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Biomedical subjects

V Nayak

Publications and source records attributed to V Nayak.

15 recordsLinked to original sources
PubMed2006

Effects of hTERT on metal ion-induced genomic instability.

There is currently a great interest in delayed chromosomal and other damaging effects of low-dose exposure to a variety of pollutants which appear collectively to act through induction of stress-response pathways related to oxidative stress and ageing. These have been studied mostly in the radiation field but evidence is accumulating that the mechanisms can also be triggered by chemicals, especially heavy metals. Humans are exposed to metals, including chromium (Cr) (VI) and vanadium (V) (V), from the environment, industry and surgical implants. Thus, the impact of low-dose stress responses may be larger than expected from individual toxicity projections. In this study, a short (24 h) exposure of human fibroblasts to low doses of Cr (VI) and V (V) caused both acute chromosome damage and genomic instability in the progeny of exposed cells for at least 30 days after exposure. Acutely, Cr (VI) caused chromatid breaks without aneuploidy while V (V) caused aneuploidy without chromatid breaks. The longer-term genomic instability was similar but depended on hTERT positivity. In telomerase-negative hTERT- cells, Cr (VI) and V (V) caused a long lasting and transmissible induction of dicentric chromosomes, nucleoplasmic bridges, micronuclei and aneuploidy. There was also a long term and transmissible reduction of clonogenic survival, with an increased beta-galactosidase staining and apoptosis. This instability was not present in telomerase-positive hTERT+ cells. In contrast, in hTERT+ cells the metals caused a persistent induction of tetraploidy, which was not noted in hTERT- cells. The growth and survival of both metal-exposed hTERT+ and hTERT- cells differed if they were cultured at subconfluent levels or plated out as colonies. Genomic instability is considered to be a driving force towards cancer. This study suggests that the type of genomic instability in human cells may depend critically on whether they are telomerase-positive or -negative and that their sensitivities to metals could depend on whether they are clustered or diffuse.

Apoptosis↗
PubMed2005

Protection of mouse bone marrow against radiation-induced chromosome damage and stem cell death by the ocimum flavonoids orientin and vicenin.

In a previous study, orientin and vicenin, the water-soluble plant flavonoids, protected mice against radiation lethality (Uma Devi et al., Radiat. Res. 151, 74-78, 1999). To study bone marrow protection, adult Swiss mice were exposed to 0-6 Gy 60Co gamma rays 30 min after an intraperitoneal injection of 50 microg/ kg body weight of orientin/vicenin. Chromosomal aberrations in bone marrow were studied at 24 h postirradiation. Stem cell survival was studied using the exogenous spleen colony (CFU-S) assay. Radiation produced a dose-dependent increase in aberrant cells as well as in the yield of the different types of aberrations (breaks, fragments, rings and dicentrics) and a decrease in CFU-S. Pretreatment with either flavonoid significantly reduced the aberrant cells and different aberrations and increased the number of CFU-S compared to the respective radiation-alone groups. The dose modification factors for 50% reductions in the number of CFU-S were 1.6 for orientin and 1.7 for vicenin. The present finding that very low nontoxic doses of orientin and vicenin provide efficient protection against bone marrow damage at clinically relevant radiation doses suggests their potential for protection of normal tissues in radiotherapy.

Animals↗
PubMed2001

Treatment of sclerosing mesenteritis with corticosteroids and azathioprine.

Sclerosing (idiopathic) mesenteritis is a rare disease that may present with abdominal pain or bowel obstruction. A 21-year-old man was diagnosed with sclerosing mesenteritis, and treated with a partial ileal resection and defunctioning ileostomy. He was subsequently started on corticosteroids and azathioprine. Five months later, at the time of ileostomy reversal, he was disease-free. The diagnosis and management of this disease are discussed.

Adrenal Cortex Hormones↗
PubMed2001

Cystadenomas of the liver: a spectrum of disease.

