Biomedical subjects

S Akiba

Publications and source records attributed to S Akiba.

At least 109 records · Page 6Linked to original sources

PubMed1993

Enhancement of phospholipase A2 activation by phosphatidic acid endogenously formed through phospholipase D action in rat peritoneal mast cell.

Contribution of phosphatidic acid (PA) generated by activated phospholipase (PL) D to PLA2 activation was studied in rat peritoneal mast cells. Exogenous didecanoyl PA induced arachidonate liberation in the permeabilized cells which was inhibited by p-bromophenacyl bromide. Upon exposure of the cells to ethanol in a high enough concentration to prevent PA formation, A23187-induced arachidonate liberation was suppressed by 50% and the rest was completely inhibited by p-bromophenacyl bromide. In contrast, propranolol, which enhanced PA accumulation, significantly increased the arachidonate liberation. These results suggest that A23187-induced PLA2 activation may be potentiated, at least in part, by PA generated through PLD action.

Animals↗

PubMed1993

Evidence for an increase in the association of cytosolic phospholipase A2 with the cytoskeleton of stimulated rabbit platelets.

Following stimulation of rabbit platelets with thrombin, phospholipase A2 (PLA2) activity increased in the Triton X-100-insoluble residue. Although the PLA2 activity was dependent on the protein content of the residue from the stimulated cells, the specific activity was higher than that in the case of unstimulated cells. The enzyme activity was inhibited by p-bromophenacyl bromide and increased significantly with 0.5-10 microM Ca2+. The enzyme hydrolyzed phospholipids having an arachidonoyl residue more effectively than ones with a linoleoyl residue. In addition, 70% of the enzyme activity was immunoprecipitated with a monoclonal antibody against cytosolic PLA2 of rabbit platelets, while it was inhibited by only 20% by an antibody that neutralizes the activity of group II PLA2. These results suggest an increase in the association of cytosolic PLA2 with cytoskeleton upon stimulation of rabbit platelets.

Animals↗

PubMed1993

Enhancement of A23187-induced arachidonic acid liberation by vasopressin is sensitive to genistein in rabbit platelets.

A mechanism by which vasopressin enhances phospholipase A2 activation in rabbit platelets was investigated. Stimulation of the platelets with vasopressin enhanced arachidonic acid liberation, as well as aggregation and ATP secretion in the presence of submaximal concentration of A23187, although vasopressin alone had no effect. The vasopressin-enhanced liberation was inhibited by p-bromophenacyl bromide, a phospholipase A2 inhibitor, and by genistein, a tyrosine kinase inhibitor. Though epinephrine also caused a similar enhancement of the liberation, this effect of epinephrine was insensitive to genistein. Staurosporine, a protein kinase C inhibitor, completely suppressed phorbol 12-myristate 13-acetate-enhanced arachidonic acid liberation, but suppressed the vasopressin-induced enhancement only slightly. These results suggest that vasopressin-enhanced phospholipase A2 activation may be regulated by a genistein-sensitive mechanism, most likely by a protein tyrosine kinase-mediated pathway, but not by guanine nucleotide-binding protein- or protein kinase C-mediated pathway.

Acetophenones↗

PubMed1993

Noncancer disease incidence in the atomic bomb survivors: 1958-1986.

