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Biomedical subjects

S Akiba

Publications and source records attributed to S Akiba.

At least 91 records · Page 5Linked to original sources

Cancer mortality in Minamata disease patients exposed to methylmercury through fish diet.

We report here a historical cohort study on cancer mortality among Minamata disease (MD) patients (n = 1,351) in Kagoshima and Kumamoto Prefectures of Japan. Taking into account their living area, sex, age and fish eating habits, the residents (n = 5,667; 40 years of age or over at 1966) living in coastal areas of Kagoshima, who consumed fish daily, were selected as a reference group from the six-prefecture cohort study conducted by Hirayama et al. The observation periods of the MD patients and of the reference group were from 1973 to 1984 and from 1970 to 1981, respectively. Survival analysis using the Poisson regression model was applied for comparison of mortality between the MD patients and the reference group. No excess of relative risk (RR) adjusted for attained age, sex and follow-up period was observed for mortality from all causes, all cancers, and non-cancers combined. Analysis of site-specific cancers showed a statistically significant decrease in mortality from stomach cancer among MD patients (RR, 0.49; 95% confidence interval, 0.26-0.94). In addition, a statistically significant eight-fold excess risk, based on 5 observed deaths, was noted for mortality from leukemia (RR, 8.35; 95 % confidence interval 1.61-43.3). It is, however, unlikely for these observed risks to be derived from methylmercury exposure only. Further studies are needed to understand the mechanisms involved in the observed risks among MD patients.

Adult↗

Effect of berbamine on cytosolic phospholipase A2 activation in rabbit platelets.

The effect of berbamine, a biscoclaurine alkaloid, on cytosolic phospholipase A2 activation in rabbit platelets was investigated. Berbamine inhibited arachidonic acid liberation induced by thrombin but not that by ionomycin. The alkaloid did not affect thrombin-stimulated Ca2+ mobilization. Ca(2+)-dependent translocation of cytosolic phospholipase A2 to membranes, or the activity of partially purified cytosolic phospholipase A2. Furthermore, berbamine had no effect on the thrombin-elicited increase in cytosolic phospholipase A2 activity. However, berbamine suppressed arachidonic acid liberation in platelets stimulated with GTP-binding protein activators. Although incubation of platelet membranes with a GTP analogue decreased the islet-activating protein-catalyzed ADP-ribosylation of an approximately 40 kDa protein in the membranes, pretreatment of the membranes with berbamine did not influence the decrease in ADP-ribosylation. These results suggest that berbamine may impair GTP-binding protein-mediated activation of cytosolic phospholipase A2, probably without influencing the enzyme translocation to membranes or the increase in the enzyme activity, and thus may cause the suppression of thrombin-induced arachidonic acid liberation.

Alkaloids↗

Effect of total adipose weight and systemic hypertension on left ventricular mass in children.

To investigate the effect of obesity and hypertension on left ventricular (LV) mass in children, we performed echocardiography and measured the height, weight, and blood pressure of 267 healthy children (145 boys and 122 girls) aged 12 years. The percentage of body fat was estimated using bioelectric impedance to derive the total adipose weight and lean body weight. End-diastolic measurements of LV parameters were obtained from M-mode echocardiograms. The LV mass was calculated by using the formula of Devereux et al. A strong positive correlation was demonstrated between non-normalized LV mass and height or other measures of body size. Systolic blood pressure was weakly correlated with non-normalized LV mass in boys. The impact of height on LV mass differed between boys and girls. Thus, different allometric formulas to normalize the LV mass for height were determined, using the height to the 3.1 and 1.9 powers for boys and girls, respectively. Regression analysis revealed that only total adipose weight affected the normalized LV mass, and that the effect of total adipose weight was greater in girls than in boys. The obese children had a significantly greater normalized LV mass than the nonobese children. The increase in the LV mass due to obesity appeared to be eccentric, because of the lack of an association between the indices of obesity and relative wall thickness. Our data indicate that appropriate normalization of LV mass is necessary for each study population, and that LV hypertrophy due to obesity begins in childhood.

Adipose Tissue↗

Increased receptor-mediated phospholipase D activation and Ca2+ mobilization in peritoneal polymorphonuclear leukocytes from streptozotocin-induced diabetic rats.

