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Biomedical subjects

A Bhargava

Publications and source records attributed to A Bhargava.

At least 55 records · Page 3Linked to original sources

Developmental regulation of human gamma- and beta-globin genes in the absence of the locus control region.

Two lines of transgenic mice carrying a normal 40-kb Kpn I beta-globin cluster transgene lacking the locus control region (LCR) were analyzed for the expression of human gamma- and beta-globin genes during mouse development. After RNase protection assays, the ratios of human G gamma-, A gamma-, or beta-mRNAs relative to endogenous mouse zeta + alpha mRNAs were obtained for each stage of development. The two gamma transgenes were expressed in day-11.5 blood (embryonic stage) and day-13.5 blood (early fetal stage), but their expression was markedly decreased by day 16.5 of fetal life. Expression of the beta transgene was essentially absent at day 13.5, appeared at a low level by day 16.5, and was maximal by day 18.5, reaching a level similar to that observed in adult mice. Therefore, developmentally regulated expression of the human gamma- and beta-globin transgenes was obtained in the absence of the LCR. The relative expression of human gamma- and beta-globin genes was also examined in mice carrying 40-kb Kpn I beta-cluster transgenes with two different base substitutions associated with nondeletion forms of hereditary persistence of fetal hemoglobin (HPFH), -202 C-->G G gamma HPFH and -117 G-->A A gamma HPFH. The ratio of G gamma- to beta-globin transcripts was markedly increased in red blood cells of adult mice from three different lines carrying the transgene with the -202 G gamma HPFH mutation. This result confirms our previous preliminary results (Tanaka et al: Ann NY Acad Sci, 612:167, 1990) indicating that the -202 G gamma HPFH phenotype was reproduced in transgenic mice. The relatively low levels of G gamma-mRNA expression in adult mice carrying the non-HPFH transgene excludes a major influence of the 3' beta-globin enhancer, present upstream of the G gamma gene because of the tandem repeat insertion, as a factor in the persistent G gamma gene expression observed in blood of adult mice carrying the -202 G gamma HPFH transgene. This conclusion is also supported by the fact that, in mice carrying the -117 A gamma HPFH transgene, G gamma-globin mRNA was detected in blood of adult animals only at low levels similar to that observed in the non-HPFH lines. However, the A gamma-HPFH phenotype was not reproduced in the transgenic lines carrying the -117A gamma HPFH mice.

Animals↗

Estimating the variations and autocorrelations in dietary intakes on weekdays and weekends.

The high incidence of breast cancer in the U.S. and the possible link with dietary fat has led to the development of educational programmes for reducing women's fat intakes by agencies such as the National Cancer Institute and the U.S. Department of Agriculture. In this paper, we analyse the effects of an intervention on the intakes of 12 nutrients by 37 women in the Houston area. We estimate a dynamic random effects model by maximum likelihood to estimate the between and the within variations and the autocorrelations using 7 consecutive food records before and after the intervention programme. The main findings are that the pattern of within variations differs during weekdays and weekends. Secondly, the mean intakes of nutrients such as beta-carotene and ascorbic acid tend to be lower on weekends. Lastly, the intervention programme reduced the overall fat intakes and also increased the variation in the consumption of foods high in fats during weekdays. We discuss the implications of the results for the design of further studies.

Adult↗

Breast cancer marker Ca549. A multicenter study.