Using the longitudinal data of the Adult Health Study (AHS) cohort collected during 1958-1986, we examined for the first time the relationship between exposure to ionizing radiation and the incidence of 19 nonmalignant disorders in the A-bomb survivors. Affected individuals were ascertained through the three-digit codes of the International Classification of Diseases which are encoded in the AHS database subsequent to diagnoses made on the basis of general laboratory tests, physical examinations, and history-taking conducted during biennial AHS examinations. The disease onset time was estimated using the mid-point between the AHS examination data when the disease was initially reported and the previously attended disease-free examination date. Dosimetry System 86 organ doses judged to be most appropriate were used. Tests of dose effects were performed assuming a linear relative risk model with stratified background incidence. For the entire study period, significant excess risk was detected for uterine myoma (P < 0.001), chronic liver disease and cirrhosis (P = 0.006), and thyroid disease (P < 0.0001), defined broadly as the presence of one or more of certain noncancerous thyroid conditions. The incidence of myocardial infarction was shown to be increased (P = 0.03) in later years (1968-1986) among the younger heavily exposed AHS subjects, confirming the results of the recent Life Span Study (LSS) noncancer mortality report on coronary heart disease. The findings for uterine myoma may serve as additional evidence indicating benign tumor growth as a possible consequence of radiation exposure. Our results indicating the involvement of radiation in the development of liver diseases are consistent with the report of increased mortality from liver cirrhosis with radiation dose in the LSS cohort. An effect of age at exposure was detected for nonmalignant thyroid disease (P = 0.02), with an increased risk for those exposed who were under 20 years of age, but not for older survivors. Thus the AHS data suggest that thyroid glands in the young are more radiosensitive not only to the development of malignancies, but also to the development of nonmalignant disorders as well. The findings hold independently of the dose effects observed for thyroid cancer. This study also shows that for the period 1958-1986 new occurrences of lens opacity are not increased with radiation dose (P = 0.39) in the AHS subjects.

Adult↗

PubMed1993

Radiation-associated lung cancer: a comparison of the histology of lung cancers in uranium miners and survivors of the atomic bombings of Hiroshima and Nagasaki.

A binational panel of Japanese and American pulmonary pathologists reviewed tissue slides of lung cancer cases diagnosed among Japanese A-bomb survivors and American uranium miners and classified the cases according to histological subtype. Blind reviews were completed on slides from 92 uranium miners and 108 A-bomb survivors, without knowledge of population, sex, age, smoking history, or level of radiation exposure. Consensus diagnoses were obtained with respect to principal subtype, including squamous-cell cancer, small-cell cancer, adenocarcinoma, and less frequent subtypes. The results were analyzed in terms of population, radiation dose, and smoking history. As expected, the proportion of squamous-cell cancer was positively related to smoking history in both populations. The relative frequencies of small-cell cancer and adenocarcinoma were very different in the two populations, but this difference was accounted for adequately by differences in radiation dose or, more specifically, dose-based relative risk estimates based on published data. Radiation-induced cancers appeared more likely to be of the small-cell subtype, and less likely to be adenocarcinomas, in both populations. The data appeared to require no additional explanation in terms of radiation quality (alpha particles vs gamma rays), uniform or local irradiation, inhaled vs external radiation source, or other population difference.

Adenocarcinoma↗

PubMed1992

Biscoclaurine alkaloids inhibit receptor-mediated phospholipase A2 activation probably through uncoupling of a GTP-binding protein from the enzyme in rat peritoneal mast cells.

The mechanism underlying the inhibitory effect of biscoclaurine (bisbenzylisoquinoline) alkaloids on phospholipase A2 activation in the signalling system of stimulated rat peritoneal mast cells was studied. Cepharanthine, berbamine and isotetrandrine inhibited antigen- and compound 48/80-induced arachidonic acid liberation, but not diacylglycerol formation or histamine release. They had no effect on A23187-induced arachidonic acid liberation, which was prevented by p-bromophenacyl bromide, a known phospholipase A2 inhibitor, and also did not affect phospholipase A2 activity in a cell-free system including an exogenous phospholipid substrate. Each alkaloid also inhibited arachidonic acid liberation induced by guanosine 5'-O-(3-thiotriphosphate) in saponin-permeabilized mast cells, and by mastoparan or NaF plus AlCl3 intact cells. Furthermore, each alkaloid abolished the inhibitory effect of islet-activating protein on the compound 48/80-induced arachidonic acid liberation. These data suggest that these alkaloids suppress the receptor-mediated phospholipase A2 activation through, at least in part, uncoupling of a GTP-binding protein from the enzyme, rather than by affecting the enzyme directly.

