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Biomedical subjects

S Nath

Publications and source records attributed to S Nath.

At least 19 recordsLinked to original sources
PubMed2005

Transactivation of the epidermal growth factor receptor by cag+ Helicobacter pylori induces upregulation of the early growth response gene Egr-1 in gastric epithelial cells.

BACKGROUND AND AIMS: Helicobacter pylori, in particular cytotoxin associated gene (cag)+ strains, have been shown to enhance gastric epithelial cell proliferation in vivo, an effect that likely contributes to gastric carcinogenesis. Early growth response gene 1 (Egr-1) is a crucial regulator of cell growth, differentiation, and survival, which is known to play a role in carcinogenesis and cancer progression. The aims of this study were to: (1) examine whether H pylori could upregulate Egr-1 in gastric epithelial cell lines; (2) determine whether there was a differential response to infection with different strains; (3) examine the role of the cag pathogenicity island in this process; and (4) elucidate the molecular mechanisms leading to Egr-1 upregulation. METHODS AND RESULTS: We found that infection of AGS cells with cag+H pylori resulted in a rapid (1-2 hours) but transient increase in Egr-1 mRNA and protein levels whereas coculture with cag- isolates did not elicit this response. Furthermore, two independent cagE- isogenic mutants of H pylori also demonstrated impaired ability to upregulate Egr-1. Upregulation of Egr-1 protein was inhibited by the extracellular regulated kinase (ERK)1/2 inhibitor PD98059 and overexpression of dominant negative MEK1 downregulated Egr-1 luciferase reporter gene activity. Treatment of AGS cells with the epidermal growth factor receptor (EGFR) kinase inhibitors PD153035 and AG1478 resulted in a reduction in H pylori mediated Egr-1 upregulation, demonstrating that EGFR transactivation plays a role in this early cellular process. CONCLUSIONS: Our findings show that cag+H pylori cause rapid induction of Egr-1 in gastric epithelial cells which may contribute to H pylori mediated pathogenesis.

Antigens, Bacterial↗
PubMed2004

Electron transfer interaction of dihydroxyquinones with amine quenchers: dependence of the quenching kinetics on the aliphatic and aromatic nature of the amine donors.

Studies on the electron transfer (ET) interaction of 1,4-dihydroxy-9,10-anthraquinone and 6,11-dihydroxy-5,12-naphthacenequinone with aliphatic and aromatic amine (AlA and ArA, respectively) donors have been investigated in acetonitrile solutions. Steady-state (SS) measurements show quenching of the quinone fluorescence by amines, without indicating any change in the shape of the fluorescence spectra. No significant change in the absorption spectra of the quinones is also observed in the presence of the amines. For all the quinone-amine pairs, the bimolecular quenching constants (kq) estimated from SS and time-resolved measurements are found to be similar. Variation in the kq values with the oxidation potentials of the amines indicates the involvement of the ET mechanism for the quenching process. A reasonably good correlation between the kq values and the free energy changes (deltaG0) for the ET reactions following Marcus' outer-sphere ET theory also supports this mechanism. It is seen that for both the quinone-ArA and quinone-AlA systems, the kq values initially increase and then get saturated at some diffusion-controlled limiting values (kqDC) as deltaG0 values gradually become more negative. Interestingly, however, it is seen that the kqDC value for the quinone-AlA systems is substantially lower than that for quinone-ArA systems. Such a large difference in the kqDC values between quinone-AlA and quinone-ArA systems is quite unusual. Present results have been rationalized based on the assumption that an orientational restriction is imposed for the encounter complexes in quinone-AlA systems to undergo ET reactions, which arises because of the localized (at amino nitrogen) shapes of the highest-occupied molecular orbitals (HOMO) of AlA in comparison to the pi-like HOMO of the ArA.

Amines↗
PubMed2004

Chromosome aberrations in de novo acute myeloid leukemia patients in Kuwait.

Cytogenetic analysis was successfully performed at the time of diagnosis in 45 patients with de novo acute myeloid leukemia, including 10 children and 35 adults. In approximately 73% of AML patients (35 patients) clonal chromosome abnormalities were detected at the time of diagnosis. Twelve patients (22.8%) had apparently normal karyotypes. Recurring aberrations found in 22 of patients with abnormal karyotypes included t(15;17)(q22;q11), t(8;21)(q22;q22), inv(16)(p13q22), trisomy 8, monosomy 7 and del(5q). The highest frequency of chromosome changes was observed in AML-M3. The occurrence of the classical cytogenetic abnormalities was not a ubiquitous phenomenon. In 11 patients previously not described miscellaneous clonal chromosomal abnormalities were detected. Clonal chromosomal abnormalities detected in AML have shown correlations between specific recurrent chromosomal abnormalities and clinico-biological characteristics of the patients, therefore have been repeatedly shown to constitute markers of diagnostic and prognostic significance. Moreover, ongoing cytogenetic analysis can identify new nonrandom chromosome aberrations in AML and contribute to the identification of novel genes involved in the development of cancer, which can lead to better understanding of the disease pathogenesis.

