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Showing papers by "Rajesh Kumar published in 2006"


Journal ArticleDOI
TL;DR: A model for the transition from weakly to strongly metastatic melanomas in which TGFbeta-type signalling upregulates genes expressing vasculogenic/extracellular matrix remodelling factors and Wnt signal inhibitors, coinciding with a downregulation of genes downstream of Wnt signalling is suggested.
Abstract: The molecular biology of metastatic potential in melanoma has been studied many times previously and changes in the expression of many genes have been linked to metastatic behaviour. What is lacking is a systematic characterization of the regulatory relationships between genes whose expression is related to metastatic potential. Such a characterization would produce a molecular taxonomy for melanoma which could feasibly be used to identify epigenetic mechanisms behind changes in metastatic behaviour. To achieve this we carried out three separate DNA microarray analyses on a total of 86 cultures of melanoma. Significantly, multiple testing correction revealed that previous reports describing correlations of gene expression with activating mutations in BRAF or NRAS were incorrect and that no gene expression patterns correlate with the mutation status of these MAPK pathway components. Instead, we identified three different sample cohorts (A, B and C) and found that these cohorts represent melanoma groups of differing metastatic potential. Cohorts A and B were susceptible to transforming growth factor-beta (TGFbeta)-mediated inhibition of proliferation and had low motility. Cohort C was resistant to TGFbeta and demonstrated high motility. Meta-analysis of the data against previous studies linking gene expression and phenotype confirmed that cohorts A and C represent transcription signatures of weakly and strongly metastatic melanomas, respectively. Gene expression co-regulation suggested that signalling via TGFbeta-type and Wnt/beta-catenin pathways underwent considerable change between cohorts. These results suggest a model for the transition from weakly to strongly metastatic melanomas in which TGFbeta-type signalling upregulates genes expressing vasculogenic/extracellular matrix remodelling factors and Wnt signal inhibitors, coinciding with a downregulation of genes downstream of Wnt signalling.

524 citations


Journal ArticleDOI
TL;DR: Prenatal sex determination followed by selective abortion of female fetuses is the most plausible explanation for the low sex ratio at birth in India.

396 citations


Journal Article
TL;DR: In this paper, the authors conducted field surveys in both the urban and the rural populations at Bangalore, Chandigarh, Delhi and Kanpur with the help of a structured and validated questionnaire for diagnosis of asthma and COPD.
Abstract: Introduction Population prevalence of chronic obstructive pulmonary disease (COPD) and its relationship with tobacco smoking, environmental tobacco smoke (ETS) exposure and other variables were studied in adult subjects of 35 years and above at four different centres in India. Question-items for the diagnosis of COPD were included in the questionnaire used for the field study on asthma epidemiology. Methods Field surveys were conducted in both the urban and the rural populations at Bangalore, Chandigarh, Delhi and Kanpur with the help of a structured and validated questionnaire for diagnosis of asthma and COPD. Separate sets of questions were used for the diagnoses of the two diseases. A two-stage stratified sample design was employed where a village or an urban locality formed the first stage unit and a household formed the second stage unit. A uniform methodology was used at all the four centres and the analyses were done at the central coordinating centre--Chandigarh. Chronic obstructive pulmonary disease, defined by chronic bronchitis (CB) criteria, was diagnosed from the presence of cough and expectoration on most of the days for at least three months in a year for two consecutive years or more. Results Chronic obstructive pulmonary disease was diagnosed in 4.1% of 35295 subjects, with a male to female ratio of 1.56:1 and a smoker to nonsmoker ratio of 2.65: 1. Prevalence among bidi and cigarette smokers was 8.2% and 5.9%, respectively. Odds ratio (OR) for COPD was higher for men, elderly individuals, lower socio-economic status and urban (or mixed) residence. Environmental tobacco smoke exposure among nonsmokers had an OR of 1.4(95% CI 1.21-1.61). Combined exposure to both ETS and solid fuel combustion had higher OR than for ETS exposure alone. Conclusions Population prevalence of COPD is very high in India with some centre to centre differences. Smoking of both bidis and cigarettes, and ETS exposure among nonsmokers, were two important risk factors at all centres. It is important to employ uniform methodology for assessment of national burden and disease-surveillance programme.

