Biomedical subjects

S Akiba

Publications and source records attributed to S Akiba.

At least 55 records · Page 3Linked to original sources

PubMed1999

Thymidine phosphorylase in human esophageal squamous cell carcinoma.

BACKGROUND: Experimental evidence has shown that thymidine phosphorylase (dThdPase) is identical to platelet-derived endothelial cell growth factor (PD-ECGF) and has angiogenic activity. The enzymatic activity of dThdPase was needed for the angiogenesis by the enzyme. These observations were catalysts for the current study. METHODS: The authors examined retrospectively the expression of the angiogenic factor dThdPase in 163 primary esophageal squamous cell carcinomas and its association with angiogenesis and clinicopathologic findings. To determine whether dThdPase expression was a prognostic factor after adjustment for the established prognostic factors and microvessel count, the authors conducted a survival analysis using the Cox proportional hazards model. RESULTS: dThdPase was expressed significantly more frequently (P < 0.001) in esophageal carcinomas (83 of 163, 50.9%) than in adjacent nonneoplastic esophageal tissue samples (20 of 163, 12.3%). Microvessel counts were significantly higher (P < 0.001) in dThdPase positive carcinomas (18.3+/-6.2) than in dThdPase negative carcinomas (8.2+/-7.5). Significant correlations were observed between dThdPase expression and numerous clinicopathologic findings, including pT, pN, pM categories; lymphatic invasion; venous invasion; and residual tumors. Prognostic variables studied using a Cox hazard regression model confirmed that dThdPase expression was an independent prognostic factor in esophageal squamous cell carcinoma, although pN category was the best predictor of patient survival. CONCLUSIONS: This study indicated that in esophageal squamous cell carcinoma, dThdPase expression is associated with angiogenesis and is an unfavorable prognostic factor. These findings implied that the inhibition of dThdPase would improve the prognoses of some patients with dThdPase positive esophageal tumors.

Aged↗

PubMed1999

Transglycosylation activity of the endo-beta-1,4-glucanase from Aspergillus niger IFO31125 and its application.

Endo-beta-1,4-glucanase from Aspergillus niger was found to have an endo-type transglycosylation activity. The enzyme effectively transferred cellooligosaccharide residues to various 1-alkanols in the presence of cellopentaose as the oligosaccharide donor. By incubating the enzyme with 1-octanol and cellopentaose in the presence of acetonitrile, 1-octyl-cellotrioside was synthesized. The product was isolated by silica gel column chromatography and analyzed by mass spectrometry. p-NP-beta-Glc, p-NP-beta-Gal, p-NP-beta-GlcNAc, Ser, and Thr were also possible acceptors for the transglycosylation activity of the enzyme.

Journal Article↗

PubMed1999

Acceleration of Ca2+ ionophore-induced arachidonic acid liberation by thrombin without the proteolytic action toward the receptor in human platelets.

We investigated the regulation of arachidonic acid liberation catalyzed by group-IV cytosolic phospholipase A2 (cPLA2) in human platelets upon stimulation with thrombin through interaction with protease-activated receptor-1 (PAR-1) or glycoprotein Ib. Leupeptin, a protease inhibitor, completely inhibited thrombin-induced arachidonic acid liberation and Ca2+ mobilization, with inhibition of its protease activity. However, preincubation with thrombin in the presence of leupeptin potentiated Ca2+ ionophore-induced arachidonic acid liberation. The preincubation did not affect the intracellular Ca2+ level or cPLA2 activity in response to ionomycin. Human leukocyte elastase, which cleaves glycoprotein Ib, did not inhibit the enhancement of arachidonic acid liberation by thrombin in the presence of leupeptin. However, the effect of thrombin with leupeptin was abolished by a peptide corresponding to residues 54-65 of hirudin (hirudin peptide), which impairs the binding of thrombin to PAR-1. Furthermore, Phe-Pro-Arg chloromethyl ketone (PPACK)-thrombin, which binds to platelets but has no protease activity, also enhanced Ca2+ ionophore-induced arachidonic acid liberation. In contrast, trypsin with leupeptin did not mimic the effect of thrombin with leupeptin, and furthermore trypsin-induced arachidonic acid liberation was insensitive to hirudin peptide. On the basis of the present results, we suggest that thrombin may accelerate cPLA2-catalyzed arachidonic acid liberation through non-proteolytic action toward PAR-1 but not toward glycoprotein Ib in co-operation with the proteolytic action leading to Ca2+ mobilization.

