Search PubMed⌕ Search

Biomedical subjects

S Narayan

Publications and source records attributed to S Narayan.

At least 19 recordsLinked to original sources
PubMed2001

DNA damage-induced cell cycle checkpoints involve both p53-dependent and -independent pathways: role of telomere repeat binding factor 2.

Treatment of colon cancer cells with MNNG causes DNA damage with reduced telomeric signals in a p53-dependent manner, but increased cell cycle arrest in S-G(2)/M by both p53-dependent and independent mechanisms. Results also indicate that cellular levels of TRF2 may play a critical role in MNNG-induced cell cycle arrest and apoptosis of colon cancer cells.

Apoptosis↗
PubMed2001

Upstream stimulating factor-1 (USF1) and USF2 bind to and activate the promoter of the adenomatous polyposis coli (APC) tumor suppressor gene.

The adenomatous polyposis coli (APC) gene product is involved in cell cycle arrest and apoptosis, and loss of function is associated with the development of colorectal carcinogenesis. Although it has been demonstrated that the APC gene is inducible, its transcriptional regulation has not been elucidated. Therefore, we characterized the promoter region of the APC gene and transcription factors required for basal expression. The APC gene has a TATA-less promoter and contains consensus binding sites for Octamer, AP2, Sp1, a CAAT-box, and three nucleotide sequences for E-box A, B, and M. The E-boxes are functional in several cancer cell lines and upstream stimulating factor-1 (USF1) and USF2 interact with these sites, with a preferred sequence-specificity for the B site. Analysis of activation of the cloned APC promoter by USF1 and USF2 in transient transfection assays in HCT-116 cells demonstrated that mutation of the E-box B site completely abolished the basal promoter activity. Further, the ectopic USF1 and USF2 expression in HCT-116 cells with deletion mutations of E-box A, B, and M sites showed that these E-boxes contribute to USF1- and USF2-mediated transcriptional activation of the APC promoter, with maximum promoter activity being associated with the E-box B site. Thus, USF1 and USF2 transcription factors are critical for APC gene expression.

Adenomatous Polyposis Coli Protein↗
PubMed2001

Palladium-catalyzed tandem bis-allylation of isocyanates.

A tandem bis-allylation of p-toluenesulfonyl isocyanate can be achieved by palladium-catalyzed three-component coupling reaction with allylstannanes and allyl chlorides. A high level of regioselectivity can be obtained by the appropriate choice of the allylic substituents. The reaction mechanism and the regiochemistry of the reaction can be explained by formation of an amphoteric bis-allylpalladium intermediate. This bis-allylpalladium intermediate undergoes an initial electrophilic attack on one of the allyl moieties followed by a nucleophilic attack on the other.

Journal Article↗
PubMed2001

p53-dependent transcriptional regulation of the APC promoter in colon cancer cells treated with DNA alkylating agents.

The APC (adenomatous polyposis coli) gene product is involved in cell cycle arrest and in apoptosis. The loss of APC function is associated with the development of colorectal carcinogenesis. In previous studies, we have shown that the APC gene is inducible and that the DNA damage-induced level of APC mRNA requires p53. In the present study, we examined the role of p53 in the transcriptional regulation of APC promoter and characterized two p53-binding sites on the cloned APC promoter (pAPCP). Results of electrophoretic mobility shift assay showed specific interactions of p53 protein with p53-binding site oligonucleotides. The DNA-protein complex formed in electrophoretic mobility shift assay was competed with unlabeled excess of p53-binding site oligonucleotide, unaffected with p53-binding site mutant or Sp1-binding site oligonucleotides, and supershifted with anti-p53 antibodies. In a transient transfection assay, the pAPCP promoter activity was lower in HCT-116(p53(+/+)) cells versus HCT-116(p53(-/-)) cells. p53-dependent down-regulation was further confirmed after co-transfection of pAPCP plasmid with pCMV-p53 into HCT-116(p53(-/-)) and SAOS-2 (p53-negative) cells. However, the treatment of cells with DNA alkylating agents methylmethane sulfonate and N-methyl-N'-nitro-N-nitrosoguanidine, which cause phosphorylation of p53 at Ser(15) and Ser(392), induced pAPCP promoter activity in HCT-116(p53(+/+)) cells. Other than p53-binding sites, using deletion mutation constructs, we have shown that N-methyl-N'-nitro-N-nitrosoguanidine-induced transcriptional activation of the pAPCP promoter in HCT-116(p53(+/+)) cells depended upon the Sp1-binding site and the E-box B site. From these results, we conclude that unphosphorylated p53 can down-regulate and phosphorylated p53 can up-regulate the pAPCP promoter activity involving the p53, Sp1, or E-box B elements. These studies are important to understanding the role of p53 and APC in DNA damage-induced cell cycle arrest and/or apoptosis of cancer cells.

