Prevalence of adult-onset multifactorial disease among offspring of atomic bomb survivors.

The first study to examine whether parental radiation exposure leads to increased heritable risk of common adult-onset multifactorial diseases (i.e., hypertension, diabetes mellitus, hypercholesterolemia, ischemic heart disease, and stroke) was conducted among 11,951 participants in the clinical examination program out of a potential of 24,673 mail survey subjects who were offspring of survivors born from May 1946 through December 1984. Logistic regression analyses demonstrated no evidence of an association between the prevalence of multifactorial diseases in the offspring and parental radiation exposure, after adjusting for age, city, gender and various risk factors. The odds ratio (OR) for a paternal dose of 1 Gy was 0.91 [95% confidence interval (CI) 0.81-1.01, P = 0.08], and that for a maternal dose of 1 Gy was 0.98 (95% CI 0.86-1.10, P = 0.71). There was no apparent effect of parental age at exposure or of elapsed time between parental exposure and birth, but male offspring had a low odds ratio (OR = 0.76 at 1 Gy) for paternal exposure, but cautious interpretation is needed for this finding. The clinical assessment of nearly 12,000 offspring of A-bomb survivors who have reached a median age of about 50 years provided no evidence for an increased prevalence of adult-onset multifactorial diseases in relation to parental radiation exposure.

Psychological effects of forest environments on healthy adults: Shinrin-yoku (forest-air bathing, walking) as a possible method of stress reduction.

OBJECTIVES: Shinrin-yoku (walking and/or staying in forests in order to promote health) is a major form of relaxation in Japan; however, its effects have yet to be completely clarified. The aims of this study were: (1) to evaluate the psychological effects of shinrin-yoku in a large number of participants; and (2) to identify the factors related to these effects. METHODS: Four hundred and ninety-eight healthy volunteers took part in the study. Surveys were conducted twice in a forest on the same day (forest day) and twice on a control day. Outcome measures were evaluated using the Multiple Mood Scale-Short Form (hostility, depression, boredom, friendliness, wellbeing and liveliness) and the State-Trait Anxiety Inventory A-State Scale. Statistical analyses were conducted using analysis of variance and multiple regression analyses. RESULTS: Hostility (P<0.001) and depression (P<0.001) scores decreased significantly, and liveliness (P=0.001) scores increased significantly on the forest day compared with the control day. The main effect of environment was also observed with all outcomes except for hostility, and the forest environment was advantageous. Stress levels were shown to be related to the magnitude of the shinrin-yoku effect; the higher the stress level, the greater the effect. CONCLUSIONS: This study revealed that forest environments are advantageous with respect to acute emotions, especially among those experiencing chronic stress. Accordingly, shinrin-yoku may be employed as a stress reduction method, and forest environments can be viewed as therapeutic landscapes. Therefore, customary shinrin-yoku may help to decrease the risk of psychosocial stress-related diseases, and evaluation of the long-term effects of shinrin-yoku is warranted.

Use of tacrolimus, a potent antifibrotic agent, in bleomycin-induced lung fibrosis.

Idiopathic pulmonary fibrosis has a poor prognosis and few efficacious treatments. The immunosuppressant cyclosporin A has been shown to inhibit tumour growth factor (TGF)-beta-induced collagen deposition in vitro, and is widely used in Japan as a potent antifibrotic agent. Tacrolimus (FK506) is another attractive immunosuppressant, which may be useful in the treatment of pulmonary fibrosis. The aim of the present study was to elucidate the antifibrotic effect of FK506. The inhibitory effect of FK506 on collagen synthesis in cultured lung fibroblastic cells, TIG-3-20, and its antifibrotic effect on bleomycin (BLM)-induced pulmonary fibrosis in mice was investigated. FK506 inhibited TGF-beta-induced collagen synthesis, and suppressed the expression of TGF-beta type I receptor (TbetaR-I) in TIG-3-20 cells. Consistent with the in vitro findings, FK506 treatment starting on day 6 attenuated BLM-induced pulmonary fibrosis, in part, via reduced TbetaR-I expression. FK506 treatment in the acute BLM injury phase unexpectedly increased pro-inflammatory cytokine levels in bronchoalveolar lavage fluid and enhanced lung injury, resulting in poor survival. In conclusion, the present results suggest that FK506 has a potent antifibrotic effect and may be useful for the treatment of pulmonary fibrosis, although its use in the acute inflammatory phase may exacerbate lung injury.