191 citations


Journal ArticleDOI
TL;DR: XRCC1 Arg399Gln and hOGG1 Ser326Cys polymorphisms seem to exert the predominant modulating effect on irradiation-specific DNA repair capacity and the capacity to repair DNA oxidative damage, respectively.
Abstract: We investigated association between polymorphisms in DNA repair genes and the capacity to repair DNA damage induced by gamma-irradiation and by base oxidation in a healthy population. Irradiation-specific DNA repair rates were significantly decreased in individuals with XRCC1 Arg399Gln homozygous variant genotype (0.45 +/- 0.47 SSB/10(9) Da) than in those with wild-type genotype (1.10 +/- 0.70 SSB/10(9) Da, P=0.0006, Mann-Witney U-test). The capacity to repair oxidative DNA damage was significantly decreased among individuals with hOGG1 Ser326Cys homozygous variant genotype (0.37 +/- 0.28 SSB/10(9) Da) compared to those with wild-type genotype (0.83 +/- 0.79 SSB/10(9) Da, P=0.008, Mann-Witney U-test). Investigation of genotype combinations showed that the increasing number of variant alleles for both XRCC1 Arg399Gln and APE1 Asn148Glu polymorphisms resulted in a significant decrease of irradiation-specific repair rates (P=0.008, Kruskal-Wallis test). Irradiation-specific DNA repair rates also decreased with increasing number of variant alleles in XRCC1 Arg399Gln in combination with variant alleles for two other XRCC1 polymorphisms, Arg194Trp and Arg280His (P=0.002 and P=0.005, respectively; Kruskal-Wallis test). In a binary combination variant alleles of hOGG1 Ser326Cys and APE1 Asn148Glu polymorphisms were associated with a significant decrease in the capacity to repair DNA oxidative damage (P=0.018, Kruskal-Wallis test). In summary, XRCC1 Arg399Gln and hOGG1 Ser326Cys polymorphisms seem to exert the predominant modulating effect on irradiation-specific DNA repair capacity and the capacity to repair DNA oxidative damage, respectively.

184 citations


Journal Article
TL;DR: Prevalence estimates of asthma in adults in this study, although lower than several previously reported figures, point to a high overall national burden of disease.
Abstract: Background There is limited information on field epidemiology of bronchial asthma in Indian adults. Objectives To estimate prevalence of bronchial asthma in different regions of India and to define risk factors influencing disease prevalence. Methods A field study was conducted at Chandigarh, Delhi, Kanpur and Bangalore through a two stage stratified (urban/ rural) sampling and uniform methodology using a previously validated questionnaire. Asthma was diagnosed if the respondent answered affirmatively both to (a) whistling sound from chest, or chest tightness, or breathlessness in morning, and (b) having suffered from asthma, or having an attack of asthma in the past 12 months, or using bronchodilators. Besides demographic data, information on smoking habits, domestic cooking fuel used, atopic symptoms, and family history suggestive of asthma was also collected. Univariate and multivariate logistic regression modelling was performed to calculate odds ratio of various potential risk factors. Results Data from 73605 respondents (37682 men, 35923 women) were analysed. One or more respiratory symptoms were present in 4.3-10.5% subjects. Asthma was diagnosed in 2.28%, 1.69%, 2.05 and 3.47% respondents respectively at Chandigarh, Delhi, Kanpur and Bangalore, with overall prevalence of 2.38%. Female sex, advancing age, usual residence in urban area, lower socio-economic status, history suggestive of atopy, history of asthma in a first degree relative, and all forms of tobacco smoking were associated with significantly higher odds of having asthma. Conclusion Prevalence estimates of asthma in adults in this study, although lower than several previously reported figures, point to a high overall national burden of disease.

173 citations


Patent
13 Dec 2006
TL;DR: In this article, a modular force sensor for telerobotic surgery is presented, which includes a tube portion including a plurality of strain gauges, a proximal tube portion for operably coupling to a shaft of a surgical instrument that may be operably coupled to a manipulator arm of a robotic surgical system, and a distal tube part for proximally coupling to the wrist joint coupled to an end portion.
Abstract: A modular force sensor apparatus, method, and system are provided to improve force and torque sensing and feedback to the surgeon performing a telerobotic surgery. In one embodiment, a modular force sensor includes a tube portion including a plurality of strain gauges, a proximal tube portion for operably coupling to a shaft of a surgical instrument that may be operably coupled to a manipulator arm of a robotic surgical system, and a distal tube portion for proximally coupling to a wrist joint coupled to an end portion.

154 citations


Patent
19 Oct 2006
TL;DR: In this article, a surgeon can display and manipulate internal details of an anatomic structure being treated on a computer display screen to supplement primary images generally of an external view of the structure.
Abstract: To assist a surgeon performing a medical procedure, auxiliary images generally indicating internal details of an anatomic structure being treated are displayed and manipulated by the surgeon on a computer display screen to supplement primary images generally of an external view of the anatomic structure. A master input device controlling a robotic arm in a first mode may be switched by the surgeon to a second mode in order to function instead as a mouse-like pointing device to facilitate the surgeon performing such auxiliary information display and manipulation.

