Association of allergies in children younger than 3 years with levels of maternal intake of n-3 polyunsaturated fatty acids or fish during pregnancy: A nationwide birth cohort study, the Japan Environment and Children's Study.

BACKGROUND: N-3 polyunsaturated fatty acids (PUFAs) have anti-inflammatory properties and are expected to prevent the onset of allergies. However, epidemiological studies investigating the relationship between child allergies and maternal intake of n-3 PUFAs or fish have yielded inconsistent results. METHODS: Following exclusions from a dataset comprising 103,057 records from the Japan Environment and Children's Study, 72,105 participants were divided into five groups according to mothers' intake of n-3 PUFAs or fish during pregnancy to assess the risk of their children being diagnosed with allergy by 3 years old. Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) for child allergies were calculated using multivariable logistic regression analyses with reference to the lowest intake group. RESULTS: Levels of maternal intake of n-3 PUFAs or fish showed inverted associations (i.e., reduced risk) with the incidence of physician-diagnosed allergic rhinoconjunctivitis or parent-reported symptoms of current rhinitis with eye symptoms at different time points and the cumulative incidence from birth to 3 years of age. Inverted associations were also found for current wheeze at 1-<2 years of age and current eczema at 1-<2 and 0-<3 years of age. However, for food allergies, no significant associations were observed in the incidence in each group compared with the lowest intake group at any age. CONCLUSIONS: The findings suggest that n-3 PUFA intake during pregnancy may reduce the risk of developing allergic diseases and symptoms in children. In addition, consumption of n-3 PUFAs or fish is very unlikely to increase the risk of allergy given that the results are from a country with high fish consumption. TRIAL REGISTRATION: UMIN000030786 https://rctportal.niph.go.jp/detail/um?trial_id=UMIN000030786.

Association between Maternal Vitamin D Intake and Infant Allergies: The Japan Environment and Children's Study.

Maternal nutrition during pregnancy is one of the factors affecting the health of offspring. There are conflicting findings about the association between maternal vitamin D status and the development of allergic diseases in offspring. The purpose of this study is to evaluate the association between maternal vitamin D intake and the development of allergic diseases in offspring at 1 y of age. From an ongoing nationwide birth cohort study (the Japan Environment and Children's Study), we obtained information on maternal vitamin D intake, determined by a food frequency questionnaire, and parent-reported physician-diagnosed allergic diseases in offspring at 1 y of age. From the full dataset of 103,062 pregnancies, we analyzed complete data for 82,592 mother-offspring pairs. The prevalence of physician-diagnosed asthma, food allergy, and atopic dermatitis in the children was 2.5%, 6.6%, and 4.3%, respectively. The mean (± standard deviation) maternal vitamin D intake was 4.7±4.7 µg/d, which is much lower than the recommended amount in Japan (7 µg/d). After adjustment for various covariates, the odds ratios were significantly higher for asthma in the 2nd quintile and for food allergies in the 3rd and 4th quintiles compared with the 1st quintile. However, there were no clear associations between maternal vitamin D intake and the development of allergic diseases in offspring at 1 y of age, even in a large nation-wide cohort study. Protective effects of vitamin D supplementation remain unclear.

Impact of Low Ambient Temperature on the Occurrence of Spontaneous Intracerebral Hemorrhage-Analysis of Population-Based Stroke Registry in Toyama, Japan.

OBJECTIVE: Although several studies have reported that some meteorological factors such as ambient temperature and atmospheric pressure, affect the incidence of spontaneous intracerebral hemorrhage (ICH), the correlation remains unclear. This retrospective time-series analysis was aimed to clarify the effects of meteorological parameters on the incidence of ICH. MATERIALS AND METHODS: Data of patients with ICH were obtained from a population-based survey of acute stroke patients between April 2016 and March 2019. All days during the study period were categorized into "no ICH day" when no ICHs occurred, "single ICH day" when only one ICH occurred, and "cluster day" when two or more ICHs occurred. Meteorological data were compared for among the three categories. RESULTS: 1,691 ICH patients from 19 hospitals were registered. In a total of 1,095 days, 250 were categorized as no ICH days, 361 as single ICH days, and 484 as cluster days. Daily ambient temperature declined in parallel with the daily number of ICHs, and it was a significant predictor for single ICH days and cluster days. Furthermore, the incidence of ICH in patients aged 65 years or above, men, those who emerged at home, those with modified Rankin Scale 3-5; and those with hypertension; and ICHs in the basal ganglia, brain stem, and cerebellum were more likely to be affected by low ambient temperature. CONCLUSION: Daily ambient temperature was significantly associated with ICH incidence. Patients' activity, history of hypertension, and location of hemorrhage were also related to the impact of low ambient temperature on the incidence of ICH.

