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S Shankar

Publications and source records attributed to S Shankar.

At least 37 records · Page 2Linked to original sources
PubMed2001

Computer modeling of small heat-shock metalloprotease of the human malaria parasite Plasmodium vivax.

We present here computer generated model of N-terminal fragment, amino acids (aa) 36-245, of a Plasmodium vivax heat shock metalloprotease called PVHSP28, whose gene was cloned and characterised earlier. The fragment showed homology with HSPs from many organisms, including Escherichia coli and Haemophilus influenzae. PVHSP28 had the signature sequence 'HEXXH' and 'EXXXD' of Zinc metalloproteases. Being the first malarial HSP possessing metalloprotease activity, PVHSP28 is an ideal target for the design of new anti-malarial drugs. However, except for a small region (aa 62-132) which had 24.6% sequence similarity with 1TAQ (a DNA polymerase), it did not show sequence similarity with any published structures in protein data bank. Hence it could not be modelled using any automated modeling programs. We modelled 36-245 aa of PVHSP28 using predicted secondary structure as well as experimentally determined and predicted properties of the protein on the basis of its amino acid sequence, using various Internet tools and in-house package MODEL. The model was energy minimised using Sander's module of AMBER 5.0, working on a Silicon Graphics machine, with all atom force field.

Amino Acid Sequence↗
PubMed2001

Computer aided study of ligand binding with catalytic domain of Avian sarcoma virus integrase and its ligand binding loops.

We have carried out 1 nanosecond (ns) Molecular Dynamics (MD) simulations of the drug Y3 (4-acetylamino-5-hydroxynaphthalene- 2, 7-disulfonic acid) complexed with catalytic domain of Avian sarcoma virus Integrase (ASV-IN), both in vacuum and in the presence of explicit solvent. Starting models were obtained on the basis of PDB co- ordinates (1A5X) of ASV-IN-Y3 complex. Mn(2+) cation was present in the active site. To neutralize the positive charge in the presence of explicit solvent, eight Cl(-)anions were added. Energy Minimization (EM) and MD simulations, for both the systems, were carried out using Sander's module of AMBER5.0 with all atom force field. We also carried out 1 ns MD simulation on two flexible loops--L1 (Gly54-Gln62) and L2 (Trp138-Met155) playing crucial role in interaction of IN with the drug, under differing environmental conditions (vacuum, aqueous and organic solvent methanol). Comparison of the conformational changes in the loops, monomer and dimer is presented in the paper. Our results showed that the conformation of the loop region was closest to crystallographic data in case of monomer and constrained loops in aqueous environment. However, the dimer in vacuum was more stable than monomer. The beta sheet structure of the monomer in aqueous environment was unstable. Latter also took long time for equilibration. The box formed by loops L1 and L2 from two sub units (IINA and INB) of the dimer satisfies prerequisites for ligand recognition site and seems to be the functional biological unit.

Amino Acid Sequence↗
PubMed2000

Combined effect of tumor necrosis factor-related apoptosis-inducing ligand and ionizing radiation in breast cancer therapy.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potent endogenous activator of the cell death pathway and functions by activating the cell surface death receptors 4 and 5 (DR4 and DR5). TRAIL is nontoxic in vivo and preferentially kills neoplastically transformed cells over normal cells by an undefined mechanism. Radiotherapy is a common treatment for breast cancer as well as many other cancers. Here we demonstrate that ionizing radiation can sensitize breast carcinoma cells to TRAIL-induced apoptosis. This synergistic effect is p53-dependent and may be the result of radiation-induced up-regulation of the TRAIL-receptor DR5. Importantly, TRAIL and ionizing radiation have a synergistic effect in the regression of established breast cancer xenografts. Changes in tumor cellularity and extracellular space were monitored in vivo by diffusion-weighted magnetic resonance imaging (diffusion MRI), a noninvasive technique to produce quantitative images of the apparent mobility of water within a tissue. Increased water mobility was observed in combined TRAIL- and radiation-treated tumors but not in tumors treated with TRAIL or radiation alone. Histological analysis confirmed the loss of cellularity and increased numbers of apoptotic cells in TRAIL- and radiation-treated tumors. Taken together, our results provide support for combining radiation with TRAIL to improve tumor eradication and suggest that efficacy of apoptosis-inducing cancer therapies may be monitored noninvasively, using diffusion MRI.

