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Biomedical subjects

N Sinha

Publications and source records attributed to N Sinha.

At least 55 records · Page 3Linked to original sources
PubMed1998

An Escherichia coli ccm (cytochrome c maturation) deletion strain substantially expresses Hydrogenobacter thermophilus cytochrome c552 in the cytoplasm: availability of haem influences cytochrome c552 maturation.

The maturation of Hydrogenobacter thermophilus cytochrome c552 in the cytoplasm of Escherichia coli is unique among bacterial c-type cytochromes. It is now shown to be matured in a strain lacking the whole set of ccm (cytochrome c maturation) genes that are normally required for c-type cytochrome biogenesis in E. coli. As this cytochrome is thermostable we propose that the apocytochrome c552 has sufficient tertiary structure to allow the haem to slot into its binding pocket, which in turn triggers the spontaneous covalent attachment between apocytochrome c552 and haem. The ccm deletion strain of E. coli, derived from a strain that synthesizes elevated levels of endogenous c-type cytochromes, also produces larger amounts of cytoplasmic H. thermophilus cytochrome c552 than a reference strain. This implies that elevated production of c-type cytochromes is not a consequence of high activity of ccm genes but rather an enhanced ability to supply haem, a view that is supported by the increase in thermophilic cytochrome c552 biogenesis that occurs in a reference strain following supplementation of growth media with delta-aminolevulinic acid.

Aminolevulinic Acid↗
PubMed1998

Pressure zone used and the occurrence of mitral regurgitation in Inoue balloon mitral commissurotomy.

Mitral regurgitation (MR) is a known complication of Inoue balloon mitral commissurotomy (BMC) and has been variously ascribed to the presence of severe subvalvular pathology (SVP), preexisting MR, calcification, or oversizing. The pressure zone used--with the low pressure zone (LPZ) the lower half of the spectrum of sizes available out of a single balloon, and the high pressure zone (HPZ) the upper two levels, i.e., within 2 mm of its maximum size--could have a bearing on the occurrence of MR, but has not been studied before. We analysed 251 consecutive patients (mean age 28.6 + 9.7 years), undergoing BMC from October 1993 onwards, with pliable, non-calcific, splittable (bilateral dark zones present) valves with not more than trivial MR (1 + in grades of 1-4). Balloon sizing was done with standard formula using height with stepwise dilatation starting 2 mm below the reference size. Thirty-two patients additionally had severe SVP. Patients were divided into two groups, HPZ-BMC and LPZ-BMC, depending upon the final balloon size needed for a successful result. Incidence of MR (2+ or more) was significantly lower in the LPZ BMC (18%) vs. HPZ BMC (32.2%) (P < 0.05). Moderate to severe MR (3+/4+) was also less in LPZ BMC (2.8%) vs. HPZ BMC (8.2%) (P < 0.05). Amongst patients with severe SVP, 3/15 (20%) developed MR in the LPZ-BMC group (all mild only) as against 8/17 (42%) (P < 0.05) in the HPZ-BMC group with half of them having moderate to severe MR. In 54 patients where the reference size had to be exceeded, no patient (0/8) developed MR as long as the higher size was in the LPZ of the particular balloon used as compared to 17/46 (36.9%) who developed MR when the size used fell in the HPZ. We conclude that the pressure zone used has a strong bearing on the occurrence of MR in Inoue BMC and that a low-pressure strategy could avoid MR.

Adult↗
PubMed1998

Unusual presentation during childhood of left ventricular myxoma.

Amongst all primary cardiac tumors, myxomas are the commonest, and their commonest site of origin is the left atrium. Myxomas originating in the left ventricle are rare. When seen, they usually present with a history of systemic embolisation and/or syncopal episodes, with constitutional symptoms being absent. We report here a child with left ventricular myxoma who presented with a prolonged febrile illness.

Aortic Valve↗
PubMed1998

Isolation and characterization of two knotted-like homeobox genes from tomato.

Homeobox genes are known to play a role in developmental regulation. The knotted-like homeobox (knox) genes fall into two classes. The class I knox genes like knl, stml, and knatl are involved in maintaining meristem identity in cells. The function of class II knox genes is at yet undetermined. We have characterized two knox genes from tomato. LeT6 and LeT12 map to distinct chromosome locations that are different from the location for a recently cloned knox gene from tomato, tknl, confirming that plant homeobox genes are not clustered on chromosomes. These genes have a distinct expression pattern. Unlike other class I knl-like genes, LeT6 is expressed in developing lateral organs and developing ovaries in flowers. LeT12 is more ubiquitously expressed in the mature plant. RNA in situ localization data suggest that both these genes may have a role to play in formative events in ovule and embryo morphogenesis.

