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S Arora

Publications and source records attributed to S Arora.

At least 37 records · Page 2Linked to original sources
PubMed2002

The in vitro antimutagenic activity of Triphala--an Indian herbal drug.

A study to evaluate an antimutagenic potential of water, chloroform and acetone extracts of Triphala has been made in an Ames histidine reversion assay using TA98 and TA100 tester strains of Salmonella typhimurium against the direct-acting mutagens, 4-nitro-o-phenylenediamine (NPD) and sodium azide, and the indirect-acting promutagen, 2-aminofluorene (2AF), in the presence of phenobarbitone-induced rat hepatic S9. A combination drug 'Triphala' - a composite mixture of Terminalia bellerica, T. chebula and Emblica officinalis, has been used in traditional system of medicine for the treatment of many malaises, such as heart ailments and hepatic diseases. The drug was sequentially extracted with water, acetone and chloroform at room temperature. The study revealed that water extract was ineffective in reducing the revertants induced by the mutagens. The results with chloroform and acetone extracts showed inhibition of mutagenicity induced by both direct and S9-dependent mutagens. A significant inhibition of 98.7% was observed with acetone extract against the revertants induced by S9-dependent mutagen, 2AF, in co-incubation mode of treatment. Various spectroscopic techniques, namely 1H-NMR, normal 13C-NMR, distortionless enhancement by polarization transfer (DEPT-90 and DEPT-135), UV and IR, are under way to identify the polyphenolic compounds from an acetone extract.

Acetone↗
PubMed2002

Antimutagenic activities of acetone and methanol fractions of Terminalia arjuna.

The antimutagenic effect of benzene, chloroform, acetone and methanol fractions from Terminalia arjuna, a well-known medicinal plant, was determined against Acid Black dye, 2-aminofluorene (2AF) and 4-nitro-o-phenylenediamine (NPD) in TA98 Frameshift mutagen tester strain of Salmonella typhimurium. Among the different fractions, the antimutagenic effect of acetone and methanol fractions was more than that observed with other fractions. Co-incubation and pre-incubation modes of experimentation did not show much difference in the antimutagenic activity of the extracts. Moreover, these fractions inhibited the S9-dependent mutagens, 2AF and Acid Black dye more effectively than the direct-acting mutagens. Studies are under way to isolate and elucidate the nature of the antimutagenic factor in acetone and methanol fractions.

Acetone↗
PubMed2002

Alterations in p53 and pRb pathways and their prognostic significance in oesophageal cancer.

The pRb (p16-pRb-cyclin D1) and p53 (p53-MDM2-p21) pathways play a critical role in tumorigenesis. To evaluate which of these cell cycle regulatory proteins are related to patients' prognosis, a comprehensive analysis of alterations in these components was carried out in 100 ESCCs (oesophageal squamous cell carcinoma) using immunohistochemistry and correlated with clinicopathological parameters by univariate analysis. Overexpression of p53, MDM2 and cyclin D1 proteins was observed in 73, 42 and 67% of the cases, respectively, while loss of expression of p21, p16 and pRb was observed in 36, 45 and 75% of the cases, respectively. Multiple logistic regression analysis revealed that loss of p16 immunoreactivity was a significant risk factor for tumour stage (pT) (Odds Ratio (OR)=3.3), whereas the loss of pRb was a significant risk factor for nodal metastasis (pN) (OR=8.8). MDM2 overexpression emerged as the most significant risk factor for distant organ metastasis (pM) (OR=4.6). Of the ESCC patients who underwent oesophagectomy, 50 cases were followed-up for a maximum period of 44 months and median of 16 months. Survival analysis revealed that Cyclin D1 overexpression is an adverse prognosticator for disease-free survival, as well as overall survival, and tumour stage (pT) is an adverse prognosticator for disease-free survival. In conclusion, these data support a model of oesophageal cancer pathogenesis in which both the pRb and p53 pathways are inactivated and suggests an in-depth evaluation of the clinical utility of these putative markers is warranted.

Adult↗
PubMed2002

Potential dangers of the Valsalva maneuver and adenosine in paroxysmal supraventricular tachycardia--beware preexcitation.

