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Biomedical subjects

N Chandra

Publications and source records attributed to N Chandra.

At least 19 recordsLinked to original sources
PubMed2006

A family case of fertile human 45,X,psu dic(15;Y) males.

We report on a familial case including four male probands from three generations with a 45,X,psu dic(15;Y)(p11.2;q12) karyotype. 45,X is usually associated with a female phenotype and only rarely with maleness, due to translocation of small Y chromosomal fragments to autosomes. These male patients are commonly infertile because of missing azoospermia factor regions from the Y long arm. In our familial case we found a pseudodicentric translocation chromosome, that contains almost the entire chromosomes 15 and Y. The translocation took place in an unknown male ancestor of our probands and has no apparent effect on fertility and phenotype of the carrier. FISH analysis demonstrated the deletion of the pseudoautosomal region 2 (PAR2) from the Y chromosome and the loss of the nucleolus organizing region (NOR) from chromosome 15. The formation of the psu dic(15;Y) chromosome is a reciprocal event to the formation of the satellited Y chromosome (Yqs). Statistically, the formation of 45,X,psu dic(15;Y) (p11.2;q12) is as likely as the formation of Yqs. Nevertheless, it has not been described yet. This can be explained by the dicentricity of this translocation chromosome that usually leads to mitotic instability and meiotic imbalances. A second event, a stable inactivation of one of the two centromeres is obligatory to enable the transmission of the translocation chromosome and thus a stably reduced chromosome number from father to every son in this family.

Chromosome Aberrations↗
PubMed2004

Interleukin (IL)-1, IL-6, and IL-8 predict mucosal toxicity of vaginal microbicidal contraceptives.

Inflammation of the female reproductive tract increases susceptibility to HIV-1 and other viral infections and, thus, it becomes a serious liability for vaginal products. Excessive release of proinflammatory cytokines may alter the mucosal balance between tissue destruction and repair and be linked to enhanced penetration and replication of viral pathogens upon chemical insult. The present study evaluates four surface-active microbicide candidates, nonoxynol-9 (N-9), benzalkonium chloride (BZK), sodium dodecyl sulfate, and sodium monolaurate for their activity against human sperm and HIV, and their capacity to induce an inflammatory response on human vaginal epithelial cells and by the rabbit vaginal mucosa. Spermicidal and virucidal evaluations ranked N-9 as the most potent compound but were unable to predict the impact of the compounds on vaginal cell viability. Interleukin (IL)-1 release in vitro reflected their cytotoxicity profiles more accurately. Furthermore, IL-1 concentrations in vaginal washings correlated with cumulative mucosal irritation scores after single and multiple applications (P < 0.01), showing BZK as the most damaging agent for the vaginal mucosa. BZK induced rapid cell death, IL-1 release, and IL-6 secretion. The other compounds required either more prolonged or repeated contact with the vaginal epithelium to induce a significant inflammatory reaction. Increased IL-8 levels after multiple applications in vivo identified compounds with the highest cumulative mucosal toxicity (P < 0.01). In conclusion, IL-1, IL-6, and IL-8 in the vaginal secretions are sensitive indicators of compound-induced mucosal toxicity. The described evaluation system is a valuable tool in identifying novel vaginal contraceptive microbicides, selecting out candidates that may enhance, rather than decrease, HIV transmission.

Animals↗
PubMed2004

Inferring gene regulatory networks from raw data--a molecular epistemics approach.

Biopathways play an important role in the functional understanding and interpretation of gene function. In this paper we present the results of an iterative algorithm for automatically generating gene regulatory networks from raw data. The algorithm is based on an epistemics approach of conjecture (hypothesis formation) and refutation (hypothesis testing). These operations are performed on a matrix representation of the gene network. Our approach also provides a way of incorporating external biological knowledge into the model. This is done by pre-assigning portions of the matrix--which represent previously known background knowledge. This background knowledge helps make the results closer to a human's rendition of such networks. We illustrate our approach by having the computer replicate a gene regulatory network generated by human scientists at an academic lab.