Amino Acid Sequence↗
PubMed1998

Overexpression of a homeobox gene, LeT6, reveals indeterminate features in the tomato compound leaf

The cultivated tomato (Lycopersicon esculentum) has a unipinnate compound leaf. In the developing leaf primordium, major leaflet initiation is basipetal, and lobe formation and early vascular differentiation are acropetal. We show that engineered alterations in the expression of a tomato homeobox gene, LeT6, can cause dramatic changes in leaf morphology. The morphological states are variable and unstable and the phenotypes produced indicate that the tomato leaf has an inherent level of indeterminacy. This is manifested by the production of multiple orders of compounding in the leaf, by numerous shoot, inflorescence, and floral meristems on leaves, and by the conversion of rachis-petiolule junctions into "axillary" positions where floral buds can arise. Overexpression of a heterologous homeobox transgene, kn1, does not produce such phenotypic variability. This indicates that LeT6 may differ from the heterologous kn1 gene in the effects manifested on overexpression, and that 35S-LeT6 plants may be subject to alterations in expression of both the introduced and endogenous LeT6 genes. The expression patterns of LeT6 argue in favor of a fundamental role for LeT6 in morphogenesis of leaves in tomato and also suggest that variability in homeobox gene expression may account for some of the diversity in leaf form seen in nature.

Journal Article↗
PubMed1998

Small aortic annulus: a functional definition.

BACKGROUND & OBJECTIVE: Small aortic annulus is conventionally associated with poor outcome after aortic valve replacement (AVR). Contrarily, several patients have excellent follow-up results after AVR with 19, 20 or 21 size Medtronic Hall (MH) or Sorin Carbocast (SC) prostheses. This disparity prompted a relook at the semantics of a small aortic annulus. METHODS: Available survivors of isolated AVR with #19, #20 or #21 prostheses - 13 with 19 SC or 20 MH valves (Group A) and 29 with 21 SC or MH valves (Group B) were studied. Disparity between actually implanted prostheses versus predicted prosthetic size (tissue annulus diameter) was analysed according to nomograms of Rowlatt et al, NIH Plehn, Kishimoto formula and Sievers composite criteria. Preoperative and follow-up echocardiographic assessments were used for hemodynamic and prosthetic function indices. RESULTS: Both groups were similar in age, height, weight, BSA, BMI, mean NYHA class, CTR, preoperative peak gradient (PG) (92. 0 +/- 29.55 vs 102.88 +/- 33.65), mean gradient (MG) (56.8 +/- 24.6 vs 61.55 +/- 16.56), LVEDD (50.75 +/- 10.92 vs 56.0 +/- 13.5), LVESD (34.37 +/- 13.32 vs 38.52 +/- 13.85) and LVEF (67.5 +/- 12.5 vs 63.9 +/- 14.3). By developmental indices of Rowlatt et al. and NIH, no valve annulus could be designated as narrow. By Sievers composite nomogram all implanted valves were undersized by echocardiographic parameters, in normal range by angiographic criteria and oversized by anatomic autopsy data. Implanted valves in both groups were bigger than Plehn-predicted size (18.16 +/- 1.48 in GrA, 19.46 +/- 1. 10 in GrB). Valve size indices (VSI) (GrA 16.16 +/- 2.85 GrB 14.24 +/- 1.64) and geometric orifice area indices (VAI: valve area index) (GrA 1.50 +/- 0.28 vs 1.41 +/- 0.19) and postoperative rest PG (GrA 47.2 +/- 18.6 GrB 33.8 +/- 9.9) and MG (GrA 27.2 +/- 12.9 vs 19.0 +/- 9.9) were acceptable. LVEDD and LVESD regressed in both groups. LV mass indices regressed from 218.56 +/- 100.85 to 128.17 +/- 27.7 in GrA and 238.94 +/- 102.5 to 134.22 +/- 34.72 in GrB. Performance indices of implanted valves and postoperative aortic valve resistances were correlative. CONCLUSIONS: The size of the implanted prostheses per se does not denote narrowness. Patient-prosthesis mismatch may be considered if predicted prosthesis has VSI <12 mm/m2, VAI <1.31 cm2/m2 or prosthesis orifice diameter <19 mm which may indicate annular enlargement.

