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Biomedical subjects

J P Singh

Publications and source records attributed to J P Singh.

At least 19 recordsLinked to original sources

Reduced fouling and enhanced microbial inactivation during online sterilization of cheese whey using UV coil reactors in series.

The effectiveness of coil UV reactor series for the online sterilization of cheese whey was compared to those of the single conventional and coil reactors at various flow rates (5-70 mL/min). The residence time varied from 168 to 12 min and from 48 to 24 min for the single and the series reactors, respectively. Hundred percent destruction efficiency could not be achieved in the single reactors whereas in the coil reactor series the destruction efficiency reached 100% at the flow rates of 35 and 40 mL/min. The rate of microbial destruction was described by polynomial equation for the single coil reactor and by exponential equations for the single conventional reactor and the coil reactor series. The temperature of the effluent decreased with the increase in flow rate in all the reactors. The maximum effluent temperatures in the single conventional reactor, single coil reactor and coil reactor series were 45.8, 46.1, and 36.4 degrees C (Deltat = 20.8, 21.1, 11.4 degrees C), respectively. The flow in all the reactors was laminar (R ( e ) = 1.39-20.10) and the Dean number was in the range of 1.09-15.41 in the coil reactors. Visual observation revealed less fouling on the UV lamps of coil reactors than on that of the conventional reactor due to the impact of Dean flow. The total operating time during which 100% destruction efficiency is achieved prior to the advent of fouling was 240 min in the coil reactor series compared to only 45 min in the conventional reactor.

Bioreactors↗

Peptide alkaloids from Zizyphus sativa bark.

Two new cyclopeptide alkaloids, sativanine-N and sativanine-O were isolated from the stem bark of Zizyphussativa and their structures were established by spectral analysis.

Alkaloids↗

Thrombin and PAR-1 stimulate differentiation of bone marrow-derived endothelial progenitor cells.

Endothelial progenitor cells (EPCs) from the bone marrow play an important role in vascular response to injury and ischemia. The mediators involved in the mobilization, recruitment, proliferation and differentiation of EPCs are not fully understood. In this study, the role of coagulation factor thrombin and protease-activated receptor-1 (PAR-1) on bone marrow-derived cell proliferation and differentiation was investigated. Bone marrow cells (BMCs) were isolated from C57/BL6 mice and plated on fibronectin-coated flasks. Cell characteristics, proliferation and the expression of endothelial cell markers were determined using immunohistochemistry, thymidine uptake and fluorescence activated-cell sorting (FACS), respectively. The results show that thrombin stimulated enrichment of bone marrow cells with endothelial morphology, exhibiting acetylated-low-density lipoprotein (LDL) uptake and isolectin staining. Thrombin or PAR-1-activating peptide produced a 2- to 3-fold increase in the total number of cells as well as an increase in vascular endothelial (VE)-cadherin-positive cells. Thrombin treatment of VE-cadherin-negative cells prepared after cell sorting resulted in the generation of 3- to 4-fold higher VE-cadherin-positive cells than the untreated cultures. Increase in VE-cadherin-positive cells was inhibited by hirudin and efegatran. These results provide first evidence for a novel activity of thrombin and PAR-1 on bone marrow progenitor cell proliferation and EPC differentiation, and suggest their potential role in vascular regeneration and recanalization of thrombus.

Animals↗

Random amplified polymorphic DNA (RAPD) analysis of Mycobacterium tuberculosis strains in India.

The usefulness of random amplification of polymorphic DNA (RAPD) analysis for typing Indian strains of M. tuberculosis was investigated. M. tuberculosis H37Rv, M. tuberculosis DT and 42 clinical isolates of M. tuberculosis were subjected to RAPD-PCR using 7 random decamer primers. All 7 primers were found to be differentiated and produced specific RAPD profiles. The polymorphic amplicons served as RAPD markers for M. tuberculosis. The dendrograms, obtained by different primers, showed the discriminatory ability of the primers. RAPD analysis provided a rapid and easy means of identifying polymorphism in M. tuberculosis isolates, and it was found to be a valuable alternative epidemiological tool. In addition, the results of the present study showed heterogeneity in the M. tuberculosis strains in the population studied.