132 citations


Journal ArticleDOI
TL;DR: Elevated arsenic exposure via drinking water was prevalent in some of the counties and exposure to arsenic from food and cigarette smoke, mainly as inorganic arsenic, are major determinants of arsenic exposure at very low concentrations of arsenic in drinking water.
Abstract: Inorganic arsenic is a potent human carcinogen and toxicant which people are exposed to mainly via drinking water and food. The objective of the present study was to assess current exposure to arsenic via drinking water in three European countries. For this purpose, 520 individuals from four Hungarian, two Slovakian and two Romanian countries were investigated by measuring inorganic arsenic and methylated arsenic metabolites in urine by high performance liquid chromatography with hydride generation and inductively coupled plasma mass spectrometry. Arsenic in drinking water was determined by atomic absorption spectrometry. Significantly higher concentrations of arsenic were found in both the water and the urine samples from the Hungarian counties (median: 11 and 15 microg dm(-3), respectively; p < 0.001) than from the Slovakian (median: 0.94 and 4.5 microg dm(-3), respectively) and Romanian (median: 0.70 and 2.1 microg dm(-3), respectively) counties. A significant correlation was seen between arsenic in water and arsenic in urine (R(2)= 0.46). At low water arsenic concentrations, the relative amount of dimethylarsinic acid (DMA) in urine was increased, indicating exposure via food. Also, high body mass index was associated with higher concentrations of arsenic in urine (p= 0.03), mostly in the form of DMA. Smokers had significantly higher urinary arsenic concentrations than non-smokers (p= 0.03). In conclusion, elevated arsenic exposure via drinking water was prevalent in some of the counties. Exposure to arsenic from food, mainly as DMA, and cigarette smoke, mainly as inorganic arsenic, are major determinants of arsenic exposure at very low concentrations of arsenic in drinking water.

128 citations


Journal ArticleDOI
TL;DR: Some of the genes regulated by trophoblast in endometrial stromal cells are already known to be regulated by progesterone and show the endocrine function of trophOBlast during pregnancy and open a wide field of investigation.
Abstract: Investigating the interaction of human endometrium and trophoblast during implantation is difficult in vitro and impossible in vivo. This study was designed to analyze the effect of trophoblast on endometrial stromal cells during implantation by comprehensive gene profiling. An in vitro coculture system of endometrial stromal cells with first-trimester trophoblast explants was established. Trophoblast and endometrial stromal cells were separated after 24 h. Gene expression of endometrial stromal cells after coculture was compared with the gene expression of endometrial stromal cells cultured alone by microarray analysis. We confirmed the expression of distinct genes using real-time PCR. Genes up-regulated included those for inflammatory response, immune response, and chemotaxis (pentraxin-related gene 3, chemokine ligands, IL-8, IL-1 receptors, IL-18 receptor, IL-15, IL-15 receptor, TNF-α-induced protein 6, and IL-6 signal transducer), regulators of cell growth (IGF-binding proteins 1 and 2) and signal tr...

128 citations


Journal ArticleDOI
TL;DR: In this article, the authors investigated the prevalence of HIV-1 in young people attending antenatal and sexually transmitted infection (STI) clinics in India and found that the age-standardised HIV prevalence in women aged 15-24 years in southern states fell from 1·7% to 1·1% in 2000-04 (relative reduction 35%; p trend trend trend = 0·0008), but reductions were more modest in their northern counterparts.

115 citations


Journal Article
TL;DR: A substantial proportion of population in India has current or past smoking habit with higher prevalence among males than females and the quit-rates have been low in spite of the various anti-tobacco measures.
Abstract: Background Population prevalence of tobacco smoking especially with reference to detailed habits such as the amount smoked, the smoking forms, quit-rates and relationship with demographic variables were studied at four different centres in India along with the study on epidemiology of asthma and chronic obstructive pulmonary disease. Methods The study population included adults of over 15 years of age selected with two-stage stratified random sample design. A specifically designed questionnaire was used for the study. Results There were 11496 (15.6%) ever smokers in the study sample of 73605 subjects. Among 37682 males, 10756 (28.5%) were ever smokers and among 35923 females, 740 (2.1%) were ever smokers. Bidi was the commonest form of smoking, more so in the rural areas. The mean number of cigarettes/bidis smoked per day was 14 (+/- 11.5) and the mean age of starting smoking was 20.5 (+/- 20.0) years. Increasing age, low socio-economic status and rural residence were important factors associated with smoking. Vigorous anti-tobacco measures under the tobacco control programmes yielded only a quit-rate of 10 percent. Nearly 14% of ever smokers had some respiratory symptoms. Conclusions A substantial proportion of population in India has current or past smoking habit with higher prevalence among males than females. The quit-rates have been low in spite of the various anti-tobacco measures. There is a significant respiratory morbidity associated with smoking.

