Changes of ROS during a two-day ultra-marathon race.

To assess oxidative stress (OS) induced by endurance exercise, concentrations of serum reactive oxygen species (ROS) were determined in 70 Japanese male amateur runners completing a two-day ultra-marathon race. Serum ROS levels were analyzed at three time points: before the race (baseline), after the 1st day race (mid-race), and after the 2nd day race (goal) (post-race). The means (SE) of ROS were 151.4(3.7) (U. CARR.), 168.7(4.4), and 156.8(4.4), respectively. Significant positive trends were noted between age and serum ROS concentrations at the three race points (p<0.05 for all). After adjusting for age, BMI and average monthly running distance, the baseline serum ROS concentrations were positively associated with completion times of the first-day race, in particular (p<0.05), suggesting that the concentrations may predict physical performance. The ROS production increased at mid-race (p<0.05), but the levels returned to baseline levels at post-race, indicating that an antioxidant defense system may develop post-race to reduce OS.

Cancer and other causes of death among female beauticians.

A retrospective cohort study was done of the mortality between 1953 and 1977 among 7,736 Japanese female beauticians who were registered from 1948 to 1960 in Fukuoka Prefecture, Japan. Mortalities from tuberculosis, heart disease, accidents, and all causes were significantly decreased as compared with the mortalities of general population in the prefecture. Observed deaths from all cancers combined were almost equal to those expected (148 observed vs. 139.26 expected). Among site-specific cancers studied, only slightly increased mortality from stomach cancer was statistically significant (61 observed vs. 45.59 expected). No measurable excess mortality was observed for the other sites of cancer.

Cancer and other causes of death among leprosy patients.

A follow-up study was done on the mortality from 1956 to 1975 among 2,383 Japanese patients with leprosy who were admitted to a leprosarium in Japan. The leprosy was classified into two types: lepromatous and tuberculoid. Irrespective of the type of leprosy or the sex of leprosy patient, mortalities were increased from tuberculosis, pneumonia and bronchitis, nephritis and nephrosis, and from total causes. The suicide rate was high among female patients. Deaths from total malignant neoplasms were higher than expected among patients with lepromatous leprosy for both sexes (49 observed vs. 44.02 expected), whereas they were lower than expected among patients with tuberculoid leprosy (35 observed vs. 36.83 expected); however, the differences were not statistically significant. Mortalities from cancers of the cervix and the esophagus among females with lepromatous leprosy were significantly higher. The risk of lymphoreticular cancers was not increased.

Accelerated declining tendency of human T-cell leukemia virus type I carrier rates among younger blood donors in Kumamoto, Japan.

The annual age- and sex-specific human T-cell leukemia virus type I carrier rate of blood donors in Kumamoto, Kyushu, Japan from 1986 to 1990 revealed that the carrier rates of all the age groups below 50 years declined linearly in both sexes (P less than 0.005). Furthermore, the annual declining rates relative to the carrier rates of 16-19-year-old and 20-29-year-old males were higher than those of all of the older males (P less than 0.02), and all female age groups below 50 years had higher relative declining rates than 50-64-year-old females (P less than 0.05). Although several factors, such as a notification program at obstetric clinics, methodological and technical improvement of the assays, wider knowledge of human T-cell leukemia virus type I infection in the latter years, and immigration of individuals from a nonendemic area, might cause an absolute decline of the carrier rate of the blood donors, these factors could not explain the acceleration of the relative declining rate among younger donors. Therefore, this acceleration represents the tendency of the general population.

Incidence of adult T-cell leukemia/lymphoma among human T-lymphotropic virus type I carriers in Saga, Japan.

Using a population-based cancer registry, we tabulated 69 definite adult T-cell leukemia/lymphoma cases (36 males and 33 females) and 2.20 expected cases (0.95 for males and 1.25 for females) diagnosed from 1981 to 1983 in Saga, Japan. The number of human T-lymphotropic virus type I carriers was computed by applying sex- and age-specific anti-human T-lymphotropic virus type I antibody positive rates among blood donors at the blood center in 1986 to the whole population of Saga Prefecture in 1982. The age-specific incidence rates among male human T-lymphotropic virus type I carriers from 40 to 79 yr of age per 100,000 were significantly higher than those of female carriers (P less than 0.05), and the rates from 60 to 69 yr of age were the highest in both sexes. The annual crude incidence rates among carriers were 115.9 for males and 66.4 for females. The summary incidence rates with 95% confidence intervals were 115.9 (58.4 to 193.0) for males and 65.9 (30.0 to 115.9) for females. The cumulative risks were 4.5% (0.8 to 11.0) for males and 2.6% (0.3 to 7.0) for females. These morbidity figures were assumed to be underestimated partly due to the newly proposed clinical entity of adult T-cell leukemia/lymphoma.

