Search PubMed⌕ Search

Biomedical subjects

R Chopra

Publications and source records attributed to R Chopra.

At least 55 records · Page 3Linked to original sources
PubMed1999

Acute pneumonitis with pulmonary hemorrhage an uncommon and potentially fatal complication of systemic lupus erythematosus: a case report.

Acute pneumonitis with diffuse alveolar haemorrhage is potentially fatal. When it occurs in a patient of systemic lupus erythematosus, the primary disease itself may be responsible for it; rather than any complicating infection or metabolic/physiological derangement. Diagnosis of primary pulmonary involvement by systemic lupus erythematosus can only be made on open lung biopsy coupled with immunofluorescent and/or ultrastructural studies. Early diagnosis of acute pulmonary complications in systemic lupus erythematosus patients is essential as specific management is reported to improve the chances of recovery.

Adolescent↗
PubMed1998

Structure of a covalently trapped catalytic complex of HIV-1 reverse transcriptase: implications for drug resistance.

A combinatorial disulfide cross-linking strategy was used to prepare a stalled complex of human immunodeficiency virus-type 1 (HIV-1) reverse transcriptase with a DNA template:primer and a deoxynucleoside triphosphate (dNTP), and the crystal structure of the complex was determined at a resolution of 3.2 angstroms. The presence of a dideoxynucleotide at the 3'-primer terminus allows capture of a state in which the substrates are poised for attack on the dNTP. Conformational changes that accompany formation of the catalytic complex produce distinct clusters of the residues that are altered in viruses resistant to nucleoside analog drugs. The positioning of these residues in the neighborhood of the dNTP helps to resolve some long-standing puzzles about the molecular basis of resistance. The resistance mutations are likely to influence binding or reactivity of the inhibitors, relative to normal dNTPs, and the clustering of the mutations correlates with the chemical structure of the drug.

Anti-HIV Agents↗
PubMed1998

Zinc-dependent dimers observed in crystals of human endostatin.

The crystal structure of human endostatin reveals a zinc-binding site. Atomic absorption spectroscopy indicates that zinc is a constituent of both human and murine endostatin in solution. The human endostatin zinc site is formed by three histidines at the N terminus, residues 1, 3, and, 11, and an aspartic acid at residue 76. The N-terminal loop ordered around the zinc makes a dimeric contact in human endostatin crystals. The location of the zinc site at the amino terminus, immediately adjacent to the precursor cleavage site, suggests the possibility that the zinc may be involved in activation of the antiangiogenic activity following cleavage from the inactive collagen XVIII precursor or in the cleavage process itself.

Base Sequence↗
PubMed1998

BCR-ABL activates pathways mediating cytokine independence and protection against apoptosis in murine hematopoietic cells in a dose-dependent manner.

The hallmark of chronic myeloid leukemia (CML) is the chimeric tyrosine kinase oncogene bcr-abl. Since expression of bcr-abl mRNA frequently increases with disease progression and a duplication of the Philadelphia chromosome (harbouring the bcr-abl hybrid locus) represents the most frequent karyotypic abnormality in acute phase CML, we hypothesized that the level of BCR-ABL protein may affect the disease phenotype. Therefore, the biological effects of high and low levels of BCR-ABL expression were compared in growth factor-dependent and -independent myeloid and lymphoid cell lines. Our results demonstrated that low levels of BCR - ABL were sufficient to render these cell lines growth factor independent and tumorigenic, but higher levels were mandatory for additional protection against apoptotic stimuli. The provision of growth factor or an activated ras oncogene did not afford the same degree of protection as high levels of BCR-ABL and there were qualitative differences between the survival signals mediated by BCR-ABL and Bcl-2. These results have enabled us to establish a dose-dependent hierarchy of BCR-ABL induced biological effects, thus distinguishing the activation of pathways mediating protection from cytokine withdrawal from those protecting against other apoptotic stimuli.

Animals↗
PubMed1998

A truncated isoform of the human beta chain common to the receptors for granulocyte-macrophage colony-stimulating factor, interleukin-3 (IL-3), and IL-5 with increased mRNA expression in some patients with acute leukemia.

We report here a naturally occurring isoform of the human beta chain common to the receptors for granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and IL-5 (GMRbetaC) with a truncated intracytoplasmic tail caused by deletion of a 104-bp exon in the membrane-proximal region of the chain. This beta intracytoplasmic truncated chain (betaIT) has a predicted tail of 46 amino acids, instead of 432 for betaC, with 23 amino acids in common with betaC and then a new sequence of 23 amino acids. In primary myeloid cells, betaIT comprised approximately 20% of the total beta chain message, but was increased up to 90% of total in blast cells from a significant proportion of patients with acute leukemia. Specific anti-betaIT antibodies demonstrated its presence in primary myeloid cells and cell lines. Coexpression of betaIT converted low-affinity GMRalpha chains (KD 2.5 nmol/L) to higher-affinity alphabeta complexes (KD 200 pmol/L). These could bind JAK2 that was tyrosine-phosphorylated by stimulation with GM-CSF. betaIT did not support GM-CSF-induced proliferation when cotransfected with GMRalpha into CTLL-2 cells. Therefore, it may interfere with the signal-transducing properties of the betaC chain and play a role in the pathogenesis of leukemia.