Amino Acid Chloromethyl Ketones↗

PubMed1999

Obesity affects expression of progesterone receptors and node metastasis of mammary carcinomas in postmenopausal women without a family history.

Possible relationships between risk factors, such as obesity and a family history of breast cancer, and prognostic factors of mammary carcinomas were investigated by examining the body mass index of patients and the expression of estrogen (ER) and progesterone receptors (PgR), c-erbB-2 and p53, grade of histology, size of tumors and nodal status of mammary carcinomas. There was no significant difference in the body mass index of premenopausal patients either with or without a family history. For postmenopausal patients, the body mass index was significantly low in patients with a family history compared with patients without a family history. In premenopausal patients with or without a family history and in postmenopausal patients with a family history, there was no significant difference in the body mass index regardless of the mammary carcinoma prognostic factor, such as expression of ER, PgR, c-erbB-2 and p53, grade of histology, size of tumors and nodal status. However, in postmenopausal patients without a family history, body mass index was significantly high for patients with mammary carcinomas that had PgR expression and node metastasis. These results suggest that obesity may affect the PgR status and nodal status of mammary carcinomas in postmenopausal patients without a family history.

Body Mass Index↗

PubMed1999

Stimulation by ceramide of phospholipase A2 activation through a mechanism related to the phospholipase C-initiated signaling pathway in rabbit platelets.

To study the involvement of sphingolipids in glycerophospholipid metabolism, the contribution of ceramide to the activation of group IV cytosolic phospholipase A2 (cPLA2) was investigated in platelets using cell-permeable C6-ceramide (N-hexanoylsphingosine). The addition of ceramide led to potentiation of thrombin-induced activation of cPLA2 and mitogen-activated protein kinase (MAPK) as well as arachidonic acid release and lysophosphatidylcholine formation. However, ceramide by itself did not induce any response. The arachidonic acid release due to the synergistic action of ceramide and thrombin was inhibited by PD98059, a MAPK kinase inhibitor. Ceramide also stimulated thrombin-induced protein kinase C (PKC) activation, but ceramide by itself failed to do so. Furthermore, ceramide synergistically enhanced diacylglycerol (DAG) formation and Ca2+ mobilization with thrombin, and also DAG formation with Ca2+-ionophore A23187. The DAG formation in response to ceramide with thrombin or A23187, as well as arachidonic acid release with thrombin were completely inhibited by U73122, a phospholipase C (PLC) inhibitor. These results suggest that ceramide triggers PLC activation through its synergistic action with thrombin, and subsequently potentiates the sequential PKC-MAPK cascade-cPLA2 pathway, thus resulting in enhancement of arachidonic acid release.

Animals↗

PubMed1999

Ceramide enhances susceptibility of membrane phospholipids to phospholipase A2 through modification of lipid organization in platelet membranes.

The effects of ceramide on agonist-stimulated phospholipase A2 (PLA2) activity were studied in platelets. Cell-permeable C6-ceramide (N-hexanoylsphingosine) exogenously added to platelet suspension enhanced U46619-stimulated arachidonic acid release and lysophosphatidylcholine production. Treatment of platelets with sphingomyelinase also led to an enhancement of the release. The enhanced arachidonic acid release by exogenous ceramide was completely inhibited by methyl arachidonyl fluorophosphonate, a cytosolic PLA2 inhibitor. However, U46619-stimulated PLA2 activity was not significantly potentiated by ceramide. These results suggest that enrichment of ceramide in membranes causes modification of intermolecular organization, leading to increased susceptibility of substrate phospholipids to PLA2.

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

PubMed1999

Possible protective effect of milk, meat and fish for cerebrovascular disease mortality in Japan.

