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Background: Podocyte specific proteins are dysregulated in diabetic nephropathy, though the extent of their expression loss is not identical and may be subject to different regulatory factors. Quantifying the degree of loss may help identify the most useful protein to use as an early biomarker of diabetic nephropathy., Methodology/principal Findings: Protein expression of synaptopodin, podocin and nephrin were quantified in 15 Type 2 diabetic renal biopsies and 12 control patients. We found statistically significant downregulation of synaptopodin (P<0.0001), podocin (P = 0.0002), and nephrin (P<0.0001) in kidney biopsies of diabetic nephropathy as compared with controls. Urinary nephrin levels (nephrinuria) were then measured in 66 patients with Type 2 diabetes and 10 healthy controls by an enzyme-linked immunosorbent assay (Exocell, Philadelphia, PA). When divided into groups according to normo-, micro-, and macroalbuminuria, nephrinuria was found to be present in 100% of diabetic patients with micro- and macroalbuminuria, as well as 54% of patients with normoalbuminuria. Nephrinuria also correlated significantly with albuminuria (rho = 0.89, p<0.001), systolic blood pressure (rho = 0.32, p = 0.007), and correlated negatively with serum albumin (rho = -0.48, p<0.0001) and eGFR (rho = -0.33, p = 0.005)., Conclusions/significance: These data suggest that key podocyte-specific protein expressions are significantly and differentially downregulated in diabetic nephropathy. The finding that nephrinuria is observed in a majority of these normoalbuminuric patients demonstrates that it may precede microalbuminuria. If further research confirms nephrinuria to be a biomarker of pre-clinical diabetic nephropathy, it would shed light on podocyte metabolism in disease, and raise the possibility of new and earlier therapeutic targets.

Background: Few studies have examined the possible effects of reproductive factors on cardiovascular disease (CVD) risks in Asian women., Methods: A cohort of 267,400 female textile workers in Shanghai, China, was administered a questionnaire at enrolment (1989-91) and followed for mortality through 2000. Relative risks (hazard ratios) for ischaemic heart disease (IHD), ischaemic stroke and haemorrhagic stroke were calculated using Cox proportional hazards modelling, adjusting for relevant co-variates., Results: Risks were not consistently associated with age at menopause, parity, stillbirths, miscarriages or duration of lactation. An increasing trend in IHD mortality risk, but not stroke, was observed with decreasing age at menarche. There was no evidence of increased CVD mortality risk by oral or injectable contraceptive use or induced abortions. As expected, greater mortality rates from CVD and increased CVD risks were also observed with smoking., Conclusions: Use of steroid contraceptives, induced abortions and reduced parity from China's one-child-per-family policy has not had an adverse effect on risk of CVD mortality in this cohort.

Objective: To investigate chronic obstructive pulmonary disease (COPD) mortality among textile workers., Methods: A total of 267,400 Chinese female textile employees were monitored for COPD mortality from 1989 to 2000. Textile factories in the cohort were classified into 10 industrial sectors. Age-adjusted mortality, standardized mortality ratios (SMRs) and 95% CIs were calculated by sector. In addition, RRs (HRs) adjusted for smoking and age were calculated for exposure to cotton and silk textile work compared with the other sectors in the cohort., Results: A majority of textile sectors had lower or similar COPD mortality (age-adjusted SMRs=0.58-1.15) compared with the general female population in the city of Nanjing, China. SMRs for cotton and silk workers were, respectively, 1.02 (95% CI: 0.81 to 1.28) and 2.03 (95% CI: 1.13 to 3.34). Compared with all other textile sectors in the cohort, there was greater COPD mortality among cotton workers (HR=1.40, 95% CI: 1.03 to 1.89) and silk workers (HR=2.54, 95% CI: 1.47 to 4.39)., Conclusion: Elevated COPD mortality among cotton workers is consistent with previous reports of adverse respiratory effects of cotton dust. The higher rate of COPD deaths among silk workers was unexpected.

Objective: Exposure to endotoxin has been consistently associated with a reduced risk of lung cancer. However, there is a paucity of information regarding temporal aspects of this relationship. The objective of this study was to investigate the associations between contiguous windows of endotoxin exposure and risk of lung cancer., Methods: Data were reanalyzed from a case-cohort study (602 cases, 3,038 subcohort) of female textile workers in Shanghai, China. Cumulative endotoxin exposure was partitioned into two windows: ≥20 and <20 years before risk. Exposure-response relations were examined using categorical and non-linear (semi-parametric) models, accounting for confounding by previous exposure windows., Results: There was an inverse trend of decreasing risk of lung cancer associated with increasing levels of endotoxin exposure ≥20 years before risk (p trend = 0.02). Women in the highest two categories of cumulative exposures had hazard ratios of 0.78 (95% CI 0.60-1.03) and 0.77 (95% CI 0.58-1.02) for lung cancer, respectively, in comparison with unexposed textile workers. There was, however, a weaker association and not statistically significant between lung cancer and endotoxin exposure accumulated in the more recent window (<20 years before risk)., Conclusion: Results provide further evidence that endotoxin exposure that occurred 20 years or more before risk confers the strongest protection against lung cancer, indicating a possible early anti-carcinogenic effect. Further studies are needed to better understand the underlying biological mechanisms for this effect.

Objective: Diabetic kidney disease (DKD) is the single leading cause of kidney failure in the U.S., for which a cure has not yet been found. The aim of our study was to provide an unbiased catalog of gene-expression changes in human diabetic kidney biopsy samples., Research Design and Methods: Affymetrix expression arrays were used to identify differentially regulated transcripts in 44 microdissected human kidney samples. DKD samples were significant for their racial diversity and decreased glomerular filtration rate (~25-35 mL/min). Stringent statistical analysis, using the Benjamini-Hochberg corrected two-tailed t test, was used to identify differentially expressed transcripts in control and diseased glomeruli and tubuli. Two different web-based algorithms were used to define differentially regulated pathways., Results: We identified 1,700 differentially expressed probesets in DKD glomeruli and 1,831 in diabetic tubuli, and 330 probesets were commonly differentially expressed in both compartments. Pathway analysis highlighted the regulation of Ras homolog gene family member A, Cdc42, integrin, integrin-linked kinase, and vascular endothelial growth factor signaling in DKD glomeruli. The tubulointerstitial compartment showed strong enrichment for inflammation-related pathways. The canonical complement signaling pathway was determined to be statistically differentially regulated in both DKD glomeruli and tubuli and was associated with increased glomerulosclerosis even in a different set of DKD samples., Conclusions: Our studies have cataloged gene-expression regulation and identified multiple novel genes and pathways that may play a role in the pathogenesis of DKD or could serve as biomarkers.

Penguins (Sphenisciformes) inhabit some of the most extreme environments on Earth. The 60+ Myr fossil record of penguins spans an interval that witnessed dramatic shifts in Cenozoic ocean temperatures and currents, indicating a long interplay between penguin evolution and environmental change. Perhaps the most celebrated example is the successful Late Cenozoic invasion of glacial environments by crown clade penguins. A major adaptation that allows penguins to forage in cold water is the humeral arterial plexus, a vascular counter-current heat exchanger (CCHE) that limits heat loss through the flipper. Fossil evidence reveals that the humeral plexus arose at least 49 Ma during a 'Greenhouse Earth' interval. The evolution of the CCHE is therefore unrelated to global cooling or development of polar ice sheets, but probably represents an adaptation to foraging in subsurface waters at temperate latitudes. As global climate cooled, the CCHE was key to invasion of thermally more demanding environments associated with Antarctic ice sheets.

