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Sudhir Srivastava

Publications and source records attributed to Sudhir Srivastava.

At least 19 recordsLinked to original sources
PubMed2006

Chemical constituents and antifilarial activity of Lantana camara against human lymphatic filariid Brugia malayi and rodent filariid Acanthocheilonema viteae maintained in rodent hosts.

Lymphatic filariasis continues to be a major health problem in tropical and subtropical countries. A macrofilaricidal agent capable of eliminating adult filarial parasites is urgently needed. In the present study, we report the antifilarial activity in the extract of stem portion of the plant Lantana camara. The crude extract at 1 g/kg for 5 days by oral route killed 43.05% of the adult Brugia malayi parasites and sterilized 76% of surviving female worms in the rodent model Mastomys coucha. A 34.5% adulticidal activity along with sterilization of 66% of female worms could be demonstrated in the chloroform fraction. Remarkable antifilarial activity was observed in the adult B. malayi transplanted gerbil model where up to 80% of the adult worms could be killed at the same dose and all the surviving female parasites were found sterilized. The extract was also found effective against a subcutaneous rodent filariid Acanthocheilonema viteae maintained in Mastomys coucha, where it exerted strong microfilaricidal (95.04%) and sterilization (60.66%) efficacy with mild macrofilaricidal action. Two compounds, oleanonic acid and oleanolic acid, isolated from hexane and chloroform fractions showed LC100 at 31.25 and 62.5 mug/ml, respectively, on B. malayi in vitro. This is the first ever report on the antifilarial efficacy of Lantana camara.

Animals↗
PubMed2006

Wuchereria bancrofti: effect of single and multiple larval inoculations on infection dynamics and development of clinical manifestations in non-human primate Presbytis entellus.

We earlier reported the successful experimental transmission of Wuchereria bancrofti from humans to the Indian leaf monkey (Presbytis entellus) [Misra, S., Tyagi, K., Chatterjee, R.K., 1997. Experimental transmission of nocturnally periodic Wuchereria bancrofti to Indian leaf monkey (Presbytis entellus). Experimental Parasitology 86,155-157.; Dube, A., Murthy, P.K., Puri, S.K., Misra-Bhattacharya, S., 2004. Presbytis entellus: a primate model for parasitic disease research. Trends in Parasitology 20(8), 358-360.] using a small number of animals. The present study, involving 27 langur monkeys, found the development of pathological manifestations ranging from filarial fever, lymphangitis, lymphadenitis, hydrocoele, and limb edema to minor histopathological changes in tissues after single, double, triple, or multiple inoculations of infective larvae of W. bancrofti recovered from Culex quinquefasciatus fed on human microfilaraemic blood. Thirty-eight percent of the infected langurs developed detectable microfilaraemia in their blood. Single or double larval exposure resulted in better worm establishment than multiple exposures with small numbers of larvae. All of the langurs receiving a single large inoculum and 85.71% of those receiving two inoculations harbored adult parasites. Worm establishment decreased with increasing number of larval inoculations. In all, 60% of infected langurs developed classical gross-pathological symptoms of lymphatic filariasis. Of these, 29.16% developed thickening of the lymphatics, 25% suffered from periodic rise in rectal temperature, and 16.66% developed scrotal swelling with presence of microfilariae in the hydrocoele fluid. Only one out of 25 langurs (4%) developed acute limb edema. It appeared that a single inoculum of a large number of infective larvae was able to induce maximum pathology. Fifty-six percent of the infected langurs acquired a peculiar sitting posture, retracting both the hind limbs, usually after 4-5 months of larval inoculation and eventually resulting in reduced mobility. Oral administration of diethylcarbamazine (citrate) at 12mg/kg for 12 consecutive days to one langur caused 80% suppression in microfilaraemia on day 8, killing all the adult parasites. Of the two immunosuppressed (cortisone- or prednisolone-treated) male rhesus monkeys included in the study, neither developed any of the above lymphatic symptoms or parasites after receiving larval inoculations on two or three occasions; however, a rise in rectal temperature in one of the animals was noticed. The present study thus reveals that the Indian leaf monkey, P. entellus, may serve as an ideal non-human primate model of human bancroftian filariasis for carrying out longitudinal studies on pathology, host-parasite interactions, and preclinical evaluation of candidate anti-filarial drugs or vaccines.

