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Biomedical subjects

R Bhatia

Publications and source records attributed to R Bhatia.

At least 73 records · Page 4Linked to original sources
PubMed1999

Epidemiological characteristics of poliomyelitis in Delhi, 1997.

OBJECTIVE: To describe the epidemiological characteristics of poliomyelitis in Delhi in 1997 after four consecutive statewide immunization campaigns with oral polio vaccine (OPV). METHODS: Stool samples were collected from 158 cases of acute flaccid paralysis (AFP) along with their age, sex, residential address, immunization history and dates of onset of paralysis, reporting and investigation. The samples were processed for isolation of polioviruses. In addition, historical data on vaccination coverage surveys and OPV testing were reviewed. These data were analyzed to understand the epidemiological patterns of poliomyelitis in Delhi. RESULTS: Of 158 cases of AFP, about 23% were investigated within 2 days of onset of paralysis. Two samples each were collected from 97 (61%) cases, and one each from the remaining cases. Detection of 158 cases of AFP gave an incidence of 1.34 per 100,000 population. About 36% (57/158) of AFP cases excreted poliovirus, mostly (53/158) wild poliovirus. Of the wild poliovirus isolates, 72% (38/53) and 25% (13/53) were serotypes P1 and P3 respectively; 2 isolates were P2. Almost 95% (146/154) of AFP cases and all the laboratory confirmed cases (excreting wild poliovirus) occurred in children below 5 years of age. Only one-third of AFP (55/158) or laboratory confirmed cases (18/53) had received 3 or more doses of OPV before onset of paralysis. About one-fourth of cases in both the categories were totally unvaccinated. AFP cases occurred round the year but peaked in November-December. Peaks were always observed during July-August in the past. The cases were widely scattered without any obvious clustering in any locality. CONCLUSIONS: Poliomyelitis has declined substantially in Delhi. The study underscores the need for further efforts to improve vaccine coverage levels, AFP surveillance, and cold chain maintenance to achieve the complete interruption of transmission.

Child↗
PubMed1998

Comparative analysis of autografting in chronic myelogenous leukemia: effects of priming regimen and marrow or blood origin of stem cells.

The aims of this study were (1) to evaluate the effect of intermediate (cyclophosphamide alone) or intensive (mitoxantrone, cytosine arabinoside, cyclophosphamide) priming on the cytogenetic response in mobilized bone marrow (BM) or peripheral blood (PB) progenitors in patients with chronic myelogenous leukemia (CML), (2) to determine the incidence of cytogenetic remissions after mobilized progenitor transplantation in CML, and (3) to determine the effect of in vivo priming on the ability to select Philadelphia chromosome-negative (Ph-negative) CD34(+)HLA-DR- cells from mobilized BM or PB in quantities sufficient for transplantation. Between February 1994 and March 1997, 44 patients were enrolled in three sequential protocols. Although the duration of neutropenia after only cyclophosphamide mobilization was shorter, clinical morbidity for the intermediate and intensive priming protocols was similar. Cytogenetic responses in mobilized PB progenitors were similar after mobilization with either intermediate or intensive chemotherapy. The degree of Ph negativity in the mobilized product correlated with disease stage at the time of mobilization (early chronic phase [ECP] > late CP > accelerated phase). Cytogenetic responses after transplantation with mobilized progenitors obtained after the different regimens were similar. The cytogenetic status of the graft predicted the cytogenetic status of marrow obtained 3 weeks after transplantation whereas cytogenetic responses 3, 6, and 12 months after transplantation correlated with the number of BCR/ABL-negative CD34(+)HLA-DR- cells, but not the number of Ph-negative metaphases in the graft. In patients with ECP CML, mobilized PB collections yielded significantly more CD34(+)HLA-DR- cells than from steady state or mobilized BM. CD34(+)HLA-DR- cells were Ph negative and polyclonal (X-chromosome inactivation) in the majority of ECP CML patients, before and after mobilization and irrespective of the mobilization regimen. Because infusion of large numbers of Ph-negative CD34(+)HLA-DR- cells predicted superior outcome after transplantation, approaches in which CD34(+)HLA-DR- cells are selected from mobilized PB may result in longer lasting and clinically significant cytogenetic responses after transplantation.