Patent
26 Sep 2006
TL;DR: In this article, a system and method for processing real-time rapid capture, annotation and creation of an annotated hyper-video map for environments is presented, which is further enhanced with textual, audio and hyperlink annotations that enable the user to see, hear, and operate in an environment with cognitive awareness.
Abstract: The present invention provides a system and method for processing real-time rapid capture, annotation and creation of an annotated hyper-video map for environments. The method includes processing video, audio and GPS data to create the hyper-video map which is further enhanced with textual, audio and hyperlink annotations that will enable the user to see, hear, and operate in an environment with cognitive awareness. Thus, this annotated hyper-video map provides a seamlessly navigable, situational awareness and indexable high-fidelity immersive visualization of the environment.

Journal ArticleDOI
TL;DR: In CKD, FGF-23 levels rose with decreasing creatinine clearance rates and increasing plasma phosphorus levels, and rapidly decreased post-transplantation suggesting F GF-23 is cleared by the kidney.
Abstract: Background: The phosphatonins fibroblast growth factor-23 (FGF-23) and FRP-4 are inhibitors of tubular phosphate reabsorption that may play a role in the hyperphosphatemia associate

Journal ArticleDOI
TL;DR: The results show that the genetic variation in XR CC1, XRCC3 and NBS1 influence lung cancer susceptibility among women, and that combinations of risk alleles in the two HR genes can enhance the effects.

Journal ArticleDOI
TL;DR: It is suggested that XPD 751Gln allele is a potential genetic marker for susceptibility to esophageal adenocarcinoma.
Abstract: Mechanisms behind the strong associations of esophageal adenocarcinoma risk with gastroesophageal reflux (GOR) and body mass remain to be defined. In a nationwide population-based case-control study, we examined associations of polymorphisms in the DNA repair genes XPD, XPC, XRCC1 and XRCC3 with risk of esophageal adenocarcinoma, squamous-cell carcinoma (SCC) and gastric cardia adenocarcinoma, and paid special attention to possible interactions with symptomatic reflux or body mass. We collected blood samples from 96, 81 and 126 interviewed incident cases of esophageal adenocarcinoma, esophageal SCC and gastric cardia adenocarcinoma, respectively, and 472 randomly selected controls, frequency-matched with regard to age and sex. DNA was extracted and polymorphisms in XPD codon 751 (Lys-->Gln), codon 312 (Asp-->Asn), C insertion in intron 10 of XPD, XPC codon 939 (Lys-->Gln), XRCC1 codon 399 (Arg-->Gln) and XRCC3 codon 241 (Thr-->Met) were examined using PCR-RFLP. Odds ratios (ORs) derived from multivariate logistic regression with adjustments for potential confounding factors estimated relative risks. XPD codon 751 Lys/Gln and Gln/Gln genotypes, compared with Lys/Lys genotype, were both associated with a more than doubled risk for esophageal adenocarcinoma (OR=2.4; 95% CI=1.4-4.4; OR=2.7, 95% CI=1.3-5.9). The combined effects of these genotypes and symptomatic GOR or body mass showed borderline significant deviation from additivity. Excess risks for esophageal SCC were also noted for XPD 751Gln variant genotypes. Other studied variants were not found to be related to the three tumors. Our study suggests that XPD 751Gln allele is a potential genetic marker for susceptibility to esophageal adenocarcinoma.

Journal ArticleDOI
TL;DR: Interestingly, while the cbr1-1 mutation reduced the accumulation of hydroxy fatty acids in seeds by 85%, the effects on 18:1 and 18:2 desaturation reactions were much less, suggesting that there is competition in developing seeds among the several reactions that utilize reduced cytochrome b5.
Abstract: Summary As a model for analyzing the production of novel fatty acids in oilseeds, we used the genetic and molecular techniques available for Arabidopsis to characterize modifying mutations affecting the accumulation of hydroxy fatty acids in the seeds of Arabidopsis plants that express a transgene for the castor bean fatty acid hydroxylase, FAH12. We developed a high-throughput analytical system and used it to identify three complementation classes of mutations with reduced hydroxy fatty acid accumulation from among Arabidopsis M3 seed samples derived from chemical mutagenesis. We identified one of the mutations by positional cloning as a single base pair change in a gene encoding NADH:cytochrome b5 reductase (CBR1, At5g17770). When expressed in yeast, the mutant form of the enzyme was less active and less stable than the wild-type enzyme. Characterization of homozygous mutant lines with and without the FAH12 transgene (FAH12 cbr1-1 and cbr1-1, respectively) indicated that the only detectable consequence of the cbr1-1 mutation was on desaturase and hydroxylase reactions in the developing seed. The leaf and root fatty compositions, as well as the growth, development and seed production of mutant plants were indistinguishable from wild type. Interestingly, while the cbr1-1 mutation reduced the accumulation of hydroxy fatty acids in seeds by 85%, the effects on 18:1 and 18:2 desaturation reactions were much less (<25% and <60%, respectively). These results suggest that there is competition in developing seeds among the several reactions that utilize reduced cytochrome b5.