Phospholipase D activation was investigated in peritoneal polymorphonuclear leukocytes from streptozotocin-induced diabetic rats. Stimulation of the cells with formyl-Met-Leu-Phe resulted in a time- and dose-dependent increase in phosphatidylethanol in the presence of ethanol, and this lipid formation in cells prepared from diabetic rats was enhanced as compared to that in the case of nondiabetic rats. Furthermore, the increase in the intracellular Ca2+ concentration was also enhanced in the stimulated cells from diabetic rats. Under the present conditions, N-acetyl-beta-glucosaminidase release and superoxide generation, which are known to be dependent on phospholipase D activation, were higher in the cells from diabetic rats than those in the cells from control rats. However, there was no difference in the dissociation constant and the number of binding sites for formyl-Met-Leu-Phe between the cells from diabetic and control rats. Phosphatidylethanol formation, N-acetyl-beta-glucosaminidase release and superoxide generation in response to ionomycin or 4 beta-phorbol 12-myristate 13-acetate were not enhanced in diabetic rat cells, as compared with those in control rat cells. These results suggest that receptor-mediated phospholipase D activation and Ca2+ mobilization are enhanced in diabetic rat polymorphonuclear leukocytes, which might be due to acceleration of receptor-mediated signaling.

Acetylglucosaminidase↗

Stimulation of platelet-activating factor synthesis in polymorphonuclear leukocytes from streptozotocin-induced diabetic rats.

The platelet-activating factor (PAF)-synthesizing capacity was investigated and compared in peritoneal polymorphonuclear leukocytes (PMN) from streptozotocin-induced diabetic and normal rats. PAF synthesis was significantly enhanced in the PMN from diabetic rats compared with that from normal rats stimulated with fMLP. This was manifested as the increased incorporation of [3H]acetate into PAF. Selected ion monitoring/GC/MS analysis revealed that the molecular species of PAF synthesized were mostly of the 1-hexadecyl type, and the amount synthesized in fMLP-stimulated diabetic rat PMN was 1.5 times higher than that in normal rat PMN. The fMLP-induced arachidonic acid liberation resulting from phospholipase A2 activation, was facilitated with a concomitant increase in the cytosolic Ca2+ concentration in diabetic rat PMN. The CoA-independent transacylase activity was similar in both PMN lysates, whereas acetyl-CoA:lyso-PAF acetyltransferase activity was accelerated in the diabetic rat PMN lysate. These results revealed that diabetic rat PMN has more ability to synthesize PAF, presumably due to the large increase in activated phospholipase A2 and acetyltransferase, as well as the increased cytosolic Ca2+ concentration.

Acetates↗

Prospective cohort study of risk factors for primary liver cancer in Hiroshima and Nagasaki, Japan.

We investigated risk factors for primary liver cancer among a cohort of 36,133 residents in Hiroshima and Nagasaki, Japan, originally established to examine the association between exposure to atomic bomb radiation and disease. A mail survey to study the late effects of atomic bomb radiation was conducted among the cohort between 1978 and 1981. During the subsequent follow-up period (average 8.61 years), 242 cases of primary liver cancer were identified through population-based tumor registries in the two cities. The relative risk (RR) of liver cancer was 2.23 [95% confidence interval (CI) = 1.53-3.23] for tobacco smokers compared with those who had never smoked. Alcohol use was slightly positively associated with the risk of liver cancer, and men who had quit drinking had an RR of 2.33 (95% CI = 1.34-4.07) compared with those who never drank. Among alcohol drinkers, an inverse relation between years of abstinence and the rate of liver cancer was found, possibly attributable to a confounding effect of preclinical disease. The use of female hormone preparations was modestly associated with the risk of liver cancer (RR = 1.29; 95% CI = 0.59-2.84). Other risk factors included a self-reported history of radiation therapy (RR = 1.79; 95% CI = 1.31-2.43).

Adult↗

Effects of size of carbohydrate chain on protease digestion of Aspergillus niger endo-beta-1,4-glucanase.

Three different carbohydrate-depleted enzymes were prepared from an endo-beta-1,4-glucanase of Aspergillus niger IFO31125 by treatment with endo-beta-N-acetylglucosaminidase or alpha-mannosidase. They were purified by Concanavalin A-Sepharose affinity and DEAE ion-exchange column chromatographies. The molecular sizes of these enzymes had been decreased from 40 kDa containing 9.0% carbohydrate to 39, 38, and 37 kDa with carbohydrate at 4.5, 1.3, and 0.8% (wt/wt), respectively. The native and these carbohydrate-depleted enzymes were compared in their enzymatic properties, and it was found that they were identical in their catalytic activities and both thermal and pH stabilities. However, the 37-kDa enzyme was more susceptible to proteolysis by Savinase, proteinase K, and Pronase E. On the other hand, the specific protease trypsin showed no such effect on activity of all enzymes. These results suggested that the core structure of the asparagine-linked sugar chain, which consisted of three monosaccharide residues, contributed to the high stability of the endo-beta-1,4-glucanase against protease digestion.