Animals↗
PubMed2006

Standards for plasma and serum proteomics in early cancer detection: a needs assessment report from the national institute of standards and technology--National Cancer Institute Standards, Methods, Assays, Reagents and Technologies Workshop, August 18-19, 2005.

NIST and the National Cancer Institute cosponsored a workshop on August 18-19, 2005, to examine needs for reference materials for early cancer detection. This meeting focused on standards, methods, assays, reagents, and technologies. Needs for plasma and serum proteomics, DNA methylation, and specimen reference collections were discussed, and recommendations from participants were solicited. This report summarizes the discussion and recommendations for proteomics reference materials.

Biomarkers, Tumor↗
PubMed2006

Molecular screening of cancer: the future is here.

The remarkable growth in our knowledge of the biology of cancer is leading to the identification of previously elusive pathways and networks involved in cancer causation. The development of technologies has played a pivotal role in furthering this understanding and appreciation of the complexity of tumorigenesis, and is advancing efforts to fully grasp the biology and exploit the knowledge for improvements in cancer detection, prevention, and therapy. The future of molecular screening, i.e. detection of risk or cancer via molecular determinants, has never been so close to a reality. Molecular assays employed in cancer detection and therapy are likely to revolutionize cancer treatment through individual-based diagnosis and treatment, i.e. personalized medicine. A number of detection techniques, such as the detection of aberrant DNA and RNA, the presence of auto-antibodies in serum or plasma, and protein profiling, are already in limited use for patient stratification for clinical trials and for predicting drug response.

Autoantibodies↗
PubMed2006

Use of bilateral internal thoracic arteries in CABG through lateral thoracotomy with robotic assistance in 150 patients.

BACKGROUND: Internal thoracic arteries (ITA) have been shown to offer longer graft patency. Off-pump coronary artery bypass graft surgery (CABG) through small lateral thoracotomy has been reported. The present study deals with feasibility of using bilateral ITAs (BITA) in CABG through small lateral thoracotomy facilitated by the da Vinci robotic system. METHODS: Since July 2002, 150 patients underwent CABG through small lateral thoracotomy using robotic assistance for harvesting of BITA. After single lung ventilation, three 1- to 2-cm incisions were made in the third, fifth, and seventh intercostal spaces 2 to 3 cm medial to the anterior axillary line. After insertion of camera and instrument arms, both ITAs were harvested in a completely skeletonized fashion. A small anterolateral thoracotomy was done, enlarging the camera port incision. Distal anastomoses were performed on a beating heart using nitinol surgical clips. Intercostal cryoanalgesia and local anesthetic infusion were used for pain management. RESULTS: Planned arterial revascularization was completed in 148 patients. Mean number of arterial grafts per patient was 2.6 +/- 0.8. All coronary arteries could be reached with BITA as in situ or composite grafts. There was no mortality, stroke, myocardial infarction, or wound infection. Seven patients had new onset atrial fibrillation. Four patients required exploration of postoperative bleeding. Mean postoperative length of stay was 3.6 +/- 2.9 days. CONCLUSIONS: The da Vinci robotic system was found to be safe and feasible for BITA harvesting in multivessel CABG through small lateral thoracotomy. Further follow-up for graft patency is necessary. Postoperative pain may be reduced with aggressive management strategies. The approach offers fast recovery. This sternum-sparing approach may be an evolutionary step toward closed-chest coronary artery bypass graft surgery.

Anastomosis, Surgical↗
PubMed2006

Results of the prospective multicenter trial of robotically assisted totally endoscopic coronary artery bypass grafting.