Animals↗

Early tracheostomy in closed head injuries: experience at a tertiary center in a developing country--a prospective study.

BACKGROUND: An important factor contributing to the high mortality in patients with severe head trauma is cerebral hypoxia. The mechanical ventilation helps both by reduction in the intracranial pressure and hypoxia. Ventilatory support is also required in these patients because of patient's inability to protect the airway, persistence of excessive secretions, and inadequacy of spontaneous ventilation. Prolonged endotracheal intubation is however associated with trauma to the larynx, trachea, and patient discomfort in addition to requirement of sedatives. Tracheostomy has been found to play an integral role in the airway management of such patients, but its timing remains subject to considerable practice variation. In a developing country like India where the intensive care facilities are scarce and rarely available, these critical patients have to be managed in high dependency cubicles in the ward, often with inadequately trained nursing staff and equipment to monitor them. An early tracheostomy in the selected group of patients based on Glasgow Coma Score(GCS) may prove to be life saving. Against this background a prospective study was contemplated to assess the role of early tracheostomy in patients with isolated closed head injury. METHODS: The series consisted of a cohort of 50 patients admitted to the surgical emergency with isolated closed head injury, that were not considered for surgery by the neuro-surgeon or shifted to ICU, but had GCS score of less than 8 and SAPS II score of more than 50. First 50 case records from January 2001 that fulfilled the criteria constituted the control group. The patients were managed as per ATLS protocol and intubated if required at any time before decision to perform tracheostomy was taken. These patients were serially assessed for GCS (worst score of the day as calculated by senior surgical resident) and SAPS scores till day 15 to chart any changes in their status of head injuries and predictive mortality. Those patients who continued to have a GCS score of <8 and SAPS score of >50 for more than 24 hours (to rule out concussion or recovery) underwent tracheostomy. All these patients were finally assessed for mortality rate and hospital stay, the statistical analysis was carried out using SPSS10 version. The final outcome (in terms of mortality) was analyzed utilizing chi-square test and p value <0.05 was considered significant. RESULTS: At admission both tracheostomy and non-tracheostomy groups were matched with respect to GCS score and SAPS score. The average day of tracheostomy was 2.18 +/- 1.0038 days. The GCS scores on days 1, 2, 3, 4, 5, 10 between tracheostomy and non-tracheostomized group were comparable. However the difference in the GCS scores was statistically significant on day 15 being higher in the tracheostomy group. Thus early tracheostomy was observed to improve the mortality rate significantly in patients with isolated closed head injury. CONCLUSION: It may be concluded that early tracheostomy is beneficial in patients with isolated closed head injury which is severe enough to affect systemic physiological parameters, in terms of decreased mortality and intubation associated complications in centers where ICU care is not readily available. Also, in a selected group of patients, early tracheostomy may do away with the need for prolonged mechanical ventilation.

Journal Article↗

Is drug-induced toxicity a good predictor of response to neo-adjuvant chemotherapy in patients with breast cancer?--a prospective clinical study.