Objectives: Numerous epidemiological studies of lung cancer among textile workers worldwide consistently indicate reduced risks related to cotton dust exposure, presumably due to endotoxin contamination. Our objective was to investigate associations with other exposures potentially related to lung cancer, including wool and synthetic fibre dusts, formaldehyde, silica, dyes and metals, that have only been studied to a limited extent in the textile industry., Methods: We conducted a case-cohort study nested within a cohort of 267,400 women textile workers in Shanghai, China. We compared work assignments and exposure histories of 628 incident lung cancer cases, diagnosed during 1989-1998, with those of a reference subcohort of 3188 workers. We reconstructed exposures with a job-exposure matrix developed specifically for textile factories. Cox proportional hazards modelling was applied to estimate age/smoking-adjusted relative risks (hazard ratios) and risk gradients associated with job assignments and specific agents other than cotton dust and endotoxin., Results: No associations were observed for lung cancer with wool, silk or synthetic fibre dusts, or with most other agents. However, increased risks, although statistically imprecise, were noted for ≥ 10 years' exposures to silica (adjusted HR 3.5, 95% CI 1.0 to 13) and ≥ 10 years' exposures to formaldehyde (adjusted HR 2.1, 95% CI 0.4 to 11)., Conclusions: Exposures to silica and formaldehyde, although not widespread among the cohort, may have increased lung cancer risk. Silica is an established human lung carcinogen, whereas there is only weak prior evidence supporting an association with formaldehyde. Both exposures warrant consideration as potential lung carcinogens in textile manufacturing.

Breast cancers in Turkey tend to be diagnosed at advanced stages due to lack of organized comprehensive mammographic screening. In this study, factors associated with having a mammogram among healthy women of screening age in Bahcesehir county, a region in Istanbul, were investigated to assess the feasibility of organized breast cancer screening in Turkey. In this cross-sectional study, 659 healthy women aged between 40 and 69 years were surveyed. A multiple-choice questionnaire was used to obtain information regarding patient demographics, family history of cancer, and patient knowledge on mammographic screening. Factors associated with increased likelihood of having a mammogram included age older than 50 (OR=1.75; 95% CI=1.23-2.49), higher educational level (high school or university graduate; OR=1.55; 95% CI=1.07-2.25), and undergoing periodic gynecologic examinations (OR=5.53; 95% CI= 3.88-7.89). Women aged between 40 and 49 years, who were most likely to have a mammogram within the last 2 years were characterized by a higher educational level (OR=1.94; 95% CI=1.14-3.31), periodic gynecologic examinations (OR=4.06; 95% CI=2.53-6.51), and a first or second degree family history of breast cancer (OR=2.2; 95% CI= 1.06-4.50). In contrast, women aged between 50 and 69 years were more likely to have undergone mammography within the previous 2 years if they also had undergone periodic gynecologic examinations (OR=8.63; 5.04-14.77). Our findings suggest that women of lower educational level and those who do not undergo routine wellness visits with their gynecologist will need to be specifically targeted for educational outreach to achieve broad screening compliance within the population., (© 2011 Wiley Periodicals, Inc.)

Anastrepha serpentina (Wiedemann) (Diptera: Tephritidae) is sporadically captured in the Rio Grande Valley of Texas. Although its preferred hosts are in the Sapotaceae family, several varieties of Citrus, including grapefruit and oranges are listed as alternate hosts. Although Mexican fruit fly, Anastrepha ludens (Loew), is known to be a major pest of Citrus, doubt exists as to the status of Citrus as a breeding host for A. serpentina. To evaluate the host status of commercial Citrus for A. serpentina we compared oviposition and development with that of A. ludens under laboratory conditions with 'Rio Red' grapefruit (Citrus paradisi MacFayden) and 'Valencia' oranges [Citrus sinensis (L.) Osbeck] in different stages of maturity. Both fly species oviposited in early season fruit in which the eggs and larvae died in the fruit albedo. Survival of either species to the adult stage occurred in later season grapefruit. In oranges, no A. serpentina larvae survived compared with 150 A. ludens surviving to adults. Survival on both Citrus species was much lower for A. serpentina, only approximately 5% of eggs eclosed into larvae in grapefruit compared with approximatley 50% for A. ludens. In oranges approximately 16% of A. serpentina eggs eclosed compared with approximately 76% for A. ludens. In grapefruit, only one fourth as many A. serpentina larvae survived to the adult stage compared with A. ludens. Additional experiments were performed in a greenhouse on small, caged trees of la coma (Sideroxylon celastrinum H.B.K.), a Texas species of Sapotaceae. The A. serpentina females readily oviposited into these berries and normal adults emerged. The present low incidence of the adults, coupled with the high mortality during development of the larvae, suggests that Texas citrus is unlikely to support a breeding population of A. serpentina.

In middle resource countries (MRCs), cancer control programs are becoming a priority as the pattern of disease shifts from infectious diseases to non-communicable diseases such as breast cancer, the most common cancer among women in MRCs. The Middle Resource Scenarios Working Group of the BHGI 2010 Global Summit met to identify common issues and obstacles to breast cancer detection, diagnosis and treatment in MRCs. They concluded that breast cancer early detection programs continue to be important, should include clinical breast examination (CBE) with or without mammography, and should be coupled with active awareness programs. Mammographic screening is usually opportunistic and early detection programs are often hampered by logistical and financial problems, as well as socio-cultural barriers, despite improved public educational efforts. Although multidisciplinary services for treatment are available, geographical and economic limitations to these services can lead to an inequity in health care access. Without adequate health insurance coverage, limited personal finances can be a significant barrier to care for many patients. Despite the improved availability of services (surgery, pathology, radiology and radiotherapy), quality assurance programs remain a challenge. Better access to anticancer drugs is needed to improve outcomes, as are rehabilitation programs for survivors. Focused and sustained government health care financing in MRCs is needed to improve early detection and treatment of breast cancer., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

International collaborations like the Breast Health Global Initiative (BHGI) can help low and middle income countries (LMCs) to establish or improve breast cancer control programs by providing evidence-based, resource-stratified guidelines for the management and control of breast cancer. The Problem Solving Working Group of the BHGI 2010 Global Summit met to develop a consensus statement on problem-solving strategies addressing breast cancer in LMCs. To better assess breast cancer burden in poorly studied populations, countries require accurate statistics regarding breast cancer incidence and mortality. To better identify health care system strengths and weaknesses, countries require reasonable indicators of true health system quality and capacity. Using qualitative and quantitative research methods, countries should formulate cancer control strategies to identify both system inefficiencies and patient barriers. Patient navigation programs linked to public advocacy efforts feed and strengthen functional early detection and treatment programs. Cost-effectiveness research and implementation science are tools that can guide and expand successful pilot programs., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

The Breast Health Global Initiative (BHGI) brought together international breast cancer experts to discuss breast cancer in low resource countries (LRCs) and identify common concerns reviewed in this consensus statement. There continues to be a lack of public and health care professionals' awareness of the importance of early detection of breast cancer. Mastectomy continues to be the most common treatment for breast cancer; and a lack of surgeons and anesthesia services was identified as a contributing factor in delayed surgical therapy in LRCs. Where available, radiation therapy is still more likely to be used for palliation rather than for curative treatment. Tumor receptor status is often suboptimally performed due to lack of advanced pathology services and variable quality control of tissue handling and processing. Regional pathology services can be a cost-effective approach and can serve as reference, training and research centers. Limited availability of medical oncologists in LRCs often results in non-specialist providing chemotherapeutic services, which requires additional supervision and training. Palliative care is an emerging field in LRCs that requires investment in training and infrastructure development. A commitment and investment in the development of breast cancer care services by LRC governments and health authorities remains a critical need in LRCs., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