Acute Disease↗
PubMed1998

Respiratory syncytial virus infection in adult BMT recipients: effective therapy with short duration nebulised ribavirin.

Respiratory syncytial virus (RSV), a common cause of both upper and lower respiratory tract infection (LRTI) in infants and children, is rarely described as an infective agent in adults. It has been reported in bone marrow transplant (BMT) recipients and patients with malignancy immunosuppressed by chemotherapy. Such reports are often associated with a high mortality. We report an outbreak of RSV infection which occurred predominantly in BMT recipients in which early investigation and institution of ribavirin therapy resulted in all patients making a full recovery.

Adult↗
PubMed1998

A comparative analysis of lipid-complexed and liposomal amphotericin B preparations in haematological oncology.

No comparative clinical information on the properties of lipid-associated amphotericin preparations is presently available. In this single-centre retrospective analysis over a 5-year period the indications, efficacy and toxicity of true liposomal amphotericin (AmBisome) were compared with a lipid complexed preparation (Abelcet). In a novel approach APACHE III scores were used in addition to neutrophil counts, disease status and additional immunosuppression to accurately assess the severity of illness in both groups and enable valid comparison. Overall, AmBisome at a median dose of 1.9 mg/kg/d was found to have similar clinical outcome to Abelcet at a median dose of 4.8 mg/kg/d. Nephrotoxicity and electrolyte abnormalities were similar in both groups. Rigors and febrile episodes were more common with Abelcet. Prospective randomized comparative trials are required to clarify the optimum dosages and therapeutic and economic issues associated with these agents.

Adult↗
PubMed1998

Specificity and synergism of polypeptide growth factors in stimulating the synthesis of proteoglycans and a novel high molecular weight anionic glycoprotein by articular chondrocyte cultures.

OBJECTIVE: To determine the specificity of and possible synergism among polypeptide growth factors (PGF) on the net synthesis of proteoglycan and a novel high molecular weight anionic glycoprotein (HMW AG), of roughly 540 kDa, by articular chondrocyte cultures. METHODS: Confluent articular chondrocyte cultures were labeled with either [35S]SO4 or [3H]glucosamine and [35S]SO4 and stimulated by adding the individual PGF or combinations of the PGF. Alcian blue dye precipitation was used for direct rapid quantification of newly synthesized proteoglycans from the media of the 35S labeled cultures. To assess the effects of the PGF on the synthesis of the HMW AG, a toluidine blue dye batch precipitation method was used for isolation of anionic glycoconjugates from the media of the 3H and 35S labeled articular chondrocyte cultures, followed by chondroitinase ABC digestion and gradient sodium dodecyl sulfate polyacrylamide gel electrophoresis. RESULTS: Optimal concentrations of transforming growth factor-beta1 (TGF-beta), insulin-like growth factor-1 (IGF), and platelet derived growth factor (PDGF) stimulated net proteoglycan synthesis per cell by 178, 106, and 101%, respectively. In combinations, TGF-beta + PDGF, TGF-beta + IGF, and PDGF + IGF gave stimulations of proteoglycan synthesis of 418, 384, and 217%, respectively. HMW AG net synthesis was induced by all 3 PGF, but the degree of induction was much greater with TGF-beta. CONCLUSION: Net proteoglycan synthesis by articular chondrocyte cultures is synergistically stimulated by the addition of optimal concentrations of combinations of TGF-beta + PDGF and TGF-beta + IGF, but not PDGF + IGE Net HMW AG synthesis is preferentially stimulated by TGF-beta.

Animals↗
PubMed1998

In vitro suppression of transforming growth factor-beta induced stimulation of glycosaminoglycan synthesis by acetylsalicylic acid and its reversal by misoprostol.