Algorithms↗
PubMed2001

Interaction of coumarin derivatives with human serum albumin: investigation by fluorescence spectroscopic technique and modeling studies.

Interactions of several 7-aminocoumarins with human serum albumin (HSA) were studied by using fluorescence spectroscopic technique and modeling studies. There is a large change in fluorescence spectral parameters like intensity, emission maxima and anisotropy for all aminocoumarins. There were two binding sites for cou-1, 311 and a single binding site for other coumarins. The binding constant(s) are large for all coumarins reflective of a strong binding. These spectral studies show that structural variants at the third, fourth and seventh position affects binding. The probable location of these coumarins in domain II has been predicted based on modeling. The effect of structural modification on the efficiency of binding was obtained for various other coumarins, using modeling.

Binding Sites↗
PubMed2001

Detoxification of aqueous zinc using fluorapatite--bearing lean grade rock phosphate.

Detoxification of aqueous zinc was studied using the adsorption technique by application of fluorapatite bearing low grade phosphate as a sorbent. The effects of particle size of adsorbent, contact time, initial concentration of zinc and temperature on the adsorption process were studied. Initial rate of adsorption of zinc increases with time up to 30 min and thereafter it reaches equilibrium. Percent adsorption is adversely affected by increase in initial concentration of zinc and increase in particle size of sorbent. Adsorption processes follow first order kinetics and are found to be exothermic.

Absorption↗
PubMed2000

Genotoxicity evaluation of heat shock in gold fish (Carassius auratus).

Genotoxicity evaluation of heat shock was carried out in Carassius auratus. The genotoxicity end points studied were nuclear anomalies (micronucleus assay), chromosomal aberrations, DNA damage (comet assay) and cell proliferation. The heat shock temperatures used were 34 degrees C, 36 degrees C and 38 degrees C. The results demonstrated that heat shock causes the induction of micronucleus at all the three temperature studied. Heat shock also inhibited cell proliferation at 38 degrees C and caused aberrations in the metaphase chromosomes at 34 degrees C and 36 degrees C. Comet assay demonstrated single strand DNA damage at all the three temperatures. The results obtained indicate that heat shock is a genotoxicant.

Animals↗
PubMed2000

Trisomy 4p and partial monosomy 18q due to paternal translocation t(4;18) (p11; q21.3).

A carrier status for balanced translocation in either of the parents increases the risk of congenital malformation in the offspring. A case of multiple congenital anomalies in a female newborn was found to be associated with trisomy 4p and partial monosomy 18q as a result of a reciprocal translocation, t(4; 18) (p11; q21.3) in the father. The clinical and cytogenetic findings are compared with characteristic features of trisomy 4p, monosomy 18q and two similar cases reported earlier.

Abnormalities, Multiple↗
PubMed2000

Cardiopulmonary resuscitation with a hydraulic-pneumatic band.

Improved blood flow during cardiopulmonary resuscitation (CPR) has been shown to enhance survival from cardiac arrest. Chest compression with a circumferential pneumatic vest enhances blood flow, but the size, weight, and energy consumption of the inflation system limit its portability and, thereby, have made clinical studies difficult. The purpose of this investigation was to study an improved circumferential chest compression device that uses a constricting band that is pneumatically actuated. The constricting band applies its force to a hydraulic cushion that contacts the anterior and lateral aspects of the chest. The hydraulic cushion transfers the circumferential constriction to inward force. CPR was performed on subjects 5 mins after induction of ventricular fibrillation, with the hydraulic-pneumatic band system (HB-CPR), with a pneumatic vest system (PV-CPR), and with standard manual CPR (S-CPR), each done for 2 mins in randomized order. Aortic and right atrial pressures were measured with micromanometers. Coronary perfusion pressure was calculated as the mean difference between the aortic and right atrial pressures during the release phase of chest compression. Aortic pressure and coronary perfusion pressure with HB-CPR and PV-CPR were improved over S-CPR, and HB-CPR produced comparable pressures to those of PV-CPR. The system for performing HB-CPR, however, was substantially lighter (10 vs. 50 kg) and consumed less energy (300 vs. 1000 watts) than that for PV-CPR. Thus, HB-CPR appears to produce a similar improvement in hemodynamics over S-CPR as PV-CPR but may be more portable than PV-CPR. Therefore, HB-CPR may allow larger scale testing of circumferential chest compression approaches.