OBJECTIVES: To describe the wide variation in presentation of cystadenomas of the liver and to delineate useful tests for diagnosis and effective surgical treatment. DESIGN: A case series. SETTING: A university-affiliated hospital. PATIENTS: Four patients (3 women, 1 man) having cystadenoma of the liver, 2 of whom had associated mesenchymal stroma. MAIN OUTCOME MEASURES: Serum and cyst fluid carcinoembryonic antigen (CEA) and CA19-9 levels, type of surgery, morbidity and recurrence rates. RESULTS: Cyst fluid CEA and CA19-9 levels were elevated. One patient had resection, 2 had complete enucleation and 1 had partial enucleation. There were no deaths. Morbidity included 1 wound infection; there were no biliary fistulas. The patient with partial enucleation had a radiologically confirmed recurrence. CONCLUSIONS: Analysis of cyst fluid CEA and CA19-9 is useful for diagnosis; besides hepatic resection, complete enucleation should be considered as a reasonable treatment for patients with this disease.

Adult↗
PubMed2000

Effect of doxorubicin on cell survival and micronuclei formation in HeLa cells exposed to different doses of gamma-radiation.

PURPOSE: The present study was undertaken to obtain an insight into the combined effects of doxorubicin with radiation on the cell survival and micronuclei induction in HeLa cells. MATERIAL AND METHODS: HeLa S3 cells were allowed to grow till they reached plateau phase, inoculated with 10 micrograms/ml doxorubicin hydrochloride and then exposed to 0, 0.5, 1, 2 and 3 Gy gamma-radiation. Clonogenicity of cells was measured using the colony forming assay, micronuclei formation using the micronucleus assay. RESULTS: The treatment of HeLa cells with doxorubicin (adriamycin) for 2 hours before exposure to different doses of gamma-radiation resulted in a significant and dose-dependent decline in the cell survival and cell proliferation when compared to the PBS + irradiation group. Conversely, the frequency of micronuclei increased in a dose-related manner in both the PBS + irradiation and doxorubicin + irradiation groups. The pretreatment of HeLa cells with doxorubicin before irradiation to various doses of gamma-rays resulted in a significant elevation in the frequency of micronuclei when compared with the concurrent PBS + irradiation group. The dose-response relationship for both PBS + irradiation and doxorubicin + irradiation groups was linear. The correlation between cell survival and micronuclei induction was also determined for PBS or doxorubicin + irradiation group, where the clonogenicity of cells declined with the increase in micronuclei formation. The correlation between cell survival and micronuclei induction was linear quadratic for both PBS + irradiation and doxorubicin + irradiation groups. CONCLUSION: From our study it can be concluded that combination treatment with doxorubicin and radiation increased the genotoxic effect of the either treatment given alone.

Antineoplastic Agents↗
PubMed2000

Synthetic protein design: construction of a four-stranded beta-sheet structure and evaluation of its integrity in methanol-water systems.

The characterization of a four-stranded beta-sheet structure in a designed 26-residue peptide Beta-4 is described. The sequence of Beta-4 (Arg-Gly-Thr-Ile-Lys-(D)pro-Gly-Ile-Thr-Phe-Ala-(D)Pro-Ala-Thr-Val-Leu-P he-Ala-Val-(D)Pro-Gly-Lys-Thr-Leu-Tyr-Arg) was chosen such that three strategically positioned (D)Pro-Xxx segments nucleate type II' beta-turns, which facilitate hairpin extension. A four-stranded beta-sheet structure is determined in methanol from 500 MHz 1H NMR data using a total of 100 observed NOEs, 11 dihedral restraints obtained from vicinal JCalphaH-NH values and 10 hydrogen bonding constraints obtained from H/D exchange data. The observed NOEs provide strong evidence for a stable four-stranded sheet and a nonpolar cluster involving Ile8, Phe10, Val15 and Phe17. Circular dichroism studies in water-methanol mixtures provide evidence for melting of the beta-sheet structure at high water concentrations. NMR analysis establishes that the four-stranded sheet in Beta-4 is appreciably populated in 50% (v/v) aqueous methanol. In water, the peptide structure is disorganized, although the three beta-turn nuclei appear to be maintained.