Acute Disease↗
PubMed2003

Anteversion of the femoral neck in Indian dry femora.

The purpose of this study was to estimate the average angle of femoral neck anteversion in an Indian population. A total of 300 dry femora were classified by standard anatomical norms into male and female types and left-side and right-side types. They were evaluated by the Kingsley Olmsted and parallelograph methods, and the data were statistically analyzed. The average angles of anteversion obtained were 8.1 degrees and 8.3 degrees by the Kingsley Olmsted and parallelograph methods, respectively. The average female-type bone showed about 3 degrees more anteversion than the male-type bone. The average left-sided bone showed about 1.6 degrees more anteversion than the right-sided bone. A statistically significant difference existed between the sexes and the sides. The Kingsley Olmsted and parallelograph methods were found to be comparable with a correlation coefficient of 0.99. Altogether, 42.33%, 57.66%, and 79.00% of bones had readings of 5 degrees -10 degrees, 0 degrees -10 degrees, and 0 degrees -15 degrees, respectively. Thus, femoral neck anteversion has been found to be less in the Indian population than in Western populations.

Bone Wires↗
PubMed2001

Role of calcium in acute hyperthermic myocardial injury.

INTRODUCTION: We hypothesized that intracellular calcium overload may play an important role in heat-induced myocardial injury. This postulate was investigated using a model of isolated guinea pig papillary muscle in which resting tension was measured as an indirect indicator of cytosolic free-calcium concentration and the fluorescence changes of Fluo-3 AM dye was measured as a direct indicator of cytosolic free-calcium concentration. METHODS AND RESULTS: Excised guinea pig right ventricular papillary muscles were attached to a force transducer in a high-flow tissue bath and superfused with Tyrode's solution at 37 degrees +/- 0.5 degrees C. The temperature was rapidly changed to between 38.0 degrees and 56.0 degrees C for 60 seconds and then returned to 37.0 degrees C. Hyperthermia caused a reversible increase in resting tension at temperatures between 45 degrees and 50 degrees C and irreversible contracture at > or =50 degrees C. Rapid cooling contracture experiments and experiments measuring fluorescence of myocytes loaded with 5 microM Fluo-3 AM dye demonstrated that the hyperthermia-induced rise in resting tension was likely due to an increase in intracellular calcium content. Inhibition of the sarcoplasmic reticulum calcium pump with 20 microM thapsigargin resulted in irreversible contracture of the papillary muscles at temperatures between 45 degrees and 50 degrees C and significant increases in Fluo-3 fluorescence at 48 degrees C. Blockade of sarcolemmal calcium channels with 0.5 mM cadmium or 40 microM verapamil did not attenuate the heat-induced increase in resting tension and Fluo-3 fluorescence. CONCLUSION: Hyperthermia causes an increase in resting tension of cardiac muscle that most likely is mediated by a calcium channel-independent increase in calcium permeability of the sarcolemmal membrane and/or release of stored intracellular calcium.

Acute Disease↗
PubMed2001

A metadata framework for interoperating heterogeneous genome data using XML.

The rapid advances in the Human Genome Project and genomic technologies have produced massive amounts of data populated in a large number of network-accessible databases. These technological advances and the associated data can have a great impact on biomedicine and healthcare. To answer many of the biologically or medically important questions, researchers often need to integrate data from a number of independent but related genome databases. One common practice is to download data sets (text files) from various genome Web sites and process them by some local programs. One main problem with this approach is that these programs are written on a case-by-case basis because the data sets involved are heterogeneous in structure. To address this problem, we define metadata that maps these heterogeneously structured files into a common eXtensible Markup Language (XML) structure to facilitate data interoperation. We illustrate this approach by interoperating two sets of essential yeast genes that are stored in two yeast genome databases (MIPS and YPD).

Databases, Genetic↗
PubMed2000

Kinetic model of ATP synthase: pH dependence of the rate of ATP synthesis.

