Collaboration of local government and experts responding to increase in environmental radiation level due to the nuclear disaster: focusing on their activities and latest radiological discussion.

Activities were introduced in Kashiwa city in the Tokyo metropolitan area to correspond to the elevated environmental radiation level after the disaster of the Fukushima Daiichi nuclear power plant. These were based on a strong cooperation between local governments and experts. Ambient dose rate and radioactivity of foodstuff produced inside of the city have been monitored. Representative ambient dose rates around living environments have almost already become their original levels of the pre-accident because of the decontamination activity, natural washout and effective half-lives of radioactivity. The internal annual dose due to radioactive cesium under the policy of 'Local Production for Local Consumption' is estimated as extremely low comparing the variation range due to natural radioactivity. Systematic survey around a retention basin has been started. All of these latest monitoring data would be one of the core information for the policy making as well as a cost-benefit discussion and risk communication.

Relationship between epicardial adipose tissue and subclinical coronary artery disease in patients with extra-cardiac arterial disease.

OBJECTIVE: Epicardial adipose tissue (EAT) and mediastinal adipose tissue (MAT) are linked to coronary artery disease (CAD). The association between EAT, MAT, and severity of CAD in known extra-cardiac arterial disease was investigated. DESIGN AND METHODS: Sixty-five cardiac asymptomatic patients (mean age 65 ± 8 years, 69% male) with peripheral arterial disease, carotid stenosis, or aortic aneurysm underwent coronary computed tomography angiography. Patients were divided into non-significant (<50% stenosis, N = 35), single vessel (N = 15) and multi-vessel CAD (N = 15). EAT and MAT were quantified on computed tomography images using volumetric software. RESULTS: Subgroups did not significantly differ by age, gender, or cardiovascular risk factors. Median EAT was 99.5, 98.0, and 112.0 cm(3) (P = 0.38) and median MAT was 66.0, 90.0, and 81.0 cm(3) (P = 0.53) for non-significant, single vessel, and multi-vessel CAD, respectively. In age- and gender-adjusted analysis, only EAT was significantly associated with CAD (odds ratio [OR] 1.12 [95% confidence interval, 1.01-1.25] per 10 cm(3) increase in EAT; P = 0.04). This remained in multivariate-adjusted analysis (OR 1.21 [1.04-1.39]; P = 0.01). CONCLUSIONS: In patients with known extra-cardiac arterial disease, CAD is correlated with EAT, but not with MAT. These results suggest that EAT has a local effect on coronary atherosclerosis, apart from the endocrine effect of visceral fat.

The p75 receptor mediates axon growth inhibition through an association with PIR-B.

The Nogo receptor and paired immunoglobulin-like receptor B (PIR-B) are receptors for three myelin-derived axon-growth inhibitors, including myelin-associated glycoprotein (MAG). In this study, we report that the p75 receptor is required for the signal transduction of PIR-B, which interacted with p75 upon ligand binding. In addition, p75 was required for activation of Src homology 2-containing protein tyrosine phosphatase (SHP), which is induced by MAG binding to PIR-B. Mice carrying a mutation in the p75 gene showed promotion of axonal regeneration after optic nerve injury. Thus, our results indicate that p75 has a critical role in axon growth inhibition in specific neuronal tracts.

Magnetic alignment experiment of fine graphite-crystals dispersed in He gas oriented to study alignment of crystalline-axes of nano-sized non-magnetic particles.