Melatonin sensitises shikonin-induced cancer cell death mediated by oxidative stress via inhibition of the SIRT3/SOD2-AKT pathway.

Recent research suggests that melatonin (Mel), an endogenous hormone and natural supplement, possesses anti-proliferative effects and can sensitise cells to anti-cancer therapies. Although shikonin (SHK) also possesses potential anti-cancer properties, the poor solubility and severe systemic toxicity of this compound hinders its clinical usage. In this study, we combined Mel and SHK, a potentially promising chemotherapeutic drug combination, with the aim of reducing the toxicity of SHK and enhancing the overall anti-cancer effects. We demonstrate for the first time that Mel potentiates the cytotoxic effects of SHK on cancer cells by inducing oxidative stress via inhibition of the SIRT3/SOD2-AKT pathway. Particularly, Mel-SHK treatment induced oxidative stress, increased mitochondrial calcium accumulation and reduced the mitochondrial membrane potential in various cancer cells, leading to apoptosis. This drug combination also promoted endoplasmic reticulum (ER) stress, leading to AKT dephosphorylation. In HeLa cells, Mel-SHK treatment reduced SIRT3/SOD2 expression and SOD2 activity, while SIRT3 overexpression dramatically reduced Mel-SHK-induced oxidative stress, ER stress, mitochondrial dysfunction and apoptosis. Hence, we propose the combination of Mel and SHK as a novel candidate chemotherapeutic regimen that targets the SIRT3/SOD2-AKT pathway in cancer.

Melatonin triggers the anticancer potential of phenylarsine oxide via induction of apoptosis through ROS generation and JNK activation.

Melatonin, a safe endogenous hormone and a natural supplement, has recently been recognized to have antiproliferative effects and the ability to sensitize cells to other anticancer therapies. Phenylarsine oxide (PAO) has anticancer potential but it is considered as a toxic agent. In this study we combined melatonin to reduce the toxicity while securing the anti-cancer effects of PAO. Cell viability was determined by MTT assay, whereas cytotoxic assays were performed using an LDH cytotoxicity assay kit. Cell cycle analysis, Annexin V/PI staining, the mitochondrial membrane potential (MMP), mitochondrial calcium and reactive oxygen species (ROS) generation were analyzed using flow cytometry. Sytox stained cells were visualized by fluorescence microscopy and the expression of proteins was detected by western blotting. Melatonin increased the anticancer potential of PAO by decreasing the cell viability and increasing LDH release in various cancer cells. The mode of cell death was determined to be typical apoptosis, as evidenced by Annexin V/PI-stained cells, PARP cleavage, and caspase-3 activation, and with significant modulations in the expression of proapoptotic, antiapoptotic and cell cycle-related proteins. ROS generation played a critical role in induction of cell death by this combined treatment, which is validated by reversal of cytotoxicity upon cotreatment with NAC. Furthermore, the activation of MAPKs, especially JNK, contributed to the induction of cell death, accompanied by endoplasmic reticulum stress and autophagy, affirmed by the abrogation of cytotoxicity after JNK-IN-8 and TUDCA application. Melatonin showed promising potential as a chemotherapeutic agent in combination with PAO to achieve a better anticancer response.

Dietary intake of fish and n-3 polyunsaturated fatty acids and risk of postpartum depression: a nationwide longitudinal study - the Japan Environment and Children's Study (JECS).

BACKGROUND: Pregnant women require increased levels of n-3 polyunsaturated fatty acids (PUFAs) due to the demands of the growing fetus. Although some evidence indicates that maternal intake of fish and n-3 PUFAs is associated with reduced risk of postpartum depression, the results are inconsistent. METHODS: We investigated whether dietary consumption of fish and/or n-3 PUFAs during pregnancy is associated with a reduced risk of maternal postpartum depression at 6 months after delivery and of serious mental illness at 1 year in a Japanese population. After exclusion and multiple imputation from a dataset comprising 103 062 pregnancies obtained in the Japan Environment and Children's Study, we evaluated 84 181 and 81 924 women at 6 months and 1 year after delivery, respectively. RESULTS: Multivariable logistic regression showed a reduced risk of postpartum depression at 6 months in the second to fifth quintiles v. the lowest quintile for fish and n-3 PUFA intake, with trend tests also revealing a significant linear association. At 1 year after delivery, fish intake was associated with a reduced risk of serious mental illness in the second to fifth quintiles v. the lowest quintile for fish and in the third to fifth quintiles v. the lowest quintile for n-3 PUFA intake, with trend tests also revealing a significant linear association. CONCLUSIONS: Women with higher fish and/or n-3 PUFA intake showed reduced risk of postpartum depression at 6 months after delivery and of serious mental illness at 1 year after delivery.