The most common hosts for the West Indian fruit fly, Anastrepha obliqua (Macquart) (Diptera: Tephritidae) are fruit in the family Anacardiaceae (mango [Mangifera L.] and mombin [Spondias L.] species). However, similar to many of the tropical fruit flies of major economic importance, this species attacks several other families of crop fruit, including Annonaceae (cherimoya, Annona cherimola Mill.), Myrtaceae (guava, Psidium L.), Oxalidaceae (carambola, Averrhoa carambola L.), Passifloraceae (granadilla, Passiflora quadrangularis Mill.), and Sapotaceae [mamey sapote, Pouteria sapota (Jacq.) H. E. Moore & Steam]. In the family Rutaceae the economically important genus Citrus has been reported and until recently considered a host for this fruit fly. In this study, we reviewed the taxonomy of A. obliqua, tested specific chemicals that may inhibit oviposition, compared egg-to-adult survival of A. obliqua on preferred hosts and on grapefruit (Citrus X paradisi Macfad.), and measured fruit tissue-specific developmental rates of A. obliqua and the known citrus breeding Mexican fruit fly, Anastrepha ludens (Loew) (Diptera: Tephritidae), from egg to pupae. Our literature review shows much confusion concerning the taxonomy of this and related Anastrepha species, including synonymies and confusion with other species. The deterrent effect of the highest concentration of flavonoids for oviposition, although significant, was not absolute. Experiments carried out under laboratory conditions showed 15-40 times greater survival of A. ludens (whose preferred hosts include Rutaceae) on grapefruit compared with A. obliqua for both tree attached and harvested fruit. Experiments of survival of developing stages over time showed that the two species oviposit into different tissues in the fruit, and mortality is much higher for the West Indian fruit fly in the flavedo and albedo of the fruit compared with the Mexican fruit fly.

Methyl bromide fumigation is widely used as a phytosanitary treatment. Mexican fruit fly, Anastrepha ludens (Loew) (Diptera: Tephritidae), is a quarantine pest of several fruit, including citrus (Citrus spp.), exported from Texas, Mexico, and Central America. Recently, live larvae have been found with supposedly correctly fumigated citrus fruit. This research investigates the efficacy of the previously approved U.S. Department of Agriculture-Animal and Plant Health Inspection Service treatment schedule: 40 g/m3 methyl bromide at 21-29.4 degrees C for 2 h. Tolerance ofA. ludens to methyl bromide in descending order when fumigated in grapefruit (Citrus X paradisi Macfad.) is third instar > second instar > first instar > egg. Two infestation techniques were compared: insertion into fruit of third instars reared in diet and oviposition by adult A. ludens into fruit and development to the third instar. Inserted larvae were statistically more likely to survive fumigation than oviposited larvae. When fruit were held at ambient temperature, 0.23 +/- 0.12% of larvae were still observed to be moving 4 d postfumigation. Temperatures between 21.9 and 27.2 degrees C were positively related to efficacy measured as larvae moving 24 h after fumigation, pupariation, and adult emergence. Coating grapefruit with Pearl Lustr 2-3 h before fumigation did not significantly affect the proportion of third instars moving 24 h after fumigation, pupariating, or emerging as adults. In conclusion, fumigation with 40 g/m3 methyl bromide for 2 h at fruit temperatures >26.7 degrees C is not found to be inefficacious for A. ludens. Although a few larvae may be found moving >24 h postfumigation, they do not pupariate.

Background: Polymorphisms in sex hormone receptor-encoding genes may alter the activity of sex hormone receptors and thereby affect susceptibility to breast cancer and related outcomes., Methods: In a case-control study of women from Shanghai, China, we examined the risk of breast cancer and fibrocystic breast conditions associated with the ESR1 PvuII (rs2234693) and XbaI (rs9340799) and AR CAG repeat ((CAG)(n)) and GGC repeat ((GGC)(n)) polymorphisms among 614 women with breast cancer, 467 women with fibrocystic conditions, and 879 women without breast disease. We also evaluated whether risk differed by the presence/absence of proliferative changes (in the extratumoral epithelium or fibrocystic lesion), menopausal status, or body mass index (BMI). Age-adjusted odds ratios (ORs) and 95% confidence intervals (95% CI) were calculated using logistic regression., Results: Only associations with AR (CAG)(n) and (GGC)(n) genotypes were detected. Allocating AR (CAG)(n) genotypes into six categories, with the (CAG)(22-24)/(CAG)(22-24) genotype category designated as the reference group, the (CAG)(>24)/(CAG)(>24) genotype category was associated with an increased risk of fibrocystic breast conditions (OR, 1.8; 95% CI, 1.1-3.0). Relative to the AR (GGC)(17)/(GGC)(17) genotype, the (GGC)(17)/(GGC)(14) genotype was associated with elevated risks of incident breast cancer (OR, 2.6; 95% CI, 1.3-5.4) and fibrocystic conditions (OR, 2.3; 95% CI, 1.1-4.5). Results did not differ according to proliferation status, menopausal status, or BMI., Conclusion: Although these data lend support for a link between AR variation and breast disease development, given the low frequency of the putative risk-conferring genotypes and other constraints, further confirmation of our results is needed., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Recent studies indicate that the Notch signaling pathway plays an important role in the development of diabetic kidney disease and focal segmental glomerulosclerosis (FSGS). Here we analyzed the degree of expression and localization of Notch ligands (Jagged1 and Delta1) and activated (cleaved) receptors (Notch1 and Notch2) in healthy human kidneys and in renal biopsies from a wide variety of kidney diseases. These included patients with minimal change disease, membranous nephropathy, lupus nephritis ISN/RPS classes III/IV/V, hypertensive nephrosclerosis, crescentic glomerulonephritis, tubulointerstitial fibrosis, IgA nephropathy, diabetic kidney disease, and FSGS. We found that cleaved Notch1, Notch2, and Jagged1 are expressed on podocytes in proteinuric nephropathies and their level of expression correlated with the amount of proteinuria across all disease groups. The degree of glomerulosclerosis correlated with podocyte expression of cleaved Notch1, while the severity of tubulointerstitial fibrosis and the estimated glomerular filtration rate correlated with expression of cleaved Notch1 in the tubulointerstitium. Hence, our results raise the possibility that Notch pathway activation is a common mechanism in the pathophysiology of a wide range of acquired renal diseases.

Some phytosanitary irradiation treatment research against tephritid fruit flies (Diptera: Tephritidae) has used artificially infested fruit with the unstated and untested assumption that the method adequately simulated a natural situation. We compare grapefruit, Citrus paradisi Macfayden, naturally infested by Mexican fruit fly, Anastrepha ludens (Loew), via oviposition until larvae reached the late third instar versus insertion of diet-reared third instars into holes made in grapefruits 24 h before irradiation; the latter technique has been used in other studies. Both infestation techniques resulted in statistically indistinguishable results, indicating that insertion of diet-reared third instar Mexican fruit fly into holes bored into grapefruit and subsequently sealed 24 h before irradiation would adequately represent natural infestation and could be used to develop a radiation phytosanitary treatment of the insect in grapefruit when prevention of adult emergence is used as the measure of efficacy. Nevertheless, it may not be advisable to extend this conclusion to other fruit fly/fruit combinations without doing appropriate comparison studies. Dissection of puparia from nonirradiated control insects that failed to emerge as adults showed a relatively even distribution of mortality among the developmental stages within the puparium. In contrast, dissection of puparia from irradiated third instars that did not emerge as adults revealed a sharp attenuation in development from cryptocephalic to phanerocephalic pupae demonstrating this transition to be the developmental step most affected by radiation.