Adult↗
PubMed1998

Cloning and sequencing of the cDNA for an RNA-binding protein from the Mexican axolotl: binding affinity of the in vitro synthesized protein.

A full length cDNA for an RNA-binding protein (axolotl RBP) with consensus sequence (RNP-CS) from the Mexican axolotl, Ambystoma mexicanum, has been cloned from a subtraction library. In vitro translation with synthetic mRNA and subsequent hybrid-arrested translation with a specific antisense oligonucleotide confirms that the axolotl RBP cDNA encodes an approx. 16 kDa polypeptide. Computer-assisted analyses revealed amino acid similarities of 58-60% to various RNA-binding proteins and a 90 amino acid region at the amino-terminal end constituting the putative RNA-binding domain (RNP-CS) with two highly conserved motifs, RNP2 and RNP1. Phylogenetic analysis suggests that the putative RNA-binding protein from axolotl is unique. A binding assay with radiolabeled axolotl RBP showed that this RNA-binding protein bound strongly with poly(A) and to a lesser degree with poly(U), but not at all with poly(G), poly(C), or DNA.

Ambystoma mexicanum↗
PubMed1998

Inhibition of BCR-ABL expression with antisense oligodeoxynucleotides restores beta1 integrin-mediated adhesion and proliferation inhibition in chronic myelogenous leukemia hematopoietic progenitors.

Chronic myelogenous leukemia (CML) is characterized by the continuous proliferation and abnormal circulation of malignant hematopoietic progenitors. This may be related to the unresponsiveness of CML progenitors to beta1 integrin adhesion receptor-mediated inhibition of progenitor proliferation by the marrow microenvironment. In hematopoietic cell lines, the BCR-ABL oncogene product, p210(BCR-ABL), interacts with a variety of cytoskeletal elements important for normal integrin signaling. We studied the role of p210(BCR-ABL) in abnormal integrin function in CML by evaluating the effect of inhibition of BCR-ABL expression with antisense oligodeoxynucleotides (AS-ODNs) on integrin-mediated adhesion and proliferation inhibition of malignant primary progenitors from CML marrow. Preincubation of CML CD34(+)HLA-DR+ (DR+) cells with breakpoint-specific AS-ODNs significantly increased adhesion of CML progenitors to stroma and fibronectin (FN). Pretreatment with breakpoint-specific ODNs also resulted in significant inhibition of CML progenitor proliferation after ligand or antibody-mediated beta1 integrin engagement. Breakpoint-specific ODNs were significantly more effective in restoring CML progenitor adhesion and proliferation inhibition than control ODNs. BCR-ABL mRNA and p210(BCR-ABL) levels in CML CD34(+) cells were significantly reduced after incubation with breakpoint-specific AS-ODN. These studies indicate a role for BCR-ABL in abnormal circulation and defective integrin-dependent microenvironmental regulation of proliferation of CML hematopoietic progenitors.

Cell Adhesion↗
PubMed1998

The heart of metamorphosing Mexican axolotl but not that of the cardiac mutant is associated with the upregulation of Hox A5.

The Mexican axolotl (Ambystoma mexicanum) is a facultative neotene which rarely undergoes metamorphosis in the wild. We now report for the first time a dramatic increase in the expression of HoxA5 in axolotl hearts as determined by RT-PCR and in situ hybridization analyses during spontaneous metamorphosis. The Mexican axolotl has a naturally occurring mutation called gene c which allows hearts in homozygous (c/c) embryos to form but never to beat. RT-PCR analysis has not shown any significant differences of HoxA5 expression in normal and mutant hearts. The predicted open reading frame of our already published partial cDNA clone of HoxA5 was confirmed by expressing it as a fusion protein with Glutathione transferase (GST fusion protein). Phylogenetic analysis with the deduced amino acid sequence of the isolated cDNA of the axolotl homolog of the murine HoxA5 shows that the axolotl sequence clusters more closely with the human and mouse HoxA5 homologs than with axolotl sequence. Western blot analysis revealed that anti-mouse HoxA5 antibody recognizes the axolotl HoxA5 protein.

Ambystoma mexicanum↗
PubMed1998

Interferon-alpha restores beta1-integrin-dependent, collagen-mediated platelet aggregation in a patient with chronic myelogenous leukemia.

