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Community Health Services↗
Biomedical subjects
N Chatterjee
Publications and source records attributed to N Chatterjee.
Tumor variants by hormone receptor expression in white patients with node-negative breast cancer from the surveillance, epidemiology, and end results database.
PURPOSE: Hormone receptor expression (presence-positive or absence-negative) may reflect different stages of one disease or different breast cancer types. Determining whether hormone receptor expression represents one or more breast cancer phenotypes would have important paradigmatic and practical implications. METHODS: Breast cancer records were obtained from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database. The study included 19,541 non-Hispanic white women with node-negative breast cancer. Standard tumor cell characteristics and breast cancer-specific survival were analyzed by independent estrogen receptor (ER+ and ER-), independent progesterone receptor (PR+ and PR-), and joint ERPR expression (ER+PR+, ER+PR-, ER-PR+, and ER-PR-). RESULTS: Age frequency density plots by hormone receptor expression showed two overlapping breast cancer populations with early-onset and/or late-onset etiologies. Independent ER+ and PR+ phenotype were associated with smaller tumor sizes, better grade, and better cancer-specific survival than ER- and PR- breast cancer types. Joint ERPR phenotype exhibited biologic gradients for tumor size, grade, and cancer-specific survival, which ranked from good to worse for ER+PR+ to ER+PR- to ER-PR+ to ER-PR-. CONCLUSION: Variations of standard tumor cell characteristics and breast cancer-specific survival by hormone receptor expression in white patients with node-negative breast cancer suggested two breast cancer phenotypes with overlapping etiologies and distinct clinical features.
Adult↗
Pseudo-likelihood estimates of the cumulative risk of an autosomal dominant disease from a kin-cohort study.
Wacholder et al. [1998: Am J Epidemiol 148:623-629] and Struewing et al. [1997: N Engl J Med 336:1401-1408] have recently proposed a design called the kin-cohort design to estimate the probability of developing disease (penetrance) associated with an autosomal dominant gene. In this design, volunteers (probands) agree to be genotyped and one also determines the disease history (phenotype) of first-degree relatives of the proband. They used this design to estimate that the chance of developing breast cancer by age 70 in Ashkenazi Jewish women who carried mutations of the genes BRCA1 or BRCA2 was 0.56, a figure that was lower than previously estimated from highly affected families. The method that they used to estimate the cumulative risk of breast cancer, while asymptotically correct, does not necessarily produce monotone estimates in small samples. To obtain monotone, weakly parametric estimates, we consider separate piecewise exponential models for carriers and non-carriers. As the number of intervals on which constant hazards are assumed increases, however, the maximum likelihood score equations become unstable and difficult to solve. We, therefore, developed alternative pseudo-likelihood procedures that are readily solvable for piecewise exponential models with many intervals. We study these techniques through simulations and a re-analysis of a portion of the data used by Struewing et al. [1997] and discuss possible extensions.
Adolescent↗
Association and aggregation analysis using kin-cohort designs with applications to genotype and family history data from the Washington Ashkenazi Study.
When a rare inherited mutation in a disease gene, such as BRCA1, is found through extensive study of high-risk families, it is critical to estimate not only age-specific penetrance of the disease associated with the mutation, but also the residual effect of family history once the mutation is taken into account. The kin-cohort design, a cross-sectional survey of a suitable population that collects DNA and family history data, provides an efficient alternative to cohort or case-control designs for estimating age-specific penetrance in a population not selected because of high familial risk. In this report, we develop a method for analyzing kin-cohort data that simultaneously estimate the age-specific cumulative risk of the disease among the carriers and non-carriers of the mutations and the gene-adjusted residual familial aggregation or correlation of the disease. We employ a semiparametric modeling approach, where the marginal cumulative risks corresponding to the carriers and non-carriers are treated non-parametrically and the residual familial aggregation is described parametrically by a class of bivariate failure time models known as copula models. A simple and robust two-stage method is developed for estimation. We apply the method to data from the Washington Ashkenazi Study [Struewing et al., 1997, N Engl J Med 336:1401-1408] to study the residual effect of family history on the risk of breast cancer among non-carriers and carriers of specific BRCA1/BRCA2 germline mutations. We find that positive history of a single first-degree relative significantly increases risk of the non-carriers (RR = 2.0, 95% CI = 1.6-2.6) but has little or no effect on the carriers.