Fibroadenomas are the most common benign breast condition among women and account for up to 50% of all breast biopsies being performed. Although considered a benign condition, fibroadenomas utilize substantial resources for management and treatment to rule out potential malignancies. Dietary factors may influence benign fibrocystic breast conditions, but little is known of their association with fibroadenomas. We examined possible associations between a broad spectrum of circulating biomarkers of dietary intake and risk of fibroadenomas. Participants were women in a breast self-examination trial in Shanghai, China who were diagnosed with fibroadenomas (n = 258) and 1035 controls. Conditional logistic regression was used to estimate adjusted odds ratios (OR) and 95% CI. Isoflavone concentrations were inversely associated with risk of fibroadenomas. Adjusted OR (95% CI) for the highest versus the lowest quartile of plasma concentration were 0.36 (0.16-0.79; P-trend < 0.001) for daidzein and 0.39 (0.19-0.84; P-trend = 0.010) for genistein. We also observed inverse associations between higher percentages of the RBC (n-3) fatty acids, eicosapentaenoic acid (EPA) ([0.38 (0.19-0.77); P-trend = 0.007] and docosapentaenoic acid (DPA) [0.32 (0.15-0.70); P-trend = 0.024], and fibroadenoma risk. Circulating concentrations of carotenoids, vitamin C, retinol, and ferritin were not associated with fibroadenoma risk. The inverse associations between plasma isoflavone concentrations and RBC EPA and DPA and fibroadenoma risk suggest that higher intakes of soy foods and fatty fish may lower the risk of fibroadenomas.

Fibroadenomas are common benign breast conditions among women and account for approximately 50% of breast biopsies performed. Dietary factors are known to influence benign breast conditions in the aggregate, but little is known of their association specifically with fibroadenoma. Our objective in this study was to evaluate the association between dietary and other factors and fibroadenoma risk. A case-control study, nested in a randomized trial of breast self-examination (BSE) in Chinese textile workers in Shanghai, China, was conducted between 1989 and 2000. The study sample included 327 affected women and 1070 controls. Women were administered a FFQ and a questionnaire that elicited reproductive and gynecological history and other information. Odds ratios, as estimates of relative risks, were calculated using multivariate conditional logistic regression. Significant decreasing trends in risk of fibroadenoma were observed with intake of fruits and vegetables and with number of live births, and a reduced risk was also associated with natural menopause, oral contraceptive use, and moderate exercise (walking and gardening). Increased risk of fibroadenoma was associated with heavy physical activity in one's 20s, breast cancer in a first-degree relative, and a history of prior benign breast lumps; and significant increasing trends in risk were observed with numbers of BSE per year and years of education. In conclusion, a diet rich in fruits and vegetables and the use of oral contraceptives may reduce risk of fibroadenoma.

We sought to examine the pathogenic role of excessive VEGF-A expression in podocytes, since it has been reported that diabetic nephropathy and other glomerular diseases are associated with increased VEGF-A expression. The induction of podocyte-specific VEGF164 overexpression in adult transgenic mice led to proteinuria, glomerulomegaly, glomerular basement membrane thickening, mesangial expansion, loss of slit diaphragms, and podocyte effacement. When doxycycline-mediated VEGF164 was stopped, these abnormalities reversed. These findings were associated with reversible downregulation of metalloproteinase 9 and nephrin expression. Using transmission electron microscopy, we established that VEGF-A receptor-2 (VEGFR2) was expressed in podocytes and glomerular endothelial cells. We also found that VEGF164 induced VEGFR2 phosphorylation in podocytes. Further, we were able to co-immunoprecipitate VEGFR2 and nephrin using whole kidney lysates, confirming interaction in vivo. This implies that autocrine and paracrine VEGF-A signaling through VEGFR2 occurs in podocytes and may mediate the glomerular phenotype caused by VEGF164 overexpression. Thus, we suggest that podocyte VEGF164 overexpression in adult mice is sufficient to induce glomerular filtration barrier structural and functional abnormalities similar to those present in murine diabetic nephropathy.

Background: Strenuous occupational physical activity and physical demands may be risk factors for adverse reproductive outcomes., Methods: A retrospective study in the Shanghai, China textile industry study collected women's self-reported reproductive history. Occupational physical activity assessment linked complete work history data to an industry-specific job-exposure matrix. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by multivariate logistic regression for the first pregnancy outcome and utilized generalized estimating equations to consider all pregnancies per woman., Results: Compared with women employed in sedentary jobs, a reduced risk of miscarriage was found for women working in jobs with either light (OR 0.18, 95% CI: 0.07, 0.50) or medium (OR 0.24, 95% CI: 0.08, 0.66) physical activity during the first pregnancy and over all pregnancies (light OR 0.32, 95% CI: 0.17, 0.61; medium OR 0.43, 95% CI: 0.23, 0.80). Frequent crouching was associated with elevated risk (OR 1.82, 95% CI: 1.14, 2.93; all pregnancies per woman)., Conclusions: Light/medium occupational physical activity may have reduced miscarriage risk, while specific occupational characteristics such as crouching may have increased risk in this cohort., (2010 Wiley-Liss, Inc.)

Heparin cofactor II (HCII) is a serine protease inhibitor (serpin) that has been shown to be a predictor of decreased atherosclerosis in the elderly and protective against atherosclerosis in mice. HCII inhibits thrombin in vitro and HCII-thrombin complexes have been detected in human plasma. Moreover, the mechanism of protection against atherosclerosis in mice was determined to be the inhibition of thrombin. Despite this evidence, the presence of HCII in human atherosclerotic tissue has not been reported. In this study, using samples of coronary arteries obtained from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study, we explore the local relationship between HCII and (pro)thrombin in atherosclerosis. We found that HCII and (pro)thrombin are co-localized in the lipid-rich necrotic core of atheromas. A significant positive correlation between each protein and the severity of the atherosclerotic lesion was present. These results suggest that HCII is in a position to inhibit thrombin in atherosclerotic lesions where thrombin can exert a proatherogenic inflammatory response. However, these results should be tempered by the additional findings from this, and other studies, that indicate the presence of other plasma proteins (antithrombin, albumin, and alpha(1)-protease inhibitor) in the same localized region of the atheroma.

Vector perturbations sourced by topological defects can generate rotations in the lensing of background galaxies. This is a potential smoking gun for the existence of defects since rotation generates a curl-like component in the weak lensing signal which is not generated by standard density perturbations at linear order. This rotation signal is calculated as generated by cosmic strings. Future large scale weak lensing surveys should be able to detect this signal even for string tensions an order of magnitude lower than current constraints.

Increases in risk of breast cancer in successive generations of migrants to the United States from China and rapid temporal changes in incidence rates in China following social and economic changes clearly implicate environmental factors in the etiology of this disease. Case-control and cohort studies have provided evidence that at least some of these factors may be dietary. Iron, an essential element necessary for cell function, has also been demonstrated to have potential carcinogenic and co-carcinogenic activities. Iron overload, which was previously uncommon, has become more common in the United States than iron deficiency and may be increasing in China concurrently with dramatic increases in meat consumption. A case-control study nested in a cohort of women in Shanghai, China, was conducted to evaluate possible associations between risk of proliferative and nonproliferative fibrocystic changes as well as breast cancer and dietary iron intake and plasma ferritin levels. Plasma ferritin levels and reported dietary iron intake were compared in 346 women with fibrocystic changes, 248 breast cancer cases and 1,040 controls. Increasing ferritin levels were significantly associated with increasing risk of nonproliferative fibrocystic changes (OR: 2.51, 95% CI: 1.16-5.45, p trend = 0.04). Similar, but weaker, trends were observed for proliferative changes and for breast cancer. Risk of breast cancer relative to the risk of fibrocystic changes was associated with dietary iron intake in women with nonproliferative fibrocystic changes (OR: 2.63, 95% CI: 1.04-6.68, p = 0.02). In conclusion, this study finds significant associations between iron (stored and dietary) and fibrocystic disease and breast cancer., (2009 UICC.)