Aspergillus niger↗

Prevalence of hepatitis B surface antigen, hepatitis B e antigen and antibody, and antigen subtypes in atomic bomb survivors.

On the basis of previous studies showing an association between hepatitis B surface antigen (HBsAg) positivity and radiation exposure in atomic bomb (A-bomb) survivors, we investigated further the active state of hepatitis B virus (HBV) infection by incorporating tests for hepatitis B e antigen (HBeAg) and hepatitis B e antibody (anti-HBe) and HBsAg subtypes into our biennial health examinations. Among 6548 A-bomb survivors for whom HBsAg was assayed between July 1979 and July 1981, 129 persons were HBsAg positive. HBeAg and anti-HBe were measured in 104 of these persons and subtypes of HBsAg in 98 persons. Among those exposed to radiation (average liver dose 0.58 Sv), the odds ratio of HBsAg positivity tended to increase with radiation dose (P for trend = 0.024). The P values for association between the prevalence of HB e antigen and radiation dose and between the prevalence of anti-HBe and radiation dose were 0.094 and 0.17, respectively. The HB antigen subtype adr was predominant over other subtypes in both Hiroshima and Nagasaki, but the distribution of subtypes did not seem to differ in relation to radiation dose. These results suggested that A-bomb survivors remain in an active state of HBV infection and that the mechanism(s) of seroconversion may be impaired.

Adolescent↗

Increased cytosolic phospholipase A2 activity is not accompanied by arachidonic acid liberation in U46619-stimulated rabbit platelets.

Stimulation of rabbit platelets with U46619 as well as thrombin significantly increased cytosolic phospholipase A2 activity. However, arachidonic acid liberation in response to U46619 was slight compared with that evoked by thrombin. Ionomycin enhanced arachidonic acid liberation induced by thrombin, but had no effect on that by U46619, although ionomycin further increased both thrombin- and U46619-induced Ca2+ mobilization. However, stimulation with U46619 followed by addition of NaF plus AlCl3 synergistically induced arachidonic acid liberation. These results suggest that phosphorylation and translocation to membranes of cytosolic phospholipase A2 are necessary but not sufficient for arachidonic acid liberation by the enzyme upon receptor stimulation, and that another factor, such as GTP-binding protein, may be further required for the hydrolytic action of the enzyme.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Prevalence rate of thyroid diseases among autopsy cases of the atomic bomb survivors in Hiroshima, 1951-1985.

To examine the radiogenic risk of latent thyroid cancer, thyroid adenoma, colloid/adenomatous goiter and chronic thyroiditis, the data for 3821 subjects collected in the course of autopsies of atomic bomb survivors in Hiroshima from 1951 to 1985 by the Radiation Effects Research Foundation (RERF) were analyzed using a logistic model. About 80% of the autopsies were performed at RERF and the remainder at local hospitals. The frequencies of the above diseases were not associated with whether the underlying cause of death was cancer. However, note that our results may be influenced by potentially biasing factors associated with autopsy selection. The relative frequency of latent thyroid cancer (greatest dimension < or = 1.5 cm but detectable on a routine microscopic slide of the thyroid gland) increased as the radiation dose increased and was about 1.4-fold greater at 1 Gy than in the 0-Gy dose group. The relative occurrence of thyroid adenoma also increased as radiation dose increased, and was about 1.5-fold greater at 1 Gy than in the 0-Gy dose group. Sex, age at the time of the bombing or period of observation did not significantly modify the radiogenic risks for thyroid adenoma or latent thyroid cancer. No statistically significant association was found between radiation exposure and the rates of colloid/adenomatous goiter and chronic thyroiditis. The possible late effect of atomic bomb radiation on the frequency of benign thyroid diseases is discussed on the basis of these data.

Adenoma↗

Contribution of phospholipases A2 and D to arachidonic acid liberation and prostaglandin D2 formation with increase in intracellular Ca2+ concentration in rat peritoneal mast cells.