A prospective study on primary gastric stump cancer following partial gastrectomy for benign gastroduodenal diseases.

A prospective study was made on 3827 Japanese patients who had undergone partial gastrectomy for benign gastroduodenal diseases to examine whether they are at a high risk of mortality from primary gastric stump cancer (PGSC) and whether the risk is determined by the surgical procedure. The patients were followed up from the time of surgery (from 1948 to 1970) to June 30, 1981. Of 3,701 patients (96.7%), the vital status at the end of observation was determined, the total person-years at risk being 62,286.33. The observed deaths were compared with the expected deaths calculated from the mortality rates of Japan. An elapsed time of 10 years from operation to death was set not only to exclude possible recurrent, remaining, or multiple cancers but also to allow a certain latency period for the development of PGSC. The observed and expected deaths from PGSC were 11 and 52.85, respectively, the ratio being 0.21 (p less than 0.01). The ratios were uniformly less than 1 for both sexes and across three operative groups: Billroth I, Billroth II with Braun's anastomosis; or Billroth II without Braun's anastomosis. No difference was observed between the death rates from PGSC by operation type. The possible role of the postoperative nonphysiological (pathological) environment or duodenogastric reflux in gastric stump carcinogenesis was not detected in the present study.

Investigation of postmortem functional changes in human cerebral arteries.

This study demonstrated the time-dependent changes in postmortem responses of isolated human middle cerebral artery strips to vasodilators. The relaxation induced by prostaglandin (PG) I2 or nitroglycerin remained stable for 24 h postmortem. In arterial strips precontracted with PGF2 alpha, substance P and bradykinin both elicited relaxation that was almost completely abolished by removal of the endothelium. The endothelium-dependent response to both peptides was significantly degraded in strips obtained > 12 h postmortem. These results indicate a selective functional or anatomical vulnerability of the vascular endothelium compared with that of the vasodilator mechanisms of the smooth muscle in the postmortem period. However, cerebral arteries isolated from human cadavers within 12 h postmortem should be adequate for studies of both smooth muscle and endothelial reactivity to vasodilators.

Covalent coupling of a steroid to microwell plates for use in a competitive enzyme-linked immunosorbent assay.

The covalent coupling of a model steroid, 17 alpha-hydroxypregnenolone, to the wells of the microtiter plate, CovaLink NH, for use in a competitive enzyme-linked immunosorbent assay is described. This plate has secondary amino groups bound to its surface. A carboxylated derivative of the steroid was coupled to the amino group to form an amide bond in a single step using a water-soluble carbodiimide, 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (10 mM) as coupling reagent in the presence of N-hydroxysuccinimide (1 mM). After carrying out a competitive immune reaction, antibodies bound to immobilized steroids were estimated by means of a second antibody-enzyme conjugate. The non-specific background was reduced with blocking agents which did not interfere with the immune reaction between antibodies and the steroids coupled to the plastic surface. The following two procedures were effective for this purpose: pretreatment of wells with 0.01% Tween 20 solution followed by 0.5% bovine serum albumin in phosphate buffered saline, and addition of 0.01% Tween 20 to the assay buffer. With this method, the preparation of steroid-enzyme conjugates is unnecessary and optimization of conditions for ELISA procedures can be achieved in a simple manner.

Use of screening tests to assess cancer risk and to estimate the risk of adult T-cell leukemia/lymphoma.

We developed methods to assess the cancer risks by screening tests. These methods estimate the size of the high risk group adjusted for the characteristics of screening tests and estimate the incidence rates of cancer among the high risk group adjusted for the characteristics of the tests. A method was also developed for selecting the cut-off point of a screening test. Finally, the methods were applied to estimate the risk of the adult T-cell leukemia/lymphoma.