Paroxysmal supraventricular tachycardia (PSVT) is a common clinical problem. Valsalva maneuver and adenosine are effective therapies for many patients with PSVT, although any conversion to an irregular or wide complex tachycardia should prompt consideration of a preexcitation syndrome. We report a case where the Valsalva maneuver and adenosine, in a patient with PSVT and previously undiagnosed Wolff-Parkinson-White syndrome, caused atrial fibrillation and led to a haemodynamically unstable wide complex tachycardia and ventricular fibrillation. In PSVT, where preexcitation has not been excluded, the Valsalva maneuver and adenosine can be potentially dangerous.

Journal Article↗
PubMed2001

Chromodomain protein Swi6-mediated role of DNA polymerase alpha in establishment of silencing in fission Yeast.

Although DNA replication has been thought to play an important role in the silencing of mating type loci in Saccharomyces cerevisiae, recent studies indicate that silencing can be decoupled from replication. In Schizosaccharomyces pombe, mating type silencing is brought about by the trans-acting proteins, namely Swi6, Clr1-Clr4, and Rhp6, in cooperation with the cis-acting silencers. The latter contain an autonomous replication sequence, suggesting that DNA replication may be critical for silencing in S. pombe. To investigate the connection between DNA replication and silencing in S. pombe, we analyzed several temperature-sensitive mutants of DNA polymerase alpha. We find that one such mutant, swi7H4, exhibits silencing defects at mat, centromere, and telomere loci. This effect is independent of the checkpoint and replication defects of the mutant. Interestingly, the extent of the silencing defect in the swi7H4 mutant at the silent mat2 locus is further enhanced in absence of the cis-acting, centromere-proximal silencer. The chromodomain protein Swi6, which is required for silencing and is localized to mat and other heterochromatin loci, interacts with DNA polymerase alpha in vivo and in vitro in wild type cells. However, it does not interact with the mutant pol alpha and is delocalized away from the silent mat loci in the mutant. Our results demonstrate a role of DNA polymerase alpha in the establishment of silencing. We propose a recruitment model for the coupling of DNA replication with the establishment of silencing by the chromodomain protein Swi6, which may be applicable to higher eukaryotes.

Base Sequence↗
PubMed2001

Use of chimeric proteins to investigate the role of transporter associated with antigen processing (TAP) structural domains in peptide binding and translocation.

The transporter associated with antigen processing (TAP) comprises two subunits, TAP1 and TAP2, each containing a hydrophobic membrane-spanning region (MSR) and a nucleotide binding domain (NBD). The TAP1/TAP2 complex is required for peptide translocation across the endoplasmic reticulum membrane. To understand the role of each structural unit of the TAP1/TAP2 complex, we generated two chimeras containing TAP1 MSR and TAP2 NBD (T1MT2C) or TAP2 MSR and TAP1 NBD (T2MT1C). We show that TAP1/T2MT1C, TAP2/T1MT2C, and T1MT2C/T2MT1C complexes bind peptide with an affinity comparable to wild-type complexes. By contrast, TAP1/T1MT2C and TAP2/T2MT1C complexes, although observed, are impaired for peptide binding. Thus, the MSRs of both TAP1 and TAP2 are required for binding peptide. However, neither NBD contains unique determinants required for peptide binding. The NBD-switched complexes, T1MT2C/T2MT1C, TAP1/T2MT1C, and TAP2/T1MT2C, all translocate peptides, but with progressively reduced efficiencies relative to the TAP1/TAP2 complex. These results indicate that both nucleotide binding sites are catalytically active and support an alternating catalytic sites model for the TAP transport cycle, similar to that proposed for P-glycoprotein. The enhanced translocation efficiency of TAP1/T2MT1C relative to TAP2/T1MT2C complexes correlates with enhanced binding of the TAP1 NBD-containing constructs to ATP-agarose beads. Preferential ATP interaction with TAP1, if occurring in vivo, might polarize the transport cycle such that ATP binding to TAP1 initiates the cycle. However, our observations that TAP complexes containing two identical TAP NBDs can mediate translocation indicate that distinct properties of the nucleotide binding site per se are not essential for the TAP catalytic cycle.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Cisplatin induces modifications in the development of cell surface patterns of ciliates.