BRCA2 Protein↗
Somatostatin suppresses endothelin-1-induced rat hepatic stellate cell contraction via somatostatin receptor subtype 1.
BACKGROUND & AIMS: Hepatic stellate cells (HSCs) are considered therapeutic targets to decrease portal hypertension. To elucidate some of the hemodynamic effects of somatostatin (SST) on portal pressure, the presence and function of SST receptors (SSTRs) on HSCs were investigated. METHODS: SSTR messenger RNA expression, and SSTR presence was investigated using reverse-transcription polymerase chain reaction, real-time quantitative polymerase chain reaction, Western blotting, and immunohistochemistry. The function of SSTRs was studied by examining the effects of SST and specific SSTR agonists on endothelin-1(ET-1)-induced HSC contraction. RESULTS: Specific amplicons for SSTR subtypes 1, 2, and 3 were demonstrated in rat liver and in activated HSCs. The presence of SSTR subtypes 1, 2, and 3 was confirmed by Western blotting. With immunohistochemistry, a strong staining of HSCs was obtained for SSTR subtypes 1, 2, and 3 in CCl4-treated rats, but not in normal rat liver. Incubation of HSCs on collagen gels with buffer, 10(-8) mol/L SST, and 2 x 10(-8) mol/L ET-1 resulted in collagen surface area decreases of 5.5% +/- 3.3%, 6.8% +/- 4.4%, and 49.8% +/- 8.3%, respectively. Relative contraction of gels preincubated with 10(-8) mol/L SST followed by 2 x 10(-8) mol/L ET-1 or vice versa as compared with maximal contraction (100%) with 2 x 10(-8) mol/L ET-1 were 72.6% +/- 17.9% and 76.2% +/- 12.6%, respectively (P < 0.05). SSTR agonist 1, but not SSTR agonist 2 or 3, was able to counteract the contractile effect of ET-1. CONCLUSIONA: Activated rat HSCs bear SSTR subtypes 1, 2, and 3. SST causes significant partial inhibition of ET-1-induced contraction of activated HSCs, mainly by stimulation of SSTR subtype 1.
Animals↗
A marginal likelihood approach for estimating penetrance from kin-cohort designs.
The kin-cohort design is a promising alternative to traditional cohort or case-control designs for estimating penetrance of an identified rare autosomal mutation. In this design, a suitably selected sample of participants provides genotype and detailed family history information on the disease of interest. To estimate penetrance of the mutation, we consider a marginal likelihood approach that is computationally simple to implement, more flexible than the original analytic approach proposed by Wacholder et al. (1998, American Journal of Epidemiology 148, 623-629), and more robust than the likelihood approach considered by Gail et al. (1999, Genetic Epidemiology 16, 15-39) to presence of residual familial correlation. We study the trade-off between robustness and efficiency using simulation experiments. The method is illustrated by analysis of the data from the Washington Ashkenazi Study.
Algorithms↗
A bivariate cure-mixture approach for modeling familial association in diseases.
For modeling correlation in familial diseases with variable ages at onset, we propose a bivariate model that incorporates two types of pairwise association, one between the lifetime risk or the overall susceptibility of two individuals and one between the ages at onset between two susceptible individuals. For estimation, we consider a two-stage estimation procedure similar to that of Shih (1998, Biometrics 54, 1115-1128). We evaluate the properties of the estimators through simulations and compare the performance with that from a bivariate survival model that allows correlation between ages at onset only. We apply the methodology to breast cancer using the kinship data from the Washington Ashkenazi Study. We also discuss potential applications of the proposed method in the area of cure modeling.
Age of Onset↗
Vitamin D, calcium, and vitamin D receptor polymorphism in colorectal adenomas.