Cerebrovascular disease was a leading cause of death from 1955 to 1980 in Japan. The mortality rate from this disease has decreased sharply in recent decades. This downward trend seems to correspond to the dietary habits of Japanese. Data from a large prospective cohort study were analyzed to examine the association between dietary habits and cerebrovascular disease mortality in Japan. The subjects for this analysis were 223,170 men and women aged 40 to 69 at baseline in December 1965. There were 6,168 deaths in men and 4,862 deaths in women due to cerebrovascular disease (ICD7: 330-334) during the follow-up period from January 1966 to December 1981. Rate ratio (RR) and 95% confidence interval (95% CI) adjusted for sex, attained age, follow-up period, prefecture, cigarette smoking, alcohol drinking and occupation was used for comparison. In this study, the risk of mortality from cerebrovascular disease was inversely associated with dairy milk, meat and fish consumption. Therefore the joint effect of dairy milk, meat and fish (DMF) as animal fat and protein was of interest. In the binary analysis, DMF (D, M, F) means the combination of dairy milk (1-3 times/week or more), meat (1-3 times/week or more) and fish (4 times/week or more). Thus DMF (d, m, f) was the reference group having dairy milk (less than 1 time/week), meat (less than 1 time/week) and fish (less than 4 times/week). For the disease, the RR of DMF (D, M, F) was 0.68 with 95% CI of 0.63 to 0.74, relative to the reference group. Furthermore the joint effect of DMF was more strongly associated with cerebral haemorrhage (ICD7: 331, DMF (D, M, F); RR: 0.63, 95% CI: 0.55-0.70) than with cerebral embolism and thrombosis (ICD7: 332, DMF (D, M, F); RR: 0.79, 95% CI: 0.70-0.89). These findings suggest that the increasing intake of animal fat and/or protein may have played a key role in reducing cerebrovascular disease in Japan.

Adult↗

PubMed1999

Asthma-like disease in the children living in the neighborhood of Mt. Sakurajima.

We conducted self-administered questionnaire surveys of school children living in the vicinity of Mt. Sakurajima using ATS-DLD questionnaire. In this paper, we report the results of analysis comparing the proportion of children with asthma-like disease in the area exposed to the volcanic ash and gases released by Mt. Sakurajima and control areas. Asthma-like disease was ascertained using ATS-DLD questionnaire and the definition proposed by the study group established by Environmental Protection Agency in Japan. The proportion of children with asthma-like disease was not different between the exposed and control groups. The odds ratio of asthma-like disease comparing the exposed and control groups was 1.1 and its 95% confidence interval was 0.7-1.8 (P = 0.583). When the exposed area was divided into Tarumizu city. Sakurajima town and Kagoshima city, none of them showed an elevated proportion of children with asthma-like disease when compared with the control area. In the entire study population including both the exposed and control groups, the proportion of children with asthma-like disease was 6 and 3% in boys and girls, respectively. These values were quite similar to those obtained from a survey of 45,674 school children in western districts in Japan in 1992. In conclusion, the present study indicates that the proportion of children with asthma-like disease is not elevated in the exposed area. Further investigations are necessary to confirm our conclusions.

Air Pollutants↗

PubMed1999

Relationship between ambient sulfur dioxide levels and neonatal mortality near the Mt. Sakurajima volcano in Japan.

We examined the association between neonatal mortality and ambient sulfur dioxide (SO2) levels in the neighborhood of Mt. Sakurajima, Yamashita public health district of Kagoshima City, during the period between 1978 and 1988. The analysis using Poisson regression models showed that the monthly average level of SO2 was positively associated with the neonatal mortality (P = 0.002). When the SO2 levels were categorized into four groups to estimate the relative risk (RR) of neonatal mortality using the lowest exposure category as a reference, the RR increased with elevated exposure levels (P for trend < 0.001) and was the highest in the group with the highest level of exposure (RR = 2.2, 95% confidence interval; 1.2-4.1). Other than SO2, we also examined the number of eruptions, the amount of ashfall, and the average level of suspended particulate matter. None of these factors was associated with neonatal mortality. Although the present study suggests that increase in SO2 levels has had an adverse effect on neonatal mortality in the neighborhood of Mt. Sakurajima, it is difficult to determine the source of the SO2. Further studies are necessary to elucidate the mechanisms of the excess neonatal mortality probably associated with the volcanic SO2 levels.

Air Pollutants↗

PubMed1999

Ultraviolet radiation and health: from hazard identification to effective prevention.

