Biomedical subjects

Masahiro Nakao

Publications and source records attributed to Masahiro Nakao.

At least 19 recordsLinked to original sources

PubMed2006

Prospective cohort study of the risk of prostate cancer among rotating-shift workers: findings from the Japan collaborative cohort study.

Shift workers have been reported to have an increased risk of some cancers. However, the risk of prostate cancer in shift workers is not known to have been examined previously. This study prospectively examined the association between shift work and risk of prostate cancer incidence among 14,052 working men in Japan enrolled in a large-scale prospective cohort. A baseline survey was conducted between 1988 and 1990. Subjects were asked to indicate the most regular work schedule they had undertaken previously: day work, rotating-shift work, or fixed-night work. During 111,974 person-years, 31 cases of prostate cancer were recorded. The Cox proportional hazards model was used to estimate the risk, with adjustments for age, family history of prostate cancer, study area surveyed, body mass index, smoking, alcohol drinking, job type, physical activity at work, workplace, perceived stress, educational level, and marriage status. Compared with day workers, rotating-shift workers were significantly at risk for prostate cancer (relative risk = 3.0, 95% confidence interval: 1.2, 7.7), whereas fixed-night work was associated with a small and nonsignificant increase in risk. This report is the first known to reveal a significant relation between rotating-shift work and prostate cancer.

Adult↗

PubMed2006

Spectrophotometric determination of anthracycline anticancer agents with aluminum(III) and chromazurol S in a nonionic surfactant micellar medium.

A simple and highly sensitive spectrophotometric method for the determination of anthracycline anticancer agents, such as Daunorubicin hydrochloride (DAU), was established by using aluminum(III) and Chromazurol S (CAS) in a nonionic surfactant micellar medium. In the case of determination of DAU, the apparent molar absorptivity was 1.3 x 10(5) dm3 mol(-1) cm(-1) at 615 nm. Beer's law was obeyed in the concentration range of 0.028 - 2.82 microg ml(-1) for DAU. Owing to no need for solvent extraction, this method could be applied to assays of DAU and related drugs in pharmaceutical preparations.

Aluminum↗

PubMed2006

[Epidemiological survey of sexually transmitted male urethritis in Kyoto Prefecture].

The data of sexually transmitted urethritis in males have been collected at 24 institutes in Kyoto Prefecture since October, 2002. The data collected from January to December in 2004 are summarized herein. A total of 1,275 patients were diagnosed with urethritis during this period. Microbiological examinations isolated Neisseria gonorrhoeae alone in 368 (29%), Chlamydia tracomatis alone in 336 (26%), both in 85 (7%), and others in 453 (36%). Male patients under 20 years old tended to have Chlamydial urethritis, alone or combined with gonococcal infection, and had a predominant infectious source, a non-commercial-sexual-worker female partner, suggesting a profound problem in sexual life of adolescents. The urologist preferred to use quinolones as the first therapeutic modality against male urethritis. However, drug resistance of N. gonorrhoeae, especially against quinolones, has rapidly progressed, which was also observed by a sensitivity examination test. Antibiotics should be used adequately against male urethrits according to the recent guidelines.

Adolescent↗

PubMed2005

Creation of Rhizopus oryzae lipase having a unique oxyanion hole by combinatorial mutagenesis in the lid domain.

Combinatorial libraries of the lid domain of Rhizopus oryzae lipase (ROL; Phe88Xaa, Ala91Xaa, Ile92Xaa) were displayed on the yeast cell surface using yeast cell-surface engineering. Among the 40,000 transformants in which ROL mutants were displayed on the yeast cell surface, ten clones showed clear halos on soybean oil-containing plates. Among these, some clones exhibited high activities toward fatty acid esters of fluorescein and contained non-polar amino acid residues in the mutated positions. Computer modeling of the mutants revealed that hydrophobic interactions between the substrates and amino acid residues in the open form of the lid might be critical for ROL activity. Based on these results, Thr93 and Asp94 were further combinatorially mutated. Among 6,000 transformants, the Thr93Thr, Asp94Ser and Thr93Ser, Asp94Ser transformants exhibited a significant shift in substrate specificity toward a short-chain substrate. Computer modeling of these mutants suggested that a unique oxyanion hole, which is composed of Thr85 Ogamma and Ser94 Ogamma, was formed and thus the substrate specificity was changed. Therefore, coupling combinatorial mutagenesis with the cell surface display of ROL could lead to the production of a unique ROL mutant.