BACKGROUND: Robotic technology has been proven safe and efficacious in the performance of mitral valve repair and atrial septal defect repair. This report describes a Food and Drug Administration-sanctioned multicenter study of the safety and efficacy of the da Vinci system (Intuitive Surgical, Inc, Mountain View, CA) for totally endoscopic coronary artery bypass (TECAB) surgery. METHODS: Patients requiring left anterior descending (LAD) coronary artery revascularization were eligible. The procedure was performed with femoro-femoral cardiopulmonary bypass (CPB), endoaortic balloon occlusion, and thoracoscopy. All aspects of the procedure were performed with the robotic system, from internal mammary artery harvest to coronary anastomosis. RESULTS: Ninety-eight patients requiring single-vessel LAD revascularization were enrolled at 12 centers. Thirteen patients (13%) were excluded intraoperatively (eg, failed femoral cannulation, inadequate working space). In 85 patients (69 men, age 58 +/- 10 years) who underwent TECAB, CPB time was 117 +/- 44 minutes, cross-clamp time was 71 +/- 26 minutes, and hospital length of stay was 5.1 +/- 3.4 days. There were five (6%) conversions to open techniques. There were no deaths or strokes, one early reintervention, and one myocardial infarction (1.5%). Three-month angiography was performed in 76 patients, revealing significant anastomotic stenoses (> 50%) or occlusions in 6 patients. Overall freedom from reintervention or angiographic failure was 91%. CONCLUSIONS: Robotic TECAB was accomplished with no mortality, low morbidity, and angiographic patency and reintervention rates comparable with published data. Although the use of CPB was a limitation of the technique, this experience represents a step toward more advanced procedures, such as multivessel or off-pump TECAB.

Adult↗
PubMed2006

Joint National Cancer Institute-Food and Drug Administration workshop on research strategies, study designs, and statistical approaches to biomarker validation for cancer diagnosis and detection.

Cancer remains the second leading cause of death in the United States, in spite of tremendous advances made in therapeutic and diagnostic strategies. Successful cancer treatment depends on improved methods to detect cancers at early stages when they can be treated more effectively. Biomarkers for early detection of cancer enable screening of asymptomatic populations and thus play a critical role in cancer diagnosis. However, the approaches for validating biomarkers have yet to be addressed clearly. In an effort to delineate the ambiguities related to biomarker validation and related statistical considerations, the National Cancer Institute, in collaboration with the Food and Drug Administration, conducted a workshop in July 2004 entitled "Research Strategies, Study Designs, and Statistical Approaches to Biomarker Validation for Cancer Diagnosis and Detection." The main objective of this workshop was to review basic considerations underpinning the study designs, statistical methodologies, and novel approaches necessary to rapidly advance the clinical application of cancer biomarkers. The current commentary describes various aspects of statistical considerations and study designs for cancer biomarker validation discussed in this workshop.

Biomarkers, Tumor↗
PubMed2005

Recent advances in biomarkers for cancer diagnosis and treatment.

With the availability of new technologies and the increased interest of medical practitioners to use molecular biomarkers in early detection and diagnosis, and in the prediction of therapeutic treatment efficacy and clinical outcomes, the academic and research institutions, as well as the pharmaceutical industry, have increased their efforts to develop novel molecular biomarkers for several human diseases, including cancer. The identification of molecular biomarkers also enables the development of a new generation of diagnostic products and to integrate diagnostics and therapeutics. This integrated approach will aid in 'individualizing' the medical practice. Here, we address issues related to the development of biomarkers, novel technological platforms used for drug development, future technologies and strategies for validating biomarkers for their clinical utility.

Biomarkers, Tumor↗
PubMed2005

Preparation and characterization of candidate reference materials for telomerase assays.

BACKGROUND: Telomerase has been measured in body fluids of cancer patients, and clinical tests for telomerase may have utility as noninvasive, cost-effective methods for the early detection of cancer. However, telomerase activity measured by common methods such as the telomerase repeat amplification protocol (TRAP) and telomerase reverse transcriptase catalytic subunit (hTERT) mRNA by reverse transcription-PCR (RT-PCR) varies among laboratories. METHODS: We prepared a CHAPS buffer lysate from cultured A549 cells and stored it at -80 degrees C. Telomerase activity was measured by TRAP/PCR and real-time TRAP/PCR in conjunction with RT-PCR measurements of hTERT mRNA. Activity measured with use of the robot-assisted TRAP (RApidTRAP) multicapillary electrophoresis system was compared with single-capillary and slab-gel measurements in the range 10 to 10 000 cell equivalents. RESULTS: Preparations made after flash freezing and sonication of cells were approximately 3-fold more active. Although the slab-gel and capillary instruments detected telomerase activity, the multicapillary instrument was better suited for high-throughput studies. Measurements of telomerase by TRAP/real-time PCR and hTERT mRNA/RT-PCR yielded reproducible titrations in the range 10 to 10 000 cell equivalents (CVs, 1%-8% and 1%-3%, respectively). CONCLUSIONS: We have prepared and characterized a candidate reference material that appears to be suitable for use in a wide range of assays of telomerase activity and expression.