Although chronic kidney disease (CKD) is common, only a fraction of CKD patients progress to end-stage renal disease. Molecular predictors to stratify CKD populations according to their risk of progression remain undiscovered. Here we applied transcriptional profiling of kidneys from transforming growth factor-beta1 transgenic (Tg) mice, characterized by heterogeneity of kidney disease progression, to identify 43 genes that discriminate kidneys by severity of glomerular apoptosis before the onset of tubulointerstitial fibrosis in 2-week-old animals. Among the genes examined, 19 showed significant correlation between mRNA expression in uninephrectomized left kidneys at 2 weeks of age and renal disease severity in right kidneys of Tg mice at 4 weeks of age. Gene expression profiles of human orthologs of the 43 genes in kidney biopsies were highly significantly related (R(2) = 0.53; P < 0.001) to the estimated glomerular filtration rates in patients with CKD stages I to V, and discriminated groups of CKD stages I/II and III/IV/V with positive and negative predictive values of 0.8 and 0.83, respectively. Protein expression patterns for selected genes were successfully validated by immunohistochemistry in kidneys of Tg mice and kidney biopsies of patients with IgA nephropathy and CKD stages I to V, respectively. In conclusion, we developed novel mRNA and protein expression signatures that predict progressive renal fibrosis in mice and may be useful molecular predictors of CKD progression in humans.

Objective: To study the membrane expression of endothelial protein C receptor (mEPCR) in the renal microvasculature in lupus nephritis (LN) as a potential marker of injury and/or prognostic indicator for response to therapy., Methods: mEPCR expression was analysed by immunohistochemistry in normal kidney and in 59 biopsies from 49 patients with LN. Clinical parameters were assessed at baseline, 6 months and 1 year., Results: mEPCR was expressed in the medulla, arterial endothelium and cortical peritubular capillaries (PTCs) in all biopsies with LN but not in the cortical PTCs of normal kidney. Positive mEPCR staining in >25% of the PTCs was observed in 16/59 biopsies and associated with poor response to therapy. Eleven (84.6%) of 13 patients with positive staining for mEPCR in >25% of the PTCs and follow-up at 6 months did not respond to therapy, compared with 8/28 (28.6%) with mEPCR staining in < or =25% PTCs, P = 0.0018. At 1 year, 10 (83.3%) of 12 patients with positive mEPCR staining in >25% of the PTCs did not respond to therapy (with two progressing to end-stage renal disease) compared with 8/24 (33.3%) with positive staining in < or =25% of the PTCs, P = 0.0116. Although tubulo-interstitial damage (TID) was always accompanied by mEPCR, this endothelial marker was extensively expressed in the absence of TID suggesting that poor response could not be attributed solely to increased TID. mEPCR expression was independent of International Society of Nephrology/Renal Pathology Society class, activity and chronicity indices., Conclusion: Increased mEPCR expression in PTCs may represent a novel marker of poor response to therapy for LN.

Introduction: To investigate possible associations between miscarriage and occupational exposures in the Shanghai textile industry., Methods: A retrospective cohort study of miscarriages among 1752 women in the Shanghai textile industry was conducted. Reproductive history was self-reported by women and occupational work histories were collected from factory personnel records. Occupational exposures were assigned by linking work history information to an industry-specific job-exposure matrix informed by factory-specific textile process information and industrial hygiene assessments. Estimates of cotton dust and endotoxin exposure were also assigned. Odds ratios (OR) and 95% CI were estimated by multivariate logistic regression, with adjustment for age at pregnancy, educational level, smoking status of the woman and her spouse, use of alcohol, and woman's year of birth., Results: An elevation in risk of a spontaneously aborted first pregnancy was associated with exposure to synthetic fibres (OR 1.89, 95% CI 1.20 to 3.00) and mixed synthetic and natural fibres (OR 3.31, 95% CI 1.30 to 8.42). No increased risks were observed for women working with solvents, nor were significant associations observed with quantitative cotton dust or endotoxin exposures. Associations were robust and similar when all pregnancies in a woman's reproductive history were considered., Conclusions: Occupational exposure to synthetic fibres may cause miscarriages, and this possibility should be the subject of further investigation.

From 1998 to 1991, an in-person baseline interview was administered to approximately 267,400 female textile workers in Shanghai, China. The cohort was followed until July 2000 for incident cancer cases. Incidence rate ratios (RR) for 12 types of cancers in users of oral contraceptives (OCs) were calculated using Cox Proportional Hazards analysis. There was a reduced risk of uterine corpus cancer for women who had ever used OCs (RR = 0.68, 95% CI = 0.45-1.04) and a trend of decreasing risk with increasing duration of use (p = 0.015). There was an increased risk of colon cancer in women who had used OCs for 10 years or more (RR = 1.56, 95% CI = 1.01-2.40) and an increased risk of rectal cancer in women who had ever used OCs (RR = 1.31, 95% CI = 0.98-1.75), with a trend of increasing risk with increasing duration of use (p = 0.017), but these associations may have been due to uncontrolled confounding by physical activity or other non-causal factors. No associations were observed between OCs and the risk of all cancers combined or for any of the nine other cancers. It is unlikely that the use of OCs has contributed to the temporal trends in cancer incidence in China in recent decades.

The incidence of End Stage Renal Disease (ESRD) is approximately 50% higher in men than women. In order to understand the molecular basis of this gender disparity, we examined sex specific gene expression patterns in control and diseased, human and murine kidney samples. Using the Affymetrix platform we performed comprehensive gene expression analysis on 42 microdissected human kidney samples (glomeruli and tubules). We identified 67 genes with gender biased expression in healthy human kidneys and 24 transcripts in diseased male and female human kidneys. Similar analysis performed in mice using male and female control and doxorubicin induced nephrotic syndrome kidneys identified significantly larger number of differentially expressed transcripts. The majority of genes showing gender biased expression either in diseased human and murine kidneys were different from those differentially expressed in healthy kidneys. Only 9 sexually dimorphic transcripts were common to healthy human and murine kidneys and five showed differential regulation in both human and murine diseased kidneys. In humans, sex biased genes showed statistical enrichment only to sex chromosomes while in mice they were enriched to sex chromosomes and various autosomes. Thus we present a comprehensive analysis of gender biased genes in the kidney. We show that sexually dimorphic genes in the kidney show species specific regulation. Our results also indicate that male and female kidneys respond differently to injury. These studies could provide the basis for the development of new treatment strategies for men and women with kidney disease.

