, but not presented on the external surface of H69AR cells (Mirski & Cole, 1991). In the present study, in vitro translation and molecular cloning techniques were used to determine the relative levels of mRNA corresponding to the 3.186 antigen. In addition, a cDNA clone containing an insert of approximately 1.4 kb was obtained by screening an H69AR cDNA library with 125I-MAb 3.186. Fragments of this cloned DNA hybridised to a single mRNA species of approximately 1.6 kb that was 5 to 6-fold elevated in H69AR cells. Partial DNA sequencing and restriction endonuclease mapping revealed identity of the cloned DNA with p36, a member of the annexin/lipocortin family of Ca2+ and phospholipid binding proteins.

Annexins↗
PubMed1989

Identification and nucleotide sequence of the minimal replicon of the low-copy-number plasmid pBS2.

The plasmid pBS2 has a low copy number and is endogenous to Bacillus subtilis. The replication of this plasmid depends on the function of most of the host's dna genes including dnaB, which is unique to B. subtilis and is required for both the initiation of chromosome replication and the DNA-membrane association. We have identified the region that is essential for the replication of pBS2 and determined the complete 2279-bp nucleotide sequence of this region. In this region, there are two stretches of sequence homologous to the 18-bp consensus sequence which commonly appears at the origin of replication of plasmids pUB110 and pC194. The entire region contains six sizable open reading frames. Two of them are probably translated. One open reading frame, designated ORF A, coding for 269 amino acids, has significant homology, in terms of amino acid sequence, with the open reading frame of the gene for the Rep U protein of plasmid pUB110. The similarities between pBS2 and other plasmids suggest that the pBS2 may also replicate as a rolling circle, which appears to be the salient feature of a mechanism of replication that is common to small plasmids in gram-positive bacteria.

Amino Acid Sequence↗
PubMed1989

Isolation and survival of gentamicin resistant Enterobacter aerogenes on finger tips of hospital personnel.

Enterobacter aerogenes was isolated from the finger tips of 13.3 percent of hospital personnel while they were working in the wards. Gentamicin resistant strains were isolated more frequently than gentamicin sensitive. Carriage rate of E. aerogenes was higher among nurses than other staff members. There was no correlation between antibiotic resistance, capsular serotypes and survival of these strains on finger tips. The property of prolonged survival on finger tips is chromosomal in nature and not mediated by conjugative or non-conjugative plasmids.

Cross Infection↗
PubMed1986

Effect of serotonin on T lymphocyte proliferation in vitro in healthy individuals.

The direct effect of different concentrations of serotonin on T lymphocyte proliferation in vitro was seen in 20 normal individuals. It has been observed that the neurotransmitter had a suppressive effect on mitogen-induced lymphocyte proliferation. This study shows that the effect of serotonin on the immune system is direct.

Cells, Cultured↗
PubMed1983

Immunofluorescence test for the epidemiological monitoring of acute haemorrhagic conjunctivitis cases.

An epidemic of acute haemorrhagic conjunctivitis (AHC) occurred in and around Chandigarh, north India, during June, July and August 1981. Considering the difficulty of virus isolation, the indirect immunofluorescence test was used for the demonstration of virus-specific antigen in the cytoplasm of exfoliated conjunctival cells, using reference antisera. The epidemic appeared to be primarily due to enterovirus type 70. The method was found suitable for the rapid diagnosis of AHC cases and for detecting subclinical infection among healthy subjects and convalescent carriers. During follow-up, it was observed that some of the AHC cases were shedding virus-infected conjunctival cells for a prolonged period, even after clinical recovery and during convalescence, before they became free from virus. In the absence of virus isolation, this method can be considered as suitable for the epidemiological monitoring of AHC.

Acute Disease↗