Adult↗
PubMed1997

Did homeodomain proteins duplicate before the origin of angiosperms, fungi, and metazoa?

Homeodomain proteins are transcription factors that play a critical role in early development in eukaryotes. These proteins previously have been classified into numerous subgroups whose phylogenetic relationships are unclear. Our phylogenetic analysis of representative eukaryotic sequences suggests that there are two major groups of homeodomain proteins, each containing sequences from angiosperms, metazoa, and fungi. This result, based on parsimony and neighbor-joining analyses of primary amino acid sequences, was supported by two additional features of the proteins. The two protein groups are distinguished by an insertion/deletion in the homeodomain, between helices I and II. In addition, an amphipathic alpha-helical secondary structure in the region N terminal of the homeodomain is shared by angiosperm and metazoan sequences in one group. These results support the hypothesis that there was at least one duplication of homeobox genes before the origin of angiosperms, fungi, and metazoa. This duplication, in turn, suggests that these proteins had diverse functions early in the evolution of eukaryotes. The shared secondary structure in angiosperm and metazoan sequences points to an ancient conserved functional domain.

Amino Acid Sequence↗
PubMed1997

A gene fusion at a homeobox locus: alterations in leaf shape and implications for morphological evolution.

Compound leaves are seen in many angiosperm genera and are thought to be either fundamentally different from simple leaves or elaborations of simple leaves. The knotted1-like homeobox (knox) genes are known to regulate plant development. When overexpressed in homologous or heterologous species, this family of genes can cause changes in leaf morphology, including excessive leaf compounding in tomato. We describe here an instance of a spontaneously arisen fusion between a gene encoding a metabolic enzyme and a homeodomain protein. We show that the fusion results in overexpression of the homeodomain protein and a change in morphology that approximates the changes caused by overexpression of the same gene under the control of the cauliflower mosaic virus 35S promoter in transgenic plants. Exon-shuffling events can account for the modularity of proteins. If the shuffled exons are associated with altered promoters, changes in gene expression patterns can result. Our results show that gene fusions of this nature can cause changes in expression patterns that lead to altered morphology. We suggest that such phenomena may have played a role in the evolution of form.

Base Sequence↗
PubMed1997

A bias in the alphabeta T cell receptor variable region gene usage in Takayasu's arteritis.

Takayasu's arteritis (TA) is a chronic large vessel vasculitis with a predilection for the aortic arch and its branches. T lymphocytes may be important in the pathogenesis, as they have been found to infiltrate the vascular lesions. To elucidate further the role of T cells in the disease, we studied circulating CD4+ and CD8+ T cells, expression of the activation marker (HLA-DR), marker for naive (CD45RA) and primed (CD45RO) cells and the different variable alpha/beta (AV/BV) gene segments on them. The TCR AV/BV repertoire was studied using a panel of 15 T cell receptor (TCR) V-specific MoAbs by flow cytometry in 18 patients and 23 age- and sex-matched controls. Patients had a higher percentage of AV12S1 (P < 0.05), BV6S7 (P < 0.05) and BV9 (P < 0.001)-bearing CD4+ cells. Patients also had a higher frequency of expansions, i.e. of T cell populations with an abnormally high TCR AV/BV gene usage. In patients' CD4+ subset of cells, there were 22 expansions out of 231 analyses (9.5%), whereas in controls, four were expanded out of 310 analyses (1%) (P < 0.001). For CD8+ cells, the frequency of expansions was 32 in 231 analyses (14%) in patients and nine out of 304 analyses in controls (3%) (P < 0.01). In addition, there was a correlation between CD4+ expansions and disease activity; nine out of 10 patients with active disease in comparison with two out of eight patients with inactive disease (P < 0.01) had an expansion. Some of the expanded populations in patients were phenotypically characterized and observed to be HLA-DR+, CD28+, CD45RA+ and CD45RO+, with a greater proportion being CD45RO+. Patients had a higher percentage of expression of HLA-DR on both CD4+ and CD8+ T cells (P < 0.01). The percentages of naive and primed CD4+ and CD8+ T cells, gammadelta+ T cells and natural killer cells were comparable to those in the control group.