Vegetable and fruit intake and stroke mortality in the Hiroshima/Nagasaki Life Span Study.

BACKGROUND AND PURPOSE: Fruits and vegetables are known for their beneficial effects on chronic diseases. The purpose of the present study was to investigate the protective effect of a diet rich in fruits and vegetables on total stroke mortality and its 2 main subtypes in men and women separately. METHODS: A prospective cohort study of 40 349 Japanese men and women was initiated in 1980-1981 and followed until 1998. Fruit and vegetable intake was assessed at baseline on the basis of the response to a food frequency questionnaire. During the 18-year follow-up period, deaths from stroke were registered. RESULTS: A total of 1926 stroke deaths were identified during the follow-up period. An increasing frequency of intake of green-yellow vegetables and fruit was associated with a reduced risk of death from intracerebral hemorrhage and cerebral infarction. Daily intake of green-yellow vegetables was associated with a significant 26% reduction in the risk of death from total stroke in men and women compared with an intake of once or less per week. The protective effect associated with daily fruit and vegetable intake was observed for both cerebral infarction and intracerebral hemorrhage mortality but was slightly stronger and clearer for infarction than for hemorrhage, with a 32% reduction in men and a 30% reduction in women. Daily fruit intake was associated with a significant 35% reduction in risk of total stroke in men and a 25% reduction in women and was equally strong for both intracerebral hemorrhage and cerebral infarction. CONCLUSIONS: Daily consumption of green-yellow vegetables and fruits is associated with a lower risk of total stroke, intracerebral hemorrhage, and cerebral infarction mortality. The protective effects are similar in both men and women.

Vegetables and fruit intake and cancer mortality in the Hiroshima/Nagasaki Life Span Study.

The association between green-yellow vegetables and fruit consumption and risk of cancer death was investigated in a prospective study of 38 540 men and women who were atomic-bomb survivors in Hiroshima and Nagasaki, Japan. Study participants completed a dietary questionnaire in 1980-1981 and were followed-up for cancer deaths until March 1998, during which time 3136 cancer deaths were identified. Daily or almost daily fruit consumption was associated with a significant 12% reduction in total cancer mortality (RR=0.88; 95% CI, 0.80-0.96 for daily intake compared with intake once per week or less). Daily or almost daily green-yellow vegetables consumption was associated with a marginally significant 8% reduction in total cancer mortality (0.92; 0.94-1.01). Green-yellow vegetables consumption was associated with a significant reduction in liver cancer mortality (0.75; 0.60-0.95). Fruit consumption was associated with a significantly reduced risk of stomach cancer and lung cancer mortality (0.80; 0.65-0.98). Green-yellow vegetables and fruit consumption was associated with a reduction in oesophageal cancer, but these associations were not statistically significant. Neither green-yellow vegetables nor fruit consumption was associated with colorectal cancer or breast cancer mortality. These results support the evidence that daily consumption of fruit and vegetables reduces the risk of total cancer, and specifically cancers of the stomach, liver, and lung.

A prospective study of green tea consumption and cancer incidence, Hiroshima and Nagasaki (Japan).

OBJECTIVES: Laboratory and animal studies have shown a protective effect of green tea on cancer of different sites, but epidemiological evidence is limited and inconclusive. This prospective study in Japan examined the association between green tea consumption and cancer incidence. METHODS: Subjects were 38,540 people (14,873 men, mean age 52.8 years; 23,667 women, mean age 56.8 years) who responded to a mail survey carried out between 1979 and 1981. A self-administered questionnaire ascertained consumption frequency of green tea using precoded answers (never, once per day, twice to four times per day, and five or more times per day). Follow-up continued until 31 December 1994. The study analyzed solid cancers (n = 3881); hematopoietic cancers (188); cancers of all sites combined (4069); and cancer of specific sites with more than 100 cases, i.e. stomach (901), colon (432), rectum (193), liver (418), gallbladder (122), pancreas (122), lung (436), breast (281), and bladder (122). Poisson regression was used to allow for city, gender, age, radiation exposure, smoking status, alcohol drinking, body-mass index, education level, and calendar time. RESULTS: Green tea consumption was virtually unrelated to incidence of cancers under study. The relative risks of all cancers for those consuming green tea twice to four times per day and five or more times per day were 1.0 (95% confidence interval 0.91-1.1) and 0.98 (0.88-1.1), respectively, as compared with those consuming green tea once per day or less. CONCLUSION: Our findings do not provide evidence that regular green tea consumption is related to reduced cancer risks.