Alkaloids↗

PubMed1992

A 50-year projection of lung cancer deaths among Japanese males and potential impact evaluation of anti-smoking measures and screening using a computerized simulation model.

The lung cancer death rate among Japanese males was projected for 50 years to the year 2041 by a computerized simulation model. Long-term effects of anti-smoking measures and mass screening on lung cancer deaths were also evaluated. The simulation showed that the age-adjusted lung cancer death rate would increase and reach a peak of 166 per 100,000 in 1989 and then decrease to 148 per 100,000 in 2003. It then shows an increasing tendency again, up to 255 per 100,000 in 2028. The smoking initiation rates estimated from the observed lung cancer death rates showed that the changes in death rates may be attributed to a lower smoking initiation rate among those born in the 1930's. Promotion of mass screening programs is effective more quickly than anti-smoking measures but the reduction in annual cancer deaths is expected to be only 11%, even if 100% participation is achieved by the year 2000. A reduction in smoking initiation rate, on the other hand, affects lung cancer deaths very slowly. It was predicted that a 1% annual reduction in smoking initiation rate would result in a 20% decrease in the number of lung cancer deaths in 2041. A smoking cessation program is intermediate 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%. In conclusion, the combined application of all three preventive measures seems essential to realize the most effective reduction in lung cancer deaths.

Age Factors↗

PubMed1992

Hyperparathyroidism among atomic bomb survivors in Hiroshima.

To determine the effect of exposure to atomic bomb radiation on the occurrence of hyperparathyroidism, the prevalence was determined among a population of 3,948 atomic bomb survivors and their controls in Hiroshima. The diagnosis of hyperparathyroidism was based upon histopathological findings or the presence of consistent hypercalcemia and elevated levels of serum parathyroid hormone. Primary hyperparathyroidism was diagnosed in 19 persons (3 males, 16 females). Females had approximately a threefold higher overall prevalence of hyperparathyroidism than males (P less than 0.05). The prevalence rates of hyperparathyroidism increased with radiation dose (chi2(1) = 12, P less than 0.001) after adjusting for sex and age at the time of the bombing. The estimated relative risk was 4.1 at 1 Gy (95% confidence limits 1.7 to 14). There was some evidence that the effect of radiation was greater for individuals who were younger at the time of the bombing. In conclusion, exposure to atomic bomb radiation affected the occurrence of hyperparathyroidism, suggesting that doses of radiation lower than those used in radiotherapy may also induce this disorder.

Adolescent↗

PubMed1991

Serum ferritin and stomach cancer risk among a Japanese population.

Using stored serum samples collected during from 1970 to 1972 and/or 1977 to 1979 from a fixed population in Hiroshima and Nagasaki, Japan, serum ferritin, transferrin, and ceruloplasmin levels were determined immunologically for persons in whom stomach (233 cases) or lung cancer (84 cases) subsequently developed as well as for their controls. An elevated stomach cancer risk was associated with low antecedent serum ferritin levels, with more than a threefold excess among those in the lowest compared with the highest ferritin quintile. The risk did not vary with the time between blood collection and stomach cancer onset, remaining high among those with low ferritin levels 5 or more years before cancer diagnosis. Achlorhydria, diagnosed in a sample of the population about 10 years before the 1970-to-1972 blood collection and up to 25 years before cancer, was an independent marker of stomach cancer risk. In combination, low serum ferritin and achlorhydria were associated with a tenfold increase in the subsequent risk. No effect of transferrin or ceruloplasmin, independent of ferritin, was observed in the gastric cancer risk, and the risk of lung cancer was not related to these three serum proteins. These prospective findings indicate that biologic markers of an increased risk of stomach cancer can be detected long before cancer onset.