Cisplatin [cis-dichlorodiammineplatinum (II)] brings about significant quantitative modifications in the development of cell surface patterns in two unrelated ciliates: Stylonychia and Tetrahymena. Cells cultured in the presence of cisplatin exhibit the formation of supernumerary surface structures in the form of extra cilia/cirri (fused cilia) and other organized ciliary organelles. The metal-induced formation of extra primordia and their differentiation into supernumerary ciliary structures is governed by the normal rules of development. Additional structures are accommodated within the framework of a defined pattern, suggesting the existence of an overall global control of pattern formation. The modified pattern is rectified to its normal state during post-treatment fission cycles, suggesting the role of the cell membrane in correcting developmental errors.

Animals↗
PubMed2001

Alterations in MDM2 expression in esophageal squamous cell carcinoma: relationship with p53 status.

In view of the significance of MDM2 as a regulator as well as critical target of wild type p53, this study was undertaken to determine the alteration in MDM2 expression in esophageal squamons cell carcinoma (ESCC) and its relationship to clinicopathological parameters as well as p53gene and protein status. Immunohistochemical analysis of MDM2 and p53 proteins on paraffin embedded sections from 64 surgically resected ESCCs and matched histologically normal tissues showed overexpression of MDM2 protein in 23/64 (36%) ESCCs, while the histopathologically normal esophageal tissues did not show detectable level of MDM2 immunoreactivity. Interestingly, MDM2 /p53 + phenotype was observed in 37/64 (58%) cases. None of the cases with p53 mis-sense mutations (12/30, 40%) showed detectable level of MDM2 protein. Missense p53 mutations were significantly associated with discordant p53 + /MDM2 immunophenotype (p= 0.004). The most intriguing feature of the study was accumulation of MDM2 in the absence of detectable p53 in 11% of and overexpression of MDM2 and p53 in 25% of ESCCs, suggesting a p53-independent role for MDM2 in a subset of tumors. These results underscore the involvement of MDM2 in p53-dependent and -independent pathways in the pathogenesis of esophageal cancer in the Indian population.

Adult↗
PubMed2001

Alterations in cyclin D1 expression in esophageal squamous cell carcinoma in the Indian population.

PURPOSE: The p16/cyclin D1/pRb pathway plays a critical role in tumourigenesis. We recently reported alterations in expression of tumour suppressor gene products, p16 and pRb in esophageal cancer. Knowledge of alterations in cyclin D1, a vital component of this pathway in esophageal carcinomas from the Indian subcontinent, where the etiology and pathogenesis may be confounded by various unique dietary and environmental factors, is presently scanty. In order to bridge the gap between the accentuating incidence of esophageal cancer and aberrations in the components of this vital pathway, we analysed cyclin D1 expression in esophageal squamous cell carcinoma in the Indian population. METHOD: Immunohistochemical analysis of cyclin D1 expression was carried out in paraffin-embedded sections of surgically resected esophageal squamous cell carcinomas (ESCC) (70 patients) and matched with histopathologically normal esophageal tissues from a distant site. The findings were correlated with clinicopathological parameters. RESULTS: Overexpression of cyclin D1 was observed in the tumour nuclei in 41 out of 70 (59%) patients. We found concomitant alterations in 16 and cyclin D1 (p16-/CycD1+ phenotype) in 16 of the 70 patients (23%), while alterations of pRb and cyclin D1 (pRb-/CycD1+) were observed in 36 of the 70 (51%) patients of ESCCs. Cyclin D1 overexpression was significantly associated with the loss of p16 immunoreactivity (P = 0.005). The pRb- and p16-/pRb-/Cyc D+ phenotypes showed significant association with differentiation of the tumour (P = 0.005, 0.05, respectively). Kaplan-Meier analysis for disease recurrence showed increased disease recurrence in cyclin D1 overexpressed patients. Median time to disease recurrence in the cyclin D1+ group was 15 months as against 18 months observed in the cyclin D1- patients (P = 0.067; log-rank test). CONCLUSION: Alterations in at least one of the components of the p16/cyclin D1/pRb pathway in majority of the 70 patients analysed herein, and concomitant alterations in all the three proteins in 19 patients (35%) underscore the critical role of this pathway in esophageal tumourigenesis. The results of the present study taken together with our previous findings on p16 and pRb alterations in ESCCs suggest that these alterations are not mutually exclusive and may cooperatively provide greater tumour growth advantage. The prognostic significance of alterations in the expression of these components cyclin D1, p16, and pRb remains to be established in a larger cohort.

Adult↗
PubMed2001

Esophageal squamous cell carcinomas with DNA replication errors (RER+) are associated with p16/pRb loss and wild-type p53.