A multicenter study of CA549, a marker for breast cancer, was conducted using sera from 1721 patients with benign and malignant conditions by an immunoradiometric assay, BRESMARQ. Acceptable assay performance was demonstrated by studies of intra-assay (2.2% to 12% coefficient of variation [CV]), interassay (4.1% to 11.8% CV), and interlaboratory (4.8% to 8.7% CV) precision; sensitivity (.3 kU/L); linearity; recovery; high-dose hook effect (up to 10,000 kU/L); and interferences (human antimouse antibodies; protein, bilirubin, hemoglobin levels; lipid and cancer therapeutic agents). A reference interval of 0-12.5 kU/L (women) and 0-11.9 kU/L (men) was established from 746 healthy persons. The distribution of values exceeding the reference range for benign conditions was as follows: pregnant and lactating women (2%); benign breast disease (5%); and seven other benign diseases, including liver (24%), lung (19%), prostate (14%), colon, endometrial, gastric, and ovarian (< 10%). For nonbreast cancers, the distribution was Hodgkin's (7%), colon (10%), endometrial (15%), gastric (15%), lymphoma (15%), prostate (20%), ovarian (39%), and liver (45%). For breast cancer, the distribution was stage I (5%), stage II (14%), stage III (32%), and stage IV (74%). The receiver-operating characteristic analysis demonstrated the usefulness of CA549 as a marker in stage IV breast cancer.

Antibodies, Monoclonal↗

Effect of parenteral magnesium sulfate on pulmonary functions in bronchial asthma.

Eighteen patients with bronchial asthma were studied in a single-blind fashion. Each patient received an infusion of magnesium sulfate (MgSO4.7H2O 50% W/V) in a dose equivalent to 10 mmol of elemental magnesium. The airways resistance showed a significant decrease (p < 0.01) while SGaw increased significantly (p < 0.001) with MgSO4 infusion. FEV1 (p < 0.01), FEF25-75% (p < 0.05), and V50 (p < 0.05) also showed statistically significant increase (p < 0.001) with MgSO4 infusion. Significant changes in Raw (p < 0.01) and SGaw (p < 0.01) persisted at 10 and 20 min following MgSO4 infusion. No significant side effects were observed with MgSO4 infusion. It is concluded that modest improvement in airways resistance and specific conductance and only small improvement in maximal expiratory flow rates is consistent with a predominant effect of MgSO4 on large airways in patients with bronchial asthma.

Adolescent↗

The scapular fasciocutaneous flap: a new flap for reconstruction of the posterior neck.

The axial, myocutaneous and free flaps have made immediate reconstruction of head and neck defects possible. Notwithstanding this remarkable progress, defects of the posterior neck leave the reconstructive surgeon with very little choice. The scapular fasciocutaneous flap is easy to harvest, reliable and versatile, with functional and cosmetic results comparable to free flaps. We describe the anatomy and the technique of this new donor site, along with a case report.

Adult↗

Altered immunoglobulin A (IgA-1) levels in patients with advanced colorectal adenocarcinoma presenting with normal preoperative levels of carcinoembryonic antigen (CEA).

We investigated the value of serum IgA-1 as a complementary tumour marker to carcinoembryonic antigen (CEA) in the monitoring of the postoperative follow-up of 19 patients with advanced colorectal carcinoma presenting with normal levels of CEA. Mean follow-up period was 14 months (range 2-72 months). Mean number of serum specimens was 5 (range 2-9). IgA-1 assay employed rabbit antihuman IgA for binding IgA-1 from patient's serum and peanut agglutinin to detect the IgA-1 O-glycosidic structure. Ten patients developed distant metastases while nine patients had locoregional recurrence. All 19 patients had generally persistent elevation of serum IgA-1 throughout the follow-up period while serum CEA levels were subsequently elevated in only 10 patients. IgA-1 predicted recurrence with an average lead time of 8 months (range 1-19 months). On the other hand, mean lag time for CEA was 12 months (range 6-50 months). The data indicate the clinical utility of serum IgA-1 as a potential complementary tumour marker to CEA in the monitoring of the postoperative course of this particular subset of colorectal cancer patients.

Adenocarcinoma↗

The utility of squamous cell carcinoma antigen for the follow-up of patients with squamous cell carcinoma of the anal canal.