Alkylating Agents↗
PubMed2001

Control of the regioselectivity in catalytic transformations involving amphiphilic bis-allylpalladium intermediates: mechanism and synthetic applications.

Various dialkyl-substituted allyl chloride derivatives (2d-i) undergo regioselective palladium-catalyzed coupling reactions with allylstannanes (1a,b) and benzylidenemalonitrile (4), providing functionalized 1,7-octadienes in good yield. The catalytic reaction proceeds through an unsymmetrical amphiphilic bis-allylpalladium intermediate. An introductory electrophilic attack on the terminal position of the unsubstituted allyl moiety is followed by a nucleophilic attack on the alkyl-substituted allyl ligand. A theoretical analysis was performed by applying density functional theory at the B3PW91/DZ+P level to study the substituent effects on the electrophilic attack. According to the theoretical results, the high regioselectivity can be ascribed to the electronic effects of the alkyl substituents: The terminal alkyl groups destabilize the eta(1),eta(3)-bis-allylpalladium intermediate of the reaction; in addition, the alkyl substitution increases the activation barrier for the electrophilic attack.

Journal Article↗
PubMed2001

Hypoglycemia in the newborn.

Since a universal definition for hypoglycemia is lacking, an operational threshold for initiating therapy has been defined. Hypoglycemia is encountered in a variety of neonatal conditions including prematurity, growth retardation and maternal diabetes. Since hypoglycemia may be asymptomatic, routine screening for this condition in certain high risk situations is recommended. Supervised breast-feeding may be a treatment option in asymptomatic hypoglycemia. However, symptomatic hypoglycemia should always be treated with a continuous infusion of parenteral dextrose. Neonates needing dextrose infusion rates above 12 mg/kg/m should be investigated for refractory causes of hypoglycemia. Hypoglycemia has been linked to poor neuro-developmental outcome and hence aggressive screening and treatment is recommended.

Blood Glucose↗
PubMed2001

Pulmonary function tests in beta thalassemia.

To study pulmonary function tests (PFT) in multiple transfusion recipient thalassemics, PFTs were done for 30 thalassemics and 20 matched controls. Confirmed cases of thalassemia on regular transfusion therapy were the subject of study. Apart from history and physical examination of the thalassemics, serum ferritin estimation and spirometry were done. Parameters studied included lung volumes--functional residual capacity (FRC), forced vital capacity (FVC), residual volume (RV) and total lung capacity (TLC); and flow rates--forced expiratory volume in one second (FEV1), forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC), peak expiratory flow 25-75 (PEF 25-75%) and peak expiratory flow rate (PEFR). Single breath carbon monoxide diffusing capacity (DLco) and arterial blood gas (ABG) were also analysed. The mean height and weight of thalassemics were below that of age matched controls. A restrictive abnormality in PFT was found in 86.6% cases. These patients were found to have a decrease in all the lung volumes namely FVC, FRC, RV and TLC with a proportional decrease in the flow rates, FEV1, PEF 25-75% and PEF with a normal (> 0.75) FEV1/FVC ratio. DLco was decreased in all the patients with restrictive lung disease and fall in DLco showed a good correlation (r = 0.7, P < .001) with the severity of restrictive disease suggesting that some intrapulmonary pathology is likely to be responsible for the restrictive pattern. None of the cases had an obstructive or mixed pattern of pulmonary dysfunction. No correlation was found between severity of restrictive disease and the serum ferritin levels. A negative correlation with degree of hepatosplenomegaly was found. No correlation was found between severity of the defect and age, number of blood transfusions received and hemoglobin at the time of doing the test. To conclude, restrictive lung disease is the predominant abnormality in multi-transfused thalassemics, which is probably due to pulmonary parenchymal pathology. The abnormality of PFTs is not directly related to iron overload.

Adolescent↗
PubMed2001

Beryllium concentrations in ambient air and its source identification. A case study.