Adult↗
PubMed1997

A pharmacoeconomic comparison of UFT and 5-FU chemotherapy for colorectal cancer in South America.

The escalating role played by managed care organizations in the health-care system is reflected in the increased demand for cost-effectiveness analyses (CEAs) to assess the balance between economic impact and clinical efficacy. For example, the high incidence and costs associated with colorectal cancer in Latin America calls for a comprehensive economic evaluation to ensure appropriate allocation of limited health-care funds. In addition, the current call for a "societal" perspective of such analyses indicates the need for increased consideration of the concerns of both patient and health-care provider. The introduction of oral tegafur and uracil (UFT) provided the opportunity to evaluate the pharmacoeconomic advantage of the new agent compared with the standard fluorouracil (5-FU). Results of this study indicated an economic advantage for oral UFT vs a 5-FU-based regimen in the treatment of colorectal cancer in Brazil and Argentina. It was further noted that the mild toxicity profile of UFT reduced both the number of clinic visits and the need for venipuncture procedures. Noting that oral UFT may have a positive impact on quality of life in addition to its estimated economic benefit, it was concluded that prospective economic research and quality-of-life evaluations are needed to fully assess the pharmacoeconomic impact of oral UFT.

Argentina↗
PubMed1997

Immediate and follow up results of Inoue balloon mitral valvotomy in juvenile rheumatic mitral stenosis.

BACKGROUND AND AIMS OF THE STUDY: Juvenile rheumatic mitral stenosis (MS) with severe pulmonary venous and arterial hypertension (PAH) is a relatively common occurrence in developing countries. The study objectives were to evaluate the safety, efficacy and follow up of Inoue balloon mitral valvotomy (IBMV) in juveniles with rheumatic MS. METHODS: A total of 193 patients with juvenile rheumatic MS were analyzed and compared with adults, with specific reference to the effect of IBMV on hemodynamics and pulmonary vasculature in patients with severe PAH. RESULTS: Mitral valve areas were smaller (0.76 +/- 0.22 versus 0.81 +/- 0.22 cm2), while mean pulmonary arterial pressure (MPAP) (44.5 +/- 16.5 versus 38.4 +/- 15.1 mmHg) and pulmonary vascular resistance (PVR) (5.5 +/- 4.6 versus 4.41 +/- 4.04 Wood units) were greater in juvenile patients when compared with adults. There was a 99% procedural success. Juvenile patients showed an overall greater fall in MPAP and PVR when compared with adults. The incidence of severe PAH was much higher (32%) among juveniles than adults (16%). Only 5% of patients with juvenile MS with severe PAH had residual severe PAH immediately after IBMV, compared with 17% in older patients. Hemodynamic benefits (echocardiographic mean transvalvular gradient and mitral valve area) were sustained at a mean follow up of 29 months, and there was no documented case of restenosis after successful IBMV. CONCLUSIONS: We conclude that IBMV is safe and effective in juvenile rheumatic MS and provides greater hemodynamic benefit compared with adults; such benefit is sustained during a mean follow up of 29 months.

Adolescent↗
PubMed1996

Transesophageal dobutamine-atropine stress echocardiography: diagnostic accuracy for coronary stenosis detection and localization.

Transesophageal echocardiography with dobutamine-atropine stress (TE-DASE) is a recently described technique for evaluation of coronary artery disease (CAD). We undertook this study prospectively to determine the feasibility, reliability and safety of this procedure in patients with known CAD and to evaluate its diagnostic accuracy for coronary stenoses of varying severity. Thirty-seven patients who underwent coronary arteriography (CART) and TE-DASE within a 3-month interval without intervening ischemic events or revascularisation were included in the study CART and stress echograms were independently evaluated by different observers. Stenosis was measured with calipers and a > or = 50% lumen diameter stenosis was considered significant. A reduction or lack of endocardial motion and/or wall thickening on progressive incremental stress was considered an abnormal response. TE-DASE could be successfully completed in 33/37 (90%) patients. Using a modified 16-segment model of the left ventricle (LV), 15.2 +/- 0.8 segments/patient and 501/528 (95%) segments overall could be optimally evaluated. Inter-observer concordance for an abnormal response was 94%. Predictive accuracies for one-vessel disease (1-VD), two-vessel disease (2-VD) and three-vessel disease (3-VD) were 88, 58 and 23% respectively. Overall sensitivity for detection of a significant (> or = 50%) stenosis was 72% (32% for moderate (50-69%), 90% for severe (> or = 70%) stenosis) and specificity was 96%. Diagnostic accuracy for localisation of significant stenosis was 95% for the left anterior descending artery (LAD), 86% for the left circumflex artery (LCX) and 88% for the right coronary artery (RCA). There were no major complications. We conclude that TE-DASE is a safe, reliable and easily-performed procedure and provides excellent visualisation of myocardial segments. Diagnostic accuracy for detection of severe stenosis and its localisation is excellent.