OBJECTIVE: To determine if acetylsalicylic acid (ASA) suppresses the stimulatory effects of transforming growth factor-beta (TGF-beta) and insulin-like growth factor-1 (IGF-1) on glycosaminoglycan (GAG) synthesis by cultured bovine articular chondrocytes (BAC), and whether such a suppression can be counteracted by the addition of misoprostol, a prostaglandin (PG) E1 analog. METHODS: Confluent cultures of BAC were pre-incubated for 2 days with ASA (Aspirin) (250 microg/ml), TGF-beta (10 ng/ml), IGF-1 (150 ng/ml), and misoprostol (80 ng/ml), separately and in different combinations, and for 2 more days with fresh medium and the same test agents in the presence of 35S-sulfate (10 microCi/ml). The radiolabelled GAG in the medium were then isolated, separated by cellulose acetate electrophoresis, and assayed for incorporated radioactivity, as a measure of GAG synthesis. RESULTS: TGF-beta, IGF-1, at their optimal concentrations, and misoprostol (80 ng/ml) stimulated GAG synthesis 2.6, 1.8, and 2.4-fold, respectively, of the control value, but ASA (250 microg/ml) showed no significant effect. ASA in combination with TGF-beta or misoprostol markedly suppressed the stimulation of GAG synthesis observed with either TGF-beta or misoprostol alone, but had no effect on the stimulation of GAG synthesis by IGF-1. Addition of misoprostol together with TGF-beta potentiated the stimulation of GAG synthesis by TGF-beta and abolished the suppressive effect of ASA on the stimulation of GAG synthesis by TGF-beta. Also, the magnitude of the stimulatory effect of misoprostol varied from batch to batch of misoprostol as well as for the same batch when it was added to the cultures either directly or after diluting with serum-free medium. CONCLUSION: In BAC cultures, ASA suppresses and misoprostol potentiates the stimulation of GAG synthesis by TGF-beta. Misoprostol also counteracts ASA induced suppression of the stimulation of GAG synthesis by TGF-beta.

Animals↗
PubMed1997

Frequency of the G6PD nt 1311 C/T polymorphism in English and Iranian populations: relevance to studies of X chromosome inactivation.

X chromosome inactivation is widely studied using DNA sequence polymorphisms and DNA methylation as a surrogate measure of inactivation, but the correlation of methylation with inactivation is not perfect. Thus, it may be better to study sequence polymorphisms expressed in the mRNA. A recent paper reported use of a silent C/T polymorphism at nt 1311 of the G6PD cDNA, and this polymorphism was reported to have a frequency of 40% in all ethnic groups. We have screened 218 English and 50 Iranian subjects by PCR and restriction digestion; 53/218 (24%) British and 22/50 (44%) Iranian subjects were heterozygous. Thus, X inactivation studies using this polymorphism may be useful in some populations, including Iran, but much less so in the UK.

Dosage Compensation, Genetic↗
PubMed1996

Expression of two alternatively spliced forms of the 5' untranslated region of the GM-CSF receptor alpha chain mRNA.

The granulocyte-macrophage colony-stimulating factor receptor (GM-CSFR) is composed of at least two chains (alpha and beta). The alpha chain binds GM-CSF specifically with low affinity, and the binding is converted to high affinity when the alpha chain is associated with the beta chain. To date, there are at least six isoforms described for the GM-CSFR alpha, all involving alternative splicing at the 3' end, which alters the coding region and hence the protein produced. To detect variants at the 5' end of the GM-CSFR alpha mRNA, RNAse protection and reverse transcriptase polymerase chain reaction (RT-PCR) assays were performed using a probe spanning nucleotides 102-392 and pairs of primers covering exons 1-4. in addition to the expected full-length transcript, two mRNAs were detected, one containing a deletion of 24 nucleotides by alternative splicing at the 3' end of exon 2 (exon 2b-deleted isoform) and another in which exon 2 was completely deleted (exon 2-deleted isoform). Together, the isoforms were more highly expressed form). Together, the isoforms were more highly expressed than the full-length sequence (TF-1 cells: full-length 36 +/- 2.8% vs. exon 2-deleted isoforms 64 +/- 5.5%). These isoforms were detected in primary hematopoietic cells, blasts from patients with acute myeloid leukemia (AML), and malignant cell lines and the relative mRNA expression for the isoforms, was always similar to that of TF-1 cells. As sequences in the 5'untranslated region can be involved in the modulation of translational efficiency, translation of constructs constructs corresponding to these exon 2 deleted isoforms was assessed using an in vitro reticulocyte lysate system. Deletion of exon 2 resulted in significantly lower in vitro translation of the receptor protein relative to the full-length sequence (53, 56, and 76% in three separate batches of reticulocytes), while deletion of exon 2b resulted in higher translation of the sequence (164, 128, and 305%; p = 0.01). These data suggest a mechanism by which expression of the GM-CSFR alpha protein may be regulated by alternatively spliced transcripts with different translational efficiencies.

Acute Disease↗
PubMed1995

Absence of N-RAS point mutations in peripheral blood cells of patients with aplastic anaemia and paroxysmal nocturnal haemoglobinurea.