Amino Acid Sequence↗

PubMed2005

Serum carotenoids and other antioxidative substances associated with urothelial cancer risk in a nested case-control study in Japanese men.

PURPOSE: We assayed whether high serum carotenoids and antioxidative substances decrease the risk of urothelial cancer in a case-control study nested in a community based cohort in Japan, that is the Japan Collaborative Cohort Study. MATERIALS AND METHODS: Information on subject life-styles and serum were collected in 1988 to 1990 and subjects were followed as late as 1999. Individuals who had or died of urothelial cancer and controls were matched for study area, sex and age. Serum was stored at -80C and analyzed in 2003. Of 14,097 male and 25,662 female subjects 40 to 79 years old there were 42 cases, which were matched to 124 controls. RESULTS: The OR for the highest to lowest tertile of serum concentration was 0.28 (95% CI 0.07 to 1.15, trend p = 0.08) for beta-carotene, 0.36 (95% CI 0.10 to 1.27, trend p = 0.10) for total carotenes and 0.31 (95% CI 0.09 to -1.09, trend p = 0.09) for total carotenoids after adjustment for smoking in addition to matching variables. High concentrations of tocopherols and xanthophylls slightly tended to decrease the risk of urothelial cancer. In contrast, serum retinol, oxidized low density lipoprotein and Cu/Zn-superoxide dismutase were not associated with urothelial cancer risk. CONCLUSIONS: Our results suggest that high serum carotenoids may decrease the risk of urothelial cancer with carotenes more effective than xanthophylls.

Aged↗

PubMed2005

A novel vitamin C analog, 2-O-(beta-D-Glucopyranosyl)ascorbic acid: examination of enzymatic synthesis and biological activity.

2-O-(beta-D-Glucopyranosyl)ascorbic acid (AA 2 beta G) isolated from a popular traditional Chinese food (Lycium fruit) was synthesized using cellulase derived from Trichoderma sp. with cellobiose as a glucose donor. 6-O-(beta-D-Glucopyranosyl)ascorbic acid as well as AA 2 beta G was also synthesized in this reaction. The vitamin C activity of AA 2 beta G was also evaluated using inherently scorbutic (osteogenic disorder Shionogi [ODS]) rats. The rats were fed vitamin C-deficient food and water containing AA 2 beta G for 21. AA 2 beta G supported their growth and the level of vitamin C in tissues was moderately maintained. The vitamin C level in some tissues depended on the hydrolytic activity of AA 2 beta G (beta-glucosidase activity) although the correlation was not statistically significant (P=0.08). The results indicate that AA 2 beta G has pro-vitamin C activity.

Administration, Oral↗

PubMed2005

Dietary habits and risk of urothelial cancer incidence in the JACC Study.

BACKGROUND: The relationships between dietary habits and urothelial cancer have been discussed in many epidemiologic studies, however, they have not been sufficiently elucidated. In the present study, the associations of dietary habits with the risk of urothelial cancer incidence were evaluated taking into consideration sex, age, and smoking habits. METHODS: The Japan Collaborative Cohort Study (JACC Study) was planned in the late 1980s as a large-scale cohort study surveying people comprehensively and detailing their lifestyles, and the study subjects were followed up until the end of 1997. Among the total of 110,792 participants, 26,464 men and 38,720 women were in areas where incident cases with cancer were identified. During the observation period, 95 men and 28 women suffered from urothelial cancer. Hazard ratios for dietary factors were calculated by Cox's proportional hazards model. RESULTS: Increasing age, male gender, and smoking history were all significantly associated with the risk of urothelial cancer. High consumption of pork was significantly associated with the risk. In contrast, high intakes of milk and fresh fish were significantly inversely associated with the risk. High intakes of Chinese cabbage and fruits were also significantly inversely associated with the risk of urothelial cancer. CONCLUSIONS: It is suggested that high intakes of milk, fresh fish, Chinese cabbage, and fruits have preventive effects against urothelial cancer.

Adult↗

PubMed2005

Association of serum phytoestrogen concentration and dietary habits in a sample set of the JACC Study.