Advanced onset of menarche and higher bone mineral density depending on vitamin D receptor gene polymorphism.

Bone mineral density (BMD) at distal forearm, and weight and height of healthy Japanese girls aged 18-19 years were measured and their age at menarche was obtained through a questionnaire. A statistically significant association was found between BMD at distal radius and vitamin D receptor (VDR) gene polymorphism at the ApaI site. The age at menarche in the population with Aa genotype was significantly earlier than that in the aa population. In addition, BMD was significantly dependent on the earlier onset of menarche in the population with genotype Aa but not in the population with genotype aa. BMD was also positively associated with the body mass index (BMI) in the population with genotype Aa. Statistical analysis suggested a stronger effect of VDR genotype on age at menarche than on BMI. Thus, we show that VDR gene polymorphism advances the age at menarche and increases BMD in cooperation with age at menarche.

Type of gallstones and deaths from stroke and coronary heart disease among cholecystectomized patients.

A total of 841 Japanese patients who had undergone cholecystectomy for choleithiasis (550 for cholesterol stones and 291 for pigment stones) from 1951 to 1970 were investigated on death from stroke, coronary heart disease (CHD) and heart disease other than CHD in relation to the type of gallstones. Compared to patients with pigment stones, those having cholesterol stones had a 50% lower risk of dying from stroke which was statistically significant. The findings support the idea that westernization of Japanese diets may be responsible both for the decline in stroke mortality and for the changing pattern of gallstones in this country. The risk of CHD among cholesterol-stone patients was higher, but not significantly so, than that of pigment-stone patients whereas mortality from heart disease other than CHD did not differ much between the two groups. There were, however, few deaths from these diseases and the findings were therefore not conclusive.

Alcohol and mortality: a cohort study of male Japanese physicians.

The relationship between drinking habit surveyed in 1965 and cause-specific mortality over 19 years was investigated in 5135 male Japanese physicians taking into account smoking habit and separating ex-drinker from non-drinker. As compared with non-drinkers, daily drinkers with high consumption had a significantly increased mortality from all causes. Drinking was significantly related to the so-called alcohol-related causes of death; upper aerodigestive cancer, liver cancer and liver cirrhosis. Mortality from acute myocardial infarction was inversely related to drinking, whereas other coronary heart disease showed a somewhat higher mortality among men consuming a large amount of alcohol than among non-drinkers. There was a weak, but significant, association between stroke and drinking, and the relation did not differ between haemorrhagic stroke and other stroke. No obvious relationship with drinking was observed for cancers of the stomach, large bowel, pancreas and lung.

Mortality in psychiatric patients, with a specific focus on cancer mortality associated with schizophrenia.

BACKGROUND: Higher mortality rates among psychiatric patients compared with the general population have been widely reported. On the other hand, lower cancer mortality for schizophrenics has been occasionally pointed out. Few studies from Japan have investigated mortality among psychiatric patients, and this study is the first large-scale follow-up in this country. METHODS: A total of 4980 patients admitted to a national mental hospital from 1948 through 1982 were followed up until 31 August 1985. The standardized mortality ratios (SMR) were calculated in comparison to the general population, using the person-years method. RESULTS: The SMR for total deaths and those for malignancy were as follows for males/females respectively: 2.55/3.02 and 0.84/1.37 for schizophrenia, 1.76/2.37 and 1.44/2.10 for depression, 2.45/3.04 and 1.18/1.82 for mania, 1.81/1.90 and 0.27/1.07 for neurosis, 5.55/4.33 and 1.85/3.34 for alcohol/drug abuse, and 3.65/3.57 and 1.01/0.72 for organic brain syndrome. CONCLUSIONS: The SMR for total deaths were significantly elevated in schizophrenia, depression, mania, neurosis, alcohol/drug abuse, and organic brain syndrome, respectively. The SMR for malignancy were not elevated nor lowered significantly in any of these disease categories. The SMR for stomach cancer in male schizophrenics was significantly lower (0.27; P < 0.05).

Coffee consumption and decreased serum gamma-glutamyltransferase and aminotransferase activities among male alcohol drinkers.