Biomarkers, Tumor↗
PubMed2005

Epidemiologic and viral factors associated with cervical neoplasia in HPV-16-positive women.

While infection with high-risk HPV is the most important risk factor for cervical cancer, HPV alone is insufficient. Our purpose was to identify viral and epidemiologic factors associated with cervical disease in HPV-16 DNA-positive women referred to colposcopy. We used a standardized interview to collect epidemiologic data from consenting women. Total nucleic acids from exfoliated cervical cells were used for all viral assays (HPV detection and typing using L1 consensus PCR with line probe hybridization, variant classification by sequencing, viral load and transcript copy determination by quantitative PCR and transcript pattern by nested RT-PCR). Cervical disease was based on colposcopic biopsy. Logistic regression was used to calculate ORs with 95% CIs. There were 115 HPV-16 positive women among 839 enrollees. By univariate analyses, age >25 years (OR = 3.05, 95% CI 1.20-7.76), smoking (OR = 3.0, 95% CI 1.19-7.56), high viral load (OR = 5.27, 95% CI 2.05-13.60), detection of both E6 and E6*I transcripts (OR = 10.0, 95% CI 2.1-47.58) and high transcript copies (OR = 5.56, 95% CI 2.05-13.60) were significant risk factors for CIN III with reference to No CIN/CIN I. Less than a third of the women (31.5%) had prototype HPV-16 detected, and variants showed no association with disease, viral load or transcription. Viral DNA and transcript copies were highly correlated, and the ratio of transcript copies to DNA copies was not changed with disease status. While viral load, transcript copies and transcript pattern were statistically associated with CIN III, none of these measures effectively discriminated between HPV-16 women with disease requiring treatment and those who could be followed. Cellular proliferation and differentiation pathways affected by HPV should be investigated as biomarkers for cervical cancer screening.

Adolescent↗
PubMed2005

Murine infection model for Mycobacterium fortuitum.

Mycobacterium fortuitum is an atypical, non-tubercular, pathogenic, rapidly growing mycobacteria. As very little is known about its virulence determinants, the absence of an animal infection model was always sorely felt. A reliable and reproducible murine infection model has been developed in which non-replicating persistence of 10(5) CFU/g tissue in kidney was observed when a standardised dosage inoculum of 5x10(7) CFU was injected intravenously. The tissue bacillary load was determined at regular intervals (10, 25, 45 and 60 days post-inoculation) in different organs, viz., kidney, spleen, lung and liver. Histopathology of kidney revealed tissue damage and granuloma-like formations which appear to be part of the host's effort to combat the infection. As IFN-gamma is known to trigger antimycobacterial effects of murine macrophages, IFN-gamma was assayed to determine the correlation between host protective measures and bacillary load in kidney. Fifteen days after infection, the level of IFN-gamma secreted by CD4+ and CD8+ T lymphocytes was high, concomitant with high tissue bacillary load, while the level sharply declined as the number of bacilli in kidney decreased 45 days post-inoculation. The invasion and proliferation of M. fortuitum ATCC 6841, when incubated with non-phagocytic (recombination activating genes (RAG) murine kidney) and phagocytic (murine peritoneal macrophages) cell lines, was assessed. M. fortuitum did not invade RAG murine kidney cell line, while the bacilli infected and proliferated freely inside murine macrophages. In conclusion, we present a reproducible murine infection model that sustains a persistent infection, the progression of which correlates meaningfully with host protective response.

Animals↗
PubMed2005

Mitochondrial DNA as a cancer biomarker.

As part of a national effort to identify biomarkers for the early detection of cancer, we developed a rapid and high-throughput sequencing protocol for the detection of sequence variants in mitochondrial DNA. Here, we describe the development and implementation of this protocol for clinical samples. Heteroplasmic and homoplasmic sequence variants occur in the mitochondrial genome in patient tumors. We identified these changes by sequencing mitochondrial DNA obtained from tumors and blood from the same individual. We confirmed previously identified primary lung tumor changes and extended these findings in a small patient cohort. Eight sequence variants were identified in stage I to stage IV tumor samples. Two of the sequence variants identified (22%) were found in the D-loop region, which accounts for 6.8% of the mitochondrial genome. The other sequence variants were distributed throughout the coding region. In the forensic community, the sequence variations used for identification are localized to the D-loop region because this region appears to have a higher rate of mutation. However, in lung tumors the majority of sequence variation occurred in the coding region. Hence, incomplete mitochondrial genome sequencing, designed to scan discrete portions of the genome, misses potentially important sequence variants associated with cancer or other diseases.