Achlorhydria↗

PubMed1991

Evaluation of cancer prevention strategies by computerized simulation model: an approach to lung cancer.

A computerized simulation model was developed to evaluate the potential impact of primary and secondary prevention on lung cancer mortality in Japan. The natural history of lung cancer was modeled as a Markovian stochastic process from cancer-free to preclinical, clinical, and finally to terminal states. The increase in mortality rate of lung cancer among males aged 75 to 79 years has been the major force of increase in the total number of lung cancer deaths in Japan. The simulation showed that this tendency would continue until the late 1990s, presumably due to the increase in the proportion of ever-smokers in that cohort, who started smoking at an earlier age than did prior generations. It was shown that the number of lung cancer deaths can be reduced either by smoking cessation or screening programs, and that the reduction is proportional to the increase in the annual smoking-cessation rate and to the annual increment in the screening rate. However, only two to three percent reduction of lung cancer deaths in the year 2001 can be expected when the annual smoking-cessation rate is raised from the current value of 0.46 percent to five percent during the period from 1991 to 2000 or when the screening rate is increased by three percent annually for the same period.

Adult↗

PubMed1991

Interactive effects between radiation and other factors on cancer risk among A-bomb survivors--an overview of RERF studies.

This paper reviews RERF cancer studies conducted to examine interactive effects between radiation and epidemiological risk factors, including smoking habits, occupation, dietary habits and OB/GYN history. Special emphasis is placed on a review of studies of interactive effects between cigarette smoking and radiation on lung cancer risk. Comments on these studies are made and proposals for future studies are presented.

Humans↗

PubMed1991

The observed relationship between the occurrence of acute radiation effects and leukemia mortality among A-bomb survivors.

In an analysis of a follow-up study of a fixed population of 73,330 atomic bomb survivors in Hiroshima and Nagasaki, the slope of an estimated dose response between ionizing radiation and leukemia mortality was found to be steeper (P less than 0.002), by a factor of 2.4, among those who reported epilation within 60 days of the bombings, compared to those who did not experience this sign of acute radiation exposure. The strength of this empirical finding as evidence of biological association in individual radiosensitivity for these two end points is studied here. The major factor complicating the interpretation of this finding as evidence of such an association is the degree of imprecision of the radiation dosimetry system used in assignment of radiation doses to the A-bomb survivors. Using models recently suggested for dealing with dosimetry errors in epidemiological analysis of the A-bomb survivor data, the sensitivity of the apparent association between leukemia mortality and severe epilation to the assumed level of dosimetry error is investigated.

Acute Disease↗

PubMed1990

Involvement of a guanine-nucleotide-binding protein-mediated mechanism in the enhancement of arachidonic acid liberation by phorbol 12-myristate 13-acetate and Ca2+ in saponin-permeabilized platelets.

A mechanism by which protein kinase C potentiates arachidonic acid (AA) liberation in rabbit platelets was examined using [3H]AA-labeled, saponin (7 micrograms/ml)-permeabilized rabbit platelets. Pretreatment of the [3H]AA-labeled platelets with 4 beta-phorbol 12-myristate 13-acetate (PMA, 10-40 nM) or 1,2-dioctanoylglycerol (DOG, 20 microM) enhanced [3H]AA liberation induced by an addition of Ca2+ (1 mM) after cell permeabilization, whereas 4 alpha-phorbol 12,13-didecanoate (80 nM) did not exert such an effect. The potentiating effects of PMA and DOG were inhibited by staurosporine (200 nM). PMA (40 nM) also potentiated [3H]AA liberation induced by guanosine 5'-[gamma-thio]triphosphate (GTP gamma S, 100 microM), 5'-guanylyl imidodiphosphate (200 microM) or NaF (20 mM) plus AlCl3 (10 microM) in the presence of Ca2+ (100 microM). The enhancement by PMA of the GTP gamma S-induced AA liberation was also inhibited by staurosporine (200 nM). Furthermore, guanosine 5'-[beta-thio]diphosphate (GDP beta S, 0.5-2 mM) suppressed the PMA (40 nM)- and DOG (20 microM)-enhanced, Ca2+ (1 mM)-dependent [3H]AA liberation. This inhibitory effect of GDP beta S was reversed by a further addition of GTP gamma S (200 microM). However, pertussis toxin (0.2-1 micrograms/ml) had no effect on the PMA-enhanced [3H]AA liberation. These results indicate a possibility that protein kinase C may potentiate AA liberation through a guanine-nucleotide-binding protein-mediated mechanism in saponin-permeabilized rabbit platelets.