Animals↗
PubMed1999

Lectins.

Lectins - carbohydrate-binding proteins involved in a variety of recognition processes - exhibit considerable structural diversity. Three new lectin folds and further elaborations of known folds have been described recently. Large variability in quaternary association resulting from small alterations in essentially the same tertiary structure is a property exhibited specially by legume lectins. The strategies used by lectins to generate carbohydrate specificity include the extensive use of water bridges, post-translational modification and oligomerization. Recent results pertaining to influenza and foot-and-mouth viruses further elaborate the role of lectins in infection.

Carbohydrate Metabolism↗
PubMed1999

Analysis and characterization of data from twinned crystals.

It is difficult but not impossible to determine a macromolecular structure using X-ray data obtained from twinned crystals, providing it is noticed and corrected. For perfectly twinned crystals, the structure can probably only be solved by molecular replacement. It is possible to detect and characterize twinning from an analysis of the intensity statistics and crystal packing density. Tables of likely twinning operators and some examples are discussed here.

Algorithms↗
PubMed1998

Structural evidence for the presence of a secondary calcium binding site in human alpha-lactalbumin.

The high-resolution X-ray crystal structure of human alpha-lactalbumin (at 1.8 A) in the presence of an elevated level of calcium reveals a new secondary calcium binding site, 7.9 A away from the primary calcium binding site known in all alpha-lactalbumin structures so far. The new calcium binding site is different from the zinc and sulfate binding sites [Ren, J., et al. (1993) J. Biol. Chem. 268, 19292-19298] but shares common features with the manganese binding site as described by Gerkin [Gerkin, T. A. (1984) Biochemistry 23, 4688-4697]. The proximity of the manganese and calcium binding region and the location of the functional site on one side of the charged surface of the alpha-lactalbumin molecule suggest that these binding sites might play a role in the formation of the lactose synthase complex.

Binding Sites↗
PubMed1996

Recent age-related trends in the use of thrombolytic therapy in patients who have had acute myocardial infarction. National Registry of Myocardial Infarction.

OBJECTIVE: To examine recent trends in the use of thrombolytic therapy in elderly patients who have had acute myocardial infarction and to determine whether failure to meet time-to-hospital presentation and electrocardiographic criteria might explain age-related differences in the use of thrombolytic therapy. DESIGN: A national registry of patients who have had acute myocardial infarction. SETTING: 1249 U.S. hospitals. PATIENTS: 350,755 patients who had an acute myocardial infarction from 1 July 1990 to 30 September 1994. MEASUREMENTS: Trends in the proportions of patients who received thrombolytic therapy were examined according to age and sex. The association between age and treatment with a thrombolytic agent was determined by crude and multivariable-adjusted analyses. RESULTS: Use of a thrombolytic agent was inversely related to patient age: Almost 51% of patients younger than age 55 years received a thrombolytic agent during hospitalization for acute myocardial infarction; this proportion decreased to 43.6% for patients aged 55 to 64 years, 33.0% for those aged 65 to 74 years, 19.0% for those aged 75 to 84 years, and 7.4% for those aged 85 years or older. However, relative increases in the use of thrombolytic therapy over time were greatest for patients in the oldest age groups. Between 1 July 1990 and 30 June 1991, 16.0% of patients aged 75 to 84 years received a thrombolytic agent compared with 21.4% between 1 June 1993 and 30 September 1994 (a 33.8% relative increase in use). Among persons aged 85 years or older, the proportion of treated patients increased from 5.3% to 9.1% over this same period (a 71.7% relative increase in use). Increases in thrombolytic use were most prominent for older women. After adjustment for sex, diagnosis by initial electrocardiogram, electrocardiogram-based infarction description, time from symptom onset to hospital presentation, and period of the acute myocardial infarction, the odds of receiving a thrombolytic agent were significantly reduced for patients in the older age groups compared with the odds for patients younger than age 55 years (for patients aged 75 to 84 years, the adjusted odds ratio was 0.27 [95% CI, 0.26 to 0.28]; for patients aged 85 years or older, the odds ratio was 0.09 [CI, 0.08 to 0.10]). CONCLUSIONS: Although older patients who have had acute myocardial infarction less commonly receive a thrombolytic agent, use of thrombolytic therapy in this population is expanding. However, substantial differences across age groups persist in the likelihood of receiving treatment, even after adjustment for potentially confounding factors. Age-related differences in thrombolytic use may not be completely explained by the degree to which older patients do not meet conventional eligibility criteria for thrombolytic therapy.