BACKGROUND: Neo-adjuvant chemotherapy is an integral part of multi-modality approach in the management of locally advanced breast cancer and it is vital to predict the response in order to tailor the regime for a patient. The common final pathway in the tumor cell death is believed to be apoptosis or programmed cell death and chemotherapeutic drugs like other DNA-damaging agents act on rapidly multiplying cells including both the tumor and the normal cells by following the same common final pathway. This could account for both the toxic effects and the response. Absence or decreased apoptosis has been found to be associated with chemo resistance. The change in expression of apoptotic markers (Bcl-2 and Bax proteins) brought about by various chemotherapeutic regimens is being used to identify drug resistance in the tumor cells. A prospective clinical study was conducted to assess whether chemotherapy induced toxic effects could serve as reliable predictors of apoptosis or response to neo-adjuvant chemotherapy in patients with locally advanced breast cancer. METHODS: 50 cases of locally advanced breast cancer after complete routine and metastatic work up were subjected to trucut biopsy and the tissue evaluated immunohistochemically for apoptotic markers (bcl-2/bax ratio). Three cycles of Neoadjuvant Chemotherapy using FAC regime (5-fluorouracil, adriamycin, cyclophosphamide) were given at three weekly intervals and patients assessed for clinical response as well as toxicity after each cycle. Modified radical mastectomy was performed in all patients three weeks after the last cycle and the specimen were re-evaluated for any change in the bcl-2/bax ratio. The clinical response, immunohistochemical response and the drug-induced toxicity were correlated and compared. Descriptive studies were performed with SPSS version 10 and the significance of response was assessed using paired t-test. Significance of correlation between various variables was assessed using chi-square test and coefficient of correlation calculated by Pearson correlation coefficient. RESULTS: There was a statistically significant correlation observed between clinical, immunohistochemical response (bcl-2/bax ratio) and the drug-induced toxicity. CONCLUSION: Responders also had significant toxicity while non-responders did not show significant toxicity following neoadjuvant chemotherapy. The chemotherapy-induced toxicity was observed to be a cost effective and reliable predictor of response to neo-adjuvant chemotherapy.

Adult↗

Squamous cell carcinoma developing in the scar of Fournier's gangrene--case report.

BACKGROUND: Squamous cell carcinoma of the scrotum is rare and its development in the scar of Fournier's gangrene is still rarer. CASE PRESENTATION: A 65-year-old gentleman presented with a small non-healing ulcer developing on right hemi-scrotum two years after the treatment for Fournier's gangrene. On histological examination it was found to be squamous cell carcinoma. He was successfully managed by surgery in the form of wide local excision and ilio-inguinal lymph node dissection followed by adjuvant radiotherapy and chemotherapy. CONCLUSIONS: Squamous cell carcinoma can develop in the scar of Fournier's gangrene after a long delay, which differentiates it from other scar carcinomas or Marjolin's ulcer.

Aged↗

Cotton Bezoar--a rare cause of intestinal obstruction: case report.

BACKGROUND: Bezoars usually present as a mass in the stomach. The patient often has a preceding history of some psychiatric predisposition. Presentation could be in the form of trichophagy followed by trichobezoar (swallowing of hair leading to formation of bezoar), orphytobezoar (swallowing of vegetable fibres). Rapunzel syndrome is a condition where the parent bezoar is in the stomach and a tail of the fibres or hair extends in to the jejunum. Presentation as intestinal obstruction due to a bezoar in the intestine without a parent bezoar in the stomach is rare, therefore we report it here. CASE REPORT: A 35 year old lady tailor with a previous history of receiving treatment for depression on account of being infertile- years after her marriage, presented to the surgical emergency department with features of acute intestinal obstruction. Exploratory laparotomy and enterotomy revealed a cotton bezoar in the terminal ileum without a parent bezoar in the stomach. She was managed by resection of the affected segment of the ileum and end-to-end anastomosis of the bowel. In the postoperative period the patient gave a history of ingesting cotton threads whenever she was depressed. CONCLUSION: Presence of cotton bezoar is rare and an intestinal bezoar in the absence of parent bezoar in the stomach is still rarer.

Adult↗

Toward quantitative simulation of germinal center dynamics: biological and modeling insights from experimental validation.