Journal ArticleDOI
TL;DR: Three isolates ofPseudomonas aeruginosa showed plant growth promoting activity and induced systemic resistance in rice against Rhizoctonia solani G5 and increased seed yield and purified peroxidase showed antifungal activity against phytopathogenic fungi.
Abstract: Three isolates ofPseudomonas aeruginosa were used for seed treatment of rice; all showed plant growth promoting activity and induced systemic resistance in rice againstRhizoctonia solani G5 and increased seed yield. Production of salicylic acid (Sal) byP. aeruginosa bothin vitro andin vivo was quantified with high performance liquid chromatography. All three isolates produced more Sal in King’s B broth than in induced roots. Using a split root system, more Sal accumulated in root tissues of bacterized site than in distant roots on the opposite site of the root system after 1 d, but this difference decreased after 3 d. Sal concentration 0–200 g/L showed no inhibition of mycelial growth ofR. solani in vitro, while at ≥300 g/L it inhibited it.P. aeruginosa-pretreated rice plants challenged inoculation withR. solani (as pathogen), an additional increase in the accumulation of peroxidase was observed. Three pathogenesis-related peroxidases in induced rice plants were detected; molar mass of these purified peroxidases was 28, 36 and 47 kDa. Purified peroxidase showed antifungal activity against phytopathogenic fungiR. solani, Pyricularia oryzae andHelminthosporium oryzae.

Journal ArticleDOI
TL;DR: Although computed tomography is a noninvasive imaging modality that is widely used for staging in patients with lymphoma, it cannot provide information about malignant cutaneous lesions.
Abstract: Summary Background The diagnosis of primary cutaneous lymphoma (PCL) is currently based on clinical and histological findings and/or relatively invasive procedures such as bone marrow and fine-needle lymph node biopsies. Although computed tomography (CT) is a noninvasive imaging modality that is widely used for staging in patients with lymphoma, it cannot provide information about malignant cutaneous lesions. Objectives To investigate the usefulness of 18F-fluorodeoxyglucose (FDG)–positron emission tomography (PET) in the management of PCL. Methods We retrospectively analysed 31 FDG-PET studies in 19 patients with PCL [15 T-cell non-Hodgkin lymphoma (NHL) and four B-cell NHL]. There were 10 men and nine women (age range 23–84 years, mean ± SD 54 ± 16). Eleven FDG-PET studies were performed for initial staging and 20 FDG-PET studies were performed for restaging following therapy. Results of FDG-PET were compared with those of CT. Clinical parameters and/or biopsy results of lesions served as reference for the accuracy of PET and CT in evaluating local and metastatic lesions. Results For the initial staging, FDG-PET had a sensitivity of 82% for the evaluation of local disease and 80% for the detection of distant metastasis. The corresponding values for CT were 55% and 100%, respectively. For restaging of cutaneous lymphoma, FDG-PET had a sensitivity of 86% and specificity of 92% for local recurrence/residual disease and a sensitivity of 100% and specificity of 100% for distant metastasis. The corresponding values for CT were 50% and 83% for local recurrence/residual disease and 100% and 67% for distant metastasis. Conclusions FDG-PET has a potential value for initial staging and restaging following therapy in patients with PCL. FDG-PET has higher diagnostic value than CT in the detection both of local disease and distant metastasis.