Dietary intake of fish and ω-3 polyunsaturated fatty acids and physician-diagnosed allergy in Japanese population: The Japan Environment and Children's Study.

OBJECTIVE: Emerging evidence from epidemiologic studies and clinical trials indicates that ω-3 polyunsaturated fatty acids (PUFAs) may have a preventive or therapeutic effect on allergy, although the results remain controversial. The aim of this study was to investigate the association between intake of fish and ω-3 PUFAs with risk for lifetime prevalence of physician-diagnosed allergy in a Japanese population. METHODS: Study participants were 78 621 pregnant women and 42 831 male partners from The Japan Environment and Children's Study. History of physician-diagnosed allergy (asthma, allergic rhinitis/pollinosis, allergic conjunctivitis, or atopic dermatitis) was determined by self-administered questionnaire survey. Dietary intake of fish and ω-3 PUFAs was estimated using a food frequency questionnaire. RESULTS: Contrary to our hypothesis, an increased risk for allergy was found by multivariable logistic regression in females, especially in allergic rhinitis/pollinosis, allergic conjunctivitis, or atopic dermatitis for fish intake and in allergic rhinitis/pollinosis or allergic conjunctivitis for ω-3 PUFAs. As for male partners, risk for allergic rhinitis/pollinosis or atopic dermatitis was increased for both fish and ω-3 PUFA intake. No statistically significant results were observed for the risk for asthma in either women or men. CONCLUSION: Fish and ω-3 PUFA intake were associated with increased risk for some allergic diseases. Further research is warranted to confirm these findings in individuals with high fish consumption.

High frequency of vitamin D deficiency in current pregnant Japanese women associated with UV avoidance and hypo-vitamin D diet.

BACKGROUND: As a consequence of indoor occupations and reduced exposure to sunlight, concerns have been raised that vitamin D deficiency is widespread in developed countries. Vitamin D is known to be associated with increased risks of morbidity and mortality in various diseases. OBJECTIVE: To investigate the serum vitamin D status and its relation with life-style factors in pregnant Japanese women. METHODS: Among a cohort for 3,327 pregnant women who participated in an the adjunct study of the Japan Environment and Children's Study during 2011-2013, in which data were obtained on various life-style factors, including both dietary intake of vitamin D and frequency of UV exposure, this study consisted of 1,592 pregnant women, from whom 2,030 serum samples were drawn in Jan, Apr, Jul, and Oct, and the association between serum 25(OH)D level and life-style factors were analyzed using linear mixed models. RESULTS: Serum 25(OH)D levels were less than 20ng/mL in 1,486 of 2,030 samples (73.2%). There was an obvious seasonal change, with serum 25(OH)D levels of less than 20 ng/mL in 89.8% and 47.8% of samples in spring (April) and autumn (October), respectively. Both the frequency spent under sunlight and dietary intake of vitamin D were significantly associated with serum 25(OH)D level. An increase in sunlight exposure of more than 15 min for 1 to 2 days per week in non-winter, or dietary intake of 2 µg/day of vitamin D resulted in an elevation of 1 ng/mL in serum 25(OH)D levels. CONCLUSION: These findings indicate that vitamin D deficiency is very severe in Japanese pregnant women, especially those rarely exposed to sunlight. The benefits of UV rays should also be informed of when its risk is alerted, and clinicians should propose the adequate UV exposure level.

Protective effect of dihydromyricetin on hyperthermia-induced apoptosis in human myelomonocytic lymphoma cells.