As models of immune system dynamics are developed, it is important to validate them with specific experimental data in order to understand their shortcomings and guide them toward becoming predictive. In this paper, we examine whether a particular mathematical model of germinal center dynamics, proposed by Oprea and Perelson, can reproduce experimental data from two specific primary responses, namely those directed against the haptens 2-phenyl-5-oxazolone and (4-hydroxy-3-nitrophenyl)acetyl. We develop formulas for estimating response-specific model parameters, as well as constraints for validating the model. In addition, we outline a general methodology for translating a continuous/deterministic model, expressed as a set of ordinary differential equations, into a discrete/stochastic framework. This methodology is used to create a new implementation of the Oprea and Perelson model that enables comparison with data on individual germinal centers. We conclude that while the model can reproduce the average dynamics of splenic germinal centers, it is at best incomplete and does not reproduce the distribution of individual germinal center behaviors. In addition to suggesting possible extensions to the model which can reconcile the dynamics with some aspects of the experimental data, we make a number of specific predictions that can be tested by in vivo experiments to obtain further insights and validation.

Antibody Affinity↗

Genetic factors contribute to the variance in frequency domain measures of heart rate variability.

Power spectral analysis of heart rate variability (HRV) provides quantitative phenotypic markers of autonomic nervous system activity. Reported determinants of HRV only partially explain its variability in the population. The purpose of this study was to estimate the contribution of genetic factors to the variance in HRV measures and assess the heritability of HRV. Subjects who underwent Holter recordings at a routine examination were eligible, excluding subjects with congestive heart failure, coronary artery disease, diabetes mellitus and those taking cardioactive medications. We analyzed the low-frequency power (LF), high-frequency power (HF), LF/HF ratio, very low-frequency power (VLF) and total power (TP). Heritability analysis was done by studying correlations between siblings (n = 682, in 291 sibships, 517 pairs) and between spouse pairs (n = 206 pairs). Adjustments were made for sex, age, systolic and diastolic blood pressure, heart rate, coffee and alcohol intake. SAS procedure MIXED was used to estimate and test significance of correlation within sibling pairs and within spouse pairs. Results from separate models were combined to estimate the components of variance of each phenotype, i.e. variance attributable to measured covariates, additive genetic effects (heritability) and household effects. After adjusting for covariates, the correlations were consistently higher among siblings (0.21-0.26) compared to spouses (0.01-0.19). The measured covariates in general accounted for 13-40% of the total phenotypic variance, whereas genes accounted for 13-23% of the variation among HRV measures. Genetic factors contribute towards a substantial proportion of the variance in heart rate and HRV. Recognition of the genetic determinants of HRV may provide additional insight into the pathophysiology of the autonomic nervous system and offer clues toward its modulation.

Adult↗

Chemopreventive efficacy of selenium against N-nitrosodiethylamine-induced hepatoma in albino rats.

The chemopreventive/chemotherapeutic effect of sodium selenite on tricarboxylic acid cycle key enzymes was investigated against hepatoma induced by environmental carcinogen N-nitrosodiethylamine. Decreased activities of TCA cycle key enzymes such as isocitrate dehydrogenase (ICDH), succinate dehydrogenase (SDH), malate dehydrogenase (MDH) and alpha-ketoglutarate dehydrogenase (alpha-KGDH) in hepatoma and surrounding tissues of hepatoma-bearing rats were observed. Upon selenium supplementation the above biochemical changes were reverted in a dose- and duration-dependent manner. This study further confirms the chemopreventive/chemotherapeutic effect of sodium selenite which is found to be more effective in the initiation phase of carcinogenesis.

Alkylating Agents↗

Cyclopeptide alkaloids from Zizyphus jujuba.

A new cyclopeptide alkaloid, jubanine-C (1), together with known alkaloids scutianine-C (4) and zizyphine-A (5), have been isolated from the stem bark of Zizyphus jujuba and identified by spectral analysis.

Alkaloids↗

Performance evaluation of laser-induced breakdown spectrometry as a multimetal continuous emission monitor.

