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Biomedical subjects

N Sinha

Publications and source records attributed to N Sinha.

At least 37 records · Page 2Linked to original sources

Complement and cell mediated cytotoxicity by antiendothelial cell antibodies in Takayasu's arteritis.

OBJECTIVE: To study complement and cell mediated cytotoxicity by antiendothelial cell antibodies (AECA) in Takayasu's arteritis (TA). METHODS: Complement dependent cytotoxicity (CDC) and antibody dependent cellular cytotoxicity (ADCC) of AECA positive/negative TA sera were investigated by colorimetric MTT and 51Cr release assays, respectively, using human umbilical vein endothelial cells (HUVEC) as targets. RESULTS: Seven of 12 (58%) sera positive for IgG and/or IgM AECA exhibited CDC in comparison to none of the 13 AECA negative sera (p = 0.0052). The median value of CDC of the AECA positive group was 14% (range 13-21%) and that of the AECA negative group was 1% (p = 0.0012). Interleukin 1beta (10 U/ml) treatment of HUVEC resulted in enhancement in CDC of 6 of the 7 AECA positive cytotoxic sera, the median enhancement being 17% (range 7-29%). Tumor necrosis factor-alpha (100 U/ml) treatment of the targets resulted in a median enhancement by 36% (range 25-55%) in the CDC of 3 of these 7 sera. No sera exhibited ADCC at any of the effector:target ratios tested (10:1 to 100:1). CONCLUSION: AECA in TA mediate CDC against endothelial cells and may have a pathogenic role in the perpetuation of vascular damage in this disease.

Antibodies↗

Extracting weak phase information from B-->V1V2 decays

We describe a new method for extracting weak, CP-violating &Dmacr;phase information, with no hadronic uncertainties, from an angular analysis of B-->V1V2 decays, where V1 and V2 are vector mesons. The quantity sin (2)(2beta+gamma) can be cleanly obtained from the study of decays such as B(0)(d)(t)-->D*+/-rho(-/+), D(*+/-)a(-/+)(1), D(;) *0K(;) (*0), etc. Similarly, one can use B(0)(s)(t)-->D(*+/-)(s)K*-/+ to extract sin (2)gamma. There are no penguin contributions to these decays. It is possible that sin (2)(2beta+gamma) will be the second function of CP phases, after sin2beta, to be measured at B factories.

Journal Article↗

Effect of lead on Sertoli-germ cell coculture of rat.

Mixed cultures of Sertoli and germ cells were prepared from rat testes and their response to lead (Pb) was studied. Cultures consisted of a monolayer of Sertoli cells to which clusters of germ cells were attached. The effect of Pb added as lead acetate was tested at 0.0, 0.4, 4.0 and 40.0 microM for 24 and 48 h intervals. Addition of Pb to the culture medium caused germ cells to progressively detach from the Sertoli cell monolayer into the medium in a concentration and duration dependent manner Viability of the detached cells as judged by trypan blue exclusion test showed a decrease with increase in time and concentration of Pb. Significant leakage of lactate dehydrogenase (LDH) was recorded in the culture media only at the higher concentrations of 4.0 and 40.0 microM. Thus Pb at the doses tested induced cytotoxicity in rat Sertoli-germ cell coculture.

Animals↗

Primary congenital anomalies of the coronary arteries: a coronary: arteriographic study.

Geographic variations in the incidence of different congenital coronary anomalies are well known, but infrequently studied in the Indian population. Among 4,100 adult patients who underwent diagnostic coronary arteriography, 39 (0.95%) patients (34 males, 5 females) had one or more anomalous coronary arteries. Their mean age was 46.4 +/- 8.2 years (range, 26-68 years). Thirty-five (89.74%) had anomalies of origin and distribution, while the remaining four (10.25%) had coronary artery fistulae. Right coronary artery was the commonest anomalous vessel, involved in 19 (48.74%) patients. It was originating from the left sinus of Valsalva in 15 and from the non-facing aortic sinus in four patients. Anomalous left circumflex artery was the second commonest anomaly, seen in 14 (35.89%) patients. Anomalous left anterior descending artery and anomalous left coronary artery from pulmonary artery were seen in one patient each. Among patients with coronary fistulae, two had fistulae between the left anterior descending artery and the main pulmonary artery, one between the conal artery and the right atrium, while the fourth patient had fistulae from the right coronary as well as from the left anterior descending artery to the left atrium. Atherosclerotic plaques in the anomalous arteries were seen in only 13 (33.33%) patients, much less than the overall incidence of coronary artery disease in patients with congenital coronary anomalies in this series (66.66%). In four (10.25%) patients, only the anomalous vessels were involved in coronary artery disease. Thus, in a small subgroup there does not appear to be an increased risk for development of atherosclerotic coronary artery disease in anomalous coronary arteries. Recognition of coronary anomalies is important in patients undergoing coronary arteriography, coronary interventions and cardiac surgery. Variations in the frequency of primary congenital coronary anomalies may possibly have a genetic background.

