Nand Sah - Academia.edu (original) (raw)

Papers by Nand Sah

Toxicology and industrial health, Jan 25, 2016

Methyl isocyanate (MIC) is a toxic industrial chemical that is documented as a potent respiratory... more Methyl isocyanate (MIC) is a toxic industrial chemical that is documented as a potent respiratory toxicant. We investigated cell-mediated immunity (CMI) in the MIC-exposed long-term survivors and their offspring born after the Bhopal gas-leak tragedy in 1984. Several earlier reports show inconsistency in the assessment of immunological effects of MIC on the human population. In these studies, important factors including lifestyle attributes were overlooked. We incorporated these factors also in our study of the basic cell-mediated immune function in the Bhopal MIC-affected population. Twenty-seven years after exposure, we assessed the circulating T-lymphocyte frequency using E-Rosette assay. A total of 46 MIC-exposed healthy long-term survivors and their offspring were studied vis-a-vis parallel gender-age group-matched unexposed controls from Bhopal and various other regions of India. The influence of several lifestyle variabilities (smoking, alcohol intake, and tobacco chewing) on...

Agents that can suppress the activation of nuclear factor-B (NF-B) and activator protein-1 (AP-1)... more Agents that can suppress the activation of nuclear factor-B (NF-B) and activator protein-1 (AP-1) may be able to block tumorigenesis and inflammation. Oleandrin, a polyphenolic cardiac glycoside derived from the leaves of Nerium oleander, is a candidate NF-B and AP-1 modulator.

Asian Pacific Journal of Cancer Prevention Apjcp, Dec 1, 2011

The purpose of this study was to update both researchers and clinicians about the cancer incidenc... more The purpose of this study was to update both researchers and clinicians about the cancer incidence in methyl isocyanate (MIC) exposed long-term survivors and in their offspring, focusing on the etiological plausibility. In the time period 2006-2011, cancer morbidity was evaluated in the population surviving after exposure to (MIC) on December 3rd, 1984, in Bhopal. This descriptive study is based on hospital registration of 1261 cancer patients those are MIC gas victims and their subsequently born offspring. Morbidity status was studied on the basis of gender, age, organ and site with relative percentages. Cancers on specific sites, with special reference to breast (n=231) (18.31%), lung (n=103) (8.16%), tongue (n=103) (8.16%), buccal mucosa (n=94) (7.45%), cervix (n=72) (5.70%), and esophagus (n=68) (5.39%) were found in high proportions. Ovary (n=43) (3.40%), brain (n=42) (3.33%), larynx (n=40) (3.17%), non-Hodgkin's (n=31) (2.45%), gallbladder (n=29) (2.29%), stomach (n=28) (2.22%), head and neck (n=28) (2.22%), liver (n=27) (2.14%), acute lymphoid leukemia (n=24) (1.90%), rectum (n=20) (1.58%), colon (n=20) (1.58%), chronic myeloid leukemia (n=17) (1.34%), alveolus (n=17) (1.34%), Hodgkin's (n=14) (1.11%), uterus (n=14) (1.11%), multiple myeloma (n=14) (1.11%), and prostate (n=11) (0.87%) lesions were observed less frequently. Remarkably, gradual increase of cancers on different organs and sites were observed in the long- term survivors and their offspring. The present study observed some cancers which were not previously reported in this population. In addition, we also present the future research directions with systematic approaches to predict cancer risk in long-term survivors and their future generations. On the basis of this morbidity report, we suggest the need of biological surveillance through immune system biomonitoring and cytogenetic screening to predict the cancer risk in the MIC exposed population and their offspring.

Cancer Research, Jul 15, 2000

The Journal of Biological Chemistry, Jun 6, 2003

Molecular Cancer Therapeutics, Nov 1, 2003

Functional inactivation of the p53 gene and robust DNA repair capacity may be among the salient c... more Functional inactivation of the p53 gene and robust DNA repair capacity may be among the salient causes of radioresistance in tumor cells. We expressed the wild-type (wt) p53 gene in a p53-mutant human epidermoid carcinoma cell line, A431, using an adenoviral vector [adenovirus-p53 (Ad-p53), INGN 201], examined its radiosensitivity, and correlated p53 status and radiosensitivity with cellular repair functions. Using clonogenic survival assays and the terminal deoxynucleotidyl transferase-mediated nick end labeling assay for apoptosis, we demonstrated that preirradiation treatment with Ad-p53 significantly increased the radiosensitivity of A431 cells over controls. Induction of p53 expression using a construct where p53 expression was under the control of an inducible promoter also significantly increased radiosensitivity of H1299 lung tumor cells, which are otherwise null for p53. These results did not correlate with radiation-induced apoptosis but did correlate with functional impairment of DNA repair and suppressed expression of several repair-related genes, such as Ku70, DNA-dependent protein kinase, ataxia telangiectasia mutated, and X-ray-sensitive complementation group 4. Normal human fibroblast MRC-9 cells showed no impairment in the repair capability due to Ad-p53 despite the suppression of some repair genes. Expression of Ku70, which is known to mediate diverse cellular functions, correlated with the differential effects of p53 on radiosensitivity in the normal and tumor cells. (Mol Cancer Ther.