The ensemble of nano-sized crystals is expected to attain additional physical properties when preferential alignments of certain crystal-axes are achieved by a magnetic field. The reduction of temperature T may realize alignment even if the mole number of the particle N and the diamagnetic anisotropy per mole (Deltachi)(DIA) are considerably small for the nano-sized diamagnetic oxides, since alignment proceeds by the balance between the energy of rotational Brownian motion and field-induced anisotropy energy. Alignment of various basic inorganic oxides such as gypsum, quartz, forsterite, KDP or calcite, having a size of 20 nm diameter, is expected to occur by a field intensity of approximately 50 T at T = 10 K; this intensity is presently available at a high magnetic-field laboratory. It is expected that the magnetic alignment of nano-sized particles can be observed by dispersing the particles in He gas, as achieved recently for micron-sized graphite crystals; a cryogenic liquid cannot be used as a dispersing medium. Measured (Deltachi)(DIA) values accumulated for basic inorganic-oxides are explained quantitatively by assuming that individual bonding-orbital composing the material possesses a constant amount of diamagnetic anisotropy; hence the majority of diamagnetic nano-sized insulators are expected to show magnetic alignment at finite field intensity.

Cisplatin induces apoptosis in oral squamous carcinoma cells by the mitochondria-mediated but not the NF-kappaB-suppressed pathway.

Cisplatin (CDDP) is a potent DNA-damaging anticancer agent, and its cytotoxic action is exerted by the induction of apoptosis. However, activation of the transcription factor NF-kappaB results in protection against apoptosis. We examined the molecular mechanisms involved in the induction of apoptosis by CDDP as regards both suppression of NF-kappaB and activation of caspases. Human oral squamous carcinoma cells (B88) were employed in this study. We found that CDDP treatment affected neither NF-kappaB activity nor the expression levels of antiapoptotic proteins, including TRAF-1, TRAF-2, and cFLIP, in B88 cells. However, two apoptosome molecules, cytochrome c and Apaf-1, were significantly augmented in the cytoplasm by CDDP treatment. Further, the activation of caspase-9 and caspase-3, downstream molecules leading to mitochondria-mediated apoptosis, were detected after treatment with CDDP. Finally, apoptosis was also clearly observed, as evidenced by cleavage of PARP through the activation of caspase-3. These findings suggest that CDDP exerts its apoptotic action by the mitochondria-mediated activation of caspases but not by the activation of caspases due to the inhibition of NF-kappaB activity that follows the suppression of antiapoptotic proteins.

Probability of prostate cancer at various levels of per cent free prostate specific antigen in Japanese men with total PSA of 4.1-10.0 ng/ml.

Estimates for the likelihood of prostate cancer at different levels of per cent free prostate specific antigen (PSA) were derived from experience with consecutive Japanese male patients with intermediate total PSA values who underwent ultrasound-guided biopsies and/or transurethral resection of the prostate. Receiver operating characteristic (ROC) curve analysis showed that in patients with a total PSA of 4.1-10.0 ng/ml, per cent free PSA identified those with prostate cancer better than did total PSA; per cent free PSA also proved superior in the subgroup whose glands appeared benign on palpation. The probabilities of prostate cancer at per cent free PSA values of 10-15, >15-20, >20-26 and >26% were 58.3, 40.8, 25.3, 14.3 and 7.6%, respectively, when analyzed without regard to findings on palpation. In patients with palpably benign glands, the corresponding values were 55.3, 35.4, 19.6, 9.7, and 4.6%, respectively. These probabilities are lower than those reported in Western countries, probably reflecting both different patterns of practice and racial differences. Race-specific assessment is recommended before applying a clinical test.

Mitotic specific phosphorylation of serine-1212 in human DNA topoisomerase IIalpha.

It is known that topoisomerase IIalpha is phosphorylated by several kinases. To elucidate the role of phosphorylation of topoisomerase IIalpha in the cell cycle, we have examined the cell cycle behavior of phosphorylated topoisomerase IIalpha in HeLa cells using antibodies against several phospho-oligopeptides of this enzyme. Here we demonstrate that serine1212 in topoisomerase IIalpha is phosphorylated only in the mitotic phase. Using an antibody against an oligopeptide containing phosphoserine-1212 in topoisomerase IIalpha (PS1212), subcellular localization of topoisomerase IIalpha phosphorylated at serine1212 was examined by indirect immunofluorescence staining, and compared with that of overall topoisomerase IIalpha. Serine1212-phosphorylated topoisomerase IIalpha was localized specifically on mitotic chromosomes, but not on interphase chromosomes; this result contrasts with overall topoisomerase IIalpha which was observed on chomosomes in both interphase and mitosis. Serine1212-phosphorylated topoisomerase lIalpha first appeared on chromosome arms in prophase, became concentrated on the centromeres in metaphase, and disappeared in early telophase. In addition, ICRF-193, a catalytic inhibitor of topoisomerase II, prevented accumulation of serine1212-phosphorylated topoisomerase IIalpha at the centromeres. These results indicate that serine1212 of topoisomerase IIalpha is phosphorylated specifically during mitosis, and suggest that the serine1212-phosphorylated topoisomerase IIalpha acts on resolving topological constraint progressively from the chromosome arm to the centromere during metaphase chromosome condensation.