Atropine↗
PubMed1996

Takayasu's arteritis: role of Mycobacterium tuberculosis and its 65 kDa heat shock protein.

BACKGROUND: Mycobacterium tuberculosis has been implicated in the pathogenesis of Takayasu's arteritis (TA). Recently, its 65 kDa heat shock protein (HSP) has been implicated in the pathogenesis of other autoimmune diseases. We thus decided to study humoral immune response to Mycobacterium tuberculosis antigens in patients with TA. AIM: To study humoral immune response to Mycobacterium tuberculosis and its 65 kDa HSP, a putative autoantigen, in patients with TA. METHODS: Antibodies to sonicated Mycobacterium tuberculosis extract (MBA) and its recombinant 54 kDa protein were measured using ELISA in 36 patients with TA and 35 healthy controls. Levels exceeding mean +2 S.D. of the controls were taken as positive responses. RESULTS: Abnormally elevated levels of IgG, IgM and IgA antibodies against MBA were present in 6, 20 and 7 patients respectively whereas those against r65 kDa protein were present in 6, 7 and 33 patients, respectively. Though the levels of IgG antibodies were also elevated, those of IgM and IgA antibodies were elevated to a greater extent. CONCLUSIONS: Patients with TA have heightened immune response to Mycobacterium tuberculosis antigens, in particular to its 65 kDa HSP, suggesting that this organism may have a role in the immunopathogenesis of this disease.

Adolescent↗
PubMed1996

A highly efficient 24-condition matrix for the crystallization of nucleic acid fragments.

A matrix screen is presented with optimized conditions for the crystallization of nucleic acid fragments. The screen consists of 24 conditions only and utilizes minimal amounts of sample. It has been tested on a series of DNA and RNA oligomers, and yielded diffraction-quality crystals of many specimens including drug-DNA complexes. Preliminary X-ray analysis of the crystals is reported.

Chemistry Techniques, Analytical↗
PubMed1996

Use of dopamine in prevention of contrast induced acute renal failure--a randomised study.

We report the use of dopamine in renal doses (5 micrograms/kg/min) to prevent contrast induced nephropathy (CIN). Forty patients with diabetes mellitus who were undergoing coronary angiography were randomly divided into two groups. Gr I (20 patients) was infused with dopamine starting 30 min before cardiac catheterization and continued for 6 h thereafter. Gr II (20 patients) did not receive dopamine. Baseline blood chemistry was performed before catheterization and then repeated 24 h after the procedure. The mean age and sex distribution were similar in both the groups. Urograffin (76%; 120-150 ml) was used in all the cases. The mean serum creatinine and blood urea nitrogen (BUN) levels in Gr I patients before catheterization were 1.5 +/- 0.32 mg % and 16.3 +/- 8.05 mg %, respectively. The corresponding values for Gr II were 1.52 +/- 0.68 mg % and 19.6 +/- 13.4 mg %, respectively. After angiography, Gr I patients did not show significant changes in renal parameters (serum creatinine, 1.37 +/- 0.25 mg % and BUN, 14.7 +/- 5.5 mg %) while Gr II patients showed a significant rise (serum creatinine, 1.96 +/- 1.2 mg % and BUN, 23.25 +/- 12.7 mg %; P = 0.01 and P = 0.05, respectively). Ten patients in Gr II (50%) developed a 25% rise in serum creatinine levels within 24 h of injection of the contrast. None of the patients developed renal failure severe enough to warrant dialysis. Hence alterations of renal function are common after cardiac catheterization. Dopamine in renal doses appears to be an effective means to prevent deterioration in renal function induced by contrast.

Acute Kidney Injury↗