Dihydromyricetin (DMY) is a traditional herbal medicine, with a wide range of biological activities. Extreme hyperthermia (HT) can suppress the immune system; thus, protection of the immune system is beneficial in heat-related diseases, including heatstroke. In our study, we revealed the protective effect of DMY against HT-induced apoptosis and analysed the underlying molecular mechanisms. We incubated human myelomonocytic lymphoma U937 cells at 44 °C for 30 min with or without DMY and followed by further incubation for 6 h at 37 °C. Cell viability was determined by the CCK-8 assay. DMY did not cause any cytotoxic effects in U937 cells even at high doses. HT treatment alone induced significant apoptosis, which was detected by DNA fragmentation and Annexin V/PI double staining. Mitochondrial dysfunction was identified by loss of mitochondrial membrane potential (MMP) during heat stimulation. Apoptotic related proteins were involved, truncated Bid and caspase-3 were upregulated, and Mcl-1 and XIAP were downregulated. We also identified the related signalling pathways, such as the MAPK and PI3K/AKT pathways. However, changes in HT were dramatically reversed when the cells were pretreated with DMY before exposure to HT. Overall, MAPKs and PI3K/AKT signalling, mitochondrial dysfunction, and caspase-mediated pathways were involved in the protective effect of DMY against HT-induced apoptosis in U937 cells, which was totally reversed by DMY pretreatment. These findings indicate a new clinical therapeutic strategy for the protection of immune cells during heatstroke.

Mechanistic study of nonivamide enhancement of hyperthermia-induced apoptosis in U937 cells.

Hyperthermia is one therapeutic tool for damaging and killing cancer cells, with minimal injury to normal tissues. However, its cytotoxic effects alone are insufficient for quantitative cancer cell death. To overcome this limitation, several studies have explored non-toxic enhancers for hyperthermia-induced cell death. Capsaicin may be applicable as a therapeutic tool against various types of cancer. In the present study, we employed nonivamide, a less-pungent capsaicin analogue, to investigate its possible enhancing effects on hyperthermia-induced apoptosis; moreover, we analyzed its molecular mechanism. Treatment of U937 cells at 44 °C for 15 min, combined with nonivamide 50 µM, revealed enhancement of apoptosis. Significant increases in reactive oxygen species generation, mitochondrial dysfunction, and cleaved caspase-3 were observed during the combined treatment; these were accompanied by an increase in pro-apoptotic Bcl-2 family proteins and a decrease in anti-apoptotic Bcl-2 proteins. In addition, significant increases in p-JNK and p-p38 were detected, following the combined treatment. In conclusion, nonivamide enhanced hyperthermia-induced apoptosis via a mitochondrial-caspase dependent pathway. The underlying mechanism may include elevation of intracellular reactive oxygen species, mitochondrial dysfunction, and increased activation of JNK and p38.

Baicalin Augments Hyperthermia-Induced Apoptosis in U937 Cells and Modulates the MAPK Pathway via ROS Generation.

BACKGROUND/AIMS: Hyperthermia is a widely used therapeutic tool for cancer therapy and a well-known inducer of apoptosis. Although the flavonoid compound baicalin (BCN) is a potent anticancer agent for several human carcinomas, it is less potent in the human U937 myelomonocytic leukemia cell line. To explore any enhancing effects of BCN on hyperthermia-induced apoptosis, this study investigated the combined effects and apoptotic mechanisms of hyperthermia and BCN in U937 cells. METHODS: U937 cells were heat treated at 44ºC for 12 min with or without pre-treatment with BCN (10-50 µM) and then incubated for 6 h at 37 ºC with 5% CO2 and 95% air. Cell viability was analyzed by Trypan blue exclusion assay. Apoptosis was examined by DNA fragmentation, fluorescence microscopy and flow cytometry. Generation of mitochondrial trans-membrane potential (MMP), mitochondrial calcium, and reactive oxygen species (ROS) was also detected by flow cytometry. The expression of proteins related to apoptosis and signaling pathways was determined by western blotting. RESULTS: Hyperthermia alone did not reduce cell viability or induce notable levels of apoptosis, but combined hyperthermia and BCN treatment markedly augmented apoptosis by upregulating proapoptotic proteins and suppressing antiapoptotic proteins, culminating in caspase-3 activation. Mitochondrial transmembrane potential was significantly decreased, and generation of reactive oxygen species (ROS) and suppression of antioxidant enzymes were marked. Furthermore, with the combined treatment, the phosphorylated forms of JNK and p38 showed increased expression, whereas AKT was dephosphorylated. JNK-IN-8 (a JNK inhibitor) and NAC (a ROS scavenger) abrogated the apoptotic effects of the combined treatment, significantly protecting the cells and indicating the involvement of high ROS generation and the MAPK pathway in the underlying molecular mechanism. CONCLUSION: This study provides compelling evidence that hyperthermia, in combination with BCN, is a promising therapeutic strategy for enhancement of apoptosis and suggest a promising therapeutic approach for cancer.