Lung cancer, myocardial infarction, and the Grossarth-Maticek personality types: a case-control study in Fukuoka, Japan.

Grossarth-Maticek and colleagues have shown, in their prospective studies, a strong relationship of their personality types, Types 1 and 2, to cancer and coronary heart disease (CHD), respectively. Relevant information is limited from replication studies, and little is known about psychosocial factors in relation to cancer or CHD in Japan. Subjects included 95 cases of lung cancer (LC), 94 cases of myocardial infarction (MI) and 596 controls. The controls were men and women who visited a clinic for a health checkup. The Grossarth-Maticek personality types, Types 1 to 6, were assessed using the Short Interpersonal Reactions Inventory. The distributions of the 6 personality types were compared between the case and control groups, adjusting for sex and age class. The relation of each of the 6 types to LC and MI were examined in terms of odds ratio, using a logistic regression model controlling for age, sex, job status, education level, and smoking status. As regards the distribution analysis, Types 1 and 2 in the LC and MI groups each were not more prevalent than the controls, respectively. High score of the Type 1 scale was associated with a statistically nonsignificant decrease in LC risk. MI risk was significantly, positively associated with the Type 2 and 5 scales, and unexpectedly, positively related to the Type 3 scale. The present findings partly supported the Grossarth-Maticek theory, but there remain some conflicting issues to be confirmed in future studies.

Bladder-cancer incidence in relation to vegetable and fruit consumption: a prospective study of atomic-bomb survivors.

We examined the relation between consumption of 22 dietary items and subsequent bladder-cancer incidence in a cohort of atomic-bomb survivors in Japan. Subjects were 38,540 people (14,873 men and 23,667 women) who responded to a mail survey carried out between 1979 and 1981 and who had no known cancer diagnosed before the start of follow-up (1 January 1980 for men, 1 February 1981 for women). Consumption frequencies for 22 dietary items were ascertained with pre-coded answers. As of the end of 1993, there were 114 (83 men and 31 women) incident cases of bladder cancer among 450,326 person-years at risk. Statistical analysis was done using Poisson regression for grouped survival data Consumption of green-yellow vegetables and fruit were protectively associated with risk. Adjusted for gender, age, radiation exposure, smoking status, educational level, body-mass index and calendar time, the relative risk (RR) for those consuming green-yellow vegetables 2-4 times per week and almost everyday was 0.62 [95% confidence interval (CI) 0.39-0.98] and 0.54 (95% CI 0.30-0.94) respectively, as compared with those consuming once per week or less. The corresponding RR for fruit consumption was 0.50 (0.30-0.81) and 0.62 (0.39-0.99) respectively. Chicken consumption was unexpectedly associated with decreased risk, but additional adjustment for consumption did not change the relation of green-yellow vegetables or of fruit to risk. The consumption of the other dietary items, including meat and green tea, was not related to risk. The findings add to evidence that high consumption of vegetables and fruit are protective against bladder cancer.

Immunomodulatory constituents from three ascomycetes, Gelasinospora heterospora, G. multiforis, and G. longispora.

Three new 2-pyrones (2H-pyran-2-ones) called multiforisins G (3), H (1), and I (4), and a known hexaketide sordarial (2) have been isolated from an Ascomycete Gelasinospora heterospora. Among them, 1, 2, and 3 have been proved to be the immunosuppressive components of the fungus. Compounds 1, 3, and 4 have also been isolated from G. multiforis together with multiforisin A (5), which was formerly isolated from this fungus as its main immunosuppressive feature, and 1-5 have also been isolated from G. longispora. The absolute stereostructure of 2, which was not previously certain, has finally been determined to be (3'R,4'S). It has been found that the multiforisins 1, 3, and 5 in which one of the two substituents at positions 3 and 5 is a hydroxymethyl group and the other is a formyl or an acetoxymethyl group, show high immunosuppressive activity; the immunosuppressive activity of 3 does not seem to be due to inhibition of interleukin 2 (IL-2) production.

Immunosuppressive components from an Ascomycete, Diplogelasinospora grovesii.