Beryllium concentrations in atmospheric particulate and soil samples in and around a Beryllium Processing Facility (BPF) have been measured. The mean air concentration level of beryllium in and around the fence line of the BPF is 0.48 +/- 0.43 ng m(-3) (n = 397) and is mostly influenced by diurnal and seasonal changes. The observed air concentration levels were well below the prescribed ambient air quality (AAQ) standard of 10 ng m(-3). The soil concentration levels of beryllium in the study area were found to be in the range of 1.42-2.75 microg g(-1). The mass median aerodynamic diameter (MMAD) of beryllium aerosols in ambient air was found to be 6.9 microm. Source identification using the Enrichment Factor (EF) approach indicates soil as the predominant contributory source for air concentrations at the site.

Aerosols↗
PubMed2001

Hereditary palmoplantar keratoderma (four cases in three generations).

A 39-year-old man reported with progressive thickening of the skin of the hands and feet and an inability to flex his hand. It was largely asymptomatic; however, brisk walking caused excessive sweating, pain, and widening of the fissures on the soles of the feet. He was unable to walk barefooted. According to his mother, the first episode presented with blistering at 7 days of age. Ever since, the condition has steadily worsened to acquire the current status. He was married at the age of 18 years, and had a stillborn child 18 months afterwards. Presently, he has three children, two girls aged 14 and 12 years and a son aged 10 years. Both the daughters are similarly affected. While cataloguing the details of the pattern of inheritance, the mother of the index case was also found to be affected (Fig. 1). The natural history of the disease was identical. Examination of the palms was marked by pronounced thickening of the skin resulting in the masking of palmar creases. The thickening was well demarcated and its margins were prominent and surrounded by an erythematous halo. The color of the skin was yellow and waxy (Fig. 2a). Contractures were present on all the fingers; nevertheless, the deformity of the middle and distal interphalangeal joints of the little finger was prominent. The soles of the feet had a similar morphology. In addition, marked fissuring was obvious (Fig. 2b). His daughters had an identical affliction of the palms and soles. The texture and morphology of the nails were normal. Light microscopy performed on scrapings from the fissures, mounted on 10% potassium hydroxide, revealed mycelia (hyphae) and spores. Hematoxylin and eosin-stained microsections from the palms and soles showed exquisite changes in the epidermis characterized by considerable uniform orthohyperkeratosis. Hypergranulosis and acanthosis were other associated changes. In addition, perinuclear vacuolization and keratohyalin granules of varying sizes and shapes were located at the periphery of the cells. A sparse mononuclear infiltrate was located at the dermo-epidermal junction. Hyphae and spores of fungi were also identified in the stratum corneum (Fig. 3). Itraconazole, 400 mg/day in two equally divided doses, was administered with major meals for 7 days. In addition, high doses of vitamin A (100,000 IU) were given daily for 2 weeks, supplemented by 12% salicylic acid (Salicylix SF12) ointment for daytime application and an ointment containing 6% coal tar and 3% salicylic acid (Salytar) for night-time application. This treatment is useful in recalcitrant cases.

Adolescent↗
PubMed2001

Hyposplenism in alcoholic cirrhosis, facts or artifacts? A comparative analysis with non-alcoholic cirrhosis and extrahepatic portal venous obstruction.

BACKGROUND AND AIMS: Hyposplenism has been described in patients with alcoholic cirrhosis (AC). However, no data are available regarding hyposplenism in patients with non-alcoholic cirrhosis (NAC) and other forms of portal hypertension such as extrahepatic portal venous obstruction (EHPVO). The aim is to study the splenic functions in patients with AC, NAC, and EHPVO. METHODS: Splenic functions were assessed consecutively in 22 patients with AC, 21 with NAC, and 23 with EHPVO. The tests included pitted red blood cells (RBC; %) and Howell-Jolly bodies in the peripheral smear. Pitted RBCs > 2% with or without the presence of Howell-Jolly bodies were taken as indicators of hyposplenism. The splenic function in each group was compared with age-matched controls. RESULTS: Hyposplenism was found in 10 (45.45%) patients with AC, six (28.57%) with NAC and one (4.34%) with EHPVO. The mean pitted RBCs were significantly increased in patients with AC (mean 4.93 +/- 1.36% vs control 1.22 +/- 0.17%, P < 0.05), but not so with NAC (2.01 +/- 0.69%) and EHPVO (mean 0.99 +/- 0.1% vs control 0.66 +/- 0.1%, P > 0.05). Howell-Jolly bodies were seen in only four patients. The mean pitted RBCs were significantly higher among patients who were actively consuming alcohol (9.14 +/- 3.35%) compared to those who abstained at least for more than 24 weeks (2.0 +/- 1.3%, P < 0.05). CONCLUSION: Hyposplenism is more common in AC patients, particularly those who are actively consuming alcohol compared with those who abstain. Patients with NAC have a lower incidence of hyposplenism, while in EHPVO patients, it is uncommon.