Laser-induced breakdown spectroscopy (LIBS) has been evaluated as a multimetal continuous emissions monitor (CEM) at the U.S. Environmental Protection Agency (EPA) rotary kiln incinerator simulator (RKIS) facility in Raleigh, NC. Two detection systems with a bifurcated optical fiber bundle were used for simultaneously monitoring the concentrations of Be, Cd, Cr, and Hg in the test. Two calibration techniques were evaluated in the laboratory for the field measurements. On-line calibration of relative metal concentration was also performed in the simulated incinerator gas stream. Toxic metal concentrations measured with LIBS have been compared with the EPA reference method (RM) results.

Air Pollutants↗

Association of hyperglycemia with reduced heart rate variability (The Framingham Heart Study).

This study was designed to examine the association of heart rate variability (HRV) with blood glucose levels in a large community-based population. Previous reports have shown HRV to be reduced in diabetics, suggesting the presence of abnormalities in neural regulatory mechanisms. There is scant information about HRV across the spectrum of blood glucose levels in a population-based cohort. One thousand nine hundred nineteen men and women from the Framingham Offspring Study, who underwent ambulatory electrocardiographic recordings at a routine examination, were eligible. HRV variables included the SD of normal RR intervals (SDNN), high-frequency (HF, 0.15 to 0.40 Hz) and low-frequency (LF, 0.04 to 0.15 Hz) power, and LF/HF ratio. Fasting plasma glucose levels were used to classify subjects as normal (<110 mg/dl; n = 1, 779), as having impaired fasting glucose levels (110 to 125 mg/dl; n = 56), and as having diabetes mellitus (DM >/=126 mg/dl or receiving therapy; n = 84). SDNN, LF and HF power, and LF/HF ratio were inversely related to plasma glucose levels (p <0.0001). SDNN and LF and HF powers were reduced in DM subjects (4.28 +/- 0.03, 6.03 +/- 0. 08, and 4.95 +/- 0.09) and in subjects with impaired fasting glucose levels (4.37 +/- 0.04, 6.26 +/- 0.10, and 5.06 +/- 0.11) compared with those with normal fasting glucose (4.51 +/- 0.01, 6.77 +/- 0.02, and 5.55 +/- 0.02, all p <0.005), respectively. After adjusting for covariates (age, sex, heart rate, body mass index, antihypertensive and cardiac medications, systolic and diastolic blood pressures, smoking, and alcohol and coffee consumption), LF power and LF/HF ratio were lower in DM subjects than in those with normal fasting glucose (p <0.005). HRV is inversely associated with plasma glucose levels and is reduced in diabetics as well as in subjects with impaired fasting glucose levels. Additional research is needed to determine if low HRV contributes to the increased cardiovascular morbidity and mortality described in subjects with hyperglycemia.

Adult↗

Fibroblast growth factor protects nitric oxide-induced apoptosis in neuronal SHSY-5Y cells.

Fibroblast growth factor (FGF) has been shown to protect tissue damage in animal models of cerebral and myocardial ischemia. The cellular and molecular mechanisms of FGF effects have not been fully defined. In the present study, we have investigated the effect of FGF homologs on nitric oxide (NO)-mediated neuronal cell death. Addition of NO donor S-nitroso-N-acetylpenicillamine (SNAP) to cultures of human neuroblastoma SHSY-5Y cells resulted in a concentration-dependent cell death. TdT-mediated dUTP-X nick end labeling and oligonucleosome assays confirmed that NO-mediated cell death occurred through the apoptotic pathway. In the presence of 150 microM SNAP, about 40% of the cells in culture underwent apoptosis. Treatment with FGF-2 resulted in greater than 80% reduction in NO-induced cell death. FGF addition to cell cultures also enhanced cell survival without affecting cell proliferation. FGF-2 effectively inhibited NO-mediated apoptosis even when added 6 h after treatment with SNAP. Examination of other homologs of FGF on NO-mediated cell death showed that in SHSY-5Y cells, FGF-2 and FGF-4, but not other FGF homologs, inhibited NO-mediated apoptosis. These results show that FGF-2 was a potent cell survival factor and protected SHSY-5Y cells from NO-mediated apoptosis. These effects were limited to FGF-2 and FGF-4 homologs.