BACKGROUND: Phytoestrogens may be associated with a reduced risk of hormone dependent neoplasms such as prostate and breast cancers. We tried to determine the validity of the association between serum phytoestrogen concentrations and dietary habits obtained from a food frequency questionnaire used in the Japan Collaborative Cohort Study (JACC Study) for Evaluation of Cancer Risk sponsored by the Ministry of Education, Science, Sports and Culture of Japan (Monbusho). METHODS: The subjects were 151 male controls who were selected for a nested case-control study for evaluating prostate cancer risk as part of the JACC Study. Dietary habits were determined using a food frequency questionnaire at baseline, and the concentrations of genistein, daidzein, and equol in frozenstored serum samples assayed in 2002 were compared. RESULTS: Tofu intake showed a significant association with the serum concentrations of genistein and daidzein (Spearman's correlation coefficients (rs)=0.30 and 0.27, respectively), and miso soup showed a slight association with serum concentrations of these phytoestrogens. In contrast, serum concentrations of equol were not associated with dietary intake of tofu and miso soup. After adjustment for serum daidzein concentration, serum equol concentration was associated with the intake of foods containing fat, meat, and coffee, but not green tea. CONCLUSIONS: Serum genistein and daidzein concentrations were significantly associated with dietary intake of tofu, and slightly with intake of miso soup. Consumption of fat, meat, and coffee may be associated with equol production by intestinal microflora in this sample set.

Adult↗

PubMed2005

Risk factors for kidney cancer in a Japanese population: findings from the JACC Study.

BACKGROUND: The incidence of kidney cancer is high in Western and Northern Europe and North America, and low in Asia. Although the incidence of kidney cancer in Japan is lower than the rates in the other industrialized countries, there is no doubt that it is increasing. METHODS: We evaluated the risk factors for kidney cancer death using the database of the Japan Collaborative Cohort (JACC) Study (i.e., medical history, anthropometry, and lifestyle including dietary habits). The analytic cohort included 47,997 males and 66,520 females aged 40 years and older. The Cox proportional hazards model was used to determine adjusted relative risks. RESULTS: A total of 36 males and 12 females died from kidney cancer during the follow-up of 9.6+/-2.6 years and 9.9+/-2.2 years, respectively. A medical history of hypertension, a fondness for fatty food, and consumption of black tea were associated with an increased risk of kidney cancer death while an intake of taro, sweet potato and potato was associated with a decreased risk. CONCLUSIONS: The present study showed four factors to be related to kidney cancer death. However, further studies may be needed to evaluate risk factors for kidney cancer death in Japan because the number of kidney cancer death in the present study was small.

Adult↗

PubMed2004

2-O-(beta-D-Glucopyranosyl)ascorbic acid, a novel ascorbic acid analogue isolated from Lycium fruit.

A novel stable precursor of ascorbic acid (vitamin C), 2-O-(beta-D-glucopyranosyl)ascorbic acid, was isolated from both the ripe fresh fruit and dried fruit of Lycium barbarum L., a plant of the Solanaceae family. The chemical structure was inferred by instrumental analyses and confirmed by chemical synthesis. The dried fruit of Lycium barbarum L. contained ca. 0.5% of it, which is comparable to the ascorbic acid content of fresh lemons. It increased the blood ascorbic acid by oral administration to rats, and it was also detected in blood from the portal vein.

Animals↗

PubMed2004

Serum phytoestrogens and prostate cancer risk in a nested case-control study among Japanese men.

The purpose of this study was to examine whether a high serum concentration of phytoestrogens reduces the risk of prostate cancer in a case-control study nested in a community-based cohort in Japan (Japan Collaborative Cohort (JACC) Study). Information on lifestyles and sera of the subjects were collected in 1988-90, and they were followed up to 1999. Incident and dead cases of prostate cancer and controls were matched for study area and age. Phytoestrogens and sex hormones in sera stored at - 80 degrees C were measured in 2002. Of 14,105 male subjects of the cohort who donated their sera, 52 cases and 151 controls were identified. Three datasets were analyzed; 1) all subjects, 2) 40 cases and 101 controls after excluding subjects with low testosterone levels who were suspected of having had medical intervention, and 3) 28 cases and 69 controls with prostate specific antigen level of </= 10.0 ng/ml. The odds ratio (OR) for the highest level to the lowest was 0.38 (95% confidence interval (CI); 0.13, 1.13) for genistein, 0.41 (0.15, 1.11) for daidzein, and 0.34 (0.11, 1.10) for equol for the second dataset. Genistein and daidzein showed similar findings in the third one. Equol and equol/daidzein ratio showed consistent findings in all three datasets (OR = 0.39, 95% CI; 0.13, 0.89, trend P = 0.02 for the first dataset). Their effects seemed to be independent of serum sex hormones. In conclusion, serum genistein, daidzein, and equol seemed to dose-dependently reduce prostate cancer risk.