Amino Acid Sequence↗
PubMed1998

Evaluation of the antineoplastic activity of guduchi (Tinospora cordifolia) in cultured HeLa cells.

Exposure of HeLa cells to 0, 5, 10, 25, 50 and 100 microg/ml of guduchi extracts (methanol, aqueous and methylene chloride) resulted in a dose-dependent but significant increase in cell killing, when compared to non-drug-treated controls. The effects of methanol and aqueous extracts were almost identical. However, methylene chloride extract enhanced the cell killing effect by 2.8- and 6.8-fold when compared either to methanol or aqueous extract at 50 and 100 microg/ml, respectively. Conversely, the frequency of micronuclei increased in a concentration-dependent manner in guduchi-treated groups and this increase in the frequency of micronuclei was significantly higher than the non-drug-treated control cultures and also with respect to 5 microg/ml guduchi extract-treated cultures, at the rest of the concentrations evaluated. Furthermore, the micronuclei formation was higher in the methylene chloride extract-treated group than in the other two groups. The dose response relationship for all three extracts evaluated was linear quadratic. The effect of guduchi extracts was comparable or better than doxorubicin treatment. The micronuclei induction was correlated with the surviving fraction of cells and the correlation between cell survival and micronuclei induction was found to be linear quadratic. Our results demonstrate that guduchi killed the cells very effectively in vitro and deserves attention as an antineoplastic agent.

Antineoplastic Agents↗
PubMed1998

The relationship between disease activity and expert physician's decision to start major treatment in active systemic lupus erythematosus: a decision aid for development of entry criteria for clinical trials.

OBJECTIVE: To explore the relationship between patients' systemic lupus erythematosus (SLE) activity and physicians' decision to treat with steroids or alternative medication. METHODS: Baseline information and clinical status was extracted from case histories of 30 patients with lupus and represented in clinical vignettes. These vignettes were then mailed to 60 physicians (rheumatologists and immunologists with experience in the treatment of lupus), asking them in each case whether they would initiate treatment or not. The relationship between the 38 complete responses and the SLE Activity Measure (SLAM-R) and SLE Disease Activity Index (SLEDAI) lupus activity scores was analyzed using a general additive model. RESULTS: SLE disease activity measured by SLAM-R or SLEDAI is a significant predictor (p < 0.0001) of physicians' decision to initiate treatment for patients with lupus. Variation between physicians was observed but was mostly due to a few outliers. Some other variations remained unexplained by patients' SLE disease activity, damage, or by specific organ involvement. CONCLUSION: We present reference tables and curves for research that may be used as a basis to derive standardized quantitative criteria for entry in clinical trials. More research is needed on how these tools can be used by clinicians to guide them in their decision to treat or not.

Allergy and Immunology↗
PubMed1996

Micronuclei-induction and its correlation to cell survival in HeLa cells treated with different doses of adriamycin.

The treatment of HeLa cells with different concentrations of adriamycin (0, 5, 10, 25, 50 and 100 microg/ml) resulted in a significant and dose-dependent decline in the cell survival. Conversely, the frequency of micronuclei increased in a concentration-dependent manner. The micronuclei-induction and cell survival were found to be inversely related.

Antibiotics, Antineoplastic↗
PubMed1996

Treatment of mice with a novel antineoplastic agent taxol before irradiation increases the frequency of micronuclei in the bone marrow.