The contribution of phospholipases A2 (PLA2) and D (PLD) activation to arachidonic acid liberation and prostaglandin D2 (PGD2) formation was studied in stimulated rat peritoneal mast cells. Stimulation of the cells with ionomycin induced time-dependent and Ca(2+)-concentration-dependent increase in arachidonic acid liberation and PGD2 formation, and the Ca(2+)-dependent increase was especially remarkable at extracellular Ca2+ concentration higher than 200 microM. Staurosporine did not induce any effect on the arachidonic acid liberation, indicating that protein kinase C is not involved in the liberation. Addition of ethanol to the cells decreased the ionomycin-stimulated arachidonic acid liberation to 40% of the control, while it decreased the PGD2 formation almost completely, with the increase in phosphatidylethanol formation. Propranolol, a phosphatidate phosphohydrolase inhibitor, caused similar effects. p-Bromophenacyl bromide, a PLA2 inhibitor, inhibited partially the arachidonic acid liberation. The inhibition of the liberation by combination of p-bromophenacyl bromide and ethanol was additive and reached approximately 90%. Under the conditions used p-bromophenacyl bromide did not influence significantly the PLD activity assessed by the phosphatidylethanol formation. Histamine release was decreased by ethanol treatment to 35% of the control. These results suggest that more than half of the total arachidonic acid liberation is mediated by the sequential pathway of PLD/phosphatidate phosphohydrolase/diacylglycerol lipase and more than half of histamine release is also dependent on PLD activation, while the PGD2 formation is fully mediated by the pathway. PLA2 also contributes to arachidonic acid liberation but to a lower extent.

Acetophenones↗

A case-control interview study of breast cancer among Japanese A-bomb survivors. I. Main effects.

Women with breast cancer (cases = 196) and without the disease (controls = 566), selected from the Life Span Study sample of A-bomb survivors and nonexposed residents of Hiroshima and Nagasaki, Japan, and matched on age at the time of the bombings, city, and estimated radiation dose, were interviewed about reproductive and medical history. A primary purpose of the study was to identify strong breast cancer risk factors that could be investigated further for possible interactions with radiation dose. As expected, age at first full-term pregnancy was strongly and positively related to risk. Inverse associations were observed with number of births and total, cumulative period of breast feeding, even after adjustment for age at first full-term pregnancy. Histories of treatment for dysmenorrhea and for uterine or ovarian surgery were associated positively and significantly with risk at ages 55 or older, a finding that requires additional study. Other factors related to risk at older ages were the Quetelet index (weight [kg]/height [cm]2) at age 50, history of thyroid disease, and hypertension. Neither age at menarche nor age at menopause was associated significantly with risk. Subjects appeared to be poorly informed about history of breast cancer or other cancer in themselves or in their close relatives; this finding suggests that innovative strategies may be required when studying familial cancer patterns in Japanese populations.

Adult↗

A case-control interview study of breast cancer among Japanese A-bomb survivors. II. Interactions with radiation dose.

Three breast cancer risk factors were evaluated in terms of their interactions with radiation dose in a case-control interview study of Japanese A-bomb survivors. Cases and controls were matched on age at the time of the bombings and radiation dose, and dose-related risk was estimated from cohort rather than case-control data. Each factor--age at first full-term pregnancy, number of deliveries, and cumulative lactation period summed over births--conformed reasonably well to a multiplicative interaction model with radiation dose (the additive interactive model, in which the absolute excess risk associated with a factor is assumed to be independent of radiation dose, was rejected). An important implication of the finding is that early age at first full-term pregnancy, multiple births, and lengthy cumulative lactation are all protective against radiation-related, as well as baseline, breast cancer. Analyses by age at exposure to radiation suggest that, among women exposed to radiation in childhood or adolescence, a first full-term pregnancy at an early age following exposure may be protective against radiation-related risk.

Adult↗

Analysis of cancer risk related to longitudinal information on smoking habits.

Radiation Effects Research Foundation (RERF) has followed the RERF Life Span Study (LSS) cohort consisting of atomic bomb survivors and unexposed subjects for more than 40 years. The information on their lifestyles, including smoking habits, has been collected in the past 25 years through two mail surveys of the entire LSS cohort and three interview surveys of a subcohort for the biennial medical examination program. In the present study an attempt was made to consolidate the information of smoking habits obtained from the five serial surveys, and then a risk analysis was conducted to evaluate the effect of updating the smoking information on the smoking-related risk estimates for lung cancer. The estimates of smoking-related risk became larger and estimates of dose-response became sharper by updating smoking information using all of the data obtained from the five serial surveys. Analyses were also conducted for cancer sites other than lung. The differences in risk estimates between the two approaches were not as evident for the other cancer sites as for lung.