Background: Although benign breast changes are more common than breast cancer, little evidence regarding risk factors for benign breast conditions is available. Omega-3 (n-3) fatty acids have antiinflammatory and antiproliferative actions and may be important in reducing the risk of benign conditions. There is a lack of research on the association of n-3 fatty acids with risk of benign fibrocystic breast changes., Objectives: The objectives of the study were to evaluate the role of n-3 and other fatty acids in the development of benign proliferative fibrocystic conditions (PFCs) and nonproliferative fibrocystic conditions (NPFCs) in the breast and to evaluate the progression of fibrocystic changes in breast cancer., Design: We conducted a case-control study to determine erythrocyte fatty acid concentrations in 155 women with NPFCs, 185 women with PFCs, 241 women with breast cancer (127 with nonproliferative and 114 with proliferative changes in the noncancerous extratumoral mammary epithelium), and 1,030 control subjects. We estimated the relative risk of NPFCs, PFCs, and breast cancer with proliferative and nonproliferative changes in extratumoral tissue compared with the risk of these changes alone., Results: Women in the highest quartile of eicosapentaenoic acid concentrations were 67% less likely to have an NPFC alone or with breast cancer and 49% less likely to have breast cancer than were women with PFCs. gamma-Linolenic acid (18:3n-6) was positively associated with all fibrocystic and cancerous conditions. Palmitic:palmitoleic acid (n-7 saturation index) was inversely associated with risk in all comparisons., Conclusion: Our results support a protective effects of n-3 fatty acid intake and the n-7 saturation index against benign fibrocystic breast changes and the progression of proliferative changes to breast cancer.

CYP19A1 encodes for aromatase, which irreversibly converts androgens to estrogens; variation in this gene may affect individual susceptibility to breast cancer and other sex hormone-dependent outcomes. In a case-control study nested within a breast self-examination trial conducted in China, we examined whether CYP19A1 polymorphisms (rs1870049, rs1004982, rs28566535, rs936306, rs11636639, rs767199, rs4775936, rs11575899, rs10046, and rs4646) were associated with risk of breast cancer and fibrocystic breast conditions. Cases were diagnosed with breast cancer (n = 614) or fibrocystic breast conditions (n = 465) during 1989 to 2000. Controls were free of breast disease during the same period (n = 879). Presence of proliferative changes within the extratumoral tissue of women with breast cancer and the lesions of women with fibrocystic conditions only was assessed. None of the polymorphisms were associated with overall risk of breast cancer or fibrocystic breast conditions. Differences in breast cancer risk, however, were observed by proliferation status. The risk of breast cancer with (but not without) proliferative fibrocystic conditions was increased among women homozygous for the minor allele of rs1004982 (C), rs28566535 (C), rs936306 (T), and rs4775936 (C) relative to those homozygous for the major allele [age-adjusted odds ratios (95% confidence intervals), 2.19 (1.24-3.85), 2.20 (1.27-3.82), 1.94 (1.13-3.30), and 1.95 (1.07-3.58), respectively]. Also, haplotypes inferred using all polymorphisms were not associated with overall risk of either outcome, although some block-specific haplotypes were associated with an increased risk of breast cancer with concurrent proliferative fibrocystic conditions. Our findings suggest that CYP19A1 variation may enhance breast cancer development in some women, but further confirmation is warranted.

Although anti-DNA antibodies have been decisively linked to the pathogenesis of lupus nephritis, the mechanisms have not been conclusively determined. Recently, we reported that anti-DNA antibodies may contribute to kidney damage by upregulation of proinflammatory genes in mesangial cells (MC), a process involving both Fc receptor-dependent and independent pathways. In investigating the mechanism by which pathogenic anti-DNA antibodies modulate gene expression in MC, we found that the pathogenic anti-DNA antibody 1A3F bound to high mobility group binding protein 1 (HMGB1), an endogenous ligand for TLR2/4 and RAGE (receptor for advanced glycation end products). Interestingly, HMGB1 treatment of MC induced a similar pattern of genes as stimulation with 1A3F. Furthermore, HMGB1 and 1A3F exhibited a synergistic proinflammatory effect in the kidney, where increased expression of HMGB1 was found in lupus patients but not in patients with other types of renal disease. TLR2/Fc and RAGE/Fc inhibited the proinflammatory effects of 1A3F on MC. Finally, we found enhanced susceptibility of lupus prone MRL-lpr/lpr (MRL/lpr) as compared to normal BALB/c derived MC to pathogenic anti-DNA antibody and LPS stimulation (in particular enhanced chemokine synthesis), in addition to significantly increased expression of TLR4. Our results suggest that gene upregulation in MC induced by nephritogenic anti-DNA antibodies is TLR2/4 and RAGE-dependent. Finally, HMGB1 may act as a proinflammatory mediator in antibody-induced kidney damage in systemic lupus erythematosus (SLE).

A key determinant of breast cancer outcome in any population is the degree to which cancers are detected at early stages of disease. Populations in which cancers are detected at earlier stages have lower breast cancer mortality rates. The Breast Health Global Initiative (BHGI) held its third Global Summit in Budapest, Hungary in October 2007, bringing together internationally recognized experts to address the implementation of breast healthcare guidelines for early detection, diagnosis, and treatment in low- and middle-income countries (LMCs). A multidisciplinary panel of experts specifically addressed the implementation of BHGI guidelines for the early detection of disease as they related to resource allocation for public education and awareness, cancer detection methods, and evaluation goals. Public education and awareness are the key first steps, because early detection programs cannot be successful if the public is unaware of the value of early detection. The effectiveness and efficiency of screening modalities, including screening mammography, clinical breast examination (CBE), and breast self-examination, were reviewed in the context of resource availability and population-based need by the panel. Social and cultural barriers should be considered when early detection programs are being established, and the evaluation of early detection programs should include the use of well developed, methodologically sound process metrics to determine the effectiveness of program implementation. The approach and scope of any screening program will determine the success of any early detection program as measured by cancer stage at diagnosis and will drive the breadth of resource allocation needed for program implementation., ((c) 2008 American Cancer Society.)

Objective: A case-cohort study was conducted to investigate associations between occupational exposures and endometrial cancer nested within a large cohort of textile workers in Shanghai, China., Methods: The study included 176 incident endometrial cancer cases diagnosed from 1989 to 1998 and a randomly-selected age-stratified reference subcohort (n = 3,061). Study subjects' complete work histories were linked to a job-exposure matrix developed specifically for the textile industry to assess occupational exposures. Hazard ratios (HR) and 95% confidence intervals were calculated using Cox proportional hazards modeling adapted for the case-cohort design, adjusting for age at menarche and a composite variable of gravidity and parity., Results: An increased risk of endometrial cancer was detected among women who had worked for > or =10 years in silk production (HR = 3.8, 95% CI 1.2-11.8) and had exposure to silk dust (HR = 1.7, 95% CI 0.9-3.4). Albeit with few exposed women (two cases and eight subcohort women), there was a 7.4-fold increased risk associated with > or =10 years of silica dust exposure (95% CI 1.4-39.7)., Conclusions: The findings suggest that some textile industry exposures might play a role in endometrial carcinoma and should be further replicated in other occupational settings., (Published 2008 Wiley-Liss, Inc.)

Several gene array studies have suggested that osteopontin (Opn) expression strongly correlates with albuminuria and glomerular disease. Urinary Opn concentration and kidney Opn immunoreactivity were found to be increased in patients with steroid-sensitive nephrotic syndrome. In addition, renal Opn mRNA was increased in the Ins2(Akita) mouse model of type 1 diabetic nephropathy, in the LPS-induced albuminuria model, and in glomeruli of puromycin aminonucleotide-induced nephrotic rats. Opn knockout mice did not develop albuminuria in response to LPS injection, and Opn knockout mice were protected from diabetes-induced albuminuria and mesangial expansion. In the glomerulus, Opn immunostaining was increased specifically in podocytes. Treatment of podocytes with recombinant Opn activated the NF-kappaB pathway, increased expression of urokinase plasminogen activator and matrix metalloproteinases 2 and 9, and increased podocyte motility. Taken together, these results indicate that Opn plays an important role in the development of albuminuria, possibly by modulating podocyte signaling and motility.

