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A Natarajan

Publications and source records attributed to A Natarajan.

At least 19 recordsLinked to original sources
PubMed2001

Poly-L-proline type II peptide mimics based on the 3-azabicyclo[3.1.0]hexane system.

This paper describes conformational studies of proline-templated amino acids (PTAAs) based on the 3-azabicyclo[3.1.0]hexane system as well as conformational studies on short peptides composed of these PTAAs. NOE data, coupling constants, and molecular modeling are consistent with a flattened boat conformation for monomeric and oligomeric residues based on this bicyclic system. NMR studies on dimeric and trimeric oligomers are consistent with a populated poly-L-proline type II conformation in CDCl3 and D2O. Solution studies and molecular modeling predicts phi approximately -70 degrees, psi approximately 131 degrees, chi 1 approximately -57 degrees, and chi 2 approximately -158 degrees for oligomeric residues.

Bridged Bicyclo Compounds, Heterocyclic↗
PubMed2001

Human eHAND, but not dHAND, is down-regulated in cardiomyopathies.

The progression of cardiomyopathy to congestive heart failure is often associated with the expression of fetal cardiac-specific genes. In mice, the basic helix-loop-helix transcription factors, dHAND and eHAND, are expressed in a cardiac chamber-specific fashion and are essential for fetal cardiac development, but are down-regulated in the adult. Their expression in specific chambers of healthy and diseased human hearts has not been studied previously. Human dHAND and eHAND were mapped to human chromosomes 4q33 and 5q33, respectively, by fluorescent in situ hybridization. RNA from the four chambers of healthy human adult hearts, and from hearts of patients with several forms of cardiomyopathy, was obtained and assayed for dHAND and eHAND expression. Unlike in mice, dHAND expression was observed in all four chambers of the healthy human adult heart, but was diminished in the right atrium. In contrast, eHAND was expressed in the right and left ventricles, but was downregulated in both atrial chambers. We examined tissue from 15 human cardiomyopathic hearts obtained during cardiac transplantation or by endomyocardial biopsy for alterations in HAND gene expression. dHAND expression was unchanged in all forms of cardiomyopathy tested. However, cardiac expression of eHAND was severely down-regulated in six of six patients with ischemic cardiomyopathy and six of six patients with dilated cardiomyopathy. This study demonstrates that human dHAND and eHAND have unique spatial patterns of expression within human cardiac chambers. Downregulation of eHAND in ischemic and dilated cardiomyopathy suggests a correlation between eHAND dysregulation and the evolution of a subset of cardiomyopathies.

Adolescent↗
PubMed2000

Glucose uptake rates of single E. coli cells grown in glucose-limited chemostat cultures.

To evaluate the extent to which single-cell glucose uptake rates determine the overall specific growth rate of a culture, dilute chemostat cultures of Escherichia coli BL21 were grown in defined medium under glucose limitation. The glucose uptake dynamics of the cell population was examined at the single-cell level using the fluorescent glucose analog, 2-NBDG. Between dilution rates of 0.12 h(-1) and 0.40 h(-1), mean cellular protein content and steady-state, extracellular glucose concentrations increased with increasing dilution rate. However, the distribution of 2-NBDG uptake rates in the population remained constant over the range of dilution rates studied. This indicates that the growth of cells in continuous culture is not limited by the maximum rate of uptake of glucose but by the availability of glucose for transport. The work represents an example of how quantitative flow cytometry can be applied to gain detailed insight into microbial growth physiology.

4-Chloro-7-nitrobenzofurazan↗
PubMed2000

A sensitive method to detect initiation of growth in Streptococcus gordonii using ribosomal RNA operon-reporter gene fusions.

A system for studying the early growth response of Streptococcus gordonii to environmental stimuli has been developed. A reporter gene, encoding alpha-amylase, has been integrated into an rRNA operon to monitor changes in cellular physiology associated with the initiation of growth. Two such strains with single integrants have been characterized during the transition from lag phase to exponential growth. Synthesis of the reporter is correlated to growth initiation in both strains, and the reporter enzyme is detectable with sufficient sensitivity. Comparison of the expression profiles of the two rrn operons containing the reporter gene suggests that they are differentially expressed over the course of growth.

Artificial Gene Fusion↗
PubMed1999

A flow injection flow cytometry system for on-line monitoring of bioreactors.