Journal Article
TL;DR: The urban way of living is leading to an increase in the prevalence of the well-known risk factors for, as well as the rate of, coronary heart disease in northern India.
Abstract: BACKGROUND In the West, urbanization has been accompanied by a rise in the rate of coronary heart disease. This trend has gone hand in hand with an increased consumption of processed, energy-dense food and dependence on machines for physical work. To examine whether a similar trend is underway in northern India, the prevalence of and risk factors for coronary heart disease were compared in rural, semi-urban and urban communities. METHODS AND RESULTS A total of 7,169 adults were interviewed and examined during 1995-2000 in cross-sectional cluster sample surveys from a rural area of Haryana (Raipur Rani block), two semi-urban areas of Punjab (Mandi Gobindgarh and Morinda), and Chandigarh city. The study, which covered people in the age-group of 35+ years, also estimated the lipid, glucose and insulin levels of a sub-sample of 186 persons who did not have coronary heart disease or hypertension. The prevalence of coronary heart disease among males in the villages, towns and city was 1.7%, 2.5% and 7.4%, respectively, and among females, 1.5%, 3.4% and 7.1%,respectively. The age- and sex-adjusted prevalence odds ratio of coronary heart disease, in comparison to the villages, was 1.9 (95% CI; 1.1-3.2) in the towns and 4.9 (95% CI: 2.9-8.2) in the city. Hypertension, diabetes, obesity and physical inactivity were significantly more common in the urban areas, while the rate of tobacco smoking was significantly higher in the rural areas ( p 0.05). The quantity of the food items commonly consumed, as well as the frequency with which particular items were consumed, varied across the rural, semi-urban and urban areas ( p< 0.05). The urban population had significantly higher levels of lipids and serum insulin than did the rural population, but a lower level of plasma glucose ( p< 0.05). CONCLUSION The urban way of living is leading to an increase in the prevalence of the well-known risk factors for, as well as the rate of, coronary heart disease. Attempts to preserve the traditional lifestyle are necessary in order to prevent an epidemic of coronary heart disease in the developing countries.

Journal Article
TL;DR: Daily oral administration of isoproterenol hydrochloride a beta-receptor agonist to normal innervated and denervated adult male Swiss albino mice confirmed its ability to induce skeletal muscle hypertrophy and reverse denervation atrophy respectively.
Abstract: β-Adrenergic agonists possess powerful skeletal muscle specific protein anabolic effects in addition to their lipolytic actions in different vertebrates. Chronic administration of these drugs produce skeletal muscle hypertrophy in rats, mice and chicks. The drugs reportedly stimulate skeletal muscle growth by

Journal ArticleDOI
TL;DR: The da Vinci mentoring console has the potential to improve resident participation in surgical robotics cases, enhance resident education in surgical training programs engaged in surgical Robotics, and improve patient safety during robotic surgery.
Abstract: Background: One of the most significant limitations of surgical robots has been their inability to allow multiple surgeons and surgeons-in-training to engage in collaborative control of robotic sur...

Journal ArticleDOI
TL;DR: The findings suggest that altered repair and detoxification due to genetic polymorphism may influence the occurrence of p53 mutations in bladder cancer.

Journal Article
TL;DR: Environmental tobacco smoke exposure during childhood is an important risk factor for asthma and respiratory symptoms in non-smoking adults and both during childhood and adulthood were significantly associated with asthma prevalence.
Abstract: Background. Exposure to environmental tobacco smoke (ETS ) is a risk factor for childhood asthma. Its association with asthma in adults is less clear. Methods. In a multicentric population study on asthma prevalence in adults, specific enquiries were made into childhood and adulthood exposure to household ETS, and its relationship with asthma diagnosis were analysed. Results. From a total of 73605 respondents, 62109 were studied after excluding current or past smokers. Overall observed prevalence of asthma was 2.0% (men 1.5%,women 2.5%, p<0.001). Of all asthma patients, history of ETS exposure was available in 48.6 percent. Prevalence of asthma in the ETS exposed subjects was higher compared to non-exposed individuals (2.2% vs 1.9%, p<0.05). Multiple logistic regression analysis showed a higher risk of having asthma in persons who were exposed to ETS compared to those not exposed (odds ratio [OR] 1.22,95% CI 1.08-1.38) after adjusting for age, gender, usual residence, exposure to biomass fuels and atopy. Stratification of ETS exposure revealed that exposure during childhood and both during childhood and adulthood were significantly associated with asthma prevalence. Exposure only in adulthood was not a significant risk factor (OR 1.13, 95% CI 0.95-1.33). Persons reporting combined environmental tobacco smoke exposure from parents during childhood and spouse during adulthood had highest risk of having asthma (OR 1.69, 95% CI 1.38-2.07). Environmental tobacco smoke exposure was also significantly associated with prevalence of respiratory symptoms such as wheezing, cough and breathlessness. Conclusions. Environmental tobacco smoke exposure during childhood is an important risk factor for asthma and respiratory symptoms in non- smoking adults.