Animals↗
PubMed2000

Image-guided percutaneous drainage of thoracic empyema: can sonography predict the outcome?

The aim of this study was to assess the safety and efficacy of image-guided percutaneous catheter drainage (IGPCD) of thoracic empyemas, and to correlate the outcome of IGPCD with the pre-procedural sonographic appearance. One hundred three patients (74 males and 29 females) with thoracic empyema (age range 1 month to 70 years, median age 28 years) underwent IGPCD. In 63 (61.17%) patients, IGPCD was the primary treatment modality; in 40 (38.84%) patients it was used after unsuccessful intercostal chest tube drainage (ICTD). Ultrasound was the main modality used for guidance; CT guidance was used in only 7 patients (6.8%). Eight- to 12-F pigtail catheters or 10- to 14-F Malecot catheters were used. The outcome was correlated with the pre-procedural US appearance (anechoic, complex non-septated or complex septated) of the empyema. The IGPCD technique was successful in 80 of 102 patients. Based on the US appearance, IGPCD was successful in 12 of 13 (92.3%) patients with anechoic empyemas; 53 of 65 (81.54%) patients with complex non-septated empyemas, and in 15 of 24 (62.5%) patients with complex septated empyemas. A statistically significant difference (p < 0.01) was seen in the outcome of IGPCD in the three categories. Twenty-two patients required further treatment: ICTD (n = 9; 2 of them later also underwent surgery); and surgery (n = 15). The duration of catheter drainage ranged from 2-60 days. No major complications were encountered. Percutaneous catheter drainage of thoracic empyemas with imaging guidance ensures accurate catheter placement with a high success and a low complication rate. Pre-procedural US can predict the likelihood of success of IGPCD.

Adolescent↗
PubMed2000

Visually guided locomotion and computation of time-to-collision in the mongolian gerbil (Meriones unguiculatus): the effects of frontal and visual cortical lesions.

Past research has indicated that many species use the time-to-collision variable but little is known about its neural underpinnings in rodents. In a set of three experiments we set out to replicate and extend the findings of Sun et al. (Sun H-J, Carey DP, Goodale MA. Exp Brain Res 1992;91:171-175) in a visually guided task in Mongolian gerbils, and then investigated the effects of lesions to different cortical areas. We trained Mongolian gerbils to run in the dark toward a target on a computer screen. In some trials the target changed in size as the animal ran toward it in such a way as to produce 'virtual targets' if the animals were using time-to-collision or contact information. In experiment 1 we confirmed that gerbils use time-to-contact information to modulate their speed of running toward a target. In experiment 2 we established that visual cortex lesions attenuate the ability of lesioned animals to use information from the visual target to guide their run, while frontal cortex lesioned animals are not as severely affected. In experiment 3 we found that small radio-frequency lesions, of either area VI or of the lateral extrastriate regions of the visual cortex also affected the use of information from the target to modulate locomotion.

Animals↗
PubMed2000

Ultrasound-guided transthoracic co-axial biopsy of thoracic mass lesions.