Although interferon-alpha (IFN-alpha) induces hematologic remissions in 70% to 80% of patients with chronic myelogenous leukemia (CML) and complete or near-complete cytogenetic remissions in 10% to 20% of patients, the exact mechanisms underlying these clinical results remain unclear. We have hypothesized that IFN-alpha acts at least in part through restoration of beta1-integrin function on malignant hematopoietic progenitors that can promote adhesion of malignant progenitors to the marrow microenvironment. This may then restore microenvironmental inhibition of progenitor proliferation and induce tumor dormancy. We demonstrate that IFN-alpha administration to a patient suffering from a clinically severe bleeding diathesis reversed the defective collagen-mediated aggregation of platelets expressing normal numbers of functionally inactive collagen receptors. This is the first in vivo demonstration that IFN-alpha can up-regulate the function of adhesion receptors in CML and supports the premise that IFN-alpha induces remissions by restoring normal integrin-mediated interactions between progenitors and microenvironmental components.

Collagen↗
PubMed1998

Autologous transplantation for the treatment of chronic myelogenous leukemia.

There is evidence that benign, Ph-negative hematopoietic progenitors persist in the marrow and blood of some patients with chronic myelogenous leukemia (CML). A number of pilot studies using purged and unpurged marrow or peripheral blood autografts have demonstrated that autologous transplantation can result in transient cytogenetic responses in CML. Although not curative, this procedure may be associated with longer-than-expected patient survival and represents an alternative treatment for patients ineligible for allogeneic transplantation and not responding to interferon-alpha therapy. Several novel approaches are being developed to improve graft purging and eliminate residual leukemia post-transplantation. Such approaches may allow for long-term restoration of Ph-negative hematopoiesis following the procedure.

Bone Marrow Purging↗
PubMed1998

Tyrphostin AG957, a tyrosine kinase inhibitor with anti-BCR/ABL tyrosine kinase activity restores beta1 integrin-mediated adhesion and inhibitory signaling in chronic myelogenous leukemia hematopoietic progenitors.

Abnormal beta1 integrin receptor function may contribute to the continuous proliferation and abnormal circulation of malignant hematopoietic progenitors in chronic myelogenous leukemia (CML). Previous studies suggest that abnormal integrin function in CML progenitors is related to the presence of the BCR/ABL oncogene. BCR/ABL may alter integrin function in CML by phosphorylating cytoskeletal and/or signaling proteins important for normal integrin function. We evaluated the effect of Tyrphostin AG957, a protein tyrosine kinase (PTK) inhibitor which has activity against the p210BCR/ABL kinase, on beta1 integrin function in CML progenitors. Incubation of CML marrow CD34+HLA-DR+ cells with Tyrphostin AG957 at concentrations that did not affect colony-forming cells (CFC) viability, but which partly inhibited p210BCR/ABL kinase activity, significantly increased CML CFC adhesion to stroma and alpha4beta1 and alpha5beta1 integrin binding fragments of fibronectin (FN). CML CFC proliferation, unlike that of normal CFC, is not inhibited following integrin receptor engagement with FN or anti-integrin antibodies. AG957 did not alter CML CFC proliferation by itself, but resulted in significant inhibition of CML CFC proliferation following integrin engagement. Another PTK inhibitor, Tyrphostin AG555, which does not have anti-p210BCR/ABL kinase activity, did not affect CML CFC adhesion or proliferation. Neither AG957 nor AG555 affected normal CFC adhesion or proliferation. In BCR/ABL expressing cells, AG957 partially inhibited phosphorylation of several proteins that are BCR/ABL PTK substrates and are involved in normal integrin signaling. These studies suggest that abnormal tyrosine phosphorylation may play an important role in defective integrin function in CML progenitors.

Cell Adhesion↗
PubMed1998

Epidemiologic consequences of moderate coverage levels of measles vaccine in a district headquarter town (Alwar) in India, 1996.