BACKGROUND: Attention has long been drawn to the potentially harmful effects of coffee on health, however recent epidemiological studies have suggested unexpected, possibly beneficial effects of coffee against the occurrence of alcoholic liver cirrhosis and upon serum liver enzyme levels. METHODS: We examined the potential inverse association between coffee drinking and serum concentrations of gamma-glutamyltransferase (GGT) and aminotransferases, with special reference to interaction with alcohol consumption, in a cross-sectional study involving 12687 health examinees (7398 men and 5289 women) aged 40-69 years from over 1000 workplaces in Nagano prefecture in central Japan. Those who had a history of liver disease and/or serum aminotransferases exceeding the normal range were excluded. Possible confounding effects of alcohol consumption, body mass index, cigarette smoking, and green tea consumption were controlled through multivariate analyses. RESULTS: Increased coffee consumption was strongly and independently associated with decreased GGT activity among males (P trend < 0.0001); the inverse association between coffee and serum GGT was more evident among heavier alcohol consumers (P < 0.0001), and was absent among non-alcohol drinkers. Among females, however, coffee was only weakly related to lower GGT level. Similar inverse associations with coffee and interactions between coffee and alcohol intake were observed for serum aspartate aminotransferase and alanine aminotransferase. Intake of green tea, another popular source of caffeine in Japan, did not materially influence the liver enzyme levels. CONCLUSIONS: Our results suggest that coffee may inhibit the induction of GGT in the liver by alcohol consumption, and may possibly protect against liver cell damage due to alcohol.

The relationship between alcohol and mortality among Japanese physicians.

Based on the survey in 1965 on smoking and drinking habits of physicians in western Japan, the mortality pattern among 5139 male Japanese physicians over 12.7 years was examined in terms of drinking habit. Among six groups with different drinking habits: ex-drinker, non-drinker, occasional drinker and daily drinker whose intake of alcohol was equivalent to below 1, 1-1.9 or 2 and more go of sake (1 go of sake congruent to 27 ml of alcohol), ex-drinkers had the highest risk of dying. Mortality from all causes among non-drinkers was higher than that among occasional drinkers or the lowest daily drinkers, but the differences were not significant. Among daily drinkers, total mortality was significantly increased with the amount of alcohol. As for cause-specific mortality, cancer and stroke showed a significant positive association with alcohol. No significant inverse relationship was noted for heart disease or coronary heart disease, although non-drinkers had higher mortality than occasional or daily drinkers. There was no obvious effect of alcohol on mortality from either liver cirrhosis or accidents, but deaths from these causes were few.

Smoking and mortalities from cancer, coronary heart disease and stroke in male Japanese physicians.

A cohort of 5,477 male Japanese physicians was studied to examine the relationship between smoking habits and mortalities from cancer, coronary heart disease (CHD) and stroke over 12.7 years. The logistic regression analysis based on proportional hazard models was used for statistical assessment. The risks of both lung cancer and CHD were strongly associated with smoking habits in terms of the number of cigarettes smoked per day, inhalation level and age at starting to smoke. These associations were not influenced by the effect of drinking habits. However, the risk increment of lung cancer due to cigarette smoking was fairly small as compared with the data from other studies of male Caucasians. A statistically significant association was observed between upper aerodigestive cancer and cigarette smoking. But this relationship became insignificant after adjustment for drinking habits, and the risk of heavy smokers was drastically reduced. No clear association was noted between smoking and mortalities from gastric cancer and stroke.

Alcohol and cancer in male Japanese physicians.

The relationship between alcohol and site-specific cancers was investigated in a follow-up study of 5,139 male Japanese physicians. Information on drinking habits was obtained by mail questionnaire in 1965, and cancer deaths over 12.7 years were analyzed with drinking habits classified into five categories; nondrinker, ex-drinker, occasional drinker, and daily drinker whose intake of alcohol was equivalent to less than 2 or 2 and more go of sake (1 go sake congruent to 27 ml alcohol). Both age and smoking habits were taken into account in the calculation of death rates based on man-years at risk. Logistic regression analysis was also performed on cummulative mortality data. Upper aerodigestive cancer was strongly associated with alcohol consumption, giving some confidence in the validity of the present study. Excluding ex-drinkers, the risk of stomach cancer and liver cancer was gradually increased from nondrinkers to daily drinkers with lower intake of alcohol, but no further increase was noted for daily drinkers with larger consumption. Logistic regression did not show any significant associations between drinking habits and these two cancers, but the number of deaths from liver cancer was still small. Not particular patterns were observed for cancers of the large bowel and lung.