Journal ArticleDOI
TL;DR: Screening for 683A→C nucleotide exchanges may become important in diagnosis and/or treatment of these malignancies.
Abstract: Allelic loss of chromosome 8p21–22 is a frequent event in various human cancers including mantle cell lymphoma (MCL), prostate cancer, head and neck squamous cell carcinoma (HNSCC) and bladder cancer. The tumor necrosis factor-related apoptosis inducing ligand (TRAIL) receptors, including TNFRSF10A and TNFRSF10B, are located within this chromosomal region. Since recent studies demonstrate that chronic lymphocytic leukemia (CLL) and prostate cells are TRAIL induced apoptosis, TRAIL-receptors are strong tumor suppressor candidate genes in human cancers exhibiting loss of chromosomal material in 8p21.3. However, no mutation of the TRAIL receptor genes has been reported in CLL, MCL, prostate cancer, HNSCC so far. In this study we analyzed the complete coding region of TNFRSF10A and TNFRSF10B in a series of 32 MCL and 101 CLL samples and detected a single nucleotide polymorphism (SNP) in TNFRSF10A (A683C) with tumor specific allele distribution. We examined allele distribution in 395 samples of different tumor entities (prostate cancer, n = 43; HNSCC, n = 40; bladder cancer, n = 179) and compared them to 137 samples from healthy probands. We found the rare allele of TNFRSF10A is more frequent in CLL, MCL, prostate cancer, bladder cancer and HNSCC. The A683C polymorphism did not cosegregate with other TNFRSF10A polymorphisms previously described. Thus screening for 683AC nucleotide exchanges may become important in diagnosis and/or treatment of these malignancies. © 2005 Wiley-Liss, Inc.

Journal ArticleDOI
TL;DR: There was a significant difference in SUVs between the dense and nondense normal breast, however, the maximum SUVs in the dense breasts were well below the threshold of 2.5, a widely used cutoff value for malignancy.
Abstract: This study was conducted to assess the effect of breast density, age, and menopausal status on the 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) uptake in normal breast tissue by quantitative standardized uptake values (SUV). A total of 96 patients (premenopausal 54; postmenopausal 42) with histologically proven unilateral breast cancer who underwent FDG-positron emission tomography (PET) scans for staging were included in this study. The median age was 52±11 years (range 32–79 years). Fifty-nine patients had grade III or IV mammographic density (dense breast), whereas 37 patients had grade I or II breast density (nondense) according to the ACR Lexicon criteria. In the present study, we analyzed maximum and average SUVs for contralateral normal breast. Maximum and average SUVs for normal dense breasts were 1.02±0.30 and 0.84±0.27, respectively. Similar values for the nondense breasts were 0.66±0.24 and 0.53±0.23, respectively. Both maximum and average SUVs of dense breasts were significantly higher than those of nondense breasts (p<0.001). There was no significant difference in SUVs of nipple in patients with dense and nondense breasts. There was no significant effect of age and menopausal status on SUVs of normal breast. However, there were trends of negative relationship, i.e., decreasing SUVs with increasing age. There was a significant difference in SUVs between the dense and nondense normal breast. However, the maximum SUVs in the dense breasts were well below the threshold of 2.5, a widely used cutoff value for malignancy. Menopausal status and age do not significantly affect the uptake of FDG.

Journal ArticleDOI
TL;DR: Almost three-fold differences in SSB levels were found between the "protective" and the "adverse" genotype-combinations of EPHX1 activity genotype and GSTM1 or GSTT1 genotypes, respectively.
Abstract: We investigated in a central European population, the association between genetic polymorphisms in several genes coding for xenobiotic metabolizing enzymes (CYP1A1, CYP2E1, EPHX1, GSTP1, GSTM1 and GSTT1) and in DNA repair genes (XPD, XPG, XPC and XRCC1) and the levels of single-strand breaks (SSBs) and SSB endonuclease III sensitive sites (endoIII sites) in peripheral blood lymphocytes. No significant differences in the mean levels of SSBs and endoIII sites after stratification for main confounders and occupational exposure were observed in the studied population. Significantly higher levels of SSBs were observed in individuals bearing the wild-type alleles (AA) (0.75+/-0.51SSB/10(9)Da) and heterozygous (AC) genotypes (0.67+/-0.49SSB/10(9)Da) compared to those with homozygous XPD (CC) genotype (0.43+/-0.28SSB/10(9)Da, P=0.033). A moderate increase in the levels of SSBs was also found in individuals with the homozygous XPG exon 15 wild type (GG) and heterozygous (GC) genotypes in comparison to those with the homozygous (CC) genotype (P=0.066) and in individuals with low activity EPHX1 genotype in comparison to those with high activity genotype. Nevertheless, these differences were not statistically significant. No other significant association was found. When gene-gene interactions were evaluated, a combination of EPHX1 activity genotypes with that of either XPD or XPG significantly (P=0.003 and 0.016, respectively) modulated SSB levels resulting in a three-fold difference between the "protective" and the "adverse" genotype-combinations. Almost three-fold differences in SSB levels were found between the "protective" and the "adverse" genotype-combinations of EPHX1 activity genotype and GSTM1 or GSTT1 genotypes, respectively. In conclusion, our results suggest a relation between markers of genotoxicity and polymorphisms in genes coding for xenobiotic metabolizing and DNA repair enzymes as well as a modulating effect of combinations of these polymorphisms.