Comparative analysis of HOXC-9 gene expression in murine hemochorial and caprine synepitheliochorial placentae by in situ hybridization.

Mammalian placentae exhibit wide structural diversity among different species and are formed under intricate interplay between the embryonic trophoblast and the maternal endometrial cells. Increasing evidence in the literature indicates a possible role played by homeobox genes in the complex placental organogenesis. Although the expression of all HOX 9 paralogs has been demonstrated both in highly invasive murine hemochorial placentae and in non-invasive caprine synepitheliochorial placentae, no reports so far published in the literature described the patterns of gene expression of Hoxc-9 in the murine nor those of HOXC-9 in the caprine placenta at cellular levels. We carried out comparative analyses of the location and identity of the cells expressing Hoxc-9/HOXC-9 during various stages of placentation in the murine hemochorial and caprine synepitheliochorial placentae by means of in situ hybridization using murine Hoxc-9 or caprine HOXC-9 cRNA probe, respectively. The results demonstrated that Hoxc-9 mRNA was expressed at high levels in giant trophoblast cells of murine placentae on Days 12-19, but not on Day 8. Similar analysis of caprine Day 75 and Day 100 placentae revealed that the binucleate trophoblast cells that penetrate the uterine luminal epithelial cell layer, strongly expressed HOXC-9 mRNA. Although the functional significance of Hoxc-9/HOXC-9 gene expression in trophoblast cells remains to be elucidated, it was suggested that it might play a role in the regulation of invasiveness or endocrine activities in the murine giant trophoblast cells and/or the caprine binucleate trophoblast cells.

Infrequent involvement of the anterior base in low-risk patients with clinically localized prostate cancer and its possible significance in definitive radiation therapy.

BACKGROUND: The zonal distribution and location of tumors in different subgroups of Japanese patients with clinically localized prostate cancer have not been fully described. The appropriate radiation treatment volume thus remains unclear. METHODS: Radical prostatectomy specimens of 141 consecutive patients with clinically localized prostate cancer were examined by the whole organ step-section technique. The zonal distribution and location of tumors at different levels of the gland were investigated after stratification into patient subgroups based on preoperative clinicopathological findings and risk group assessment. RESULTS: The median tumor volume was 2.8 cm3; 72 patients (51.1%) had pathologically organ-confined disease (pT2). Higher risk groups showed a statistically significant increase in tumor volume and a decrease in the rate of pathologically confirmed organ confinement. Involvement of the anterior base was found infrequently in certain patient subgroups: in only one of 20 patients (5%) with preoperative PSA <4.0 ng/ml, in three of 19 patients (15.8%) with specimen Gleason scores of 2-4 and in two of 32 patients (6.3%) identified as low-risk. CONCLUSIONS: Infrequent involvement of the anterior base in low-risk patients may be an intrinsic feature of clinically localized prostate cancer. Treatment volume modifications in these patients that reduce the radiation dose to the anterior base may be justified to avoid acute and late genitourinary toxicities.

A pilot study of intermittent androgen ablation in advanced prostate cancer in Japanese men.