The increased exposure to ultraviolet (UV) radiation due to ozone depletion is one of the most serious global health problems. The UV exposure is known to cause skin carcinoma, cataract and deteriorated immune function, but for countries like Japan, the magnitude of health effects of UV radiation is yet to be elucidated. The International Workshop on the Health Effects of Ultraviolet Radiation was held in Tokyo, Japan, on February 17-19, 1999, in attempts to visualize the size of this problem and to identify better solutions. Through this workshop, several lines of scientific evidence were provided, which clearly show that the risk of cataract and skin cancer among people living in Japan increases with the increasing level of sun exposure. We must seek, therefore, the extent to which the UV exposure of given intensity causes adverse health effects in Japanese population. Through the workshop, the importance of preventive measure was confirmed. The scientific basis of prevention is, of course, the knowledge of dose-response relationship and the current exposure status in Japanese population. It is hoped that the communications between researchers in Japan and other countries are strengthened through this workshop.

Cataract↗

PubMed1999

Influence of chronic UV exposure and lifestyle on facial skin photo-aging--results from a pilot study.

In order to better understand the effect of chronic sun exposure on facial skin photo-aging and to identify the factors affecting it, we planned a study in two areas in Japan, Akita and Kagoshima, which correspond to the low and high sun exposure environments, respectively. As a first step, we conducted a pilot study in the two areas, examining 195 subjects. Hyper-pigmentation and wrinkling were measured with a high-resolution digital video imaging system. As expected, people in Kagoshima had darker skin, higher visual grades of facial hyper-pigmentation, and more facial wrinkles than people in Akita, reflecting the difference of UV exposure levels in the two areas. Both the grades of hyper-pigmentation and number of wrinkles increased in a roughly linear fashion with the advancement of age. On the other hand, the effect of gender was different in those two skin photo-aging parameters. Women had higher hyper-pigmentation grades (P = 0.012) and less wrinkles (P = 0.004) than men. Interestingly, post-menopausal women had higher grades of hyper-pigmentation than pre-menopausal women. Neither sun exposure index for darkness nor wrinkling showed any significant differences by menopausal status. In this pilot study, we collected information on various factors, including life-styles. The results of detail analysis will be presented elsewhere. In the present analysis, we found that the grade of hyper-pigmentation was not related to total hours spent outside in life but was affected by various factors, including toe-nail zinc levels. On the other hand, the number of wrinkles was significantly related to total hours spent outside in life. The most important risk factors of non-melanoma skin cancer are chronic sun exposure, age and male sex. All of them are strongly related to higher levels of UV exposure. The present study confirmed that chronic sun exposure, age and male sex were strong risk factors of the wrinkle number. The number of wrinkles was significantly related to total hours of sun exposure in life, increased in a roughly linear fashion with the advancement of age, and was larger in men than in women. In epidemiological studies of UV-related skin cancer, the number of wrinkles, which can be easily measured with a high-resolution digital video imaging system as shown in this study, may be a good marker of total sun exposure in life.

Adult↗

PubMed1999

Epstein-Barr virus-associated gastric carcinoma in Mexico: analysis of 135 consecutive gastrectomies in two hospitals.

Epstein-Barr virus (EBV) has been implicated in the genesis of gastric carcinoma. The presence of clonal episomal viral forms in the nuclei of neoplastic gastric epithelial cells suggests that viral infection occurs before the development of gastric carcinoma. Mexico is a country at high risk for gastric cancer-it is the second cause of death among patients who die of cancer in that country. A series of 135 consecutive non-selected gastrectomies from two hospitals in Mexico City were analyzed to search for EBV in gastric carcinomas. EBV-encoded small non-polyadenylated RNA (EBER) in situ hybridization was performed on 5-microm paraffin-embedded tissue sections. Age, gender, anatomical site, histological type, and invasiveness of gastric carcinomas were obtained from the records in the corresponding Departments of Pathology. Eleven (8.15%) of the 135 cases were EBER-1-positive gastric carcinomas. Six occurred in males and five in females. In three women, the neoplasia was localized in the antrum. Five of the 11 cases were lymphoepithelioma-like carcinomas and, in two of them, an unusual foreign body-type inflammation was observed. Environmental factors could influence the distinctive pathologic features of EBV-associated gastric carcinoma in the Mexican population.