Apoptosis↗

Heritability of heart rate variability: the Framingham Heart Study.

BACKGROUND: There is evolving evidence that heart rate (HR) is genetically determined. Heart rate variability (HRV) measured by power spectral analysis provides quantitative phenotypic markers of autonomic nervous system activity. Reported determinants of HR and HRV only partially explain their variability in the population. The purpose of this study was to assess the heritability of HR and HRV and estimate the contribution of genetic factors to their variance. METHODS AND RESULTS: Subjects who underwent ambulatory recordings at a routine examination were eligible; subjects with congestive heart failure, coronary artery disease, diabetes mellitus, and those taking cardioactive medications were excluded. We analyzed high-frequency power, low-frequency power, very low-frequency power, total power, low-frequency/high-frequency ratio, and the standard deviation of normal R-R intervals from 2-hour continuous ECG recordings. Heritability analysis was done by studying correlations between siblings (n=682, in 291 sibships, 517 pairs) and between spouse pairs (n=206 pairs) after adjusting for important covariates. Results from separate models were combined to estimate the components of variance attributable to measured covariates, additive genetic effects (heritability), and household effects. After adjusting for covariates, the correlations were consistently higher among siblings (0.21 to 0.26) compared with spouses (0.01 to 0.19). The measured covariates in general accounted for 13% to 40% of the total phenotypic variance, whereas genetic factors accounted for 13% to 23% of the variation among HR and HRV measures. CONCLUSIONS: Heritable factors may explain a substantial proportion of the variance in HR and HRV. These results highlight the contribution of genetic versus environmental factors to autonomic nervous system activity.

Adult↗

Blood pressure response during treadmill testing as a risk factor for new-onset hypertension. The Framingham heart study.

BACKGROUND: Although systolic blood pressure (SBP) response to exercise has been shown to predict subsequent hypertension in small samples of men, this association has not been studied in a large population-based sample of middle-aged men and women. The purpose of this study was to examine, in normotensive subjects, the relations of SBP and diastolic blood pressure (DBP) during the exercise and recovery periods of a graded treadmill test to the risk of developing new-onset hypertension. METHODS AND RESULTS: BP data from exercise testing in 1026 men and 1284 women (mean age, 42+/-10 years; range, 20 to 69 years) from the Framingham Offspring Study who were normotensive at baseline were related to the incidence of hypertension 8 years later. New-onset hypertension, defined as an SBP >/=140 mm Hg or DBP >/=90 mm Hg or the initiation of antihypertensive drug treatment, occurred in 228 men (22%) and 207 women (16%). Exaggerated SBP (Ex-SBP 2) and DBP (Ex-DBP 2) response and delayed recovery of SBP (R-SBP 3) and DBP (R-DBP 3) were defined as an age-adjusted BP greater than the 95th percentile during the second stage of exercise and third minute of recovery, respectively. After multivariable adjustment, Ex-DBP 2 was highly predictive of incident hypertension in both men (OR, 4.16; 95% CI, 2.15, 8.05) and women (OR, 2.17; CI, 1.19, 3.96). R-SBP 3 was predictive of hypertension in men in a multivariable model that included exercise duration and peak exercise BP (OR, 1.92; CI, 1.00, 3.69). Baseline resting SBP (chi2, 23.4 in men and 34.7 in women) and DBP (chi2, 11.3 in men and 13.1 in women) had stronger associations with new-onset hypertension than exercise DBP (chi2, 16.4 in men and 6.1 in women) and recovery SBP (chi2, 6.5 in men and 2.1 in women) responses. CONCLUSIONS: An exaggerated DBP response to exercise was predictive of risk for new-onset hypertension in normotensive men and women. An elevated recovery SBP was predictive of hypertension in men. These findings may reflect subtle pathophysiological features in the preclinical stage of hypertension.

Adult↗