Recently, a novel molecular mechanism of torque generation in the F(0) portion of ATP synthase was proposed [Rohatgi, Saha and Nath (1998) Curr. Sci. 75, 716-718]. In this mechanism, rotation of the c-subunit was conceived to take place in 12 discrete steps of 30 degrees each due to the binding and unbinding of protons to/from the leading and trailing Asp-61 residues of the c-subunit, respectively. Based on this molecular mechanism, a kinetic scheme has been developed in this work. The scheme considers proton transport driven by a concentration gradient of protons across the proton half-channels, and the rotation of the c-subunit by changes in the electrical potential only. This kinetic scheme has been analyzed mathematically and an expression has been obtained to explain the pH dependence of the rate of ATP synthesis by ATP synthase under steady state operating conditions. For a single set of three enzymological kinetic parameters, this expression predicts the rates of ATP synthesis which agree well with the experimental data over a wide range of pH(in) and pH(out). A logical consequence of our analysis is that DeltapH and Deltapsi are kinetically inequivalent driving forces for ATP synthesis.

Adenosine Triphosphate↗
PubMed2000

Kinetic modeling of ATP synthesis by ATP synthase and its mechanistic implications.

Based on the torsional mechanism of ATP synthesis by ATP synthase, a kinetic scheme has been developed in this work. The scheme considers adenine nucleotide transport, binding of substrates ADP and P(i), unbinding of product ATP, and ATP synthesis. This kinetic scheme has been analyzed mathematically, and a kinetic model has been obtained to explain the experimentally observed hyperbolic Michaellian dependence of the rate of ATP synthesis on the ADP concentration by ATP synthase under physiological steady-state operating conditions. The principal results of the kinetic model have been compared with the experimental data and an estimate of the enzymological kinetic parameters V(max), K(M), and K(I) has been determined. Mechanistic implications arising from further analysis of the kinetic model have been discussed. These biological implications provide deep insight into the sequence of events leading to ATP synthesis.

Adenosine Diphosphate↗
PubMed2000

Debilitating chronic pain syndromes after presumed intraneural injections.

This report presents seven patients with severe disability established at the time of a peripheral nerve block. In most of the cases, the injection was administered as a routine procedure by an experienced anesthesiologist. The patient histories suggest that the condition, which can be resistant to all treatment, in most cases could have been avoided if careful attention had been given to the occurrence of pain during the nerve block. It is likely that the risk of devastating iatrogenic disability can be minimized if a few basic principles are respected during the administration of peripheral nerve blocks.

Adult↗
PubMed2000

Dosimetric effects of needle divergence in prostate seed implant using 125I and 103Pd radioactive seeds.

In prostate seed implants, radioactive seeds are implanted into the prostate through a guiding needle with the help of a template and real-time imaging. The ideal locations of the guiding needles and the relative positions of the seeds in each needle are determined before the implantation under the assumption that the needles inserted at different locations will remain parallel. In actual implantation, the direction of the needle is subject variation. In this work, we studied how the dosimetry quality of an implant may be affected when the guiding needles deviate from its planned orientations. Needle divergence of varying degree was simulated on spherical models and actual patient implants. It was found that needle divergence degraded the dosimetric quality of an implant: The minimum target dose, the target dose coverage and therefore the tumor biological effective dose were quantitatively decreased as compared to the reference implant. The magnitude of degradation increased almost linearly with respect to the magnitude of needle divergence. For iodine-125 implants, the average reduction in minimum target dose was about 10% and 20% for needle divergence of standard deviation of 5(0) and 10(0), respectively. The dose coverage in the target was reduced by about 1% and 3% for needle divergence of standard deviation of 5(0) and 10(0), respectively. Implants designed with palladium-103 showed additional 5% reduction in minimum target dose while the effect on dose coverage was about the same as compared to the iodine-125 implants. The degree of dosimetry degradation was shown to be dependent on the size of target volume, the seed spacing used, the use of seeding margin, and on the actual configuration of needle orientations in a given implant. One needs to minimize the physical causes of needle divergence in order to minimize its impact on planned dosimetry. The study suggests that the displacement between a needle image and its planned grid point at the base of prostate should be kept less than 5 mm in order to minimize the reduction in D(min)(<5%) and the increase in cell-survival (< a factor of 10) from the planned dosimetry.

Biophysical Phenomena↗
PubMed1999

Surface Tension of Nonideal Binary Liquid Mixtures as a Function of Composition.