Adult↗

Is axillary temperature an appropriate surrogate for core temperature?

The ideal technique for measuring temperature should be rapid, painless, reproducible and accurately reflect the core temperature. While axillary temperature is commonly used because of convenience and safety, there are conflicting reports about its accuracy. To determine whether axillary temperature can act as a surrogate for oral/rectal temperatures, a prospective comparative study was conducted. The axillary and rectal temperatures (Group 1: infants < 1 year age) and axillary and oral temperatures (Group 2: children 6-14 years age) were compared using mercury-in-glass thermometers. Various tests of agreement were applied to the data obtained. Rectal and axillary temperatures for infants agreed well; the mean difference (95% limits of agreement) between the two being 0.6 degree C (-0.3 degree C, 1.4 degrees C). Similarly, the mean difference (95% limits of agreement) between oral and axillary measurements for children aged 6-14 years was observed to be 0.6 degree C (-0.4 degree C, 1.4 degrees C). Axillary temperature appears to be an acceptable alternative to rectal/oral temperature measurements in children.

Adolescent↗

Folding and binding cascades: dynamic landscapes and population shifts.

Whereas previously we have successfully utilized the folding funnels concept to rationalize binding mechanisms (Ma B, Kumar S, Tsai CJ, Nussinov R, 1999, Protein Eng 12:713-720) and to describe binding (Tsai CJ, Kumar S, Ma B, Nussinov R, 1999, Protein Sci 8:1181-1190), here we further extend the concept of folding funnels, illustrating its utility in explaining enzyme pathways, multimolecular associations, and allostery. This extension is based on the recognition that funnels are not stationary; rather, they are dynamic, depending on the physical or binding conditions (Tsai CJ, Ma B, Nussinov R, 1999, Proc Natl Acad Sci USA 96:9970-9972). Different binding states change the surrounding environment of proteins. The changed environment is in turn expressed in shifted energy landscapes, with different shapes and distributions of populations of conformers. Hence, the function of a protein and its properties are not only decided by the static folded three-dimensional structure; they are determined by the distribution of its conformational substates, and in particular, by the redistributions of the populations under different environments. That is, protein function derives from its dynamic energy landscape, caused by changes in its surroundings.

Models, Molecular↗

Intermittent electromechanical dissociation due to mechanical prosthetic valve dysfunction.

We describe a patient who developed the rare hemodynamic phenomenon of intermittent electromechanical dissociation during normal sinus rhythm at about four months after mitral valve replacement with a Medtronic Hall prosthesis, along with resuspension of the papillary muscles using Gore-Tex sutures. Echocardiographic examination confirmed the presence of a filamentous structure that could be either suture material, tissue tag or thrombus, and was entangling intermittently in the prosthesis. The patient recovered spontaneously after a three-week symptomatic period, with no subsequent evidence of either electromechanical dissociation or the filamentous structure; normal prosthetic valve function was restored. During a subsequent three-month follow up period, the patient was asymptomatic, with normal prosthetic valve function. The diagnostic and hemodynamic aspects of this case are discussed.

Adult↗

Effect of Inoue balloon mitral valvotomy on severe pulmonary arterial hypertension in 315 patients with rheumatic mitral stenosis: immediate and long-term results.