PURPOSE: Microsatellite instability (MSI) as a determinant of propensity to esophageal squamous cell carcinoma (ESCC) at seven microsatellite markers at 2p (2p15-16), 3p (3p13, 3p14.1-3, 3p25, and 3p26) and 16q (16q12.1-3) was investigated to analyze their putative role as indicators of predisposition to esophageal malignancies. METHODS: Seven microsatellite loci were amplified by polymerase chain reaction, from surgically resected tumor tissues from 30 ESCC patients from Indian population, to assess the loss of heterozygosity (LOH) and replication error repeats (RER) and to correlate these alterations with aberrations in major cell cycle regulatory proteins and histopathological parameters. RESULTS: LOH and RER analyses at these loci demonstrated moderate microsatellite alterations, suggesting the involvement of MSI in esophageal tumorigenesis in a subset of the Indian population. MSI, defined as RER in at least two or more of the loci studied, was observed in ten of 30 (33%) patients. Twenty-two of 30 patients (73%) showed LOH at one or more loci, while 17 of the 30 patients (60%) showed RER in at least one of the loci studied. RER-positive patients showed a trend towards better prognosis when compared to RER-negative patients. MSI demonstrated a significant association with concomitant loss of p16 and pRb (p16-/pRb- phenotype) (P=0.046). Interestingly, we observed an inverse correlation between MSI and p53 mutations (P=0.03) suggesting that MSI may provide a p53-independent pathway for esophageal tumorigenesis in RER+ patients. MSI showed a trend towards longer survival and absence of distant organ metastasis (P=0.06). CONCLUSIONS: The present study demonstrates the probable role of MSI in esophageal squamous cell carcinoma in the Indian population. Instability associated with the repetitive sequences--the revealing marks of loss of DNA replication fidelity may serve as an indicator of predisposition to esophageal cancer.

Carcinoma, Squamous Cell↗
PubMed2001

Common femoral artery ligation and local debridement: a safe treatment for infected femoral artery pseudoaneurysms.

PURPOSE: The management of infected femoral artery pseudoaneurysms (IFAPs) is difficult and controversial. Use of synthetic or autologous conduit during arterial revascularization in these cases is complicated by the presence of sepsis and unavailability of autologous venous conduit. We present the results of common femoral artery (CFA) ligation and local drainage with debridement for the treatment of IFAP. METHODS: A retrospective chart review of six consecutive patients from 1995 to 1999 who presented with IFAP from intravenous drug abuse was performed. Inpatient records, anesthesia records, and outpatient clinic charts were reviewed. All patients were men with right-sided lesions. All six patients abused heroin, and five (83%) abused heroin and cocaine. All six patients had a duplex ultrasound scan, and five (83%) patients had a digital subtraction angiogram to confirm the clinical diagnosis. Proximal vascular control was achieved retroperitoneally through an oblique suprainguinal incision. After vascular isolation and test clamping of the distal external iliac artery (EIA), the pedal pulses were examined with continuous wave Doppler scan. If a Doppler signal was present, this was followed with CFA ligation and local drainage and debridement of the IFAP. RESULTS: Pain at injection site and fever with chills were present in five (83%) and three (50%) patients, respectively. A pulsatile groin mass and thigh or leg edema were present in five (83%) patients. Three patients (50%) had a palpable pedal pulse, and all six had a Doppler signal over a pedal artery at presentation. The mean white cell count was 15.6 thousand per cubic millimeter (range, 9.2-19.3). All patients had a Doppler signal over a pedal artery after distal EIA/CFA test occlusion and ligation. None of the patients required an amputation, and all six patients regained their preoperative ambulatory status. The mean follow-up period was 25 months. Two patients had mild claudication (5-6 blocks) at 18 months and 2 years after surgery. All six patients received drug rehabilitation, but they admitted to drug abuse after surgery and rehabilitation. CONCLUSION: CFA ligation and local debridement are safe treatment modalities for IFAP, if there is an intraoperative Doppler signal over a pedal artery during test occlusion of the distal EIA/CFA. CFA ligation avoids the use and therefore the risk of synthetic conduit infection, because there is a high incidence of postoperative drug injection despite aggressive drug rehabilitation.

Adult↗
PubMed2001

PCR-positive tubercular retinal vasculitis: clinical characteristics and management.

