Rescue from Stx2-Producing E. coli-Associated Encephalopathy by Intravenous Injection of Muse Cells in NOD-SCID Mice.

Shiga toxin-producing Escherichia coli (STEC) causes hemorrhagic colitis, hemolytic uremic syndrome, and acute encephalopathies that may lead to sudden death or severe neurologic sequelae. Current treatments, including immunoglobulin G (IgG) immunoadsorption, plasma exchange, steroid pulse therapy, and the monoclonal antibody eculizumab, have limited effects against the severe neurologic sequelae. Multilineage-differentiating stress-enduring (Muse) cells are endogenous reparative non-tumorigenic stem cells that naturally reside in the body and are currently under clinical trials for regenerative medicine. When administered intravenously, Musecells accumulate to the damaged tissue, where they exert anti-inflammatory, anti-apoptotic, anti-fibrotic, and immunomodulatory effects, and replace damaged cells by differentiating into tissue-constituent cells. Here, severely immunocompromised non-obese diabetic/severe combined immunodeficiency (NOD-SCID) mice orally inoculated with 9 × 109 colony-forming units of STEC O111 and treated 48 h later with intravenous injection of 5 × 104 Muse cells exhibited 100% survival and no severe after-effects of infection. Suppression of granulocyte-colony-stimulating factor (G-CSF) by RNAi abolished the beneficial effects of Muse cells, leading to a 40% death and significant body weight loss, suggesting the involvement of G-CSF in the beneficial effects of Muse cells in STEC-infected mice. Thus, intravenous administration of Muse cells could be a candidate therapeutic approach for preventing fatal encephalopathy after STEC infection.

The impact of exposure to desert dust on infants' symptoms and countermeasures to reduce the effects.

BACKGROUND: The association between particulate matter (PM), including desert dust, and allergic symptoms has not been well studied. We examined whether PM exacerbated nose/eye/respiratory symptoms in infants, with a focus on the desert dust element, and assessed possible countermeasures. METHODS: We conducted a panel study of 1492 infants from October 2014 to July 2016 in 3 regions in Japan as an adjunct study of the Japan Environment and Children's Study. Infants' daily symptom scores and behaviors were acquired by web-based questionnaires sent to mothers, who answered within a day using mobile phones. Odds ratios (OR) for symptom development per increased fine PM or desert dust exposure were estimated. Regular use of medications and behaviors on the day of exposure were investigated as possible effect modifiers. RESULTS: Infants developed nose/eye/respiratory symptoms significantly more often in accordance with fine particulate levels (adjusted OR per 10 µg/m3 increase: 1.04, 95% confidence interval [CI]: 1.01-1.07). A model including both fine particulates and desert dust showed reduced OR for fine particulates and robust OR for desert dust (adjusted OR per 0.1/km increase: 1.16, 95% CI: 1.09-1.23). An increased OR was observed both in infants who had previously wheezed and in those who had never wheezed. Receiving information on the particulate forecast, reducing time outdoors, closing windows, and regular use of leukotriene receptor antagonists were significant effect modifiers. CONCLUSIONS: Transborder desert dust arrival increased the risk of nose/eye/respiratory symptoms development in infants. Regular use of leukotriene receptor antagonists and other countermeasures reduced the risk.

Body mass index and weight change during adulthood are associated with increased mortality from liver cancer: the JACC Study.

BACKGROUND: We investigated the association of baseline body mass index (BMI) and weight change since age 20 years with liver cancer mortality among Japanese. METHODS: The data were obtained from the Japan Collaborative Cohort Study for Evaluation of Cancer Risk (JACC Study). A total of 31 018 Japanese men and 41 455 Japanese women aged 40 to 79 years who had no history of cancer were followed from 1988 through 2009. RESULTS: During a median 19-year follow-up, 527 deaths from liver cancer (338 men, 189 women) were documented. There was no association between baseline BMI and liver cancer mortality among men or men with history of liver disease. Men without history of liver disease had multivariable hazard ratios (HR) of 1.95 (95%CI, 1.07-3.54) for BMI less than 18.5 kg/m(2) and 1.65 (1.05-2.60) for BMI of 25 kg/m(2) or higher, as compared with a BMI of 21.0 to 22.9 kg/m(2). BMI was positively associated with liver cancer mortality among women and women with history of liver disease. Weight change since age 20 years was positively associated with liver cancer mortality among women regardless of history of liver disease. Women with history of liver disease had a multivariable HRs of 1.96 (1.05-3.66) for weight gain of 5.0 to 9.9 kg and 2.31 (1.18-4.49) for weight gain of 10 kg or more, as compared with weight change of -4.9 to 4.9 kg. CONCLUSIONS: Both underweight (BMI <18.5 kg/m(2)) and overweight (BMI ≥25 kg/m(2)) among men without history of liver disease, and weight gain after age 20 (weight change ≥5 kg) among women with history of liver disease, were associated with increased mortality from liver cancer.