Journal ArticleDOI
TL;DR: To investigate whether mean diffusivity values are altered in brain areas underlying cardiovascular and respiratory control in congenital central hypoventilation syndrome (CCHS), data are analyzed through positron emission tomography and electrophysiology.
Abstract: Purpose To investigate whether mean diffusivity (MD) values are altered in brain areas underlying cardiovascular and respiratory control in congenital central hypoventilation syndrome (CCHS). Materials and Methods Conventional and diffusion tensor imaging were performed in 15 CCHS and 30 control subjects, using a 3.0-Tesla MRI unit. Mean diffusivity maps were calculated from diffusion-weighted images, spatially normalized, smoothed, and compared between groups using analysis of covariance at each voxel with age as covariate. Global mean MD values of gray and white matter were determined in individual subjects and compared between groups and with age. Results Increased MD values appeared in CCHS over control subjects within multiple areas influencing breathing and cardiovascular control, including the midbrain, pons, and dorsal and ventral medulla. Other altered sites included cerebellar cortex and deep nuclei, basal ganglia, basal forebrain, and temporal and frontal cortices. Global mean MD values for gray and white matter did not differ between groups; however, gray matter MD values significantly increased with age (P < 0.02) in CCHS patients only. Conclusion Increased MD values suggest regional alterations or injury; affected areas include brainstem sites classically associated with autonomic and respiratory control. Other altered regions mediate additional physiological characteristics impaired in CCHS. J. Magn. Reson. Imaging 2006. © 2006 Wiley-Liss, Inc.

Journal ArticleDOI
TL;DR: Both sodium and guanidinium cations stabilize the alkali-denatured state at pH 13, presumably by a charge screening mechanism, and the Na(+)-stabilized conformation (B state) clearly meets with the molecular organizational definition of the generic molten globule state.

Journal ArticleDOI
TL;DR: In this article, the dynamical cluster-decay model (DCM) is extended to a positive Q-value (Qout), heavy compound system 116Ba*, with complete angular momentum and charge dispersion effects included in it, the contributions due to both the light particles (LPs) and intermediate mass fragments (IMFs) are considered to give the total cross section.
Abstract: The dynamical cluster-decay model (DCM) is extended to a positive Q-value (Qout), heavy compound system 116Ba*, with complete angular momentum and charge dispersion effects included in it. The contributions due to both the light particles (LPs) and intermediate mass fragments (IMFs) are considered to give the total cross section. Interestingly, instead of the complete IMF spectrum observed for lighter systems such as 48Cr* and 56Ni*, here two small 'windows of IMFs' are predicted, one for light masses (2 ≤ Z ≤ 9) and another for the heavy mass end of symmetric and nearly symmetric fragments (14 ≤ Z ≤ 28), in agreement with the available data for the light mass 'IMF window' and its indications of possible extension to the heavier mass fragments. Within a non-statistical model description, the definition of phase space is found to be contained in the DCM definition of the 'IMF window' for the compound nucleus process. As in experiments, the calculated excitation functions are shown to put a limit on the minimum incident centre-of-mass energy required for the production of IMFs, and it will be of further interest to observe in experiments the predicted structures in the excitation functions of both the individual fragments, like for 12C decay, and the summed-up cross sections. Also, further measurements of the total kinetic energies of the fragments are called for.

Journal Article
TL;DR: In this paper, the amplitude ratios of reflected and refracted plane waves at an imperfect interface between two dissimilar thermoelastic solid half-spaces have been investigated, and the amplitude ratio of the reflection and refraction at the interface of two semi-infinite media (i.e., Elastic/Thermo-elastic without energy dissipation, ii.
Abstract: The reflection and refraction of thermoelastic plane waves at an imperfect interface between two dissimilar thermoelastic solid half-spaces has been investigated. The thermoelastic theory without energy dissipation developed by Green Naghdi [18] has been used to study the problem. The amplitude ratios of various reflected and refracted waves are obtained for an imperfect boundary. Particular cases of normal stiffness, transverse stiffness, slip and welded boundaries are discussed. The amplitude ratios are also deduced at the interface of two semi-infinite media (i) Elastic/Thermoelastic without energy dissipation, (ii) Thermal Conducting Liquid/Thermoelastic without energy dissipation, (iii) Non-viscous Fluid/Thermoelastic without energy dissipation, (iv) Thermal Conducting Liquid/Thermal Conducting Liquid and (v) Elastic/Elastic. It is found that the amplitude ratios of various reflected and refracted waves are affected by the stiffness and thermal properties of the media. The amplitude ratios of reflected waves are also deduced for a special case of stress-free boundary.