BACKGROUND AND AIMS OF THE STUDY: Despite advances in surgical techniques, mitral valve surgery in patients with severe pulmonary arterial hypertension (PAH) causes considerable mortality and morbidity. Balloon mitral valvotomy (BMV) is an established alternative to treat high-risk surgical patients with mitral stenosis (MS). The study aims were to evaluate immediate and long-term efficacy of BMV in patients with MS and severe PAH, compared to those with mild/moderate PAH. METHODS: Among 1,125 patients who underwent Inoue BMV, 315 had severe PAH (mean pulmonary artery (PA) pressure > or = 50 mmHg (group I; 79 of these patients had suprasystemic PAH). Results from this group were compared with those of patients with mild/moderate PAH (group II). RESULTS: Group I patients were younger and more symptomatic (mean PA pressure 62 +/- 10.6 mmHg versus 32.6 +/- 8.2 mmHg in group II). Before BMV, mean transmitral gradient (17.8 +/- 6.5 versus 14.4 +/- 5.4 mmHg) and pulmonary capillary wedge pressure (PCWP) (31.6 +/- 6.1 versus 22.8 +/- 6.2 mmHg) were significantly higher, while mitral valve area (MVA) (0.66 +/- 0.2 versus 0.85 +/- 0.2 cm2) was significantly lower in group I. After BMV, PA mean pressure was significantly reduced (34.8 +/- 11.2 and 21.1 +/- 8.4 mmHg), transmitral gradient (8.0 +/- 3.9 and 6.9 +/- 3.2 mmHg) and mean PCWP (12.8 +/- 5.8 and 11.0 +/- 5.1 mmHg) in groups I and II, respectively, with a comparable increase in MVA (1.77 +/- 0.4 and 1.84 +/- 0.5 cm2). Group I patients had worse baseline hemodynamic parameters than group II, but the former had a higher absolute gain in hemodynamic parameters. Residual severe PAH after BMV was seen in 9.8% of patients, with PA pressures normalized in 9.5%. Among 79 patients with suprasystemic PA pressure (mean PA systolic pressure 116.6 +/- 28.2 mmHg), 16.5% normalized their PA pressures and 25.3% had residual severe PAH. At mean follow up of 33 months, 80.4% were in NYHA class I. Mean PA systolic pressure in 161 patients was 39.0 +/- 14.2 mmHg compared with a post-BMV value of 55.0 +/- 16.9 mmHg; thus, a sustained fall in pressure was demonstrated at follow up. CONCLUSION: Inoue BMV is safe and effective in patients with MS and severe PAH. Although these patients have worse clinical and hemodynamic parameters before BMV, they achieve a greater absolute gain in terms of improvement in all hemodynamic parameters.

Adult↗

Recurrent acute coronary events in a patient with primary antiphospholipid syndrome: successful management with intracoronary stenting.

Patients with Antiphospholipid syndrome usually present with recurrent deep vein thrombosis, pulmonary thromboembolism and thromboembolic stroke. Recurrent coronary events, though reported, are rare. We describe an unusual case of Antiphospholipid syndrome who presented with recurrent acute ischaemic events in two different coronary territories, who was managed successfully with intracoronary stenting.

Adult↗

Genetic, molecular, and morphological analysis of compound leaf development.

Leaves, the plant organs responsible for capturing and converting most of the 170 billion metric tons of carbon fixed globally each year, can be broadly grouped into two morphological categories: simple and compound. Although simple-leaved species such as corn and Arabidopsis have traditionally been favored model systems for studying leaf development, recent years have seen an increase in genetic and molecular studies of compound leaf development. Two compound-leaved species in particular have emerged as model systems: tomato and pea. A variety of mutations which alter leaf morphology in these species have been described, and analyses of these mutations have allowed the construction of testable models of leaf development. Also, the knotted-like homeobox (KNOX) genes, which were originally discovered as regulators of meristem function, now appear to have a role in compound leaf development. In addition to the recent genetic and molecular analyses of tomato and pea, insight into the nature of compound leaf development may be gained through the study of (a) heteroblasty and heterophylly, phenomena in which a range of leaf forms can be produced by a single shoot, and (b) the evolutionary origins of compound leaves.

Biological Evolution↗

Phylogenetic relationships and evolution of the KNOTTED class of plant homeodomain proteins.

Knotted-like (KNOX) proteins constitute a group of homeodomain proteins involved in pattern formation in developing tissues of angiosperms and other green plants. We conducted phylogenetic analyses of nucleotide and amino acid sequences of all known KNOX proteins in order to examine their evolution. Our analyses reveal two groups of KNOX proteins, classes I and II. Dicot and monocot sequences occur in both classes, indicating that the protein classes arose prior to the origin of the monocots. A conifer (Picea) sequence is nested within class I, suggesting that there are likely to be other copies of KNOX genes in this and other conifers. The orthology of several grass genes (including Zea Kn1, ZMKN1) is strongly supported by phylogenetic and synteny analyses. However, no compelling evidence supports the hypothesis of orthology previously proposed for several dicot genes and ZMKN1. Analysis of expression patterns suggests that the ancestral KNOX gene was expressed in all plant parts and that the propensity to be downregulated in roots and leaves evolved in the class I genes.