Adult↗

PubMed2004

Dietary habits and risk of urothelial cancer death in a large-scale cohort study (JACC Study) in Japan.

In the present study, the associations of dietary habits with the risk of urothelial cancer death were evaluated taking into consideration sex, age, and smoking habits. The Japan Collaborative Cohort Study was established in 1988-1990 and consisted of 47,997 men and 66,520 women observed until the end of 1999. A self-administered food-frequency questionnaire was used as a baseline survey. Hazard ratios for dietary factors were calculated by Cox's proportional hazards model. During the observation period, 63 men and 25 women died of urothelial cancer. Increasing age, male gender, and history of smoking were all significantly associated with increased risk of urothelial cancer death. A high intake of milk and fruits other than oranges reduced the risk significantly and dose dependently, in particular among subjects with smoking history. However, consumption of butter and yogurt had no associations with the risk. Intakes of cabbage, lettuce, green leafy vegetables, carrots, squash, tomatoes, and oranges were not significantly associated with the risk. It was suggested that urothelial cancer death could be potentially preventable by smoking cessation and regular intake of milk and fruit.

Adult↗

PubMed2003

Factors that influence the results of salvage surgery in patients with chemorefractory germ cell carcinomas with elevated tumor markers.

BACKGROUND: A standard concept for the integration of surgery into the chemotherapy-based treatment of patients with advanced germ cell carcinoma has been that surgery should be avoided in patients with serum tumor markers (alpha-fetoprotein [AFP] and human chorionic gonadotropin [HCG]) that remain elevated. However, some patients may benefit from resection under such chemorefractory conditions. The objective of this retrospective study was to clarify the outcome and clinical prognostic variables of salvage surgery in patients with disseminated (AJCC Stage II or III) testicular germ cell carcinoma or extragonadal germ cell carcinoma who had elevated serum markers. METHODS: The authors reviewed the clinical records of 24 patients who underwent salvage surgery with elevated serum AFP and/or HCG levels after at least 3 courses of cisplatin-based, systemic chemotherapy between January, 1985 and December, 2000. The survival rates were compared between the subgroups with regard to preoperative and postoperative clinical parameters using the Kaplan-Meier method and a Cox proportional hazards model. RESULTS: Ten of 24 patients (41.7%) were rendered free of disease and alive without disease after the surgery with or without adjuvant therapy at a median follow-up of 74 months (range, 24-207 months). Among the preoperative parameters, high HCG levels were associated with significantly poorer survival (hazard ratio [HR], 8.321; 95% confidence interval [95% CI], 1.0753-64.553; P = 0.043 and P = 0.016, respectively; log-rank test). In addition, patients who had visceral lesions at resection had a significantly poorer prognosis compared with patients who had retroperitoneal and/or mediastinal lymph node lesions (P = 0.038; log-rank test). Among postoperative parameters, incomplete resection and persistently high HCG levels were associated significantly with poor survival, with a risk of death from disease of 12.516-fold (95% CI, 1.786-87.781) and 9.311-fold (95% CI, 1.796-48.256), respectively. CONCLUSIONS: Salvage surgery in patients with high serum tumors markers resulted in long-term disease free status in approximately 40% of patients in a small subset with advanced germ cell carcinoma. Patients with elevated AFP levels alone (i.e., normal HCG levels) or with lymph node lesions alone seem to be good candidates for such surgery. Complete resection of target lesions and normalization of HCG levels after surgery are mandatory to achieve long-term disease free status.