Adult↗
PubMed2001

DNA alkylation-induced phosphorylation of p53 and activation of kinases in colon cancer cells.

In response to DNA damage, p53 protein transiently stabilizes and accumulates in the nucleus, where it performs its role as a transcription factor. Phosphorylation of p53 increases its sequence-specific DNA-binding activity. In the present study, we have examined the effect of methylmethane sulfonate (MMS) to HCT-116 human colon cancer cells on the phosphorylation of p53. Results show that p53 protein becomes phosphorylated at serine 15 (Ser15) and Ser392 residues after treatment with MMS in a time-dependent manner. Increased levels of phospho-p53(Ser15) and phospho-p53(Ser392) were maintained up to 50 h of the MMS treatment. We also examined the involvement of probable kinase(s), which could be responsible for MMS-induced phosphorylation of p53 at Ser15 and Ser392. In vitro phosphorylation assay, carried out with the immunoprecipates of MMS-treated cells, showed an increased phosphorylation of p53 by c-Jun kinase 1 (JNK1) at early time points (2.5 h). However, with cyclin-dependent kinase (Cdk2) and TFIIH complex associated kinase CAK, the phosphorylation of p53 was increased at later time points (25 h). The phosphorylation of p53 by Cdc2 and MAPK (p38) kinases remained unaffected in the MMS-treated versus untreated cells. The MMS-induced phosphorylation of p53 correlates with our previous findings of p53's ability for increased sequence-specific DNA-binding and transcriptional activity in the cells treated with DNA alkylating agents.

Alkylation↗
PubMed2001

Hyperfibrinogenemia in patients of diabetes mellitus in relation to glycemic control and urinary albumin excretion rate.

BACKGROUND: Diabetics have higher cardiovascular morbidity and mortality than general population and hyperfibrinogenemia is one of the important risk factors. MATERIAL AND METHODS: In the present study fibrinogen levels (dry clot weight method) were estimated in 50 diabetic subjects and 10 age, sex and body mass index matched controls and its correlation with various parameters like glycosylated hemoglobin (cation exchange resin method), urinary albumin excretion rate (Esbach's albuminometer), age, hypertension, body mass index (Kg/m2), lipid profile, smoking, duration of diabetes was studied. RESULTS: Higher plasma fibrinogen levels were found in diabetics (7.30 +/- 5.87 g/l) as compared to controls (4.06 +/- 2.5 g/l) which was statistically significant (p = 0.022). Fibrinogen levels were associated with age (r = 0.873), hypertension (p = 0.032), body mass index (r = 0.898), triglyceride level (r = 0.9396), cholesterol level (r = 0.99), glycosylated hemoglobin (r = 0.99) and urine albumin excretion rate (r = 0.930) in diabetics, in a significant manner. But, no correlation was found with sex (p > 0.05), family history (p = 0.072), duration of diabetes (r = 0.443) and smoking (p = 0.081). In controls positive correlation was found between fibrinogen level and age (r = 0.5), family history (p = 0.04), smoking (p = 0.051), body mass index (r = 0.898) and lipid profile (r > 0.5). Mean albumin excretion rate was significantly (p = 0.002) higher in diabetics (397.42 +/- 956.51 mg/min) and it was found to be associated with age (r > 0.5) and lipid profile (r > 0.5) in both diabetics and controls. No correlation was found between glycemic control and urine albumin excretion rate. CONCLUSION: Diabetics have higher fibrinogen levels, which is associated with glycemic control and urine albumin excretion rate in a statistically significant manner.

Age Factors↗
PubMed2000

Retroviral entry mediated by receptor priming and low pH triggering of an envelope glycoprotein.