Enzymes encoded by the glutathione S-tranferase mu 1 (GSTM1) and pi 1 (GSTP1) genes, which are expressed in breast tissue, catalyze the detoxification of endogenous and exogenous electrophiles. Reduced enzyme activity, due to carriage of the GSTM1 deletion or the GSTP1 Ile105Val Val allele, may therefore affect susceptibility to breast cancer and related conditions. In a case-control study of Chinese women, we examined whether these polymorphisms were associated with risk of breast cancer and fibrocystic breast conditions. Women diagnosed with breast cancer (n=615) or fibrocystic breast conditions (n=467) were compared to women without clinical breast disease (n=878). We also examined whether these associations differed by menopausal status or by presence of proliferation in the extra-tumoral epithelium among women with breast cancer and in lesions among women with fibrocystic conditions. No overall association of either GST polymorphism with risk of breast cancer or fibrocystic breast conditions was observed. There was some evidence of slightly elevated cancer risk associated with carriage of the GSTM1 null genotype and at least one GSTP1 105-Val allele (OR=1.33, 95% CI, 0.99-1.80), compared to carriage of the GSTM1 non-null and GSTP1 Ile/Ile genotypes. This relationship was stronger in women who had breast cancer with extra-tumoral tissue proliferation (OR=1.77, 95% CI, 1.03-3.04). Our results suggest that GSTM1 and GSTP1 genotypes do not individually influence susceptibility to breast cancer or fibrocystic breast conditions. The observed increased risk of breast cancer associated with joint carriage of the GSTM1 null genotype and GSTP1 105-Val allele needs confirmation in other studies.

Common variants in genes encoding for key enzymes involved in steroidogenesis may alter sex steroid hormone levels, thereby influencing susceptibility to breast carcinoma and related conditions. In a case-control study of Chinese women, we examined genotypes of the CYP11A1 pentanucleotide [(TAAAA)n] repeat (D15S520), CYP17A1 rs743572, and HSD17B1 rs605059 polymorphisms in relation to the risk of breast cancer and fibrocystic breast conditions, comparing 615 women with breast cancer and 467 women with fibrocystic breast conditions separately with 879 women without clinical breast disease. We also evaluated whether these relationships differed by the presence of proliferation in the extratumoral epithelium or fibrocystic lesions, menopausal status, or body mass index. Only CYP11A1 genotype was related to breast cancer risk, with women homozygous for the 4-repeat allele, relative to those homozygous for the 6-repeat allele, at reduced risk (age-adjusted odds ratio, 0.58; 95% confidence interval, 0.37-0.91). There was some suggestion of a stronger inverse association for breast cancer with evidence of proliferation in the extratumoral epithelium than for breast cancer without extratumoral proliferation. Breast cancer risk associated with CYP11A1 genotype did not differ by menopausal status or body mass index level. No associations between CYP11A1, CYP17A1, and HSD17B1 genotypes and risk of fibrocystic breast conditions were observed. Our findings support the possibility that common allelic variation at the CYP11A1 D15S520 locus alters breast cancer risk in Chinese women.

Albuminuria associated with sclerosis of the glomerulus leads to a progressive decline in renal function affecting millions of people. Here we report that activation of the Notch pathway, which is critical in glomerular patterning, contributes to the development of glomerular disease. Expression of the intracellular domain of Notch1 (ICN1) was increased in glomerular epithelial cells in diabetic nephropathy and in focal segmental glomerulosclerosis. Conditional re-expression of ICN1 in vivo exclusively in podocytes caused proteinuria and glomerulosclerosis. In vitro and in vivo studies showed that ICN1 induced apoptosis of podocytes through the activation of p53. Genetic deletion of a Notch transcriptional partner (Rbpj) specifically in podocytes or pharmacological inhibition of the Notch pathway (with a gamma-secretase inhibitor) protected rats with proteinuric kidney diseases. Collectively, our observations suggest that Notch activation in mature podocytes is a new mechanism in the pathogenesis of glomerular disease and thus could represent a new therapeutic target.

Background: Occupational risk factors for ovarian cancer have been investigated only to a limited extent. We conducted a case-cohort study to examine associations between occupational exposures and ovarian cancer in the textile industry., Methods: We compared 261 incident ovarian cancer cases diagnosed between 1989 and 1998 with an age-stratified reference subcohort (n = 3199) from a cohort of 267,400 textile workers in Shanghai, China. Occupational exposures were assessed by job-exposure matrices designed for the textile industry, and estimates of quantitative cotton dust and endotoxin. We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) with Cox proportional hazards modeling adapted for the case-cohort design., Results: A decreased risk of ovarian cancer was associated with ever having worked in cotton manufacturing production (HR = 0.7; 95% CI = 0.4-1.0). An increased risk was associated with ever having worked in textile finishing (2.1; 0.9-5.0). We found an increasing risk of ovarian cancer associated with cumulative exposure to silica dust (for <10 years exposure, HR = 6.8 [CI = 0.6-76]; for > or =10 years, 5.6 [1.3-23.6]), although these results are based on only 8 exposed subcohort women (0.3%) and 4 cases (1.3%). We also detected inverse risk gradients for cumulative exposures to endotoxin when exposures were lagged by 20 years (in highest quartile, HR = 0.6 [CI = 0.4-1.1])., Conclusion: Silica dust may increase the risk of ovarian cancer, and cotton dust and endotoxin may reduce risk.

Background: Proliferative benign breast conditions are associated with elevated risk of breast cancer, whereas nonproliferative conditions are not strongly associated with risk. Factors acting before onset of hyperplasia might be associated with both benign conditions and breast cancer, whereas those on the proliferative disease-to-cancer pathway would be associated only with cancer. Soy isoflavone exposure may influence breast cancer risk, but little is known of its association with benign conditions., Materials and Methods: We examined possible relationships between plasma genistein and daidzein concentrations and risk of breast disease in women, in a breast self-examination trial in Shanghai, China, diagnosed with breast cancer (n = 196) or a benign breast condition (n = 304), and 1,002 age-matched controls with no known breast disease. Benign conditions were classified as nonproliferative (n = 131) or proliferative with or without atypia (n = 173)., Results: Isoflavone concentrations were inversely associated with risk of nonproliferative and proliferative benign fibrocystic conditions, as well as with breast cancer, both with and without concomitant proliferative changes in ipsilateral noncancerous mammary epithelium (P(trend) < 0.01 for all comparisons with controls). Women in the highest quartile of plasma genistein (>76.95 ng/mL) were less likely to have breast cancer (odds ratio, 0.26; 95% confidence interval, 0.13-0.50) or benign conditions (odds ratio, 0.40; 95% confidence interval, 0.23-0.70) compared with women in the lowest quartile (<9.42 ng/mL). Observed risks for breast cancer with and without surrounding proliferative changes were not different, respectively, from observed risks for benign proliferative and nonproliferative conditions alone., Conclusion: Isoflavone exposure was inversely associated with fibrocystic breast conditions and breast cancer, and the results suggest that effects on cancer risk occur early in carcinogenesis.

Feral Mexican fruit flies, Anastrepha ludens (Loew) (Diptera: Tephritidae), were trapped in a citrus orchard in Mexico by using two types of synthetic food-odor lures, the AFF lure (Anastrepha fruit fly lure, APTIV, Inc., Portland, OR) and the BioLure (two-component MFF lure, Suterra LLC, Inc., Bend, OR). In Multilure traps (Better World Manufacturing, Inc., Miami, FL) containing water, BioLures captured about the same numbers of flies as AFF lures. In Multilure traps containing antifreeze solution, BioLures captured 2 and 5 times more flies than AFF lures in two experiments. BioLures, and AFF lures did not differ in attractiveness when used on sticky traps (Intercept trap, APTIV, Inc.; and sticky cylinder trap). Multilure traps captured >4 times as many flies as sticky traps with the exception that captures of females did not differ between Multilure and sticky traps baited with AFF lures. The percentage of females captured in Multilure traps was greater when traps were baited with BioLures compared with AFF lures, but the reverse was true for sticky traps. Sticky cylinder traps captured a higher percentage of females than Multilure traps. The most effective trap/lure combination was the Multilure trap baited with BioLure and antifreeze. In comparison with tests of these two lures in Texas, results were similar for Multilure traps, but they differed for sticky cylinder traps in that AFF lures were consistently more attractive than BioLures in Texas, but not in Mexico.