Adult↗
PubMed2005

Mitochondria as a target for early detection and diagnosis of cancer.

Mitochondrial dysfunction and mutations in mitochondrial DNA (mtDNA) have been frequently reported in cancer, neurodegenerative diseases, diabetes, and aging syndromes. The mitochondrion genome (16.5 Kb) codes only for a small fraction (estimated to be 1%) of the proteins housed within this organelle. The other proteins are encoded by the nuclear DNA (nDNA) and transported into the mitochondria. The identification of mitochondrial proteins that are aberrantly expressed in cancer cells and other diseases is now possible through recent developments in proteomic and bioinformatic technologies. These developments set the stage for a comprehensive organelle-based proteomic approach for the identification of new markers for the early detection, risk assessment, and diagnosis of cancer, and other diseases and for the identification of new targets for therapeutic prevention and intervention.

Animals↗
PubMed2005

Evaluation of serum protein profiling by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry for the detection of prostate cancer: I. Assessment of platform reproducibility.

BACKGROUND: Protein expression profiling for differences indicative of early cancer has promise for improving diagnostics. This report describes the first stage of a National Cancer Institute/Early Detection Research Network-sponsored multiinstitutional evaluation and validation of this approach for detection of prostate cancer. METHODS: Two sequential experimental phases were conducted to establish interlaboratory calibration and standardization of the surface-enhanced laser desorption (SELDI) instrumental and assay platform output. We first established whether the output from multiple calibrated Protein Biosystem II SELDI-ionization time-of-flight mass spectrometry (TOF-MS) instruments demonstrated acceptable interlaboratory reproducibility. This was determined by measuring mass accuracy, resolution, signal-to-noise ratio, and normalized intensity of three m/z "peaks" present in a standard pooled serum sample. We next evaluated the ability of the calibrated and standardized instrumentation to accurately differentiate between selected cases of prostate cancer and control by use of an algorithm developed from data derived from a single site 2 years earlier. RESULTS: When the described standard operating procedures were established at all laboratory sites, the across-laboratory measurements revealed a CV for mass accuracy of 0.1%, signal-to-noise ratio of approximately 40%, and normalized intensity of 15-36% for the three pooled serum peaks. This was comparable to the intralaboratory measurements of the same peaks. The instrument systems were then challenged with sera from a selected group of 14 cases and 14 controls. The classification agreement between each site and the established decision algorithm were examined by use of both raw peak intensity boosting and ranked peak intensity boosting. All six sites achieved perfect blinded classification for all samples when boosted alignment of raw intensities was used. Four of six sites achieved perfect blinded classification with ranked intensities, with one site passing the criteria of 26 of 28 correct and one site failing with 19 of 28 correct. CONCLUSIONS: These results demonstrate that "between-laboratory" reproducibility of SELDI-TOF-MS serum profiling approaches that of "within-laboratory" reproducibility as determined by measuring discrete m/z peaks over time and across laboratories.

Calibration↗
PubMed2005

Biomarkers in molecular medicine: cancer detection and diagnosis.

In spite of advances in diagnostics and therapeutics, cancer remains the second leading cause of death in the U.S. Successful cancer treatment depends not only on better therapies but also on improved methods to assess an individual's risk of developing cancer and to detect cancers at early stages when they can be more effectively treated. Current cancer diagnostic imaging methods are labor-intensive and expensive, especially for screening large asymptomatic populations. Effective screening strategies depend on methods that are noninvasive and detect cancers in their early stages of development. There is increasing interest and enthusiasm in molecular markers as tools for cancer detection and prognosis. It is hoped that newly discovered cancer biomarkers and advances in high-throughput technologies would revolutionize cancer therapies by improving cancer risk assessment, early detection, diagnosis, prognosis, and monitoring therapeutic response. These biomarkers will be used either as stand-alone tests or to complement existing imaging methods.

Biomarkers, Tumor↗