For direct and on-line study of the physiological states of cell cultures, a robust flow injection system has been designed and interfaced with flow cytometry (FI-FCM). The core of the flow injection system includes a microchamber designed for sample processing. The design of this microchamber allows not only an accurate on-line dilution but also on-line cell fixation, staining, and washing. The flow injection part of the system was tested by monitoring the optical density of a growing E.coli culture on-line using a spectrophotometer. The entire growth curve, from lag phase to stationary phase, was obtained with frequent sampling. The performance of the entire FI-FCM system is demonstrated in three applications. The first is the monitoring of green fluorescent protein fluorophore formation kinetics in E.coli by visualizing the fluorescence evolution after protein synthesis is inhibited. The data revealed a subpopulation of cells that do not become fluorescent. In addition, the data show that single-cell fluorescence is distributed over a wide range and that the fluorescent population contains cells that are capable of reaching significantly higher expression levels than that indicated by the population average. The second application is the detailed flow cytometric evaluation of the batch growth dynamics of E.coli expressing Gfp. The collected single-cell data visualize the batch growth phases and it is shown that a state of balanced growth is never reached by the culture. The third application is the determination of distribution of DNA content of a S. cerevisiae population by automatically staining cells using a DNA-specific stain. Reproducibility of the on-line staining reaction shows that the system is not restricted to measuring the native properties of cells; rather, a wider range of cellular components could be monitored after appropriate sample processing. The system is thus particularly useful because it operates automatically without direct operator supervision for extended time periods.

Bioreactors↗
PubMed1999

Dynamics of glucose uptake by single Escherichia coli cells.

The fluorescent glucose analog, 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose (2-NBDG), was used to measure rates of glucose uptake by single Escherichia coli cells. When cell populations were exposed to the glucose analog, 2-NBDG was actively transported and accumulated in single cells to a steady-state level that depended upon its extracellular concentration, the glucose transport capacity of the cells, and the intracellular degradation rate. The dependence upon substrate concentration could be described according to Michaelis-Menten kinetics with apparent saturation constant KM = 1.75 microM, and maximum 2-NBDG uptake rate= 197 molecules/cell-second. Specificity of glucose transporters to the analog was confirmed by inhibition of uptake of 2-NBDG by D-glucose, 3-o-methyl glucose, and D-glucosamine, and lack of inhibition by L-glucose. Inhibition of 2-NBDG uptake by D-glucose was competitive in nature. The assay for 2-NBDG uptake is extremely sensitive such that the presence of even trace amounts of D-glucose in the culture medium (approximately 0.2 microM) is detectable. The rates of single-cell analog uptake were found to increase proportionally with cell size as measured by microscopy or single-cell light scattering intensity. The assay was used to identify and isolate mutant cells with altered glucose uptake characteristics. A mathematical model was developed to provide a theoretical basis for estimating single-cell glucose uptake rates from single-cell 2-NBDG uptake rates. The assay provides a novel means of estimating the instantaneous rates of nutrient depletion in the growth environment during a batch cultivation.

4-Chloro-7-nitrobenzofurazan↗
PubMed1998

Comparison of mutant forms of the green fluorescent protein as expression markers in Chinese hamster ovary (CHO) and Saccharomyces cerevisiae cells.

Several green fluorescent protein (Gfp) mutants with increased cellular fluorescence compared to the wildtype protein have recently been generated. We have expressed and compared wildtype Gfp and mutants S65T, F100S/ M154T/V164A, F64L/S65T, and S65A/V68L/S72A under identical growth conditions in CHO and Saccharomyces cerevisiae cells. The results suggest that the last two Gfp mutants are the best candidates as reporter proteins, and they provide a high signal-to-noise ratio in both systems. Single gene copy expression of these mutant forms is easily detectable over background autofluorescence. All Gfps are highly stable within cells, with an estimated 1/2-life between 7 h (wildtype) and 70 h (F100S/M154T/V164A) in S. cerevisiae cells. Although this limits their use in examining rapid cellular events without further modification, Gfp is expected to be a useful marker for monitoring the physiological state of cells in bioreactors using on-line probes.

Animals↗
PubMed1996

Medical ethics and truth telling in the case of androgen insensitivity syndrome.

Should a physician always tell the truth to a patient? Is biomedical ethics too "politically correct" in certain situations? The second-place winner in the 1995 Logie Medical Ethics Essay Contest discusses whether telling the truth is the proper course for a physician dealing with certain patients.

Androgen-Insensitivity Syndrome↗
PubMed1996

Effect of probiotic supplementation on growth, nitrogen utilisation and serum cholesterol in broilers.

