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Biomedical subjects

P K Agarwal

Publications and source records attributed to P K Agarwal.

At least 19 recordsLinked to original sources
PubMed2006

Metabolic syndrome.

The Metabolic syndrome is a widely prevalent and multi-factorial disorder. The syndrome has been given several names, including- the metabolic syndrome, the insulin resistance syndrome, the plurimetabolic syndrome, and the deadly quartet. With the formulation of NCEP/ATP III guidelines, some uniformity and standardization has occurred in the definition of metabolic syndrome and has been very useful for epidemiological purposes. The mechanisms underlying the metabolic syndrome are not fully known; however resistance to insulin stimulated glucose uptake seems to modify biochemical responses in a way that predisposes to metabolic risk factors. The clinical relevance of the metabolic syndrome is related to its role in the development of cardiovascular disease. Management of the metabolic syndrome involves patient-education and intervention at various levels. Weight reduction is one of the main stays of treatment. In this article we comprehensively discuss this syndrome- the epidemiology, pathogenesis, clinical relevance and management. The need to do a comprehensive review of this particular syndrome has arisen in view of the ever increasing incidence of this entity. Soon, metabolic syndrome will overtake cigarette smoking as the number one risk factor for heart disease among the US population. Hardly any issue of any primary care medical journal can be opened without encountering an article on type 2 diabetes, dyslipidemia or hypertension. It is rare to see type 2 diabetes, dyslipidemia, obesity or hypertension in isolation. Insulin resistance and resulting hyperinsulinemia have been implicated in the development of glucose intolerance (and progression to type 2 diabetes), hypertriglyceridemia, hypertension, polycystic ovary syndrome, hypercoagulability and vascular inflammation, as well as the eventual development of atherosclerotic cardiovascular disease manifested as myocardial infarction, stroke and myriad end organ diseases. Conversely, treatment and consequent improvement of insulin resistance have been shown to result in better outcomes in virtually all of these conditions.

Aspirin↗
PubMed2005

Coarse and reliable geometric alignment for protein docking.

We present an efficient algorithm for generating a small set of coarse alignments between interacting proteins using meaningful features on their surfaces. The proteins are treated as rigid bodies, but the results are more generally useful as the produced configurations can serve as input to local improvement algorithms that allow for protein flexibility. We apply our algorithm to a diverse set of protein complexes from the Protein Data Bank, demonstrating the effectivity of our algorithm, both for bound and for unbound protein docking problems.

Algorithms↗
PubMed2005

Myelomatous pleural effusion.

Pleural effusions in multiple myeloma are relatively infrequent and more so myelomatous ones. We report a 66-year-old man who presented with multiple myeloma and a myelomatous right-sided pleural effusion. The diagnosis was made by repeated cytopathological pleural fluid examinations. The patient received one cycle of cyclophosphamide and methylprednisolone but despite therapy patient showed a downhill course. We reviewed the clinical features of this case and literature concerning multiple myeloma presenting as pleural effusion.

Aged↗
PubMed2001

Hydride transfer in liver alcohol dehydrogenase: quantum dynamics, kinetic isotope effects, and role of enzyme motion.

The quantum dynamics of the hydride transfer reaction catalyzed by liver alcohol dehydrogenase (LADH) are studied with real-time dynamical simulations including the motion of the entire solvated enzyme. The electronic quantum effects are incorporated with an empirical valence bond potential, and the nuclear quantum effects of the transferring hydrogen are incorporated with a mixed quantum/classical molecular dynamics method in which the transferring hydrogen nucleus is represented by a three-dimensional vibrational wave function. The equilibrium transition state theory rate constants are determined from the adiabatic quantum free energy profiles, which include the free energy of the zero point motion for the transferring nucleus. The nonequilibrium dynamical effects are determined by calculating the transmission coefficients with a reactive flux scheme based on real-time molecular dynamics with quantum transitions (MDQT) surface hopping trajectories. The values of nearly unity for these transmission coefficients imply that nonequilibrium dynamical effects such as barrier recrossings are not dominant for this reaction. The calculated deuterium and tritium kinetic isotope effects for the overall rate agree with experimental results. These simulations elucidate the fundamental nature of the nuclear quantum effects and provide evidence of hydrogen tunneling in the direction along the donor-acceptor axis. An analysis of the geometrical parameters during the equilibrium and nonequilibrium simulations provides insight into the relation between specific enzyme motions and enzyme activity. The donor-acceptor distance, the catalytic zinc-substrate oxygen distance, and the coenzyme (NAD(+)/NADH) ring angles are found to strongly impact the activation free energy barrier, while the donor-acceptor distance and one of the coenzyme ring angles are found to be correlated to the degree of barrier recrossing. The distance between VAL-203 and the reactive center is found to significantly impact the activation free energy but not the degree of barrier recrossing. This result indicates that the experimentally observed effect of mutating VAL-203 on the enzyme activity is due to the alteration of the equilibrium free energy difference between the transition state and the reactant rather than nonequilibrium dynamical factors. The promoting motion of VAL-203 is characterized in terms of steric interactions involving THR-178 and the coenzyme.