Adolescent↗

PubMed2003

The significance of thymidine phosphorylase/platelet-derived endothelial cell growth factor activity in renal cell carcinoma.

BACKGROUND: Thymidine phosphorylase (TP) is identical to platelet-derived endothelial cell growth factor (PDECGF) and has angiogenic activity. Little is known about the significance of TP/PDECGF activity in patients with renal cell carcinoma (RCC). The authors examined the enzymatic activity of TP in 66 RCC specimens and investigated the association between the level of TP activity and the stage/grade status of patients with RCC. Furthermore, the authors examined the correlation between TP/PDECGF activity and prognosis. METHODS: TP activity levels in nonfixed, fresh-frozen RCC specimens and in specimens of normal kidney were determined using a thin-layer chromatography assay. RESULTS: The activity of TP was approximately 3.5-fold greater in RCC specimens compared with normal kidney specimens. TP activity in patients with Stage III-IV RCC was 2.6-fold greater compared with TP activity in patients with Stage I-II RCC. In addition, the level of TP activity was correlated with a higher grade of RCC. Patients who had RCC with low TP activity had a longer postoperative disease-specific survival compared with patients who had RCC with high TP activity in the 5-year follow-up. CONCLUSIONS: The current study is the first to demonstrate a correlation between levels of TP activity and both disease progression and a higher grade of RCC. It also is the first to show that elevated TP activity in patients with RCC predicts a poor prognosis. The results suggest that high TP/PDECGF activity may be associated with the malignant potential of RCC and that TP/PDECGF may be a molecular therapeutic target in patients with RCC.

Adult↗

PubMed2003

Significant antitumor effect of intratumoral ethanol injection on renal cell carcinoma.

OBJECTIVE: The effects of intratumoral ethanol injection on renal cell carcinoma (RCC) heterotransplanted in nude rats were evaluated. MATERIALS AND METHODS: The OUR95AF human RCC cell line was inoculated subcutaneously into the backs of nude rats. Four weeks after transplantation, the size of tumors became 1.5-2.0 cm in maximal length, and 95% ethanol was injected intratumorally once a week for five weeks. The effectiveness of this treatment was evaluated by measurement of tumor volume, magnetic resonance (MR) imaging using Gadopentetate-diethylenetriaminepentaacetic acid (Gd-DTPA) and histological examinations. RESULTS: In the ethanol injected group, no increase in tumor volume was recognized. The growth of the tumors was significantly suppressed after the third injection. Non-enhanced parts in MR imaging were observed in the central region of the tumors at the second injection, and increased at the third injection. After the fifth injection, only small parts of non-enhanced regions remained. Degenerative necrosis was histologically found in the non-enhanced parts of the MR image. The signal to noise ratio (SNR) and the contrast to noise ratio (CNR) calculated from T1 weighted imaging using Gd-DTPA, and relative enhancement (RE) were thought to be good parameters for evaluating the effect of ethanol injections. CONCLUSION: Intratumoral ethanol injection was very effective against RCC. Five weekly injections of ethanol induced necrosis of the tumor. MR imaging using Gd-DTPA may be a useful method for evaluating the effect of ethanol injection.

Animals↗

PubMed2003

Significance of thymidine kinase activity in renal cell carcinoma.

PURPOSE: Thymidine kinase (TK) has a key role in the complementary or alternative salvage pathway of pyrimidine synthesis. Little is known about the significance of TK activity in renal cell carcinoma. We examined the activity of TK in 66 renal cell carcinomas and investigated the association of the level of TK activity with the stage and grade of renal cell carcinoma. MATERIALS AND METHODS: TK activity in nonfixed, fresh frozen renal cell carcinoma and normal kidney was determined by the DEAE cellulose disc method. RESULTS: The activity of TK was approximately 4-fold higher in normal kidney compared with renal cell carcinoma. The higher the stage and grade of renal cell carcinoma, the higher the TK activity. TK activity correlated positively with the activity of thymidine synthase, which is a key enzyme for pyrimidine synthesis in the de novo pathway. TK activity in renal cell carcinoma cells was inversely related to their sensitivity to 5-fluorouracil. CONCLUSIONS: To our knowledge this report represents the first study to demonstrate that the level of TK activity correlates with the stage and grade of renal cell carcinoma, and higher TK activity in renal cell carcinoma predicts lower sensitivity to 5-fluorouracil. These results suggest that high TK activity may be associated with the malignant potential of renal cell carcinoma and TK may be a molecular therapeutic target for this disease. In addition, the combination of TK and thymidylate synthase inhibitors may be beneficial for renal cell carcinoma.