1. The effect of dietary probiotic supplementation on the growth, nitrogen utilisation and serum cholesterol content of broiler chickens was studied in 2 trials. 2. In experiment 1, the birds receiving the 0, 75, 100, 125 mg probiotic/kg diets had weight gains of 1204.0, 1272.0, 1268.3 and 1210.5, respectively at the end of 8 weeks of feeding. The group of birds fed on the 75 mg probiotic supplemented diet retained significantly (P < 0.01) more nitrogen than the control birds. Serum cholesterol content was lower in the probiotic-supplemented birds (93.3 mg/100 ml) compared to the control birds (132.2 mg/100 ml). 3. In the second experiment the probiotic plus antibiotic-supplemented group of birds had the maximum weight gain (1148.5 g) followed by antibiotic (1141.3 g), probiotic-supplemented (1128.4 g) and control birds (1045.6 g) after 6 weeks. Nitrogen retention was greatest in the antibiotic--(48.5%) followed by the probiotic--(46.5%), probiotic plus antibiotic-supplemented groups (46.3%) compared to 40.2% in control birds. 4. The apparent metabolisable energy was greatest in birds receiving the probiotic plus antibiotic-supplemented diet (12.37 MJ/kg) followed by antibiotic--(12.00 MJ/kg), probiotic-supplemented birds (11.92 MJ/kg) than in control birds (11.62 MJ/kg). Serum cholesterol was significantly (P < 0.01) lower in probiotic-supplemented birds (86.1 mg/dl) compared to 118.4 mg/dl in control birds.

Animal Feed↗
PubMed1995

Effect of probiotic supplementation on serum/yolk cholesterol and on egg shell thickness in layers.

1. The effect of probiotic supplementation on egg production, on serum and yolk cholesterol and on egg shell thickness in 24 White Leghorn layers was studied from 28-38 weeks of age. 2. In 3 treatments the diet was supplemented with 0, 100 and 150 mg probiotic/kg food. 3. In the 100 mg probiotic group, egg production improved by 5%, and shell thickness improved slightly, with fewer thin-shelled eggs than in the control (8.6% compared to 18.6%). 4. The initial serum cholesterol concentration of 170.2 mg/dl in control birds remained similar throughout the 10-week experimental period, whereas in the 150 mg group the initial value of 176.5 mg/dl decreased to 114.3 mg by week 10. 5. Yolk cholesterol concentration was 14.69 mg in the control group and 11.28 and 11.37 mg/g in the 100 and 150 mg probiotic groups respectively. Overall mean total egg cholesterol was thus reduced by probiotic supplementation.

Animal Feed↗
PubMed1995

Preventive health care for children.

This article discusses immunization, development, vision, blood pressure, dentition, behavioral, and environmental screening for preschool children. The authors then discuss screening for children in the early school years. Injury and violence prevention and topics of sexuality for the preadolescent are also presented.

Child↗
PubMed1994

Three distinct human thymopoietins are derived from alternatively spliced mRNAs.

Thymopoietin (TP) was originally isolated as a 5-kDa 49-aa protein from bovine thymus in studies of the effects of thymic extracts on neuromuscular transmission and was subsequently observed to affect T-cell differentiation and function. We now report the isolation of cDNA clones for three alternatively spliced mRNAs that encode three distinct human T-cell TPs. Proteins encoded by these mRNAs, which we have named TP alpha (75 kDa), TP beta (51 kDa), and TP gamma (39 kDa), contain identical N-terminal regions, including sequences nearly identical to that of the originally isolated 49-aa protein, but divergent C-terminal regions. TP mRNAs are expressed in many tissues, most abundantly in adult thymus and fetal liver of the tissues so far examined. Distinct structural domains and functional motifs in TPs alpha, beta, and gamma suggest that the proteins have unique functions and may be directed to distinct subcellular compartments.

Alternative Splicing↗
PubMed1994

Multiway sequential hypothesis testing for tachyarrhythmia discrimination.