Dietary intake of fish and n-3 polyunsaturated fatty acids and risks of perinatal depression: The Japan Environment and Children's Study (JECS).

The results of several epidemiological studies and clinical trials investigating the effects of n-3 polyunsaturated fatty acids (PUFAs) on antenatal and postnatal depression remain controversial. We investigated the possible association of dietary intake of fish and n-3 PUFAs with the risks of maternal and paternal psychological distress during pregnancy and of maternal postpartum depression in Japan. From a dataset comprising 104,102 maternal registrations and 52,426 paternal registrations in The Japan Environment and Children's Study, this study analyzed complete data on questionnaires for 75,139, 79,346, and 77,661 women during early pregnancy, mid-late pregnancy, and after pregnancy, respectively, and for 41,506 male partners. Multivariable logistic regression showed reduced risk of psychological distress in the second and third quintiles for fish intake in early pregnancy and in the second to fifth quintile in mid-late pregnancy. No reductions were observed for n-3 PUFA intake in early pregnancy but in the second to fourth quintile in mid-late pregnancy. For postpartum depression, reductions were observed in the second to fourth quintile for fish intake but only in the first quintile for n-3 PUFA intake. As for paternal psychological distress, only the fourth quintile for fish intake showed a significant reduced risk but none were shown for n-3 PUFA intake. In conclusion, fish intake was associated with some reduced risk of psychological distress during pregnancy, even for male partners. The associations were weaker for n-3 PUFA intake than for fish intake.

Effect of desert dust exposure on allergic symptoms: A natural experiment in Japan.

BACKGROUND: Desert dust originating from arid and semiarid areas is transported to widespread regions, including Japan. Desert dust particles exert adjuvant effects in animals. OBJECTIVE: To examine whether desert dust enhances allergic symptoms in real-life settings and to explore its effect modifiers. METHODS: We conducted an observational study of 3,327 pregnant women during spring and fall in October 2011 to May 2013 in 3 regions in Japan as an adjunct study of the Japan Environment & Children's Study. We acquired participants' daily symptom scores by sending a questionnaire to their mobile phones on high desert-dust days (>0.07/km) and on some randomly selected other days (control days) for each participant. RESULTS: Pregnant women had an increased risk of allergic symptoms on high desert-dust days (adjusted odds ratio [OR], 1.10; 95% CI, 1.04-1.18). The increased OR was mostly driven by those who showed positive IgE to Japanese cedar pollen when pollen simultaneously dispersed (adjusted OR, 1.25; 95% CI, 1.13-1.38), whereas no clear risk increase was observed in the absence of pollen or for participants with negative IgE to Japanese cedar pollen. The risk elevation was observed from low levels of desert dust in a dose-dependent manner even on control days. CONCLUSION: Ambient desert dust level was associated with an increased risk of allergic symptoms in pollen-sensitized pregnant women when pollen was present in the air. The risk increase was dose dependent and was observed from low levels of desert dust. These results support a hypothesis that ambient desert dust particles exert adjuvant effects in human in real-life settings. TRIAL REGISTRATION: clinicaltrials.gov Identifier: UMIN000010826.

Molecular mechanisms of hyperthermia-induced apoptosis enhanced by docosahexaenoic acid: implication for cancer therapy.

To develop a non-toxic enhancer for hyperthermia-induced cell death as a potential cancer treatment, we studied the effect and mechanism of docosahexaenoic acid (DHA) on hyperthermia-induced apoptosis. Treatment with 20µM DHA and 44°C for 10min induced significant apoptosis, increased intracellular reactive oxygen species (ROS), and caspase-3 activation in U937 cells, but heat or DHA alone did not induce notable apoptosis. Decreased mitochondrial transmembrane potentials were dramatically increased by the combined treatment, accompanied by increased pro-apoptotic Bcl-2 family protein tBid, and decreased anti-apoptotic Bcl-2 and Bcl-xL. Combined hyperthermia-DHA treatment induced significant phosphorylation of protein kinase C (PKC)-δ (p-PKC-δ), and apoptosis in a DHA dose-dependent manner. Using both 20µM DHA and 44°C for 10min induced significant PKC-δ cleavage and its translocation to mitochondria. These results were also seen in HeLa cells. However, MAPKs and Akt were not affected by the treatment. In conclusion, DHA enhances hyperthermia-induced apoptosis significantly via a mitochondria-caspase-dependent pathway; its underlying mechanism involves elevated intracellular ROS, mitochondria dysfunction, and PKC-δ activation.