Avian leukosis virus (ALV) has been used as a model system to understand the mechanism of pH-independent viral entry involving receptor-induced conformational changes in the viral envelope (Env) glycoprotein that lead to membrane fusion. Here, we report the unexpected finding that ALV entry depends on a critical low pH step that was overlooked when this virus was directly compared to the classical pH-dependent influenza A virus. In contrast to influenza A virus, receptor interaction plays an essential role in priming ALV Env for subsequent low pH triggering. Our results reveal a novel principle in viral entry, namely that receptor interaction can convert a pH-insensitive viral glycoprotein to a form that is responsive to low pH.

Avian Leukosis Virus↗
PubMed2000

Kinetic analysis of Sp1-mediated transcriptional activation of the human DNA polymerase beta promoter.

In the present studies, we have examined the effect of Sp1 on the activation of the human DNA polymerase beta (beta-pol), a TATA-less promoter. A HeLa cell nuclear extract (NE) based in vitro runoff transcription system of core beta-pol promoter human DNA (pbetaP8) three-step kinetic model of transcription initiation were used to describe the kinetic effect of Sp1. The results showed that distal Sp1-binding sites in the core beta-pol promoter are important for transcriptional activation of the pbetaP8 promoter. A detailed kinetic analysis showed that Sp1 stimulates the activity of the pbetaP8 promoter through distal Sp1-binding sites by increasing the amount of recruitment, instead of stimulating the apparent rate of RPc assembly (k1). There was no significant effect of Sp1 on the apparent rate of open complex (RPo) formation (k2) or on the apparent rate of promoter clearance (k3) of the pbetaP8 promoter. These studies define the kinetic mechanisms by which Sp1 may regulate the rate of transcript formation of the pbetaP8 promoter, and these results may have implications for Sp1 regulation of TATA-less promoters.

DNA Polymerase beta↗
PubMed2000

Kinetic analysis of Sp1-mediated transcriptional activation of a TATA-containing promoter.

Using a HeLa cell nuclear extract (NE)-based in vitro runoff transcription system, we have examined the effect of Sp1 on the activation of a TATA-containing chimeric DNA polymerase beta (pAS8) promoter. The results demonstrated that the TATA element-dependent basal activity of the pAS8 promoter was stimulated 4-fold by supplementation of a Sp1-depleted HeLa cell nuclear extract (NEd) with purified human Sp1, indicating that pAS8 promoter activity is dependent upon Sp1. A detailed kinetic analysis based on a three-step kinetic model of transcription initiation showed that Sp1 stimulates the activity of the pAS8 promoter by increasing the amount of closed preinitiation complex (RP(c)) assembly as well as by enhancing the rate of promoter clearance (k(3)). There was no significant effect of Sp1 on the apparent rate of open complex (RP(o)) formation (k(2)) of the pAS8 promoter. These studies define more precisely the kinetic mechanisms by which Sp1 may regulate the rate of transcript formation of a TATA-containing promoter.

Base Sequence↗
PubMed2000

Anvirzel, an extract of Nerium oleander, induces cell death in human but not murine cancer cells.

The purpose of this study was to examine the mechanism(s) and differential cell-killing effects of Anvirzel, an extract of oleander (Nerium oleander; family-Apocynaceae), and its derivative compound Oleandrin on human, canine and murine tumor cells. Cells received different concentrations of Anvirzel (1.0 ng/ml to 500 microg/ml) or Oleandrin (0.01 ng/ml to 50 microg/ml) in both continuously treated and pulse-treated/recovery cultures. The cytotoxicity of these compounds was then determined. Both Anvirzel and Oleandrin were able to induce cell killing in human cancer cells, but not in murine cancer cells; the cell-killing potency of Oleandrin was greater than that of Anvirzel. Canine oral cancer cells treated with Anvirzel showed intermediate levels of response, with some abnormal metaphases and cell death resulting from the treatment. From these results we conclude that Anvirzel and Oleandrin act in a species-specific manner, and while testing the effectiveness of a new compound for cancer treatment, one must use not only murine but a variety of cancer cells, including those of human origin.

Animals↗
PubMed2000

Cutaneous cryptococcus infection due to C. albidus associated with Sézary syndrome.

Cryptococcus albidus is a non-neoformans species of the genus Cryptococcus and is a rare cause of disease. There have been only 13 previously reported cases of systemic disease in which this opportunistic yeast has been isolated from the lung, cerebrospinal fluid and blood. We report the first case of cutaneous Cryptococcus infection due to the species C. albidus, in a man with Sézary syndrome.

Aged↗