Adult↗

PubMed1998

Inhibition of Ca2+-independent phospholipase A2 by bromoenol lactone attenuates prostaglandin generation induced by interleukin-1 beta and dibutyryl cAMP in rat mesangial cells.

Cytokine-induced prostaglandin generation in rat mesangial cells has been suggested to be dependent on the expression of secretory phospholipase A2 (sPLA2). In the present study, we investigated the possible involvement of Ca2+-independent phospholipase A2 (iPLA2) in the generation. The results showed that bromoenol lactone, a relatively selective iPLA2 inhibitor, significantly attenuated prostaglandin E2 generation induced by interleukin-1beta and dibutyryl cAMP in parallel with the inhibition of iPLA2 activity. However, the inhibitor did not affect sPLA2 release upon stimulation, activities of sPLA2 or cytosolic phospholipase A2, or Ca2+ ionophore-induced arachidonic acid liberation. These results suggest that prostaglandin E2 generation upon stimulation may be partially mediated by iPLA2 in addition to sPLA2.

Animals↗

PubMed1998

Assay of protein-bound lipoic acid in tissues by a new enzymatic method.

A new enzymatic method for the determination of protein-bound lipoic acid was established. Bound lipoyl groups were liberated in the form of lipoyllysine by protease digestion and assayed by lipoamide dehydrogenase (NADH:lipoamide oxidoreductase, EC 1.8.1.4)-mediated NADH oxidation. NADH oxidation was coupled to reduction of the lipoyl disulfide group. Fluorescence kinetics of NADH oxidation were markedly enhanced by the addition of glutathione disulfide, recycling the enzyme-mediated lipoyl/dihydrolipoyl conversion. In the presence of a large excess of glutathione disulfide, NADH oxidation follows pseudo-first-order kinetics in terms of lipoyllysine concentration. A good linear correlation is obtained between the oxidation rate and lipoyllysine concentration up to 5 microM and the calibration curve indicates that the detection limit could be 100 nM lipoyllysine. The method was applied to protease lysates of bovine, rat, and rabbit tissues to determine lipoyllysine levels. Kidney and liver were found to have the highest content of lipoyllysine in the range of 3.9 to 4.6 nmol/g rat or rabbit wet tissue or 11.6 to 13.1 nmol/g bovine acetone powder.

Animals↗

PubMed1998

A multivariate logistic regression analysis in predicting malignancy for patients with ovarian tumors.

OBJECTIVE: Our objective was to improve the preoperative diagnosis of ovarian malignancy using a multivariate logistic regression analysis on the basis of demographic, serologic, gray-scale morphological, and Doppler variables. METHODS: One hundred seventy-one patients with ovarian tumors (120 benign, 51 malignant including 9 tumors of low malignant potential) were studied with transvaginal B-mode, color, and pulsed Doppler ultrasonography before surgery. Based on the gray-scale ultrasound imaging, each tumor was classified as a unilocular cyst, multilocular cyst, unilocular cyst with solid parts, multilocular cyst with solid parts, or solid tumor. Intratumoral blood flow velocity waveforms were recorded on all tumors except unilocular cyst and were evaluated for resistance index (RI) and peak systolic velocity (PSV). Serum CA 125 levels were also measured. RESULTS: Twenty tumors were unilocular cysts and were all benign. Seventy tumors including all unilocular cysts which showed no flows were all benign. The remaining 101 tumors (50 benign, 51 malignant including 9 tumors of low malignant potential) presented intratumoral blood flows. Univariate and multivariate logistic regression analyses were conducted to identify variables predictive of ovarian malignancy in these 101 tumors. The variables included age, menstrual state, serum CA 125 levels, B-mode classification, RI, and PSV. In univariate analysis, menopause, the positivity of CA 125 (> or = 35 U/ml), and PSV larger than or equal to 10.4 cm/s were found to be significantly associated with malignant tumors. The PSV value of 10.4 cm/s was the median in benign tumors. Multivariate analysis showed that serum CA 125 levels (> or = 35 U/ml) (P = 0.002) and PSV (> or = 10.4 cm/s) (P < 0.001) were to be independent predictors of malignancy. CONCLUSION: These results suggest that intratumoral PSV is the strongest means of differentiating benign from malignant ovarian tumors with suspicious gray-scale ultrasonographic findings.