Molecular mechanisms of hyperthermia-induced apoptosis enhanced by withaferin A.

Hyperthermia is a good therapeutic tool for non-invasive cancer therapy; however, its cytotoxic effects are not sufficient. In the present study, withaferin A (WA), a steroidal lactone derived from the plant Withania somnifera Dunal, has been investigated for its possible enhancing effects on hyperthermia-induced apoptosis. In HeLa cells, treatment with 0.5 or 1.0µM WA at 44°C for 30min induced significant apoptosis accompanied by decreased intracellular GSH/GSSG ratio and caspase-3 activation, while heat or WA alone did not induce such changes. The upregulation in apoptosis was significantly inhibited by glutathione monoethyl ester, a cell permeable glutathione precursor. Mitochondrial transmembrane potentials were dramatically decreased by the combined treatment, with increases in pro-apoptotic Bcl-2-family proteins tBid and Noxa, and downregulation of antiapoptotic Bcl-2 and Mcl-1. Combined treatment with hyperthermia and WA induced significant increases in JNK phosphorylation (p-JNK), and decreases in the phosphorylation of ERK (p-ERK) compared with either treatment alone. These results suggest that WA enhances hyperthermia-induced apoptosis via a mitochondria-caspase-dependent pathway; its underlying mechanism involves elevated intracellular oxidative stress, mitochondria dysfunction, and JNK activation.

Docosahexaenoic acid is an independent predictor of all-cause mortality in hemodialysis patients.

BACKGROUND: Dietary n-3 polyunsaturated fatty acids (PUFAs), docosahexaenoic acid (DHA) and eicosapentaenoic acid have been shown to reduce cardiovascular mortality. Patients on hemodialysis (HD) have a very high mortality from cardiovascular disease. Fish consumption reduces all-cause mortality in patients on HD. Moreover, n-3 PUFAs, especially DHA levels in red blood cells (RBCs), are associated with arteriosclerosis in patients on HD. The aim of this study was to determine whether DHA levels in RBCs predict the mortality of patients on HD in a prospective cohort study. METHODS: A cohort of 176 patients (64.1 ± 12.0 (mean ± SD) years of age, 96 men and 80 women) under HD treatment was studied. The fatty acid composition of their RBCs was analyzed by gas chromatography. RESULTS: During the study period of 5 years, 54 deaths occurred. After adjustment for 10 confounding factors, the Cox hazard ratio of all-cause mortality of the patients on HD in the highest DHA tertile (>8.1%, 15 deaths) was 0.43 (95% CI 0.21-0.88) compared with those patients in the lowest DHA tertile (<7.2%, 21 deaths). CONCLUSION: The findings suggest that the level of DHA in RBCs could be an independent predictor of all-cause mortality in patients on HD.

Endocrine disruptors (environmental estrogens) enhance autoantibody production by B1 cells.

Accumulating data suggest that endocrine disruptors affect not only the reproductive system, but also the immune system. We demonstrate here that endocrine disruptors including diethylstilbestrol (DES) and bisphenol-A (BPA) enhance autoantibody production by B1 cells both in vitro and in vivo. BWF1 mice, a murine model for systemic lupus erythematosus (SLE), implanted with Silastic tubes containing DES after orchidectomy developed murine lupus characterized by immunoglobulin G (IgG) anti-DNA antibody production and IgG deposition in the glomeruli in the kidney as well as those implanted with 17beta-estradiol (E2). Plaque-forming cells (PFC) producing autoantibodies specific for bromelain-treated red blood cells were significantly increased in mice implanted with DES and BPA. IgM antibody production by B1 cells in vitro was also enhanced in the presence of endocrine disruptors including DES and BPA. Estrogen receptor (ER) expression was upregulated in B1 cells in aged BWF1 mice that developed lupus nephritis. These results suggest that endocrine disruptors are involved in autoantibody production by B1 cells and may be an etiologic factor in the development of autoimmune diseases.

[Molecular biological approaches for environmental medicine].

A revolution in biology and medicine is taking place as a direct consequence of rapid developments in the field of molecular biology. The tremendous advances in our knowledge of basic molecular genetics and cell biology have opened the door for new methods of diagnosis, assessment of individual susceptibility to disease, and elucidation of the pathogenesis of disease. These advances will have a profound impact on the practice of occupational and environmental medicine. In this review, we intend to summarize the approaches we have applied in order to deal with the environmental problems we have faced.