BACKGROUND: Permanent androgen ablation has been the mainstay of treatment for advanced prostate cancer. However, the favorable outcome seen in recent pilot studies of intermittent androgen ablation raises the possibility of overtreatment. METHODS: This study included 35 Japanese men with advanced prostate cancer. Initial androgen ablation continued for 2 months after PSA levels decreased to <4.0 ng/ml, then was withdrawn. Androgen ablation was reinstituted 2 months after PSA reached levels >10 ng/ml, when indicated clinically or on patient request. Cycling continued until androgen independence was reached. RESULTS: Mean follow-up was 21.0 months, representing an average of 2.5 cycles. Nine patients developed androgen independence at an average of 16.0 months following androgen ablation; three of these have died. Six of the nine patients with early biochemical progression had elevated alkaline phosphatase levels at entry; five of these exhibited a flare in alkaline phosphatase activity after initiation of androgen ablation. Mean bone mineral density (BMD) in the lumbar spines of 17 patients was 81.5 mg/cm3 at 23 months following therapy. The BMD of 10 of these patients was normal for their age. Four patients suffered bone fractures, none pathological. CONCLUSIONS: Intermittent androgen ablation may be an option for patients with advanced prostate cancer and may be especially beneficial for those with initially low BMD levels. Patients with elevated alkaline phosphatase levels at entry or a flare in its activity may not be ideal candidates. Whether prolonging time to androgen independence will provide benefit remains to be investigated in a randomized, prospective study.

[Implication of two additional lateral peripheral zone biopsy in the detection of prostate cancer].

BACKGROUND: Despite the strenuous efforts in improving detection of prostate cancer, no standard technique for prostatic biopsy has been established to date. Extended tissue sampling in peripheral zone may possibly lead to enhanced prostate cancer detection. METHODS: Four hundred thirty-three candidates for ultrasound-guided prostatic biopsy were alternately assigned to two groups regarding biopsy techniques between January 1997 and June 1998, Group A, sextant biopsy group and Group B, two additional lateral peripheral zone sampling after standard sextant biopsy. The outcomes of prostatic biopsy were compared. RESULTS: Cancer detection rates were 19.2% (43/217) in Group A and 18.5% (40/216) in Group B. No statistically significant difference was noted (p > 0.05). Clinical stage, Gleason score and the presence of metastasis did not differ significantly between groups (p > 0.05). The incidence and duration of hematuria, hematospermia were essentially the same between groups (p > 0.05). High fever due to possible bacteremia developed only in Group B patients (p = 0.04). CONCLUSIONS: Routine use of additional peripheral zone biopsy is not recommended owing to the equivalent cancer detection rates between groups. The application of additional biopsy should be determined carefully since this may lead to increased incidence of serious complications.

Prospective evaluation of prostate cancer detection by prostate-specific antigen-related parameters.

BACKGROUND: The diagnostic value of prostate-specific antigen (PSA) for differentiating prostate cancer from benign prostatic conditions is limited by its lack of specificity. Several PSA-related parameters have been suggested as enhancing the discriminatory power of total PSA values, but their clinical utility should be considered preliminary until established in a prospectively evaluated cohort. METHODS: In a prospective cohort study, results of ultrasound-guided biopsy and/or transurethral resection of the prostate gland were assessed in 706 consecutive Japanese men. The clinical usefulness of total PSA, free PSA, percentage of free PSA, PSA density (PSAD), PSA density for transition zone (PSADT) and gland volume for predicting prostate cancer was investigated using receiver operating characteristic (ROC) curve analysis in 16 different patient subgroups. RESULTS: Overall, 150 of the 706 patients (21.2%) had prostate carcinoma. The ROC curve analysis showed that PSAD and PSADT were more powerful predictors of prostate cancer than total PSA in most of the 16 patient subgroups tested. The improvement in performance was modest, however. No substantial difference was noted between PSAD and PSADT. Total gland volume did not significantly affect the performance of these parameters. The use of a PSAD threshold value of 0.11-10.15 ng/mL per cm3 (or a PSADT value of 0.23-0.27 ng/mL per cm3) would have avoided 24-48% (or, for PSADT, 34-40%) of unnecessary biopsies at the cost of missing 5-10% of detectable cancers in a patient subgroup with intermediate total PSA levels. The performance of free PSA and percentage of free PSA was worse than that of any other test in this study. This may be due to inappropriate handling of sera prior to measurement. CONCLUSIONS: The discriminatory potential of total PSA for predicting prostate cancer was modestly improved by the use of PSAD and PSADT. No substantial advantage of PSADT over PSAD could be demonstrated. Stringent and standardized storage conditions should always be maintained when applying free PSA-related parameters.