Alcohol Dehydrogenase↗
PubMed2001

Immunohistochemical localization of transferrin in human breast cancer tissue.

The present study was planned to detect the iron binding protein, transferrin (TR) in paraffin sections of the human breast tumors. The distribution of transferrin has been studied in 153 cases (63 benign lesions and 90 malignant tumors). The extent of staining reaction was determined by semiquantitative grading (weak, moderate and consistent). Positivity rate for transferrin was higher (92.2%) in malignant tumors as compared to benign breast lesions (28.5%) with significant p value (P = .0001) for both the groups. The intensity was variable in both the groups, being more intense in the malignant tumors. Tumors with higher grade of malignancy presented consistent positive staining along with the lymph nodes involved. The extent of immunoreactivity revealed a significant positive correlation with axillary lymph node status. However, no significant correlation was found with the age of the patients. Thus the study of transferrin in breast tumors besides being of prognostic significance helps in the further management of malignant lesions of the breast.

Biomarkers, Tumor↗
PubMed2001

Efficacy of topical and systemic itraconazole as a broad-spectrum antifungal agent in mycotic corneal ulcer. A preliminary study.

PURPOSE: To evaluate the efficacy of topical (1%) and systemic itraconazole against common fungi such as Aspergillus and other filamentous fungi that cause mycotic corneal ulcer. METHODS: A prospective randomised, controlled study was done in 54 clinically suspected cases of fungal keratitis of which 44 were culture proven. Half the cases (n=27) with superficial involvement were treated with only topical itraconazole (1%) and the other half were treated with both topical and systemic itraconazole. RESULTS: Aspergillus, Penicillium and Fusarium were the most common fungi isolated. The ulcer resolved in 42 eyes (77%) and 12 eyes (23%) did not respond well to treatment. Four of 12 non-responding eyes were caused by Fusarium species. CONCLUSION: Itraconazole, given either topically or systemically, is effective in treating mycotic corneal ulcers.

Administration, Oral↗
PubMed2000

Immunohistochemical localization and correlation of p53 and PCNA expression in breast carcinoma.

The object of the present study is to detect the p53 tumour suppressor gene and proliferation cell nuclear antigen (PCNA) expression in breast carcinoma by immunohistochemistry and correlate them with the prognostic parameters. Total 35 cases of primary breast carcinoma were studied and classified histologically. Paraffin sections were stained by using monoclonal antibody D07 for p53 protein and PC-10 for PCNA. Out of 35 cases, 16 (45.7%) were p53 positive and 25 (71.4%) were PCNA positive. The mean PCNA labelling index (PCNA LI +/- SD) was 58.97 +/- 22.72 in tumors positive for both p53+ and PCNA+ while cases negative for p53- and positive for PCNA+ has higher PCNA LI +/- SD (59.24 +/- 18.97). The difference in the two groups was not significant. Most cases were positive for both p53+ and PCNA+ in the age group < 30 with higher mean PCNA LI +/- SD (62.20 +/- 27.13) than in the group > 30 (57.88 +/- 18.47). In the pre-menopausal group 57.1% cases were positive for p53+ with higher PCNA LI +/- SD (59.94 +/- 24.22). Maximum p53 and PCNA positivity was observed in grade III tumors (63.2% and 84.2%). The mean PCNA LI +/- SD was also highest in grade III carcinomas (66.83 +/- 13.97). No significant correlation was found between p53 and PCNA status with morphological type and tumour size except that logistic regression showed a positive correlation with tumour grade. Therefore the present study suggests that both p53 expression and PCNA are markers of poor differentiation in breast cancer.

Adult↗
PubMed2000

Fine needle aspiration of bone tumors.