Experimental studies suggest that vitamin D and calcium protect against cancer by reducing proliferation and inducing differentiation. The effects of vitamin D and calcium may be mediated by the vitamin D receptor (VDR), which is encoded by the VDR gene. The present study investigated whether calcium intake and serum vitamin D, as an integrated measure of intake and endogenous production, were associated with risk of colorectal adenoma, known precursors of invasive colorectal cancer. In addition, the interrelation among vitamin D, calcium, and FokI polymorphism of the VDR gene was investigated. Persons (239) with histologically confirmed colorectal adenomas and 228 control individuals without colorectal adenomas confirmed by sigmoidoscopy were enrolled in this case control study conducted at the National Naval Medical Center, Bethesda, MD. We observed an inverse association of serum 25-OH vitamin D [25-(OH)D] with colorectal adenoma. With each 10 ng/ml increase of serum 25-(OH)D, the risk of colorectal adenoma decreased by 26% (odds ratio 0.74, 95% confidence interval 0.60-0.92). The results provided limited evidence for a weak association between calcium intake and colorectal adenoma (odds ratio 0.97, 95% confidence interval 0.93-1.01 per each 100-mg calcium intake). However, the inverse association of serum 25-(OH)D with colorectal adenoma is suggested to be stronger in subjects with calcium intake above the median (P for multiplicative interaction 0.13). The VDR FokI polymorphism was not significantly associated with colorectal adenoma and did not modify the effect of vitamin D or calcium. In conclusion, the study results suggested a protective effect for vitamin D on colorectal adenoma.
Adenoma↗
Analysis of spatiotemporally periodic behavior in lattices of coupled piecewise monotonic maps.
We study the stability of spatiotemporally periodic orbits in 1-d lattices of piecewise monotonic maps coupled via translationally invariant coupling and periodic boundary conditions. States of such systems have independent spatial and temporal periodicities and their stability can be studied through the analysis of a single, uniquely identified reduced matrix of size kxk when the system size is MxM, for M=kN, a multiple of k. This result applies for arbitrary temporal periods and is valid for all coupled map lattice systems coupled in a translationally invariant manner with stability matrices which are irreducible and non-negative, as in the present case. Our analysis could be useful in the analysis of stability regions and bifurcation behavior in a variety of spatially extended systems.
Journal Article↗
Cetirizine inhibits bradykinin-induced cutaneous wheal and flare in atopic and healthy subjects.
BACKGROUND: Kinins are vasoactive mediators involved in allergic reactions. When applied on the skin or in the nose, bradykinin (BK) elicits inflammation that is poorly affected by previous H1-blockade. The aim of this study was to compare the possible effect of cetirizine (an H1-antagonist) on wheal and flare responses to BK, histamine, and compound 48/80 in atopic and healthy subjects. METHODS: In a randomized, double-blind, crossover study, eight atopic and eight healthy subjects received cetirizine (10 mg/day) or placebo for 3 days before cutaneous tests. Intradermal tests (IDT) and prick tests (PT) were performed with BK (20 nmol/ml for IDT and 20 micromol/ml for PT), histamine (100 microg/ml IDT and 100 mg/ml PT), and compound 48/80 (100 microg/ml IDT and 100 mg/ml PT) as positive controls and saline as negative control. The skin responses were monitored by measurement of wheal and flare areas. RESULTS: BK, histamine, and 48/80 induced wheal and flare reactions in all placebo-treated subjects. Histamine elicited larger wheal and flare reactions than BK and 48/80. IDT with BK induced four- to six-fold larger wheal and flare reaction than PT. No differences in BK-induced wheal and flare were observed between atopic and healthy subjects. In atopic subjects, cetirizine induced a significant reduction of flare reactions after the BK test (80% for IDT, and 94% for PT [P<0.01]). Moreover, cetirizine reduced significantly BK-induced wheals by 70% for IDT (P<0.01) and 65% for PT (P<0.01). A similar inhibiting effect of cetirizine was also observed in healthy subjects. CONCLUSIONS: These findings showed that the wheal and flare reactions induced by BK challenge were markedly inhibited by previous intake of cetirizine. The mechanism by which this effect is mediated cannot be established at present.
Adolescent↗
Cetirizine inhibits bradykinin-induced cutaneous wheal and flare in atopic and healthy subjects.