Amino Acid Sequence↗

Stabilization of the i-motif by intramolecular adenine-adenine-thymine base triple in the structure of d(ACCCT).

The crystal structure of d(ACCCT), solved by molecular replacement, shows a four-stranded i-motif conformation, where two parallel duplexes intercalate with one another in opposite orientations. Each duplex is stabilized by hemi-protonated C-C+ base pairing between parallel strands, and a string of water molecules bridge the cytosine N4 atoms to phosphate O atoms. This structure of d(ACCCT) shows examples of reversed Hoogsteen and Watson-Crick base pairing in both intermolecular and intramolecular manners to stabilize the tetraplex. Noticeably, the four-stranded complex is further stabilized at one end by a three-base hydrogen-bonding network, in which two adenines and a thymine form four hydrogen bonds via a reverse Hoogsteen and an asymmetric adenine-adenine base pairing. The structure of d(ACCCT) shows a similar local structure to that found in the d(TAA) part of the crystal structure of d(TAACCC) and provides further structural evidence that these base arrangements are essential for stabilizing these novel DNA super-secondary structures.

Adenine↗

Influence of sub valvular pathology on immediate results and follow up events of Inoue balloon mitral valvotomy.

We evaluated the influence of sub valvular pathology (SVP) on the immediate results and follow up events of Inoue Balloon Mitral Valvotomy (IBMY) in 206 patients with severe SVP (Group I) and compared their outcome with 206 age and sex matched patients selected from the rest of 619 patients having mild/moderate SVP (Group II). Pre-procedure echocardiographic recordings were reviewed and mitral valve morphology was evaluated using U.S. California Score. The severe SVP group had lower mitral valve areas (MVA) (0.7 cm2 vs. 0.8 cm2) and higher mean pulmonary artery pressure (MPAP) (46.3+/-16.9 mmHg vs. 40.7+/-16.25 mmHg) and mean pulmonary capillary wedge pressure (PCWP) (27.5+/-7.3 mmHg vs. 25.7+/-8.0 mmHg) (p<0.001). IBMV was done using standard technique. The procedure was technically successful in 192/206 patients (93.2%) in group I and 187/206 (91%) in group II (p=ns). The mean transmitral gradient decreased from 24.8+/-7.6 mmHg to 7.46+/-3.4 mmHg while mean PCWP fell from 27.5+/-7.3 mmHg to 12.2+/-5.6 mmHg and MPAP fell from 46.3+/-16.9 mmHg to 23.6+/-12.2 mmHg (p=<0.001). MVA increased from 0.7+/-0.2 cm2 to 1.7+/-0.4 cm2 (p=<0.001). Severe mitral regurgitation (MR) occurred in 2 patients out of which one patient, who had associated coronary artery disease, died post operatively, and moderate MR occurred in 8 patients. The results achieved in patients with severe SVP were not statistically different from those with mild/moderate SVP. The benefits achieved immediate post IBMV were sustained in 184 patients with severe SVP who were available for follow up at a mean duration of 15.2 months (range 3 months to 51 months). Thus IBMV is safe and effective in patients with severe SVP. This group of patients with severe SVP are more hemodynamically deranged pre-BMV and also achieve better hemodynamic benefit compared to those with mild/moderate SVP. Severe SVP does not have any adverse effect either on immediate results (success/occurrence of MR) or on intermediate term follow up.

Adult↗

Probing RegA/RNA interactions using electrospray ionization-fourier transform ion cyclotron resonance-mass spectrometry.

The interactions of bacteriophage T4 regA protein, a unique translational regulator, with RNAs of various size and sequence were studied using electrospray ionization-Fourier transform ion cyclotron resonance-mass spectrometry. Using very gentle interface conditions, regA/RNA complexes with a 1:1 binding stoichiometry were observed for all four target RNAs studied, consistent with solution binding studies. Competitive binding of target RNAs and their degradation products with regA demonstrated that the loss of a single nucleotide resulted in a dramatic change in binding affinity in some cases. Competitive binding of regA with four target RNAs revealed similar relative binding affinity order to that suggested by previous in vitro repression experiments. The use of sustained off-resonance irradiation for collisionally induced dissociation of a regA/RNA complex suggested the potential for directly obtaining information regarding the regA binding domain.

Bacterial Proteins↗