PURPOSE: To compare the diagnostic yield of fine-needle aspiration biopsy (FNAB) and cutting needle biopsy in thoracic lesions. MATERIAL AND METHODS: Thirty patients with thoracic mass lesions were subjected to ultrasound-guided co-axial FNAB and cutting needle biopsy using 0.7 mm aspirating and 1.0-mm cutting needles, respectively. The diagnostic yield of the individual modalities was compared with the combined yield. RESULTS: A conclusive diagnosis was obtained in 76.6% (n=23) of patients by FNAB and in 66.6% (n=20) by cutting needle biopsy. The combined diagnostic yield of FNAB and cutting needle biopsy was 93.3% (n=28) with a significant statistical difference (p<0.03) as compared to cutting biopsy alone. Of the patients, 23.2% (n=7) had benign and 76.6% (n=23) malignant aetiologies. The diagnostic yield of FNAB versus cutting needle biopsy in benign lesions was 57.1% (n=4) and 100% (n=7), respectively. The diagnostic yield of FNAB versus cutting needle biopsy in malignant lesions was 82.6% (n=19) and 56.5%, (n=13). Two patients remained undiagnosed by either modality. There were no complications. CONCLUSION: FNAB and cutting needle biopsy are complementary to each other and attempts should be made to obtain small tissue cores in addition to routine cytologic specimens in diagnosing thoracic lesions, especially in benign pathologies. US provides a safe guidance modality for lesions abutting the chest wall.

Adolescent↗
PubMed2000

Obesity differences between African-American men and women.

The purpose of this study was to examine the socio-demographic and behavioral differences related to obesity between African-American men and women. Obesity was defined as a body mass index of greater than 27.3 kg/m2 for women and 27.8 kg/m2 for men. Data were collected from 661 African-Americans, 418 women and 243 men, residing in wards 7 and 8 in Washington, DC through telephone interviews. Obesity was prevalent among 38.3% of the women and 20.1% of the men (p < 0.01). For women age 55 or older, annual income over $20K, having less than a high school education, and alcohol and tobacco consumption were associated with being overweight in the initial bivariate analysis (p < 0.05). For men, being 35 years or older and unemployment were significant factors associated with obesity. Our final analysis, when known dietary risk factors were adjusted, revealed that in women, obesity was associated with age, hard liquor consumption and non use of tobacco. For men, older age was a primary association. We concluded that gender, with increasing age, plays a significant role in predicting obesity, as defined by concurrent national standards. African American men 55 years of age or older are the most likely group to be overweight even after predisposing and behavioral risk factors are considered.

Adolescent↗
PubMed2000

Successful repair of traumatic aortic tears using left heart bypass.

Aortic tears commonly occur in multiply injured patients. Recognizing this injury is important. A chest X-ray is helpful and a CT-angiogram or aortogram confirmatory. After attending to life-threatening injuries, the aortic tear should be repaired immediately. Using the left heart bypass technique has the lowest risk of operative neurologic injury. We review our experience over the last 2 years, discuss our preferred technique and report on the outcome.

Adult↗
PubMed1999

Cancer knowledge and misconceptions among immigrant Salvadorean men in the Washington, D.C. area.

Although Salvadoreans are the fourth largest group of Hispanics in the United States, little is known about their cancer knowledge, attitudes, and practices. There are no publications assessing cancer knowledge among Salvadorean men. In this cross-sectional survey, information was gathered from 706 immigrant Salvadorean men in Washington, D.C. The majority of these men knew that smoking causes cancer and that some cancers can be cured if detected early. However, the men in this survey had inadequate knowledge about symptoms of cancer and early detection methods. The most important predictor of cancer screening among older participants was enrollment in health insurance plans. Our study suggests that Salvadorean men would participate in cancer screening efforts if they had access to medical care. Educational programs to increase awareness of cancer and availability of preventive services may help prevent cancer in this population.

Journal Article↗
PubMed1999

CT-guided fine-needle aspiration biopsy of spinal lesions.

PURPOSE: A retrospective study of CT-guided fine-needle aspiration biopsies (FNABs) of spinal lesions performed over a period of 6 years was carried out with the aim of assessing the safety and efficacy of the procedure and to analyse the various approaches used. MATERIAL AND METHODS: Ninety-three FNABs were performed in 87 patients, 4-70 years of age, under CT guidance. Lytic or mixed vertebral lesions with or without a paraspinal soft tissue component were included in the study. The approach depended on the anatomic region and part of the vertebra involved. RESULTS: A definite cytological diagnosis was obtained in 77 patients (88.5%); of these, 47 patients had benign lesions and 30 patients had neoplasms. The most common pathologies encountered were tuberculosis (n=33) and metastases (n=17). There were 10 inconclusive FNABs; these showed blood only, necrotic material or scanty material insufficient for diagnosis. There were no procedure-related complications. CONCLUSION: CT-guided FNAB is a safe and effective technique for the evaluation of spinal lesions and is helpful in planning therapy. Choosing the appropriate approach results in a low complication rate.