This paper describes the epidemiology of measles in a medium size town (population 240,000) in India where vaccine coverage levels have remained constant at around 70 per cent in the past 7 years. A retrospective community survey covering 4023 children under 10 years old detected 252 cases of measles in the previous year. This gave an annual incidence of 6.3 per cent (95 per cent CI 5.5-7). About half of the cases occurred in vaccinated children. Only 5 per cent of the cases occurred in children below 9 months of age. This age is appropriate for routine measles immunization. Despite modest coverage levels with only 54 per cent effective vaccine (estimated by a screening method), there was a modest upward shift in the age distribution of measles cases; the median age was more than 48 months.

Age Distribution↗
PubMed1998

The effect of interferon-alpha on beta-1 integrin mediated adhesion and growth regulation in chronic myelogenous leukemia.

There is considerable interest in understanding the mechanisms by which interferon-alpha can induce hematological and cytogenetic remissions and prolong survival in patients with chronic myelogenous leukemia (CML). There is evidence that the selective expansion and growth advantage of malignant hematopoietic progenitors in CML may be related, at least in part, to their deficient responsiveness to normal negative regulation by the marrow stromal microenvironment and that interferon-alpha may restore normal hematopoiesis in CML by restoring normal microenvironmental regulation of malignant CML progenitor proliferation. In normal hematopoiesis, beta1 integrin receptors mediate progenitor adhesion to stroma. Stimulation of beta1 integrin receptors on normal progenitors results in transmission of proliferation inhibitory signals. CML progenitors demonstrate defective beta1 integrin receptor-mediated adhesion and regulation of proliferation. We have shown that interferon-alpha can restore both beta1 integrin mediated adhesion as well as integrin-mediated proliferation inhibition of CML progenitors. Interferon-alpha enhances CML integrin function through direct effects on CML progenitors as well as indirect effects on stroma. Restored beta1 integrin-mediated regulation of malignant CML progenitor proliferation may result in restoration of normal hematopoiesis in CML patients treated with interferon-alpha. There is evidence that abnormal integrin mediated signaling in CML progenitors may result from abnormalities in integrin-cytoskeletal interactions induced by the p210BCR/ABL tyrosine kinase. Although the exact mechanisms by which interferon-alpha restores normal integrin signaling in CML are not known, preliminary studies indicate that this may at least partly be related to the restoration of normal integrin-cytoskeletal interactions. The above studies offer some insights into the mechanisms of abnormal hematopoietic regulation in CML and the mechanisms by which interferon-alpha may restore normal hematopoiesis, in this disease.

Antineoplastic Agents↗
PubMed1998

Transplacental transfer of measles antibody in Delhi.

OBJECTIVE: To find out the patterns of and the factors, if any, affecting the transplacental transfer of measles antibody. DESIGN: Comparison of measles antibody titres in mothers with titres in cord blood samples. METHODS: Maternal and cord blood samples from 174 full-term pregnant women of middle socio-economic status were tested for hemagglutination inhibition (HI) antibody against measles in Delhi during October 1993 to January 1995. None of the mothers had been immunized against measles. RESULTS: Antibody were undetectable in both maternal and cord samples in only 4 (2.3%) pairs. Mean maternal titre was found to be 2.94 Log2. Transplacental concentration and dilution were respectively observed in 34% and 26% of the samples. Cord titres were more often higher than the maternal values only if the maternal values were low. Overall, cord/maternal ratio of mean titre (Log2) was found to be 1.06. Although the age of the mother and parity had had no significant bearing on the transplacental transfer of measles antibody, cord titres were significantly more often higher than the maternal values as the birth weight increased (Chi-square for linear trend = 5.4; p = 0.02). CONCLUSIONS: The study failed to show appreciable concentration of measles antibodies across the placenta.

Adolescent↗
PubMed1998

Diesel exhaust exposure and lung cancer.

We evaluated the relation between occupational exposure to diesel exhaust and cancer of the lung in a meta-analysis of 29 published cohort and case-control studies. Twenty-one of the 23 studies meeting the inclusion criteria had observed relative risk estimates greater than one. Pooled effect measures weighted by study precision indicated an increased relative risk (RR) for lung cancer from occupational exposure to diesel exhaust [RR = 1.33; 95% confidence interval (CI) = 1.24-1.44]. Subanalysis of case-control (RR = 1.33; 95% CI = 1.18-1.51) vs cohort studies (RR = 1.33; 95% CI = 1.21-1.47) and of studies that controlled for smoking (RR = 1.35; 95% CI = 1.20-1.52) vs those that did not (RR = 1.33; 95% CI = 1.20-1.47) produced results that did not differ from those of the overall analysis. On the other hand, cohort studies using internal comparisons (RR = 1.43; 95% CI = 1.29-1.58) showed higher relative risks than those using external comparisons (RR = 1.22; 95% CI = 1.04-1.44). Heterogeneity between studies was reduced when we stratified studies by the occupational setting in which exposure occurred. A positive duration-response relation was evident in those studies that were stratified by employment duration. This meta-analysis supports a causal association between increased risks for lung cancer and exposure to diesel exhaust.