BACKGROUND: Kinins are vasoactive mediators involved in allergic reactions. When applied on the skin or in the nose, bradykinin (BK) elicits inflammation that is poorly affected by previous H1-blockade. The aim of this study was to compare the possible effect of cetirizine (an H1-antagonist) on wheal and flare responses to BK, histamine, and compound 48/80 in atopic and healthy subjects. METHODS: In a randomized, double-blind, crossover study, eight atopic and eight healthy subjects received cetirizine (10 mg/day) or placebo for 3 days before cutaneous tests. Intradermal tests (IDT) and prick tests (PT) were performed with BK (20 nmol/ml for IDT and 20 micromol/ml for PT), histamine (100 microg/ml IDT and 100 mg/ml PT), and compound 48/80 (100 microg/ml IDT and 100 mg/ml PT) as positive controls and saline as negative control. The skin responses were monitored by measurement of wheal and flare areas. RESULTS: BK, histamine, and 48/80 induced wheal and flare reactions in all placebo-treated subjects. Histamine elicited larger wheal and flare reactions than BK and 48/80. IDT with BK induced four- to sixfold larger wheal and flare reaction than PT. No differences in BK-induced wheal and flare were observed between atopic and healthy subjects. In atopic subjects, cetirizine induced a significant reduction of flare reactions after the BK test (80% for IDT, and 94% for PT [P < 0.01]). Moreover, cetirizine reduced significantly BK-induced wheals by 70% for IDT (P < 0.01) and 65% for PT (P < 0.01). A similar inhibiting effect of cetirizine was also observed in healthy subjects. CONCLUSIONS: These findings showed that the wheal and flare reactions induced by BK challenge were markedly inhibited by previous intake of cetirizine. The mechanism by which this effect is mediated cannot be established at present.
Adolescent↗
Noise sustained propagation: local versus global noise
We expand on prior results on noise supported signal propagation in arrays of coupled bistable elements. We present and compare experimental and numerical results for kink propagation under the influence of local and global fluctuations. As demonstrated previously for local noise, an optimum range of global noise power exists for which the medium acts as a reliable transmission "channel." We discuss implications for propagation failure in a model of cardiac tissue, and present a general theoretical framework based on discrete kink statistics. Valid for generic bistable chains, the theory captures the essential features observed in our experiments and numerical simulations.
Journal Article↗
Adaptive regulation of intestinal folate uptake: effect of dietary folate deficiency.
Folate is an essential micronutrient that, in mammals, must be obtained from exogenous sources via intestinal absorption. Previous studies have characterized different aspects of the mechanism of the intestinal folate uptake process. Much less, however, is known about regulation of this process. In this study, we examined the effect of dietary folate deficiency on intestinal folate uptake using the rat as an animal model. The results showed that dietary folate deficiency leads to a significant (P < 0.01) and specific upregulation in the transepithelial transport of folic acid. The upregulation in transepithelial folate transport 1) was found to be due to an induction in carrier-mediated folate uptake across the brush-border membrane (BBM) and was mediated via a significant (P < 0.01) increase in the maximal velocity but not the apparent Michaelis constant of the uptake process, 2) was associated with a marked increase in the steady-state mRNA level of reduced folate carrier-1 and in the level of the expressed protein at the intestinal BBM, and 3) was associated with a marked (>10-fold) increase in the activity of the intestinal BBM form of folate hydrolase. Results of this study demonstrate, for the first time, that dietary folate deficiency leads to a marked upregulation in intestinal folate uptake and in the activity of folate hydrolase. Furthermore, the upregulation in folate uptake is associated with an increase in mRNA and protein levels of folate carrier, suggesting possible involvement of a transcriptional regulatory mechanism(s) in the upregulation.
Adaptation, Physiological↗
They have not heard of AIDS: HIV/AIDS awareness among married women in Bombay.
Many married women in India have still not heard of AIDS despite increasing risks, intensive health education campaigns and widespread scientific and media attention. Cross-sectional survey data collected from 350 married women in Bombay, India, revealed that one out of three women had not heard of AIDS. The women who had not heard of AIDS had significantly fewer years of formal education, lower personal and family incomes, less exposure to the mass media and were more likely not to know of condoms in comparison to the women who had heard of AIDS. The results suggest that there are socio-economic barriers to health information. Specific interventions targeted to this group using specific channels of communication are urgently needed.