BACKGROUND: Thirty-three patients with histologic documentation of squamous cell carcinoma (SCC) of the anal canal underwent prospective serial collection of 234 serum samples for radioimmunoassay of SCC tumor-associated antigen. METHODS: There were 23 female and 10 male patients, with a median age of 55 years. Twenty-two of the 33 patients had multimodality therapy with radiation therapy and chemotherapy as initial treatment. RESULTS: The median follow-up was 22 months (range, 4-52 months), with a median of 13 serum specimens per patient (range, 1-23 specimens). Twenty-eight patients currently have no evidence of disease, 4 patients are alive with disease, and 1 patient died with disease. CONCLUSION: In these 33 patients, the sensitivity of the SCC tumor-associated antigen was 76%, specificity 86%, and positive predictive value 62%.

Adult↗

Maximum likelihood estimation of between and within variations in energy and protein intakes from infancy to adolescence for the Philippines.

The assessment of subjects' 'usual' intake of nutrients is important in assessing relationships between diet and disease and in identifying malnourished sub-groups of the populations. Estimation of the variation in intakes within subjects over time ('within variation') has importance in epidemiologic research; estimation of the between subject variation in the sample has use in defining the recommended dietary allowances that take into account the inter-individual differences. This paper estimates the between and within variances in the energy and protein intakes of 1189 Filipino children, based on 4 rounds of 24-hour recall data within a dynamic framework by means of maximum likelihood. The main findings are that the proportion of variation due to the within variance is higher for children from poorer households. Also, from the estimates of dynamic regression models for nutrient intakes of children and adults, it appears that school programmes that provide subsidized foods with good sources of protein to the poorest among school attendees will be cost effective.

Adolescent↗

Comparative roles of the Arg-Gly-Asp sequence present in the Bordetella pertussis adhesins pertactin and filamentous hemagglutinin.

Pertactin and filamentous hemagglutinin (FHA), proteins present on the surface of the gram-negative organism Bordetella pertussis, have been shown to contain the putative cell-binding sequence arginine-glycine-aspartic acid (RGD) and to promote eukaryotic cell attachment. The attachment of epithelial cells to purified pertactin and the entry of B. pertussis into human HeLa cells are both inhibited by an RGD-containing peptide derived from the pertactin sequence. In contrast, an RGD-containing peptide derived from the FHA sequence has no effect on either the attachment of epithelial cells to purified FHA or the entry of B. pertussis into HeLa cells. Staphylococcus aureus organisms coated with pertactin or FHA, purified from B. pertussis, enter HeLa cells more efficiently than S. aureus cells coated with bovine serum albumin. The pertactin-enhanced entry of S. aureus is inhibited by 75% in the presence of the RGD peptide from pertactin, whereas the RGD peptide derived from FHA has no effect on the increased entry promoted by the pertactin-coated or by the FHA-coated S. aureus. These results indicate that the active uptake of B. pertussis by certain mammalian cells may be mediated by the interaction of the RGD site found in pertactin with eukaryotic cell surface receptors.

Adhesins, Bacterial↗

Clinical significance of monoclonal proteins in chronic lymphocytic leukemia.

Serum monoclonal proteins were found in 36 of 111 (32%) chronic lymphocytic leukemia (CLL) patients studied using high-resolution agarose gel electrophoresis combined with immunofixation. In contrast, using immunoelectrophoresis (IEP) and serum protein electrophoresis (SPEP), monoclonal proteins were found in 20 and 4% of CLL patients, respectively. The presence of a monoclonal protein was associated with a median survival of 63 months compared to 103 months for individuals without a monoclonal spike (p < 0.012). This was independent of clinical stage. The data also suggests that the presence of a monoclonal protein may define a group of patients at greater risk for disease progression in the low and intermediate risk groups. (Rai stages, 0, I, II). Further follow-up will be required to determine if this is statistically significant.

Blood Proteins↗

Evaluation of a polymerase chain reaction for the diagnosis of tuberculosis.