Adolescent↗

PubMed1998

Characterization of acidic Ca(2+)-independent phospholipase A2 of bovine lung.

An acidic Ca(2+)-independent phospholipase A2 (aiPLA2) has been isolated previously from rat lung and a human cDNA has been described. This study applied the method to larger scale isolation of the native protein from the bovine lung. A polyclonal antibody was generated to a 15 amino acid synthetic peptide based on a conserved rat/human sequence. This antibody recognized a single protein band with an estimated molecular mass of approximately 29 kDa in a soluble fraction obtained from bovine lung homogenate. A 29 kDa protein that reacted with the aiPLA2 antipeptide antibody was detected in fractions containing aiPLA2 activity on sequential column chromatographies. The partially purified enzyme showed 176-fold increase over the homogenate in Ca(2+)-independent PLA2 activity at pH 4. Activity was maximal with phosphatidylcholine substrate and was significantly less with phosphatidylethanolamine and anionic phospholipids. The enzyme had no acyl group preference in phosphatidylcholine and showed no preference for oxidized substrate, but activity was less with 1-O-alkyl phosphatidylcholine. aiPLA2 activity was inhibited by a transition state phospholipid analog (MJ33, 1-hexadecyl-3-trifluoroethylglycero-sn-2-phosphomethanol), serine protease inhibitors, and the anti-peptide antibody but was insensitive to arachidonoyl trifluoromethyl ketone, bromoenol lactone, p-bromophenacyl bromide, and ATP. Analysis of N-terminal amino acid sequence for the 29 kDa protein demonstrated its high homology to human 26 kDa aiPLA2. These was no significant change in molecular mass of the protein following treatment with endoglycosidase F. Western blot of subcellular fractions from rat lung indicated aiPLA2 immunoreactivity with lamellar body, lysosomal, and cytosolic fractions. These results indicate isolation from bovine lung of a 29 kDa acidic Ca(2+)-independent phospholipase A2 homologue of the rat and human enzyme and provide evidence for specificity in the metabolism of lung surfactant phosphatidylcholine.

Amino Acid Sequence↗

PubMed1998

Inhibitory effect of the leaf extract of Ginkgo biloba L. on oxidative stress-induced platelet aggregation.

The effect of the leaf extract of Ginkgo biloba L. on platelet aggregation induced by oxidative stress was studied. The extract caused a dose-dependent inhibition of platelet aggregation stimulated with tert-butyl hydroperoxide (t-BHP) and Fe2+. Similar inhibitory activity was observed when platelets were exposed to H2O2 and Fe2+. Synergistic aggregation induced by a combination of t-BHP and Fe2+ or H2O2 and Fe2+ in association with suboptimal concentration of collagen or U46619, was prevented by the extract. However, the extract failed to inhibit aggregation in response to collagen, thrombin or U46619. Ginkgolides A, B and C inhibited platelet-activating factor-induced aggregation, but not oxidant-induced aggregation. These data suggest that the suppressive effect of the extract is specific on platelet aggregation stimulated by oxidative stress, and that this effect is involved in the mechanism related to its protective effect upon cerebral or myocardial injuries.

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

PubMed1998

Histological and biological characteristics of microinvasion in mammary carcinomas < or = 2 cm in diameter.

Fifty-two mammary carcinomas, 2 cm or less in diameter, were examined in order to clarify the morphology and biology of microinvasion. The morphological characteristics of microinvasion of carcinomas include: (i) a loss of myoepithelial cells and a rupture with concomitant loss of collagen IV and laminin in the basement membrane of involved mammary glands; and (ii) budding of carcinomas from the rupture into the stroma. When microinvasion was defined as a rupture of < 200 microm in the basement membrane with invasion, the number of microinvasions per 1 mm of basement membrane was larger in the tumors in which the area of invasion was larger. The prevalence of microinvasion showed a significant correlation with lymph node metastasis and the rate of histological deviation, while no correlation of expression of either estrogen receptors or progesterone receptors and c-erbB-2 protein was found. The study clarified that the early invasion of mammary carcinomas could be detected by the immunohistochemical method using anti-smooth muscle actin, laminin and collagen IV antibodies. The study also suggested that microinvasion might be an indicator of lymph node metastasis in mammary carcinomas < or = 2 cm diameter.

Adenocarcinoma, Papillary↗