Asian Pacific journal of cancer prevention : APJCP, 2015

The Bhopal gas tragedy involving methyl isocyanate (MIC) is one of the most horrific industrial a... more The Bhopal gas tragedy involving methyl isocyanate (MIC) is one of the most horrific industrial accidents in recent decades. We investigated the genotoxic effects of MIC in long-term survivors and their offspring born after the 1984 occurrence. There are a few cytogenetic reports showing genetic damage in the MIC-exposed survivors, but there is no information about the associated cancer risk. The same is true about offspring. For the first time, we here assessed the micronucleus (MN) frequency using cytokinesis-blocked micronucleus (CBMN) assay to predict cancer risk in the MIC-affected population of Bhopal. A total of 92 healthy volunteers (46 MIC- affected and 46 controls) from Bhopal and various regions of India were studied taking gender and age into consideration. Binucleated lymphocytes with micronuclei (BNMN), total number of micronuclei in lymphocytes (MNL), and nuclear division index (NDI) frequencies and their relationship to age, gender and several lifestyle variabilities...

International journal of obstetric anesthesia, 2010

Epidural analgesia is widely used for pain relief during labor. The purpose of this study was to ... more Epidural analgesia is widely used for pain relief during labor. The purpose of this study was to determine if ultrasound measurement of the depth from skin to epidural space before the epidural technique decreases the failure rate of labor analgesia. A secondary objective was to correlate ultrasound depth to the epidural space with actual depth of the needle at placement. In this prospective, randomized, non-blinded study, 370 parturients requesting labor epidural analgesia were randomized to receive their epidural technique by first year anesthesia residents with or without prior ultrasound determination of epidural space depth. Outcome variables included the incidence of epidural catheter replacement for failed analgesia and the number of epidural attempts and accidental dural punctures. The ultrasound group had fewer epidural catheter replacements (P<0.02), and epidural placement attempts (P<0.01) compared to the control group. Pearson's correlation coefficients compari...

Cancer research, Jan 15, 2000

Agents that can suppress the activation of nuclear factor-kappaB (NF-kappaB) and activator protei... more Agents that can suppress the activation of nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1) may be able to block tumorigenesis and inflammation. Oleandrin, a polyphenolic cardiac glycoside derived from the leaves of Nerium oleander, is a candidate NF-kappaB and AP-1 modulator. We investigated the effect of oleandrin on NF-kappaB activation induced by inflammatory agents. Oleandrin blocked tumor necrosis factor (TNF)-induced activation of NF-kappaB in a concentration- and time-dependent manner. This effect was mediated through inhibition of phosphorylation and degradation of IkappaBalpha, an inhibitor of NF-kappaB. A proprietary hot water extract of oleander (Anvirzel) also blocked TNF-induced NF-kappaB activation; subsequent fractionation of the extract revealed that this activity was attributable to oleandrin. The effects of oleandrin were not cell type specific, because it blocked TNF-induced NF-kappaB activation in a variety of cells. NF-kappaB-dependent reporter ...

Molecular cancer therapeutics, 2003

Asian Pacific journal of cancer prevention : APJCP, 2011

Asian Pacific journal of cancer prevention : APJCP, 2012

Methyl isocyanate may have a role in cancer etiology, although the link is unclear. There is evid... more Methyl isocyanate may have a role in cancer etiology, although the link is unclear. There is evidence in the literature that it can induce cancer in animals but the carcinogenic potency is weak. Pheochromocytoma of adrenal medulla and acinar cell tumors of pancreas have been observed in methyl isocyanate exposed animals. Conversely, emerging data from population-based epidemiological studies are contradictory since there is no evidence of such cancers in methyl isocyanate exposed humans. Recently, we reported a high prevalence of breast and lung cancers in such a population in Bhopal. In vitro findings appearing in the latest scientific literature suggest that genomic instability is caused by methyl isocyanate analogs in lung, colon, kidney, ovary epithelial cells, and that hepatocytes may undergo oncogenic transformation, have obvious implications. The conflicting information prompted us to present this update over the last three decades on methyl isocyanate-induced cancers after a...