Adult↗

Evaluation of cancer prevention strategies by computerized simulation model: methodological issues.

A computerized simulation model developed to evaluate the potential impact of primary and secondary prevention is discussed from methodologic perspectives. In the simulation model, named CANSAVE (Cancer Strategy Analysis and Validation of Effect), the natural history of cancer was modeled as a Markovian stochastic process from cancer-free state to death. The lung cancer death rate among Japanese males was projected for 50 years to the year 2041. The simulation showed that the age-adjusted death rate would increase and reach a peak of 166 per 100,000 in 1989 and then decrease to 148 in 2003. It then shows a tendency to increase again, up to 255 in 2028. This change may be attributed to a lower smoking initiation rate among those born in the 1930s. Promotion of mass screening programs exhibits a more prompt effect than antismoking efforts, but the reduction in annual deaths is expected to be only 11%, even if a 100% participation is realized by the year 2000. The reduction in smoking initiation rate, on the other hand, begins to show a visible effect very slowly. It was predicted that a 1% annual reduction in smoking initiation rate would result in a 20% decrease in the number of deaths in 2041. The smoking cessation program is in the middle with regard to promptness. The predicted reductions in lung cancer deaths in 2041 were 13, 47, and 66%, respectively, when the annual smoking cessation rate was increased from 0.46% (present status) to 1, 3, and 5%. The combined application of all three preventive measures seems essential to realize the most effective reduction in lung cancer deaths.

Adult↗

Thyroid diseases in cohort studies of A-bomb survivors.

A fixed population of about 120,000 subjects was selected from those A-bomb survivors and unexposed controls for the purpose of follow-up studies on their late health effects. One hundred twelve cases of thyroid cancer were found in the study period between 1958 to 1979. The relative risk increased with thyroid dose: the excess relative risk per Gray was 1.1. The prevalence of thyroid diseases was evaluated in 2,587 subjects in Nagasaki: one or more diagnoses for thyroid diseases were made in 447.

Cohort Studies↗

Prediagnostic serum selenium and zinc levels and subsequent risk of lung and stomach cancer in Japan.

Serum samples were collected in Hiroshima and Nagasaki, Japan, from 1970 to 1972 for 208 persons who in 1973-1983 developed stomach cancer; for 77 who in 1973-1983 developed lung cancer; and for controls matched for age, sex, city, and season of blood collection. Average serum levels of selenium and zinc were slightly (< 5%) but not significantly lower among the cancer cases than among controls. Smoking-adjusted risks of lung cancer were elevated only among those in the lowest quartiles of serum selenium [odds ratio (OR) = 1.8] and zinc (OR = 1.3); the trends in risk of this cancer with decreasing serum levels were neither linear nor significant. Little or no excess risk of stomach cancer was observed among those with lowest levels of selenium (OR = 1.0) or zinc (OR = 1.2). These exploratory findings add to limited data available from other reports showing slightly increased risks of lung cancer associated with low blood levels of selenium, but suggest little association with either lung or stomach cancer across normal selenium or zinc ranges in this Japanese population.

Adult↗

Incidence of female breast cancer among atomic bomb survivors, 1950-1985.

An incidence survey among atomic bomb survivors identified 807 breast cancer cases, and 20 second breast cancers. As in earlier surveys of the Life Span Study population, a strongly linear radiation dose response was found, with the highest dose-specific excess relative risk (ERR) among survivors under 20 years old at the time of the bombings. Sixty-eight of the cases were under 10 years old at exposure, strengthening earlier reports of a marked excess risk associated with exposure during infancy and childhood. A much lower, but marginally significant, dose response was seen among women exposed at 40 years and older. It was not possible, however, to discriminate statistically between age at exposure and age at observation for risk as the more important determinant of ERR per unit dose. A 13-fold ERR at 1 Sv was found for breast cancer occurring before age 35, compared to a 2-fold excess after age 35, among survivors exposed before age 20. This a posteriori finding, based on 27 exposed, known-dose, early-onset cases, suggests the possible existence of a susceptible genetic subgroup. Further studies, involving family histories of cancer and investigations at the molecular level, are suggested to determine whether such a subgroup exists.

Adult↗