The composition dependence of the surface tension of highly nonideal organic-organic and aqueous-organic nonelectrolyte solutions is described, based on the assumption that the surface layer can be treated as a separate phase located between vapor and bulk liquid phases. The Wilson, NRTL, and UNIFAC methods are used for activity coefficients of surface and bulk phases and three techniques for calculation of molar surface areas, based on Paquette areas, Rasmussen areas, and a Langmuir-type approach are tested. Comparisons of the calculated surface tensions with experimental data yield mean absolute errors, in the best case, of less than 2.5% for the systems studied, all of which exhibit highly nonideal behavior. The surface tension predictions are found to be extremely sensitive to the values of the molar surface areas used in the computation. A Langmuir-type adsorption model is formulated to determine the surface mole fractions from a knowledge of the mixture surface tension as a function of bulk composition. A novel procedure is developed to obtain the partial molar surface area of the larger organic component as a function of composition in binary aqueous-organic systems, assuming that the two components are very dissimilar in size, and that deviations in the partial molar surface area of the smaller component (water) from its pure component molar surface area contribute negligibly to the total molar surface area of the mixture. This removes the approximation of equality of partial and pure component molar surface area for the larger organic component. Use of the Langmuir-type approach with partial molar surface areas improves surface tension predictions of highly nonideal aqueous-organic mixtures by 20% over use of pure component molar surface areas. It is an important first step in the development of a thermodynamically consistent theory of surfaces for liquid mixtures based on an accurate determination of the composition dependence of partial molar surface areas for all components. Copyright 1999 Academic Press.

Journal Article↗
PubMed1998

Total loss of upper and lower lips: challenges in reconstruction.

A 2-year-old girl lost both lips after an aggressive attack of noma (gangrenous stomatitis). After an unsuccessful attempt to reconstruct her upper lip, a bipedicled chin flap was used to reconstruct both lips. The cosmetic result was good and the functional result was acceptable.

Child, Preschool↗
PubMed1998

Cancrum oris: management, incidence, and implications of human immunodeficiency virus in Zambia.

The University Teaching Hospital is situated in the Zambian capital, Lusaka. In a 15-year period (1979 to 1993), 81 child patients with cancrum oris were admitted to the pediatric plastic surgery unit. There were 29 boys and 52 girls, of whom 58 were below 3 years of age. The majority of them were from certain provinces where the population is comparatively much lower than in other provinces of Zambia. The dietary habits in cancrum orisprone provinces are quite different than those of other provinces of Zambia. Of 81 patients, 3 refused surgery, 11 died during early medical treatment, and 12 died following early minor surgery. A total of 55 patients had reconstructive surgery by one of the authors (Nath). Problems encountered during management, such as anesthesia, trismus, and choice of appropriate flaps, are discussed in this paper. The implication of human immunodeficiency virus is also addressed.

AIDS-Related Opportunistic Infections↗
PubMed1997

Entrainment mapping in patients with sustained atrioventricular nodal reentrant tachycardia: insights into the sites of conduction slowing in the slow atrioventricular nodal pathway.

The inferoposterior region of the triangle of Koch is hypothesized to be the location of the atrial insertion of the slow atrioventricular (AV) nodal pathway. However, the actual site of conduction slowing in the slow AV nodal pathway is unknown. Entrainment mapping during AV nodal reentry can localize the reentrant pathway as follows: the AH interval measured from the mapping catheter = A'H (where A' is the exit site of the reentrant circuit) minus A'A (the conduction time from A' to the site of mapping); the SH interval during entrainment = SA' (the conduction time from stimulus into the reentry circuit) plus A'H. Thus, in all cases, the SH interval should be greater than or equal to the AH interval, and the deltaAH-SH should increase as distance and conduction time (SA' and A'A) from the reentry circuit increases. Fourteen patients with typical AV nodal reentry (cycle length 346 +/- 62 ms) and 1 with fast-slow (cycle length 430 ms) underwent activation and entrainment mapping from 8 to 12 sites in the triangle of Koch and coronary sinus. Pacing was performed at 2 to 3 mA above threshold, at a cycle length 10 ms shorter than tachycardia. A mapping site was defined as being in close proximity to the circuit if the deltaAH-SH was within 120% of the shortest 20th percentile deltaAH-SH value from all measured sites. In the 14 typical cases, 45 of 83 sites (54%) in the anatomic slow pathway region fulfilled criteria for close proximity to the reentry circuit compared with 13 of 50 sites (26%) outside of this region (p = 0.005). For these patients, the shortest SH interval measured from any entrainment site was 294 +/- 58 ms (89 +/- 10% of tachycardia cycle length, range 70% to 119%), indicating that the site of slow conduction in the slow pathway during AV nodal reentrant tachycardia was distal to all mapped sites. Thus, during typical AV nodal reentry, the "slow" pathway does not conduct slowly, and its insertion is located at or within the inferoposterior or midseptal regions in most cases.