The myelodysplastic syndromes (MDS) have a significant frequency of evolution into acute myeloid leukaemia (AML). Approximately 30% of MDS patients show activating mutations of the N-RAS proto-oncogene, and these patients are at increased risk of leukaemic evolution. Long-term survivors of aplastic anaemia (AA) and paroxysmal nocturnal haemoglobinurea (PNH) are also at significant risk of developing AML. We have screened peripheral blood DNA from 42 AA patients and 15 PNH patients for the presence of N-RAS point mutations. No mutations were detected in these samples, indicating that the mechanisms of evolution into AML may be different from those in MDS.

Acute Disease↗
PubMed1995

BEAM chemotherapy and autologous bone marrow transplantation for patients with relapsed or refractory non-Hodgkin's lymphoma.

PURPOSE: To evaluate the outcome of patients with relapsed or resistant non-Hodgkin's lymphoma (NHL) undergoing high-dose chemotherapy and autologous bone marrow transplantation (ABMT) and to determine the main prognostic factors. PATIENTS AND METHODS: One hundred seven patients with relapsed or resistant intermediate-/high-grade NHL underwent high-dose carmustine, etoposide, cytarabine, and melphalan (BEAM) chemotherapy and ABMT at University College Hospitals between September 1981 and February 1993. The minimum follow-up duration of all patients is 6 months. RESULTS: At 3 months, the overall response rate to BEAM and ABMT was 73% (41% complete response and 32% partial response). The 5-year actuarial overall survival and progression-free survival rates were 41% and 35%, respectively. The early procedure-related mortality rate was 7% (eight of 107 patients). On multivariate analysis, the main prognostic factor was disease status at the time of ABMT. Patients with chemosensitive disease had an actuarial 5-year survival rate of 49% at 5 years compared with 13% for those with chemoresistant disease (P < .001). For patients considered to have chemosensitive disease at the time of transplantation, there is a significant difference in the actuarial progression-free survival rates for those who received high-dose therapy after attaining a partial response to first-line therapy (69% at 5 years) as compared with those with sensitive but relapsed disease (32% at 5 years) (P = .003). CONCLUSION: Patients with chemosensitive disease benefit most from high-dose chemotherapy, and those who receive such therapy early after achieving a partial response to first-line therapy have a high rate of cure.

Adolescent↗
PubMed1995

Hodgkin's disease: a clinicopathologic study.

One hundred and four cases of Hodgkin's disease diagnosed between July 1981 and June 1991 have been analysed. There was a definite male preponderance. Majority of the patients (82.7%) were below the age of 50 years. Mixed cellularity was the most common type (57.7%). It was followed by both nodular sclerosis and lymphocyte predominant types (16.3% each). Lymphocyte depletion Hodgkin's disease, the most aggressive variant, was the least common (9.7%). The detailed observations, as compared to the previous studies in this region as well as in other parts of the world have been presented and discussed.

Adolescent↗
PubMed1995

Bone marrow involvement in Hodgkin's disease -- clinicopathological study of seven cases.

Bone marrow involvement was observed in 7 cases amongst a total of 75 cases of Hodgkin's disease encountered between January 1981 and June 1990; thus representing an incidence of 9.3 percent. Analysis of these 7 cases showed male preponderance. The age ranged from 26 to 74 years. All patients presented within seven months of onset of symptoms; and all had symptoms at presentation. Lymphadenopathy was found in all the cases, splenomegaly was present in six; and hepatomegaly in 4 cases. Mixed cellularity and lymphocytic depletion subtypes showed the highest frequency of marrow involvement (6 cases; 85.7 percent). Alkaline phosphatase was raised in 6 cases (85.7%). All cases received standard combination chemotherapy with or without local radiation therapy. Two years follow-up revealed an overall survival of 42.9%. Replace free survival at the end of two years was zero, as all the cases relapsed within seven months of initiation of treatment.

Adult↗
PubMed1995

Epithelioid granulomas in Hodgkin's disease--prognostic significance.

Prognostic significance of non-caseating epithelioid granulomas in association with Hodgkin's disease has been studied. Such granulomas were found in 15 of the total of 104 cases of Hodgkin's disease encountered between Jan. 1981 and June 1990. These 15 patients were compared with 30 concurrent patients of Hodgkin's disease who did not have associated granulomas. All the patients were initially staged, treated and followed up for a period of two years. There was no significant difference in overall survival rate between the granuloma group and the control group. However, in relapse free survival rate in advanced stages of the disease (III & IV), although the difference between granuloma group and the control group was not statistically significant (p = 0.11), yet the relapse free survival curves revealed a tendency towards better survival with lesser number of relapses and longer remissions in granuloma group.

Adolescent↗