A multiway sequential hypothesis testing (M-SHT) algorithm is proposed for simultaneous discrimination of cardiac tachyarrhythmias--supraventricular tachycardia (SVT) and ventricular tachycardia (VT)--from normal sinus rhythm (NSR). The M-SHT algorithm calculates a likelihood function from atrio-ventricular delay measurements, and compares this function with thresholds derived from specified error probabilities for the arrhythmias to be discriminated. Performance of this algorithm was evaluated on dual channel endocardial electrograms recorded in the cardiac electrophysiology laboratory. Two databases were developed, one for development of the algorithm and another for evaluation. The M-SHT algorithm accurately classified 26 out of 28 NSR (2 misclassified as SVT), 31 out of 31 cases of SVT, and 41 out of 43 VT (2 misclassified as NSR). The average length of time taken for classification of the three rhythms was: 3.6 s for NSR, 5.0 s for SVT, and 1.6 s for VT. Unique features of this algorithm are that acceptable error rates for each arrhythmia are independently specified and accuracy can be traded off for a faster detection time, and vice versa.

Adult↗
PubMed1993

Comparison of shortening with timing of wall motion in detecting regional abnormalities of the left ventricle in coronary disease.

Clinical observations suggest that ischemic myocardium may demonstrate delayed wall motion while absolute shortening remains normal. Wall motion timing and percent shortening were examined in 25 patients (7 normal, 18 coronary disease) with 35 mm biplane left ventriculograms and coronary arteriography. Mean age was 63 +/- 2.4 years. Of 17 males and 8 females, 13 had 3 vessel, 4 had 2 vessel, and 1 had 1 vessel disease. Left ventricular regions were analyzed using the Coronary Artery Surgery Study nomenclature and quantitative computer-based analysis as well as visual based qualitative analysis. Regional percent shortening and ejection fraction were calculated from end systolic and end diastolic frames. Regional shortening times were related to global ejection time from 30 frame/sec, frame by frame analysis. Feeder arteries were stenosed ( > 70%) in 135 of 225 left ventricular regions analyzed. Computer detection (shortening and timing) identified 97/225 as abnormal (p < 0.01 vs. feeder artery stenosis) while physicians identified 79/225 as abnormal (p < 0.01 vs. feeder artery stenosis). Of the 97 computer detected abnormal regions, shortening alone detected 47, timing alone detected 39, and 11 showed both abnormalities. Timing analysis increased detection of wall motion abnormalities from 58/225 (26%) to 97/225 (43%) (p < 0.001). Timing abnormalities were noted more (92%) in basal segments, while shortening abnormalities dominated (88%) in apical segments (p < 0.001). Use of temporal measurements in wall motion analysis significantly increases the likelihood of detecting abnormal left ventricular regional wall motion when compared to shortening measurements alone.

Coronary Angiography↗
PubMed1991

The automatic implantable cardioverter-defibrillator: technology for preventing sudden cardiac death.

Sudden cardiac death is caused by a malignant heart rhythm known as ventricular fibrillation. The automatic implantable cardioverter-defibrillator (AICD) is a device that recognizes this rhythm and converts it to a normal sinus rhythm by delivering an electrical shock directly to the heart. This article reviews the technology and clinical status of AICD technology, and the ongoing research into techniques for detecting malignant arrhythmias.

Arrhythmias, Cardiac↗
PubMed1991

Sensors for implantable pacemakers.

Cardiac pacemaker technology has progressed greatly since the first implantable pacemaker was invented in the 1950s. The most recent improvement incorporates sensors that measure the body's metabolic responses and then appropriately pace according to these measurements. This article reviews this technology and examines the various sensors used in rate-responsive pacemakers.

Biosensing Techniques↗
PubMed1988

Frequencies of chromosomal aberrations induced in human blood lymphocytes by low doses of X-rays.

The dose-response for radiation-induced chromosome aberrations in human lymphocytes is usually fitted to the quadratic model. This assumes that the slope is essentially linear at low doses. Empirical observations of linearity at less than 200 mGy are, however, sparse. Some data have been published indicating a non-linear (threshold) response and these are reviewed. In particular one study with X-rays showed a plateau in response up to 50 mGy and with a significant dip below the control level at 4 mGy. The mechanism proposed to explain non-linearity is that low doses stimulate the enzymic repair capability of lymphocytes. Preliminary data are presented from a large experiment by six laboratories in which the low dose-response for X-rays has been re-examined. The plateau in the dose-response relationship, if it exists, does not extend to doses above approximately 10 mGy. No irradiated cells yielded aberration levels significantly below the control. Over the range 0-300 mGy the response can be fitted to a linear regression. There are, however, variations in sensitivity between cells from different donors. An unexpected finding was that some lymphocytes contained greater than 1 exchange aberrations. This may indicate a small subset of cells that are especially susceptible to the induction of aberrations by low doses.

Adult↗