Adolescent↗
PubMed1999

Changing the institutional practice of prolonged mechanical ventilation after coronary artery bypass graft surgery to early extubation.

Since 1997 some of our cardiac anaesthetists have, whenever possible, extubated the patients early after cardiac surgery to improve their level of comfort, to allow an early return of the cardiopulmonary physiological function, and to help reduce health care costs. After a few months of implementing this practice, an audit was carried out to evaluate the success of early extubation after coronary artery bypass graft (CABG) surgery. Over a 6-month period starting from May 1997, the perioperative data of 110 consecutive patients with good or moderate left ventricular function scheduled for elective CABG were prospectively collected and analysed. The anaesthetic regime was according to the preference of the anaesthetists. Initially consent was obtained from the surgeons when the extubation criteria were fulfilled, but subsequently as the practice became more accepted by the surgeons, extubation was initiated by the anaesthetists. Within 4 hours of admission into the intensive care unit (ICU), 50 (45.5%) of the 110 patients satisfied the early extubation criteria and were extubated. The extubation criteria are described in the article. For the remaining patients, the median duration of mechanical ventilation was 14.3 hours. The profiles of the two groups of patients and the possible reasons for not extubating early are discussed. Forty-five per cent of the patients with moderate to good ventricular function were extubated safely within 4 hours of admission into the ICU after CABG surgery. With gradual acceptance of the practice and a change in mindset amongst all the care givers, more patients can benefit from this practice. This article highlights the challenges associated with changing institutional practices with respect to the postoperative care of cardiac patients.

Analysis of Variance↗
PubMed1998

Molecular cloning of human testis mRNA specifically expressed in haploid germ cells, having structural homology with the A-kinase anchoring proteins.

We have cloned a human testis specific gene (hi), which encodes for a protein having regional homologies to the domain of A-kinase anchoring proteins. Open reading frame encodes a protein of 860 amino acids. The predicted protein has a molecular weight 95.8 kD and contains 32 cysteine residues and 34 potential phosphorylation sites. The deduced protein analysis revealed an eukaryotic secretory signal with a potential cleavage site. Northern blot analysis detected a single transcript of approximately 3.0 kb in testis and not in any other somatic tissues. Expression of hi transcript was observed only in round spermatids indicating post meiotic haploid gene expression.

Amino Acid Sequence↗
PubMed1998

Cloning of a novel human testis mRNA specifically expressed in testicular haploid germ cells, having unique palindromic sequences and encoding a leucine zipper dimerization motif.

A novel gene coding for a human sperm surface protein (HSS) has been cloned from a human testis cDNA library. The 2.5 kb cDNA (hss) contains five direct repeats, three mirror repeats, three possible stem loop structures and three unique palindromic motifs located at functionally relevant positions. Open reading frame encodes a protein of 766 amino acids. The deduced protein analysis revealed a NH2 terminus extracellular domain having a leucine zipper (LZ) motif, a transmembrane helical domain and a cytoplasmic domain at the COOH terminus. Tissue specific expression studies demonstrated the presence of hss transcript only in testis. Cell type expression of hss mRNA was observed only on the round spermatids suggesting haploid germ cell expression.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Alginate, inorganic polyphosphate, GTP and ppGpp synthesis co-regulated in Pseudomonas aeruginosa: implications for stationary phase survival and synthesis of RNA/DNA precursors.