BACKGROUND: Inflammation of retinal vessels is a known association of systemic tuberculosis. Patients with retinal vasculitis are subjected to extensive but unrewarding systemic workup. Polymerase chain reaction (PCR) is now commonly used to detect DNA of infective organisms including Mycobacterium tuberculosis. This study was undertaken to characterize the clinical characteristics of PCR-positive tubercular retinal vasculitis, so as to determine the clinical presentation, associated systemic features, management, and course of this form of vasculitis. METHODS: The clinical records of 13 patients seen between 1997 and 1999 with the diagnosis of PCR-positive tubercular retinal vasculitis from the aqueous or vitreous humor were reviewed. Recorded data included age, sex, race, visual acuity, anterior and posterior segment findings, and results of diagnostic evaluations. All received antituberculosis therapy with or without concomitant corticosteroids. Laser scatter photocoagulation was done in eyes with neovascularization. One eye with vitreous hemorrhage was subjected to pars plana vitrectomy. RESULTS: There were 9 (69.2%) male and 4 (30.7%) female patients with a median age of 20 years. The disease was bilateral in seven. The most consistent finding was the presence of vitritis in all the eyes followed by vitreous snowball opacities in 17 eyes (89.4%), neovascularization in 11 eyes (57.8%), retinal hemorrhages in 10 eyes (52.6%), neuroretinitis in 10 eyes (52.6%), focal choroiditis in 9 eyes (47.3%), vitreous/preretinal hemorrhage in 5 eyes (26.3%), and serous retinal detachment in 3 eyes (15.7%). Over a median follow-up of 12 months, all showed resolution of vasculitis with no recurrences. CONCLUSIONS: Polymerase chain reaction-positive tubercular retinal vasculitis had varied associated fundus findings. Its recognition is important so as to order only relevant diagnostic tests.

Adolescent↗
PubMed2001

Increase in mortality rates from intrahepatic cholangiocarcinoma in England and Wales 1968-1998.

BACKGROUND: The age standardised mortality rate per 100 000 population for all causes of liver tumours (International Classification of Disease 9 (ICD-9) 155) has almost doubled in England and Wales during the period 1979-1996. We further analysed the mortality statistics to determine which anatomical subcategories were involved. METHODS: Mortality statistics for liver tumours of ICD-9 155, 156, and subcategories, and for tumours of the pancreas (ICD-9 157), in England and Wales were investigated from the Office for National Statistics, London, from 1968 to 1996 inclusive. Data for 1997 and 1998 were also available on intrahepatic cholangiocarcinomas. RESULTS: There has been a marked rise in age standardised mortality rates for intrahepatic cholangiocarcinoma. Since 1993, it represents the commonest recorded cause of liver tumour related death in England and Wales. This is evident in age groups older than 45 years. In contrast, mortality trends from other primary liver tumours, including hepatocellular carcinoma, were unremarkable. CONCLUSIONS: The observed increase in mortality from intrahepatic cholangiocarcinoma may represent better case ascertainment and diagnosis due to improved diagnostic imaging, use of image guided biopsies, or increased use of ERCP. However, the trend started before ERCP was introduced nationally, mortality rates have continued to increase steadily thereafter, and there is no clear evidence that diagnostic transfers easily explains the findings. Alternatively, these observations may represent a true increase in intrahepatic bile duct tumours. Epidemiological studies are required to determine whether there is any geographical clustering of cases around the UK.

Adult↗
PubMed2001

Steady-state pharmacokinetics and tolerability of modafinil given alone or in combination with methylphenidate in healthy volunteers.

The potential for a pharmacokinetic (PK) drug-drug interaction between modafinil and methylphenidate, each at steady state, was investigated in an open-label, randomized, single-period study in 32 healthy male and female volunteers. All subjects received modafinil once daily orally for 28 days (200 mg on Days 1-7 and 400 mg on Days 8-28). On Days 22 to 28, half of the subjects also received 20 mg of methylphenidate orally 8 hours after their modafinil dose. PK profiles of modafinil were obtained on Days 21 and 28 and compared between the two groups. There were no statistically significant differences between the treatment groups in the mean changes in PK parameters for modafinil. Parameters for its metabolites were also similar between the groups, and all treatments were well tolerated. The results indicate that administration of low-dose methylphenidate 8 hours after treatment with modafinil does not appear to alter the steady-state pharmacokinetics of modafinil in healthy volunteers.

Adult↗