Alkaloids↗

PubMed1990

Smoking and serum proteins in atomic-bomb survivors in Japan.

Associations of smoking habit with serum levels of total protein as well as protein fractions were studied in a population consisting of 4,739 atomic-bomb survivors and unexposed control subjects in Hiroshima, Japan who participated in the 1979-1981 period of the Adult Health Study, an ongoing health follow-up program of the Radiation Effects Research Foundation. Smoking was strongly related to serum protein concentration after correction for age, sex, and body mass index. Among current smokers, levels of total protein, beta globulin, and gamma globulin were significantly lower and levels of alpha-1 and alpha-2 globulin were significantly higher, when compared with nonsmokers. For serum albumin levels a decrease was also noted, but it failed to attain statistical significance. Ex-smokers were indistinguishable from nonsmokers in terms of the serum protein levels analyzed. With an increase of the amount of daily cigarette consumption, monotonic increases of serum levels were observed only in alpha-1 globulin. Duration of smoking was related to increased alpha-1 and alpha-2 globulin. Smoking duration was also associated with albumin level, but the trend was not monotonic. The radiation exposure effect on serum protein level was significant in several instances but was in general much smaller than the smoking effect, and its inclusion in the regression models did not noticeably affect the association between smoking and serum proteins.

Aged↗

PubMed1990

Cigarette smoking and cancer mortality risk in Japanese men and women--results from reanalysis of the six-prefecture cohort study data.

In 1965 a cohort of 265,000 residents of 29 public health districts in six prefectures throughout Japan was established and followed between 1966 and 1981. By using survival analysis based on Poisson regression models adjusted for age, prefecture of residence, and occupation, a statistically significant dose-response relationship between cigarette smoking and mortality rate was found for cancers of the liver, pancreas, and lung in both sexes; cancers of the oral cavity, esophagus, stomach, larynx, and bladder in men; and cancer of the uterus in women. The magnitudes of relative risks were only slightly affected by adjustment for prefecture of residence or occupation. Analysis using linear relative risk models revealed that the inclusion of a quadratic term for the amount of daily cigarette consumption in addition to the linear term improved the fit of the model significantly for cancers of the esophagus and stomach in men and cancer of the stomach in women. The sex ratio of gastric cancer mortality was higher among smokers than among nonsmokers. When the follow-up period was divided into four 4-year intervals, it was noted that the relative mortality risk associated with lung cancer among males increased significantly during these time periods.

Adult↗

PubMed1989

Enhancement of arachidonic acid liberation by protein kinase C activator is partially dependent on extracellular Na+ in rabbit platelets.

In [3H]arachidonic acid-labeled rabbit platelets, pretreatment with phorbol 12-myristate 13-acetate (20 nM) or dioctanoylglycerol (20 microM) enhanced [3H]arachidonic acid liberation induced by low concentration of A23187 (150 nM). When extracellular Na+ was replaced with N-methyl-D-glucamine, the enhancement is reduced by about 50%. Similar synergistic enhancement of the liberation was obtained by using monensin (2-10 microM) or NH4Cl (5-20 mM) in place of protein kinase C activator in combination with A23187. The guanosine 5'-O-[3-thiotriphosphate] (100 microM)-induced liberation was also enhanced by a rise of extracellular pH (pH 7.0-7.8) in saponin-permeabilized platelets. These results suggest that the enhancement of arachidonic acid liberation by protein kinase C may partially be mediated by intracellular alkalinization in rabbit platelets.