Adult↗

PubMed2003

Biochemical and molecular characterization of a novel UDP-glucose:anthocyanin 3'-O-glucosyltransferase, a key enzyme for blue anthocyanin biosynthesis, from gentian.

Gentian (Gentiana triflora) blue petals predominantly contain an unusually blue and stable anthocyanin, delphinidin 3-O-glucosyl-5-O-(6-O-caffeoyl-glucosyl)-3'-O-(6-O-caffeoyl-glucoside) (gentiodelphin). Glucosylation and the subsequent acylation of the 3'-hydroxy group of the B-ring of anthocyanins are important to the stabilization of and the imparting of bluer color to these anthocyanins. The enzymes and their genes involved in these modifications of the B-ring, however, have not been characterized, purified, or isolated to date. In this study, we purified a UDP-glucose (Glc):anthocyanin 3'-O-glucosyltransferase (3'GT) enzyme to homogeneity from gentian blue petals and isolated a cDNA encoding a 3'GT based on the internal amino acid sequences of the purified 3'GT. The deduced amino acid sequence indicates that 3'GT belongs to the same subfamily as a flavonoid 7-O-glucosyltransferase from Schutellaria baicalensis in the plant glucosyltransferase superfamily. Characterization of the enzymatic properties using the recombinant 3'GT protein revealed that, in contrast to most of flavonoid glucosyltransferases, it has strict substrate specificity: 3'GT specifically glucosylates the 3'-hydroxy group of delphinidin-type anthocyanins containing Glc groups at 3 and 5 positions. The enzyme specifically uses UDP-Glc as the sugar donor. The specificity was confirmed by expression of the 3'GT cDNA in transgenic petunia (Petunia hybrida). This is the first report of the gene isolation of a B-ring-specific glucosyltransferase of anthocyanins, which paves the way to modification of flower color by production of blue anthocyanins.

Amino Acid Sequence↗

PubMed2003

Collagenolytic serine-carboxyl proteinase from Alicyclobacillus sendaiensis strain NTAP-1: purification, characterization, gene cloning, and heterologous expression.

Enzymatic degradation of collagen produces peptides, the collagen peptides, which show a variety of bioactivities of industrial interest. Alicyclobacillus sendaiensis strain NTAP-1, a slightly thermophilic, acidophilic bacterium, extracellularly produces a novel thermostable collagenolytic activity, which exhibits its optimum at the acidic region (pH 3.9) and is potentially applicable to the efficient production of such peptides. Here, we describe the purification to homogeneity, characterization, gene cloning, and heterologous expression of this enzyme, which we call ScpA. Purified ScpA is a monomeric, pepstatin-insensitive carboxyl proteinase with a molecular mass of 37 kDa which exhibited the highest reactivity toward collagen (type I, from a bovine Achilles tendon) among the macromolecular substrates examined. On the basis of the sequences of the peptides obtained by digestion of collagen with ScpA, the following synthetic peptides were designed as substrates for ScpA and kinetically analyzed: Phe-Gly-Pro-Ala*Gly-Pro-Ile-Gly (k(cat), 5.41 s(-1); K(m), 32 micro M) and Met-Gly-Pro-Arg*Gly-Phe-Pro-Gly-Ser (k(cat), 351 s(-1); K(m), 214 micro M), where the asterisks denote the scissile bonds. The cloned scpA gene encoded a protein of 553 amino acids with a calculated molecular mass of 57,167 Da. Heterologous expression of the scpA gene in the Escherichia coli cells yielded a mature 37-kDa species after a two-step proteolytic cleavage of the precursor protein. Sequencing of the scpA gene revealed that ScpA was a collagenolytic member of the serine-carboxyl proteinase family (the S53 family according to the MEROPS database), which is a recently identified proteinase family on the basis of crystallography results. Unexpectedly, ScpA was highly similar to a member of this family, kumamolysin, whose specificity toward macromolecular substrates has not been defined.

Amino Acid Sequence↗