The frequency of micronucleated polychromatic erythrocytes (MPCE) and the normochromatic erythrocytes (MNCE) and polychromatic and normochromatic erythrocyte ratio (P/N ratio) was studied at 12, 24 and 36 h postirradiation in the bone marrow of male mice treated or not with taxol before exposure to 0-4 Gy of 60Co gamma radiation. The frequency of MPCE increased with the increase in radiation dose in a dose-related manner in the irradiated control group. A peak frequency of MPCE was observed at 24 h postirradiation in irradiated control group. The pattern of increase in MNCE was similar to that of MPCE except that a highest number of MNCE was scored at 36 h postirradiation. Taxol administration to animals before irradiation resulted in a significant elevation in the frequency of MPCE and MNCE at all the postirradiation time periods studied. This increase was dose related as observed in the irradiated control group. Irradiation resulted in a dose-dependent decline in the P/N ratio at all the postirradiation time periods studied. The P/N ratio was significantly lower in the taxol + irradiated group compared to the irradiated control group at all postirradiation time periods. A maximum decline in P/N ratio was observed at 36 h postirradiation for both irradiated control and taxol + irradiated groups. The dose response for MPCE, MNCE and P/N ratio was linear quadratic for both the irradiated and taxol + irradiated groups.

Animals↗
PubMed1996

The efficacy of antimalarials in systemic lupus erythematosus.

The use of antimalarial drugs to treat systemic lupus erythematosus (SLE) is receiving increased attention. A retrospective controlled study suggested that antimalarials were useful in suppressing disease activity in SLE. A randomized discontinuation trial of hydroxychloroquine sulphate supported the clinical belief that antimalarials are of benefit in SLE of mild to moderate disease activity and might have a role as adjunctive therapy to protect against more severe relapses of SLE. A randomized trial of the ability of hydroxychloroquine sulphate to suppress articular manifestations of SLE demonstrated no consistent statistically significant benefit, although the sample size was small. Anecdotal reports and the experience of expert clinicians have suggested a corticosteroid sparing role for antimalarials, although no controlled study has been conducted to specifically address this hypothesis. Thus, the evidence favors a role for antimalarials in suppressing mild to moderate disease activity in SLE and possibly in preventing severe disease exacerbations. Their role as corticosteroid sparing agents in SLE is widely believed, but unproven.

Adrenal Cortex Hormones↗
PubMed1983

Malignant transformation in an anal condyloma acuminatum.

A 61-year-old man had malignant transformation of an anal condyloma acuminatum, demonstrated by light and electron microscopic studies. Intranuclear virus-like particles were seen in the benign condylomatous koilocytotic cells but these were absent in the malignant cells. Multinucleation, syncytial giant cells and nuclear atypia in a condyloma acuminatum are considered features of in-situ carcinomatous change. Anal condyloma acuminatum requires wide excision and thorough examination of anorectal canal in order to exclude hidden disease, which will predispose to recurrence. Homosexuality is considered a predisposing factor. The authors stress the importance of histopathologic examination of all anorectal warts to exclude malignant change.

Anus Neoplasms↗
PubMed1979

Atypical vascular proliferation in benign soft tissue tumors.

Atypical endothelial proliferation and continuing growth of small vessels were found to be the main features of two benign soft tissue tumors. Lack of history of injury and insidious onset suggested neoplasia, but the morphology was that of a reactive rather than neoplastic process. Ultrastructural study of the relationship of the endothelial cells to one another and to perithelial cells was helpful in making this distinction. The process appeared to have begun in an organizing thrombus or hematoma, in one case in relation to an occluded artery, and in the other in an abnormally vascular area of skeletal muscle. It is known that endothelial hyperplasia can occur in reparative reaction of this type. The prominent muscular development of small vessels in the cases reported here suggests that abnormal flow or intraluminal pressure could have been a stimulant to atypical growth.

Blood Vessels↗
PubMedDate not supplied

Septo-optic dysplasia (case report).

Septo optic dysplasia is a rare developmental anomaly involving bilateral optic nerve hypoplasia, midline anomalies of the brain and hypothalamo-pituitary dysfunction. A case of septo-optic dysplasia with pituitary dwarfism, optic nerve hypoplasia and absent septum pellucidum is reported.

Child↗