Two known fungal metabolites, macrophin and colletodiol, and a new stereoisomer of colletodiol named 10-epi-colletodiol, were isolated as immunosuppressive principles from an Ascomycete, Diplogelasinospora grovesii. The IC50 values of the major active component among them, macrophin, were calculated to be 0.4 and 0.3 microgram/ml against concanavalin A- and lipopolysaccharide-induced proliferations of mouse spleen lymphocytes, respectively. A new natural product, 4,8-dimethyl-1,5-dioxacyclooctane-2,6-dione, and a known fungal metabolite, isosclerone, which showed no immunosuppressive activity, were also isolated from this fungus.

The remodelling process of allogeneic and autogenous patellar tendon grafts in rats: a radiochemical study.

In order to study the remodelling of collagen fibres of transplanted tendons, one-half of the patellar tendon of the knee in 54 rats was replaced with a radioisotope (3H-proline)-labelled patellar tendon procured from a donor rat. Three transplantation models were used in this study: fresh-frozen allograft, fresh-frozen autograft (fresh-frozen isograft), and fresh autograft (fresh isograft). The percentage of old collagen was calculated as an indicator of collagen turnover from the amount of hydroxyproline and the radioactivity level of 3H-hydroxyproline in the transplanted tendons at 4, 12 and 24 weeks postoperatively. Histological evaluation was also performed at 2, 4, 12 and 24 weeks. At 4 weeks, the percentage of old collagen in the grafts from the fresh-frozen allograft group was significantly lower than in the autograft groups (20% vs. 48%). Although the percentage of old collagen in the fresh-frozen autograft group had decreased to the same level as in the fresh-frozen allograft group by 12 weeks (approximately 10%), the value was still high in the fresh autograft group at 12 weeks and remained higher (38%). Histologically, at 2 weeks, the cellularity in the fresh-frozen allograft was higher than in the fresh-frozen autograft. After 4 weeks, however, no significant difference was found between these two groups. In the fresh autograft group, the cellularity was lower than in the fresh-frozen groups at all times. In conclusion, the collagen turnover rate in the fresh-frozen allograft was the most rapid of the three transplantation models based on hydroxyproline turnover.

Gender differences in muscle strength after 20 days bed rest.

In the previous studies, when Bed rest (BR) was prolonged over 2 weeks, muscle mass and strength began progressively to become reduced. There are many publications investigating the changes in skeletal muscles during inactivity. However it is still unclear whether the changing degrees of muscle mass and strength not only in antigravity muscles but also in non-antigravity muscles differ between males and females. So, the purpose of this study is to investigate gender difference in the effect of 20 days of BR (BR 20) on regional muscle mass and strength of the arm and leg.

Water intake and urinary volume during 20 days bed-rest in young woman.

During the bed-rest in the young subjects, the water intake should be depressed, because the diuretic is probably accelerated, and then the total body water and body weight is decreased by the water loss. In our previous study in 1991, we have reported that urinary volume was gradually increased, while water intake was decreased. Therefore, it was concluded that the decrease in the water intake and the increase in the urinary volume should bring to the negative water balance. In the present study, it is studied whether urinary volume is independent on water intake during 20 days horizontal bed-rest in young woman.

Effects of 20 days bed-rest on cardio respiratory functions during sub-maximal exercise in young woman.

The purpose of present study is to know the effects of 20 days bed-rest on cardio-respiratory functions during sub-maximal exercise in different body positions which were in sitting, supine and 30 degrees head-down position respectively.

Effects of 10-days bed rest and moderate training on LBNP tolerance in young woman.

The tolerable capacity against LBNP was decreased by bed rest and recovered by physical training. The tolerable capacity was related to VO2max and LVEDd. However, the LBNP tolerance capacity should be primarily limited by factors involving venous return in LVEDd, because VO2max must be controlled by the factors.

Replacing the medial collateral ligament with an allogenic tendon graft. An experimental canine study.

In order to determine whether an allogeneic tendon could be used to replace an extra-articular ligament, the right medial collateral ligament from 11 adult dogs was replaced with a fresh-frozen allogeneic patellar tendon. At each of 3, 6, 15, 30 and 52 weeks postoperatively, one dog was killed for micro-angiographical and histological studies; at 52 weeks the remaining six dogs were killed for tensile testing. Micro-angiograms showed that the allogeneic tendon was revascularised with infiltration of the mesenchymal cells from the surrounding tissues and both ends of the graft. Histologically, the alignment of the fibroblasts and collagen bundles became more regular over time, without any immunological rejection. A biomechanical study performed at 52 weeks found no significant difference in stiffness or ultimate load between normal and reconstructed ligaments. Fresh-frozen allogeneic tendons are therefore considered useful for extra-articular ligament reconstruction.