Additive effects of estrogen deficiency and diabetes on bone mineral density in rats.

We investigated the combined effects of estrogen deficiency and diabetes on bone mineral density (BMD) and bone metabolism in rats. Ten-week-old, female rats were randomly divided into four groups: controls (C), an ovariectomized group (O), a streptozotocin-induced diabetic group (S), and a combined ovariectomy and streptozotocin-induced diabetic group (OS). The BMD of the lumbar spine and the femur were measured before grouping and at 23 weeks old. At the end of the experiment, blood samples were obtained via cardiac puncture, and bone gla protein (BGP), tartrate-resistant acid phosphatase (TRAP) and 1,25-dihydroxyvitamin D levels were measured. The rats in the C, O, S, and OS groups, in that order, had higher levels of BMD of the lumbar spine and femur at 23 weeks of age. The BGP levels in the S and OS groups were significantly lower than in C and O groups. Significantly higher 1,25-dihydroxyvitamin D was observed in the O group compared with the C, S and OS groups. No differences were obtained in TRAP among four groups. Our data suggest that the combined effects of estrogen deficiency and diabetes on BMD are not synergistic or counteractive but additive.

Altered reactivity of human cerebral arteries after subarachnoid hemorrhage.

To investigate the effects of subarachnoid hemorrhage (SAH) on the responsiveness of human cerebral arteries to vasoactive substances, the authors measured the isometric tension generated in helical strips of basilar and middle cerebral arteries isolated from human cadavers. Contractions caused by KCl, prostaglandin F2 alpha, noradrenaline, and serotonin were reduced in arteries obtained from cadavers with aneurysmal SAH damage and compared to those obtained from cadavers with no indication of intracranial diseases. Endothelium-dependent relaxation elicited by substance P and bradykinin, and endothelium-independent relaxation induced by prostaglandin I2 and nitroglycerin were also markedly decreased in arteries affected by SAH. However, the reduction in relaxation response to prostaglandin I2 was significantly less than that to the other vasodilator agents. These results indicate that human cerebral artery functions are severely impaired after SAH and that poor responses to vasoactive agents may result primarily from dysfunction of smooth-muscle cells.

Immunohistochemical classification of the localization of laminin in the thickened bronchial epithelial basement membrane of deceased bronchial asthma patients.

To ascertain histological changes in the basal lamina of the bronchial epithelial basement membrane in patients with severe bronchial asthma, an immunohistochemical study was conducted in 43 patients who died of bronchial asthma. Antibodies against laminin, a component of the lamina lucida, were utilized. The results revealed various patterns for immunoreactivity to laminin in the thickened basement membrane layer. We were able to classify these reactivities into four patterns. In Pattern A, laminin reactions branched vertically in relation to the thickened basement membrane layer. In Pattern B, laminin reactions formed lines along the lower margin of the thickened basement membrane layer. In Pattern C, laminin reactions formed lines along the upper margin of the thickened basement membrane layer. Finally, in Pattern D, no laminin reactions were observed. In addition, relationships between immunohistological characteristics of laminin and findings such as epithelial cell shedding, basal cell proliferation and basement membrane layer thickening were investigated. In many Pattern A patients, epithelial cell shedding was observed, but goblet cell hyperplasia and basal cell proliferation were barely detectable. Conversely, in numerous Pattern D patients, epithelial cell shedding was barely seen, but goblet cell hyperplasia and basal cell proliferation were marked. Hence, Patterns A and D were on opposite ends of the spectrum of morphological characteristics associated with severe bronchial asthma. In Patterns B and C, laminin reactions formed lines along the lower and upper margin of the thickened basement membrane layer, respectively. However, no marked differences existed in epithelial cell shedding and basement membrane layer thickening. The present study is thus the first to clarify that laminin reactions in the thickened basement membrane layer vary, and this feature is unique to the bronchi of patients with severe bronchial asthma.