Purpose: The risk of 12 types of cancer in relation to use of monthly injectable contraceptives was assessed in a prospective study in Shanghai, China., Methods: From 1989 to 1991, an in-person interview was administered to 267,400 female textile workers to ascertain information on risk factors for breast cancer, contraceptive use and induced abortions. The cohort was followed until July 2000 for incident cancer cases. Cox proportional hazards analysis was used to calculate incidence rate ratios for specific types of cancer in women who ever had used monthly injectable contraceptives and by length of use., Results: There was a reduced risk of uterine corpus cancer for women who had ever used monthly injectable contraceptives. No association was observed between the use of monthly injectable contraceptives and the risk of all cancers combined and for any of the 11 other cancers considered., Conclusion: There appears to be no evidence of an increased risk of cancer after exposure to monthly injectable contraceptives in our study.

Influenza A virus causes worldwide epidemics and pandemics and the investigation of memory T helper (Th) cells that help maintain serological memory following infection is important for vaccine design. In this study we investigated CD94 and NKG2 gene expression in memory CD4 T-cell clones established from the spleens of C57BL/10 (H-2(b)) and BALB/c (H-2(d)) mice infected with influenza A virus (H3N2). CD94 and NKG2A/C/E proteins form heterodimeric membrane receptors that are involved in virus recognition. CD94 and NKG2 expression have been well characterized in natural killer (NK) and cytotoxic T cells. Despite CD94 being potentially an important marker for Th1 cells involved in virus infection, however, there has been little investigation of its expression or function in the CD4 T-cell lineage and no studies have looked at in-vivo-generated Th cells or memory cells. We show in this study that in-vivo-generated CD4 Th1 cells, but not Th2 cells, exhibited full-length CD94 and NKG2A gene expression following activation with viral peptide. For NKG2A, a novel 'short' (possibly redundant) truncated isoform was detectable in a Th2 cell clone. Another member of the NK receptor family, NKG2D, but not NKG2C or E, was also differentially expressed in Th1 cells. We show here that CD94 and NKG2A may exist as multiple isoforms with the potential to distinguish helper T-cell subsets.

Background: Breast cancer incidence rates have been increasing in China over the past 2 decades. Most studies have focused on reproductive, dietary, and genetic risk factors. Little is known about the contribution of occupational exposures., Methods: We conducted a case-cohort study within a cohort of female textile workers who had participated in a randomized trial of breast self-examination in Shanghai, China. We compared 1709 incident breast cancer cases with an age-stratified reference subcohort (n = 3155 noncases). Cox proportional hazards modeling, adapted for the case-cohort design, was used to estimate hazard ratios for breast cancer in relation to duration of employment in various job processes and duration of exposure to several agents. We also evaluated the associations of cotton dust and endotoxin with breast cancer., Results: Cumulative exposures to cotton dust and endotoxin demonstrated strong inverse gradients with breast cancer risk when exposures were lagged by 20 years (trend P-values <0.001). We did not observe consistent associations with exposures to electromagnetic fields, solvents, or other chemicals., Conclusion: Endotoxin or other components of cotton dust exposures may have reduced risks for breast cancer in this cohort, perhaps acting at early stages of carcinogenesis. Replication of these findings in other occupational settings with similar exposures will be needed to confirm or refute any hypothesis regarding protection against breast cancer.

Background: The role of individual fatty acids in the development and progression of breast cancer is unclear. Although in vitro and animal experiments have supported an inverse association between intake of long chain n-3 fatty acids [primarily eicosapentaenoic acid (EPA) and docosahexaenoic acid] and breast cancer risk, findings from population studies are inconsistent. Recent studies have also shown associations between the ratio of saturated to monounsaturated fatty acids (SI) and breast cancer risk. The SI reflects the activity of several genes involved in lipid metabolism, including fatty acid synthase and steroyl coenzyme-A desaturase, that have been shown to be overexpressed in breast cancer., Objective: The purpose of this analysis was to determine the association between erythrocyte fatty acid concentrations and breast cancer risk among women participating in a randomized trial of breast self-examination in Shanghai, China., Design: We conducted a case-control study. Erythrocyte fatty acid concentrations were determined in specimens from 322 women with histologically confirmed breast cancer and 1030 frequency age-matched control women., Results: We report a significant direct association among palmitic, gamma-linolenic, palmitoleic, and vaccenic acids and risk of breast cancer. Total n-3 fatty acids, EPA, and the SI for palmitic to palmitoleic acid were associated with significantly lower risk of breast cancer., Conclusion: Our results support a protective effect of n-3 fatty acids on breast cancer risk and provide additional evidence for the importance of evaluating the ratio of fatty acids when evaluating diet and breast cancer risk.

We report a case of a 53-year-old woman who presented with anemia and abnormal uterine bleeding. Endometrial and cervical biopsies revealed infiltration by large atypical cells, which were characterized as neoplastic plasma cells. Further investigations revealed systemic plasma cell dyscrasia (i.e., plasma cell myeloma). We therefore report a case of plasma cell myeloma, initially presenting as abnormal uterine bleeding.

Background: Reduced risk of lung cancer among workers in the cotton textile industry has been observed since the 1970s. Bacterial endotoxin, a contaminant of raw cotton fiber and cotton dust, has been proposed as a protective agent that may act through the innate and acquired immune systems. We examine the association between endotoxin exposure and lung cancer risk in a cohort of female textile workers., Methods: We conducted a case-cohort study nested within a cohort of 267,400 female textile workers in Shanghai, China. We compared the cumulative exposure histories of 628 case patients diagnosed with incident lung cancer from January 1, 1989, through December 31, 1998, with those of a lung cancer-free reference subcohort of 3184 workers who were frequency matched by 5-year age-groups to all cancer patients in the cohort. Cumulative endotoxin exposure for all participants was based on historic measurements and on additional measurements for this study. Relative risks and 95% confidence intervals (CIs) were estimated by hazard ratios (HRs) from Cox proportional hazards models. We conducted exposure-response trend analyses by use of cumulative exposures with lag times of 0, 5, 10, 15, or 20 years to account for disease latency. All analyses controlled for age and smoking status. All statistical tests were two-sided., Results: Cumulative exposure to endotoxin was strongly, statistically significantly, and inversely associated with lung cancer risk. The inverse trend was greatest with a 20-year lag time, for which highest endotoxin exposure was associated with a statistically significantly 40% less risk of lung cancer (HR = 0.60, 95% CI = 0.43 to 0.83; P(trend) across quintiles = .002) than non-exposure. From a reported population rate of lung cancer among women in Shanghai of 19.1 per 100,000 for the year 2000 and the estimated reduction in risk of lung cancer observed for 20 years of endotoxin exposure in this population of workers, the incidence of lung cancer in this cohort was reduced by approximately 7.6 per 100,000 (range = 3.2-10.9 per 100,000)., Conclusions: Long-term and high-level exposure to endotoxin, compared with no exposure, appears to be associated with a reduced risk of lung cancer in this cohort.