The regulatory protein AlgR2 in Pseudomonas aeruginosa positively regulates nucleoside diphosphate kinase (Ndk) and succinyl-CoA synthetase, enzymes critical in nucleoside triphosphate (NTP) formation. AlgR2 positively regulates the production of alginate, GTP, ppGpp and inorganic polyphosphate (poly P). An algR2 mutant with low levels of these metabolites has them restored by introducing and overexpressing either the algR2 or the ndk gene into the algR2 mutant. Thus, Ndk is involved in the formation of these compounds and largely prevents the death of the algR2 mutant, which occurs early in the stationary phase. We demonstrate that the 12 kDa Ndk-pyruvate kinase (Pk) complex, previously shown to generate predominantly GTP instead of all the NTPs, has a low affinity for the deoxynucleoside diphosphates and cannot generate the dNTPs needed for DNA replication and cell division; this complex may thus be involved in regulating the levels of both NTPs and dNTPs that modulate cell division and survival in the stationary phase.

Alginates↗
PubMed1998

CT-guided transthoracic fine-needle aspiration versus transbronchial fluoroscopy-guided needle aspiration in pulmonary nodules.

PURPOSE: To evaluate the diagnostic yield of CT-guided (CTNAB) and fluoroscopy-guided transbronchial (TBNA) fine-needle aspiration cytology in pulmonary nodules and to compare their complications. MATERIAL AND METHODS: Thirty patients with pulmonary nodules not abutting upon the chest wall and inaccessible to bronchoscopy were randomised for CTNAB or TBNA. Eighteen patients underwent CTNAB and 16 TBNA. Four patients underwent both procedures. RESULTS: In the CTNAB group, a definitive diagnosis could be made in 14 (78%) out of 18 patients whereas in the TBNA group, a definitive diagnosis was made in 11 (69%) out of 16 patients. This difference was not statistically significant (p > 0.05). The final diagnosis in 29 out of 30 patients comprised primary bronchogenic carcinoma in 14 patients, metastases in 5 patients, and benign lesions in 10 patients (34%) of which 3 lesions (30%) were of tuberculous aetiology. There were 2 asymptomatic pneumothoraces in the CTNAB group and no complication was observed in the TBNA group. CONCLUSION: Both techniques were safe and effective in the diagnosis of peripheral pulmonary lesions. TBNA was best suited for lesions larger than 3 cm and located in the middle and lower lobes while CTNAB could be used for any lesions.

Adult↗
PubMed1998

Aging differentially alters forms of long-term potentiation in rat hippocampal area CA1.

Long-term potentiation (LTP) of the Schaffer collateral/commissural inputs to CA1 in the hippocampus was shown to consist of N-methyl-D-aspartate receptor (NMDAR) and voltage-dependent calcium channel (VDCC) dependent forms. In this study, the relative contributions of these two forms of LTP in in vitro hippocampal slices from young (2 mo) and old (24 mo) Fischer 344 rats were examined. Excitatory postsynaptic potentials (EPSP) were recorded extracellularly from stratum radiatum before and after a tetanic stimulus consisting of four 200-Hz, 0.5-s trains given 5 s apart. Under control conditions, a compound LTP consisting of both forms was induced and was similar, in both time course and magnitude, in young and old animals. NMDAR-dependent LTP (nmdaLTP), isolated by the application of 10 microM nifedipine (a voltage-dependent calcium channel blocker), was significantly reduced in magnitude in aged animals. The VDCC dependent form (vdccLTP), isolated by the application of 50 microM D,L-2-amino-5-phosphonvalerate (APV), was significantly larger in aged animals. Although both LTP forms reached stable values 40-60 min posttetanus in young animals, in aged animals vdccLTP increased and nmdaLTP decreased during this time. In both young and old animals, the sum of the two isolated LTP forms approximated the magnitude of the compound LTP, and application of APV and nifedipine or genestein (a tyrosine kinase inhibitor) together blocked potentiation. These results suggest that aging causes a shift in synaptic plasticity from NMDAR-dependent mechanisms to VDCC-dependent mechanisms. The data are consistent with previous findings of increased L-type calcium current and decreased NMDAR number in aged CA1 cells and may help explain age-related deficits in learning and memory.

2-Amino-5-phosphonovalerate↗