Age Factors↗
PubMed1995

Crystallization and preliminary X-ray crystallographic studies of nonhistone region of macroH2A.1.

Histone macroH2A has a novel hybrid structure consisting of a large nonhistone region and a region that closely resembles a full-length histone H2A. One key to understanding macroH2A function is determining the structure and function of its nonhistone region. The nonhistone region of one of the two known macroH2A subtypes was expressed in Escherichia coli and purified using affinity and molecular sieve chromatography. Crystals of the protein suitable for structural studies were grown from polyethylene glycol solutions by vapor equilibration techniques. The crystals belong to the hexagonal space group P6(4) (or its enantiomorph P6(2)) with unit cell parameters: a = b = 106.2 A, c = 125.9 A, alpha = beta = 90 degrees, and gamma = 120 degrees. There are four molecules in the asymmetric unit. Self-rotation function studies revealed three twofold noncrystallographic rotation axes related approximately by 222 symmetry. These crystals have 47% solvent content and diffract to 3.8 A resolution.

Crystallization↗
PubMed1994

The free radical system in ischemic heart disease.

The present work was conducted to evaluate the oxygen free radical system in 29 patients and comparing them with nine matched healthy controls of acute and chronic myocardial ischemic syndromes. The parameters assessed for oxidative stress were superoxide anion and malonyldialdehyde, and for the antioxidant defence system were superoxide dismutase, catalase and glutathione reductase. Both oxidative stress and the antioxidant defence system were altered in myocardial ischemia. Subset analysis revealed that in unstable angina and acute myocardial infarction, superoxide anion, malonyldialdehyde and glutathione reductase were elevated while superoxide dismutase and catalase levels were reduced. In stable angina only increased levels of superoxide anion and decreased levels of superoxide dismutase were found. However, this alteration was less marked than in unstable angina and acute myocardial infarction. In the post myocardial infarction group there was no alteration in any of these parameters.

Antioxidants↗
PubMed1994

Anomalous origin of right coronary artery from left aortic sinus.

Saphenous vein bypass grafting relieved myocardial ischemia caused by the anomalous origin of the right coronary artery from the left aortic sinus in a premenopausal woman. Contrary to the conventional impression, the anomaly is associated with sudden death, aborted death, angina, vasospasm, arrhythmia and cardiac dysfunction and is diagnosed more frequently on angiography. The literature is reviewed and the guidelines for diagnosis and surgical management of this not-so-rare but potentially serious anomaly are presented.

Adult↗
PubMed1993

Serotonergic mechanisms in hypertension.

Serotonin and abnormal serotonergic activity (both central and peripheral) may play a role in pathogenesis of essential hypertension. Serotonin acts chiefly via three types of receptors namely S1, S2 and S3 serotonergic receptors. Besides being vasoactive, it has some inotropic and chronotropic properties and also affects blood rheology. It has stimulating effect on renin and aldosterone secretion. The action of other vasoactive substances like norepinephrine and angiotensin II are amplified. All these physiological effects of serotonin strongly support the hypothesis that it may be involved in hypertension. The advent of serotonin antagonists in lowering blood pressure has further substantiated this hypothesis.

Animals↗