Animals↗

PubMed1989

Platelet desensitization by arachidonic acid is associated with the suppression of endoperoxide/thromboxane A2 binding to the membrane receptor.

The inhibitory mechanism of high levels of exogenously added arachidonic acid on activation of washed human platelets was investigated. While low levels of arachidonic acid (5-10 microM) induced aggregation, ATP secretion and increase in cytoplasmic free Ca2+ concentration (first phase of activation), these platelet responses did not occur significantly at high concentrations (30-50 microM). However, much higher concentrations than 80 microM again elicited these responses (second phase). The first phase of platelet activation was inhibited by cyclooxygenase inhibitor, indomethacin, whereas the second one was independent of such treatment. Thromboxane B2 was produced dose-dependently until reaching a plateau at arachidonic acid concentrations higher than 20 microM, irrespective of the lack of aggregation and secretion at high concentrations. After that the amount of free arachidonic acid which remained unmetabolized in platelets gradually increased. High concentrations of arachidonic acid as well as other polyunsaturated fatty acids caused desensitization of platelets in response to U46619, and also depressed the specific [3H]U46619-binding to the receptor as well as other polyunsaturated fatty acids. The amount free arachidonic acid needed in platelets to suppress [3H]U46619 binding corresponded to that needed to inhibit platelet aggregation. Furthermore, arachidonic acid dose-dependently induced fluidization of lipid phase of platelet membranes as detected by 1,6-diphenyl-1,3,5-hexatriene. These results suggest that the inhibition of platelet response by high levels of arachidonic acid can be attributed to interference with endoperoxide/thromboxane A2 binding to the receptor, probably due to perturbation of the membrane lipid phase due to excess amounts of free arachidonic acid remaining in the membranes.

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

PubMed1989

Differential effects of phorbol 12-myristate 13-acetate on GTP gamma S-induced diacylglycerol formation and arachidonic acid liberation in saponin-permeabilized rabbit platelets.

In rabbit platelets, collagen (50 micrograms/ml)- or thrombin (0.5 U/ml)-induced diacylglycerol formation was dose-dependently prevented by phorbol 12-myristate 13-acetate (PMA, 2-50 nM). However, collagen-induced arachidonic acid liberation and lysophosphatidylcholine formation were rather enhanced by PMA, while the thrombin-induced liberation was not. We also demonstrated with saponin-permeabilized platelets that collagen (100 micrograms/ml)-induced arachidonic acid liberation was enhanced by GTP gamma S and inhibited by GDP beta S, both dose-dependently. Since these results lead us to consider that protein kinase C affects a guanine-nucleotide-binding protein (G-protein) to modulate phospholipase A2 and C, we investigated this dual effect of PMA on arachidonic acid liberation and diacylglycerol formation induced by G-protein activator. Addition of GTP gamma S (100 microM) to saponin-permeabilized platelets significantly induced these responses, and PMA (2-10 nM)-pretreatment before the cell permeabilization inhibited diacylglycerol formation and enhanced arachidonic acid liberation and lysophosphatidylcholine formation, dose-dependently. Likewise, PMA (20 nM) had differential effects on the similar NaF (20 mM)-induced responses in intact platelets. Contrarily, 10 nM PMA had no effect on diacylglycerol formation caused by an addition of high concentration of Ca2+ (1 mM) alone after the cell permeabilization, while it still had a potentiating effect on arachidonic acid liberation under the condition. These results suggest that protein kinase C may have a dual regulatory effect on the activation of phospholipase A2 (positive feedback) and phospholipase C (negative feedback), probably through influences on two distinct G-proteins associated separately with these two enzymes.

Animals↗