A polymerase chain reaction for the specific detection of Mycobacterium tuberculosis has been developed and evaluated for clinical applicability. Primers were designed to amplify a 240 base pair region in the MPB 64 protein coding gene (nts 460-700). From among 15 different DNA templates tested (including 10 species of mycobacteria) PCR amplified the DNA from M. tuberculosis complex only, demonstrating its exquisite specificity. Sensitivity studies using serial ten-fold dilutions of M. tuberculosis bacilli determined the limit of detectability to be 10 organisms. A total of 143 clinical specimens were analysed. This consisted of 26 known non-tuberculous specimens (control group) and 117 specimens received at the Tuberculosis Diagnostic Service of AIIMS (test group). None of the specimens in the control group was positive by PCR. Out of 117 specimens in the test group, 19 were culture positive for mycobacteria and 17 of these isolates were identified as M. tuberculosis. All the specimens from which M. tuberculosis was grown were also PCR positive. The remaining two isolates were identified as mycobacteria other than M. tuberculosis and these two specimens were PCR negative. An additional 14 culture negative specimens were PCR positive yielding an overall M. tuberculosis positivity rate of 26.5% (31/117) compared to 14.5% (17/117) by culture. The superior sensitivity of PCR over culture was more evident in non-pulmonary cases where PCR picked up 10 cases in addition to three culture positives out of 69 specimens. On the other hand, out of 48 pulmonary specimens only four cases in addition to 14 culture positives were picked up by PCR.

Blotting, Southern↗

Staphylococcus lugdunensis.

A fatal case of penicillin resistant Staphylococcus lugdunensis endocarditis on a native valve damaged by rheumatic fever is described. A retrospective examination of 978 tube coagulase negative staphylococcal blood culture isolates was also performed to determine how often this species is isolated. None of the 978 isolates was identified as S lugdunensis. It is concluded that ornithine decarboxylase production is the only reliable method of identifying this species.

Aged↗

Serum magnesium levels in patients with head and neck cancer.

Serum magnesium levels have been estimated in 25 patients with head and neck cancer. The results have been compared with a group of 25 healthy controls. In cancer patients the mean value was significantly reduced when compared with the control group. A progressive, and significant, increase in serum magnesium concentration was observed following radiotherapy.

Adolescent↗

Squamous cell carcinoma antigen as a marker for squamous cell carcinoma of the anal canal.

Twenty-one patients with documented squamous cell carcinoma (SCC) of the anal canal underwent prospective serial collection of 101 serum samples for radioimmunoassay of SCC antigen to evaluate regression or progression of disease. Eighteen presented with primary SCC of the anal canal, two with metastatic disease, and one with a recurrence in the perineum. Median follow-up was 18 months. Thirteen of 22 serum samples were true-positives, and nine of 22 were false-negatives. Four of 79 serum samples were false-positives and 75 of 79 were true-negatives. The sensitivity of this test is 59% and the specificity is 95%, with the accuracy of a positive test being 76%.

Adult↗

Plasma selenium levels in patients with advanced upper gastrointestinal cancer.

Plasma selenium levels were determined at various intervals during hospitalization of 71 patients with upper gastrointestinal and other malignancies. These patients often require frequent nutritional as well as surgical or medical intervention. Attempts were made to identify, evaluate, and compensate for numerous confounding variables at each of the 374 plasma selenium determinations. Selenium levels in stable patients who were neither receiving aggressive antineoplastic therapy, nor septic, nor taking corticosteroids and who had no clinically significant metabolic imbalance were then separately analyzed. In 55 stable patients selenium levels were 28% lower than those found in 20 normal controls (mean 61.8 micrograms/L, P less than 0.0005). An analysis of all the readings showed that selenium levels were substantially decreased by recent radiotherapy or sepsis, by regional tumor spread and increased tumor burden, and by intravenous and/or enteral hyperalimentation and intravenous lipids. In contrast to these findings, levels were relatively higher in patients with an adequate oral diet or with a lesser tumor burden. The comparison between selenium levels in stable and in aggressively treated or septic patients supports the importance of the relationship of nutrition to selenium levels in cancer patients.

Adult↗