Case-Control Studies↗
PubMed1998

Outbreak of viral hepatitis B in a rural community in India linked to inadequately sterilized needles and syringes.

In India, virtually all outbreaks of viral hepatitis are considered to be due to faeco-orally transmitted hepatitis E virus. Recently, a cluster of 15 cases of viral hepatitis B was found in three villages in Gujarat State. The cases were epidemiologically linked to the use of inadequately sterilized needles and syringes by a local unqualified medical practitioner. The outbreak evolved slowly over a period of 3 months and was marked by a high case fatality rate (46.7%), probably because of concurrent infection with hepatitis D virus (HDV) or sexually transmitted infections. But for the many fatalities within 2-3 weeks of the onset of illness, the outbreak would have gone unnoticed. The findings emphasize the importance of inadequately sterilized needles and syringes in the transmission of viral hepatitis B in India, the need to strengthen the routine surveillance system, and to organize an education campaign targeting all health care workers including private practitioners, especially those working in rural areas, as well as the public at large, to take all possible measures to prevent this often fatal infection.

Adult↗
PubMed1998

Prevalence of North India of hepatitis B carrier state amongst pregnant women.

The study was undertaken to determine the hepatitis B carrier rate in North India along with the relative infectivity of the carriers. A total of 1,112 pregnant women were investigated for hepatitis B carrier state during their routine visits to antenatal clinics. All three tiers of the health care delivery system were included from four regions of North India. The sera were screened for the presence of hepatitis B surface antigen (HBsAg), hepatitis B "e" antigen (HBeAg), and antibody to hepatitis B "e" antigen (Anti-HBe) by third generation Macro ELISA tests. The average hepatitis B surface antigen carrier rate was 9.5%. The carriers were found to be of relatively low infectivity with HBeAg and Anti-HBe present in 12.0% and 25.3% of the HBsAg carriers respectively, and both these markers absent in 62.7%. It was concluded that in the past decade the hepatitis B endemicity in North India has probably increased, but the relative infectivity of the carriers remains the same.

Carrier State↗
PubMed1998

Endemic cholera in Delhi, 1995: analysis of data from a sentinel centre.

Data on cholera cases admitted to the Delhi Infectious Diseases Hospital (IDH) are presented to describe the pattern of occurrence of cholera in Delhi in 1995. Rectal swabs from 4082 cases of acute diarrhoea admitted to the IDH were examined for excretion of Vibrio cholerae. Of them, 2004(49%) and 4(0.1%) were positive for V. cholerae O1 biotype El Tor and V. cholerae O139 respectively. Most cholera cases occurred during May-September (summer and monsoon months). The period from January to March (winter) was completely free from cholera. The urban areas were not affected uniformly. Of the 80 PIN (Postal Index Number) code areas, 10 contributed to 57% of the cases. The early cases were scattered in PIN code areas distant from one another. The hospitalisation rates for cholera were the highest in children aged less than five years and declined significantly with increasing patients' age. Males had significantly higher rates than females aged up to 20 years, whereas the situation was reversed in the 20 to 39 year age group. Four per cent of the affected families had multiple cases. An estimated 1% of the household contacts of hospitalised cases of cholera were themselves hospitalised for cholera within 2 days of the first admission. Of the 260 V. cholerae O1 isolates tested, 4%, 7%, 8%, 89%, 91% and 95% were resistant to tetracycline, nalidixic acid, chloramphenicol, co-trimoxazole, streptomycin, and furazolidone respectively. The study highlights the usefulness of surveillance data to identify groups, urban areas and seasons with increased risk for cholera and to allow control measures to be focussed on those in greatest need.

Adolescent↗