Acquired Immunodeficiency Syndrome↗
AIDS-related information exposure in the mass media and discussion within social networks among married women in Bombay, India.
Married women are at high risk of acquiring HIV infection in India and health education remains the most feasible preventive tool in their context. In a survey conducted among 350 married women in Bombay, it was found that a majority had acquired information about AIDS from the mass media, especially television. Although 87% of women who knew of AIDS had been exposed to AIDS-related information in the mass media in the past four weeks, only 57% had discussed it within their social networks. Those with more exposure to AIDS information in the mass media were significantly more likely to discuss AIDS within social networks. The women were most likely to discuss AIDS with their husbands as a general social issue, followed by friends and family members and least likely to talk to husbands about AIDS as a personal issue relating to their sexual relationship. Increased frequency and duration of AIDS messages on television will have a positive influence on AIDS knowledge in this group.
Acquired Immunodeficiency Syndrome↗
The role of private physicians in STD control in two inner-city communities in Houston, Texas.
Although sexually transmitted diseases (STDs) are particularly widespread in poor, largely minority, inner-city areas, little is known about the role private physicians play in these communities in STD control. A cross-sectional mail survey of private physicians potentially involved in STD management in two inner-city communities in Houston, Texas with STD prevalence rates well above city, state, and national averages was conducted to find the level and type of STD care provided. Twenty-seven of 65 physicians completed the survey. The survey found that the preventive orientation among private providers of medical care in these inner-city communities has to be increased to effectively control STDs.
Cross-Sectional Studies↗
Transport of thiamine in human intestine: mechanism and regulation in intestinal epithelial cell model Caco-2.
The present study examined the intestinal uptake of thiamine (vitamin B(1)) using the human-derived intestinal epithelial cells Caco-2 as an in vitro model system. Thiamine uptake was found to be 1) temperature and energy dependent and occurred with minimal metabolic alteration; 2) pH sensitive; 3) Na(+) independent; 4) saturable as a function of concentration with an apparent Michaelis-Menten constant of 3.18 +/- 0.56 microM and maximal velocity of 13.37 +/- 0.94 pmol. mg protein(-1). 3 min(-1); 5) inhibited by the thiamine structural analogs amprolium and oxythiamine, but not by unrelated organic cations tetraethylammonium, N-methylnicotinamide, and choline; and 6) inhibited in a competitive manner by amiloride with an inhibition constant of 0.2 mM. The role of specific protein kinase-mediated pathways in the regulation of thiamine uptake by Caco-2 cells was also examined using specific modulators of these pathways. The results showed possible involvement of a Ca(2+)/calmodulin (CaM)-mediated pathway in the regulation of thiamine uptake. No role for protein kinase C- and protein tyrosine kinase-mediated pathways in the regulation of thiamine uptake was evident. These results demonstrate the involvement of a carrier-mediated system for thiamine uptake by Caco-2 intestinal epithelial cells. This system is Na(+) independent and is different from the transport systems of organic cations. Furthermore, a CaM-mediated pathway appears to play a role in regulating thiamine uptake in these cells.
Biological Transport↗
Preventing syphilis: lessons from a survey of two inner-city communities in Houston, Texas.
To develop a relevant, community-based prevention campaign, the authors examined, using street-intercept interviews, syphilis-related knowledge, circulation of information, and screening and treatment practices among four hundred residents of two inner-city communities in Houston, Texas, where syphilis case rates exceed city, county, and national averages. Although awareness of syphilis was near universal, one-fourth of the respondents thought syphilis was incurable, and a large proportion confused syphilis with other sexually transmitted diseases (STDs), mentioning discharge and burning or itching in the genital area as symptoms. Almost four out of five respondents were aware of free treatment and screening facilities in the local area, yet, less than two of five expressed the intention to get tested within the next month. Only 22 percent had seen or heard anything about syphilis in the past twelve months. The resultant prevention campaign is discussed along with implications for the development of comprehensive STD prevention and control campaigns in similar poor and underserved communities.
Adolescent↗