Cohort profile of the Japan Collaborative Cohort Study at final follow-up.

The Japan Collaborative Cohort Study for Evaluation of Cancer Risk (JACC Study) was established in the late 1980s to evaluate the risk impact of lifestyle factors and levels of serum components on human health. During the 20-year follow-up period, the results of the study have been published in almost 200 original articles in peer-reviewed English-language journals. However, continued follow-up of the study subjects became difficult because of the retirements of principal researchers, city mergers throughout Japan in the year 2000, and reduced funding. Thus, we decided to terminate the JACC Study follow-up at the end of 2009. As a final point of interest, we reviewed the population registry information of survivors. A total of 207 (0.19%) subjects were ineligible, leaving 110 585 eligible participants (46 395 men and 64 190 women). Moreover, errors in coding date of birth and sex were found in 356 (0.32%) and 59 (0.05%) cases, respectively, during routine follow-up and final review. Although such errors were unexpected, their impact is believed to be negligible because of the small numbers relative to the large total study population. Here, we describe the final cohort profile at the end of the JACC Study along with selected characteristics of the participants and their status at the final follow-up. Although follow-up of the JACC Study participants is finished, we will continue to analyze and publish study results.

Serum adiponectin multimer complexes and liver cancer risk in a large cohort study in Japan.

Evidence suggests a link between adiponectin, an adipocytokine, and liver tumorigenesis. Different multimer complexes of adiponectin, with low-molecular weight (LMW), middle-molecular weight (MMW) and high-molecular weight (HMW), may have different roles. Therefore the present study was performed with the aim of assessing associations between these multimers and liver cancer development. A nested case-control study (59 liver cancer cases [mean age=63.5 years] and 334 controls [62.7 years]) was conducted as a part of the Japan Collaborative Cohort (JACC) Study recruiting healthy participants, aged 40-79 years, for the follow-up period from 1988-1990 to 1999. The end point was liver cancer occurrence/death. Serum levels of HMW, MMW and LMW adiponectin were determined at baseline using an ELISA assay. Multivariate-adjusted logistic regression analyses comparing the tertile levels of adiponectin multimers showed that the groups stratified with the highest percentage of LMW tended to have lower odds ratios (ORs) than the lowest group (OR adjusted for sex, age and area=0.54 [95%CI: 0.26-1.11] and adjusted for sex, age, area, body mass index, smoking, alcohol, coffee consumption, diabetes history and HCV-antibody positivity =0.50 [95%CI: 0.22-1.15]), albeit without statistical significance (set at p<0.05). Higher percentages of circulating LMW adiponectin may lead to a reduction of liver cancer risk and relationships with multimer composition may merit further study.

The lack of relationship between an endothelin-1 gene polymorphism (Ala288ser) and incidence of hypertension: a retrospective cohort study among Japanese workers.

BACKGROUND: Some case-control association studies revealed the relationship between some endothelin-1 (ET-1) gene polymorphisms and blood pressure. Because no report was available about the relationship between any ET-1 gene polymorphism and incidence of hypertension, we examined the relationship between novel ET-1 gene polymorphism (G862T / Ala288Ser in exon 5) and incidence of hypertension by a retrospective cohort study. METHODS: The subjects were Japanese workers at a company in Shimane Prefecture in Japan. The polymorphism with genome DNA extracted from the blood of the workers was analyzed using the polymerase chain reaction confronting two pair primers method. According to the results of two regular health checkups with a 6-year interval, the study population was divided into two groups by blood pressure and antihypertensive treatment in 1998, after excluding people who had hypertension in 1992. RESULTS: There were 133 (93 males and 40 females) incidences of hypertension observed among the study population of 922 (540 males and 382 females). In the univariate analysis, odds ratios of Ala/Ser and Ser/Ser against Ala/Ala were 0.98 (95% confidence interval [CI]): 0.7-1.4) and 0.79 (95% CI: 0.4-1.6), respectively. In the multivariate analysis adjusted for sex, age, body mass index, serum total cholesterol, fasting blood sugar, and smoking and drinking habits, odds ratios for Ala/Ser and Ser/Ser against Ala/Ala were 0.97 (95% CI: 0.7-1.4) and 0.75 (95% CI: 0.4-1.5), respectively. CONCLUSIONS: The ET-1 gene polymorphism in this study did not seem to be associated with the incidence of hypertension among the Japanese workers.