Resonance, 2000

Conclusion Mitochondria serve as power houses of cells but they also possess ‘covered’ knives to... more Conclusion Mitochondria serve as power houses of cells but they also possess ‘covered’ knives to kill the cells. A number of intrinsic and extrinsic factors exist which regulate cell killing by mitochondria. Caspases are comparable to a surgeon’s knife, which can be used to sculpt organisms, get rid of wayward, redundant and incorrigibly damaged cells, but can spell doom if not

Proceedings of the National Academy of Sciences, 1999

Cellular imbalance in the levels of antioxidants and reactive oxygen species resulting in apoptos... more Cellular imbalance in the levels of antioxidants and reactive oxygen species resulting in apoptosis is directly associated with a number of parasitic infections, aging, and several genetic and multifactorial diseases. The baculovirus AcNPV-encoded antiapoptotic p35 gene prevents apoptosis induced by a variety of apoptotic agents in different systems. We demonstrate the ability of the p35 gene to inhibit oxidative stress-induced apoptosis. In vitro cultured Spodoptera frugiperda (Sf9) insect cells infected with wild-type AcNPV carrying the antiapoptotic p35 gene did not undergo apoptosis when subjected to oxidative stress generated by the exogenous application of oxidants or in vivo generation of reactive oxygen species or on direct exposure of cells to UV radiations. An AcNPV mutant carrying a deletion of the p35 gene failed to arrest cell death. Transfection of cells with a recombinant plasmid containing the p35 gene under the transcriptional control of a stress promoter (Drosophila hsp70) was also able to rescue cells from oxidative stress-induced cell death, demonstrating the direct involvement of P35. ESR spin-trapping studies conducted in vitro and in vivo demonstrated that P35 functions directly as an antioxidant by mopping out free radicals and consequently prevents cell death by acting at an upstream step in the reactive oxygen species-mediated cell death pathway.

The Journal of Pain, 2007

The purpose of this study was to compare the total epidural dose of 3 commonly used labor epidura... more The purpose of this study was to compare the total epidural dose of 3 commonly used labor epidural modalities. After local institutional review board approval, 195 laboring parturients received an epidural catheter for labor analgesia. All patients received an initial bolus of 0.1% ropivacaine (10 mL) and fentanyl (100 microg). Maintenance of labor analgesia consisted of ropivacaine 0.1% with fentanyl 2 microg/mL. Patients were then randomly assigned into 3 groups: Group 1 (continuous epidural infusion [CEI]), continuous infusion at 10 mL/h; group 2 (CEI + patient-controlled epidural analgesia [PCEA]), CEI at 5 mL/h with a demand dose of 5 mL allowed every 20 minutes with a 20 mL/h maximum dose; group 3 (PCEA), demand doses only of 5 mL every 15 minutes with a 20 mL/h maximum dose. Measured variables included total epidural dose, total bolus requests and boluses delivered, number of staff interventions, pain Visual Analog Scale (VAS; 0-100), modified Bromage scores, stage I and II labor duration, delivery outcome, and maternal satisfaction after delivery. No differences were noted with respect to pain VAS, modified Bromage scores, stage I and II labor duration, number of staff interventions, delivery outcome, and maternal satisfaction score. Total infusion dose was lower in demand dose only PCEA compared with CEI and CEI + PCEA groups (P = &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .01). Demand dose-only PCEA results in less total epidural dose compared with CEI and CEI + PCEA without affecting labor duration, motor block, pain VAS, maternal and neonatal outcomes, and maternal satisfaction. This article compares 3 commonly used labor epidural delivery modalities (traditional continuous epidural infusion, patient-controlled epidural analgesia with a background infusion, and demand dose-only patient-controlled epidural analgesia). Benefits in epidural dose reduction with demand dose only PCEA does not translate into improved maternal and neonatal outcome.

Journal of Biosciences, 2003

Host pathogen interaction results in a variety of responses, which include phagocytosis of the pa... more Host pathogen interaction results in a variety of responses, which include phagocytosis of the pathogen, release of cytokines, secretion of toxins, as well as production of reactive oxygen species (ROS). Recent studies have shown that many pathogens exert control on the processes that regulate apoptosis in the host. The induction of apoptosis upon infection results from a complex interaction of parasite proteins with cellular host proteins. Abrogation of host cell apoptosis is often beneficial for the pathogen and results in a successful host invasion. However, in some cases, it has been shown that induction of apoptosis in the infected cells significantly imparts protection to the host from the pathogen. There is a strong correlation between apoptosis and the host protein translation machinery: the pathogen makes all possible efforts to modify this process so as to inhibit cell suicide and ensure that it can survive and, in some cases, establish latent infection. This review discusses the significance of various pathways/steps during virus-mediated modulation of host cell apoptosis.

Journal of Biosciences, 2005

Journal of Biological Chemistry, 2000

activate a wide variety of cellular responses, including NF-B, AP-1, JNK, and apoptosis. Whether ... more activate a wide variety of cellular responses, including NF-B, AP-1, JNK, and apoptosis. Whether ceramide transduces these signals through the same mechanism as TNF is not known. In the present study we investigated the role of the T cell-specific tyrosine kinase p56 lck in ceramide-and TNF-mediated cellular responses by comparing the responses of Jurkat T cells with JCaM1

Journal of Biological Chemistry, 2003