Adult↗
PubMed1997

Influence of patient characteristics in the selection of patients for defibrillator implantation (the AVID Registry). Antiarrhythmics Versus Implantable Defibrillators.

The Antiarrhythmics Versus Implantable Defibrillators (AVID) trial is a prospective, randomized study of treatment for life-threatening ventricular arrhythmias. Patients who are eligible for the main trial but who are not enrolled for any reason are followed in a registry. The objective of the present study was to determine whether there are identifiable patient characteristics among these registry patients that may influence whether a patient is treated with an implantable defibrillator. The 914 patients in the registry were divided into 2 groups according to whether the primary treatment was an implantable defibrillator. The mean age of defibrillator patients was 60 years, compared with 65 years in the nondefibrillator group (p <0.001). Only 11.2% of defibrillator recipients were minorities, whereas the percentage of minorities in the nondefibrillator group was 18.7% (p <0.003). A history of recurrent ventricular fibrillation was more likely in the group treated with defibrillators (8.9% vs 4.4%, p <0.01), whereas a history of atrial fibrillation or diabetes mellitus were both significantly more likely in the nondefibrillator group. Among defibrillator patients, a higher proportion had ventricular fibrillation as the index arrhythmia; patients with ventricular tachycardia were significantly more likely to be treated without devices. In this prospective but nonrandomized cohort of patients treated for life-threatening ventricular arrhythmias, older age, minority status, and comorbidity reduced the chances that a patient would be treated with a defibrillator.

Aged↗
PubMed1997

The inhibition of growth and down-regulation of gonadotropin releasing hormone (GnRH) receptor in alphaT3-1 cells by GnRH agonist.

Gonadotropin releasing hormone (GnRH) and its analogs inhibit the growth of hormone-dependent tumors in vivo and in vitro. The inhibition of growth and proliferation of tumor cells in vitro by GnRH and its analogs indicates that the tumor suppressing effect of the hormone is only partially due to suppression of pituitary gonadotropin release which reduces circulating steroid levels that are required for proliferation. Demonstration of GnRH-binding sites on some tumors suggests a direct inhibitory effect of GnRH and its analogs. However, the mechanism by which GnRH and its analogs inhibit tumor cell growth is not known. Our hypothesis is that the inhibition of growth and proliferation of tumor cells by GnRH and its analogs are mediated through down-regulation of its receptor expression. To test this hypothesis, mouse pituitary gonadotrope cell line (alphaT3-1) was selected as a model since this is the only cell line which expresses a sufficiently high level of GnRH receptors for precise measurements of the mRNA for the receptor. Addition of GnRH agonist (D-Lys6)GnRH to the cell cultures caused a time-dependent decrease in both cell growth, as measured by cell number, and cell proliferation, as measured by [3H]thymidine incorporation into DNA. After 1 h of treatment of alphaT3-1 cells with 1 microM of (D-Lys6)GnRH, the cell number was reduced to 83.0 +/- 13.4 compared to control, decreased to 75.1 +/- 3.2 at 2 h, 63.2 +/- 0.66 at 4 h and 52.2 +/- 0.87 at 24 h. This decrease in cell number was accompanied by a parallel decrease in [3H]thymidine incorporation into DNA. The inhibition of cell growth and [3H]thymidine incorporation by treatment with 1 microM of (D-Lys6)GnRH was sustained for at least 72 h. Inhibition of alphaT3-1 cell growth and [3H]thymidine incorporation was dose-dependent; thus 10(-9) M (D-Lys6)GnRH resulted in about 30% inhibition within 4h which was comparable to 10(-6) M (D-Lys6)GnRH, whereas 10(-12) M (D-Lys6)GnRH was ineffective. Measurement of mRNA for the GnRH receptor by Northern blot analysis showed a decrease in levels of mRNA by 5% within 2 h of treatment of alphaT3-1 cells with 1 microM (D-Lys6)GnRH, by 30% at 4 h and by 50% at 24 h. In conclusion these data demonstrate that treatment of alphaT3-1 cells with (D-Lys6)GnRH causes an inhibition of cell growth and proliferation, and down-regulates the GnRH receptor mRNA levels.

Animals↗