Fine needle aspiration cytology (FNAC) was performed in 226 cases of bone tumors and the cytohistologic correlation was calculated to assess the technique's diagnostic efficacy aided by immunocytochemistry, considering histopathology as the gold standard. Of the 226 cases, 136 were malignant and 72 cases were benign tumors. In the remaining 18 cases, cytohistopathologic examination revealed no bony lesion. There were 178 evaluable cases, but the specific morphologic diagnosis on FNAC was possible only in 159 cases with one false positive and 29 false negatives. Giant cell tumor (32%) and Ewing's sarcoma (22%) were the most common bony tumors encountered in this series. The diagnostic indices were calculated by a decision matrix comparison. The overall sensitivity and specificity were 86.0 (confidence interval [CI], 80.3-90.3) and 94.7 (CI, 71.9-99.7), respectively. The positive predictive value (PPV) was as high as 99.4 (CI, 96.5-100), while the negative predictive value (NPV) was 38.3 (CI, 24.9-53.6) with positive and negative likelihood ratios of 16.338 and 0.147, respectively. Diagnosis of malignant tumors was more accurate with a PPV of 99.2 (CI, 94.8-100.0) and specificity of 94.7 (CI, 71.9-99.7), while the sensitivity was 89.0 (CI, 82.2-93.5) and NPV was 54.5 (CI, 36.6-71.5). This study highlights the usefulness of FNAC along with the use of immunocytochemistry in the rapid diagnosis of bone tumors.

Adolescent↗
PubMed2000

Immunohistochemical localization of transferrin in human breast cancer tissue.

The present study was planned to detect the iron binding protein, transferrin (TR) in paraffin sections of the human breast tumors. The distribution of transferrin has been studied in 153 cases (63 benign lesions and 90 malignant tumors). The extent of staining reaction was determined by semiquantitative grading (weak, moderate and consistent). Positivity rate for transferrin was higher (92.2%) in malignant tumors as compared to benign breast lesions (28.5%) with significant p value (p = 0.0001) for both the groups. The intensity was variable in both the groups, being more intense in the malignant tumors. Tumors with higher grade of malignancy presented consistent positive staining along with the lymph nodes involved. The extent of immunoreactivity revealed a significant positive correlation with axillary lymph node status. However, no significant correlation was found with the age of the patients. Thus the study of transferrin in breast tumors besides being of prognostic significance helps in the further management of malignant lesions of the breast.

Breast↗
PubMed1999

Construction of a multi RE module: exploitation of mechanochemistry of restriction endonucleases.

We describe the construction of a multi-immobilized restriction endonuclease module (Multi RE module). We demonstrate that the applied mechanical stress enables modulation of enzyme activity and modulation of recognition site selectivity (in oligonucleotides of approximately 200 bp) of immobilized restriction endonucleases. The central module which is consisted of different strips of immobilized restriction endonucleases allows limited digestion of a large DNA sample in a controlled manner as a function of applied mechanical stress on strips. The stress-activity relationship and the effect of repeated cycles of stress and relaxation on the immobilized strips are presented here. &copy 1999 John Wiley & Sons, Inc.

Bacterial Proteins↗
PubMed1998

Cytopathology and AgNOR counts in fine-needle aspiration cytology smears of thyroid lesions.

The object of the present work is to study the cytomorphological features and the value of silver colloidal staining method in distinguishing the non-neoplastic, benign, and malignant neoplasm in fine-needle aspiration cytology (FNAC) smears of thyroid nodules. One hundred forty histologically confirmed aspirated samples of thyroid lesions were studied and classified cytologically. These smears were stained for AgNOR counts. The number and location of AgNOR dots as well as clusters in nuclei were studied by two different observers independently. Lower AgNOR counts were recorded in cases of thyroiditis (1.375 +/- 0.414), whereas follicular carcinoma had a higher number of AgNOR counts (5.04 +/- 0.52). The clusters of AgNOR dots were centrally located in colloid goitre, but no cluster arrangement was observed in cases of carcinomas. Increased nuclear size, nucleoli, and chromocentres were helpful in the diagnosis of follicular carcinoma. AgNOR counting cannot be reliably used on an individual case basis to differentiate adenoma from carcinoma. Therefore, AgNOR study in thyroid lesions can be used as an additional diagnostic method with cytomorphological features to differentiate benign and malignant follicular neoplasms.

Adenoma↗
PubMed1998

Exercise ECG testing using different protocols in asymptomatic healthy young subjects.

Thirty four healthy young male subjects performed symptom limited exercise on Bruce protocol on treadmill machine. Hyperventilation induced labile repolarisation ST-T abnormalities were observed in 2 whereas exercise induced ST changes (upsloping ST depression in 4 and horizontal ST depression in 1) were observed in 5 additional candidates. Changes were unaccompanied by symptoms or signs and quickly reverted back to normal within 30 sec. of cessation of exercise and hence were 'probable false positives'. Sixty-eight age and sex matched volunteers (including former 34) when exercised on Master's stepper, failed to reveal any change probably due to the lack of continuous ECG monitoring device.

Adult↗