BRCA1 gene mutation and loss of heterozygosity on chromosome 17q21 in primary prostate cancer.

The tumor suppressor gene BRCA1 on chromosome 17q21 has been characterized and shown to be mutated in patients with familial breast and ovarian cancer. Several studies examined the relatives of women with breast cancer and noted an association with ovarian and prostate cancer. This study investigated 24 human prostate cancer specimens for BRCA1 gene mutations and loss of heterozygosity (LOH) on chromosome 17q21 assessed by the polymerase chain reaction. LOH was identified using 7 highly polymorphic tandem repeat markers on chromosome 17q21, in addition to an analysis of the whole coding region of the BRCA1 gene. Four of the 24 prostate cancer specimens showed LOH at one or more loci, all of which were histologically poorly differentiated (4 of 11) and stage D (4 of 15). One of the 24 cases showed a germ-line mutation of the BRCA1 gene, and a sister of this patient died of ovarian cancer. It appears that the BRCA1 gene is not frequently involved in the development of primary prostate cancer.

New DNA polymorphisms of human MMH/OGG1 gene: prevalence of one polymorphism among lung-adenocarcinoma patients in Japanese.

MMH/OGG1 is an 8-hydroxyguanine-specific DNA glycosylase/AP-lyase, one of the mutator enzymes for the excision repair of 8-hydroxyguanine. DNA polymorphisms in human MMH/OGG1 gene were newly identified and analyzed to examine a possible association with lung-cancer risk by a population-based study. Polymorphic allele 3 in hMMH/OGG1 exon 1 was significantly prevalent among Japanese patients with adenocarcinoma of the lung [odds ratio (OR): 3.152, 95% confidence interval (CI): 1.266-7.845], indicating that the excision repair of 8-hydroxyguanine may play a role in predisposition to lung cancer.

Cloning and characterization of mammalian 8-hydroxyguanine-specific DNA glycosylase/apurinic, apyrimidinic lyase, a functional mutM homologue.

8-Hydroxyguanine (8-OH-G) is one of the major DNA oxidation products implicated in mutagenesis induced by oxygen radical-forming agents, including ionizing radiation. It is also believed to be involved in spontaneous mutation induced by metabolically produced oxygen radicals. A mammalian homologue of 8-OH-G glycosylase/apurinic, apyrimidinic lyase (mutM homologue, MMH) has been identified in the EST database (for expressed sequence tags) through a homology search with yeast OGG1 protein. The human MMH protein (hMMH), 34% identical to the yeast OGG1 protein, is a member of the DNA repair protein superfamily. The hMMH gene was composed of seven exons, with the alternate last exon, exon 8, producing three major alternative splicing isoforms, because splicing of the sixth intron was optional. The hMMH protein expressed in Escherichia coli revealed the glycosylase activity and apurinic, apyrimidinic lyase activity on duplex DNA containing 8-OH-G. The hMMH protein can rescue a spontaneous mutator strain of E. coli lacking mutM and mutY. By the introduction of recombinant hMMH, the rate of mutation, the formation of rifampicin-resistant revertants, was reduced by 4-7 fold. Genomic structure analysis showed that 3' exons of the hMMH gene are transcribed on the antisense strand of the calcium-dependent calmodulin kinase 1 gene.

[Hyperbaric oxygen therapy in the successful treatment of two cases of radiation-induced hemorrhagic cystitis].

Hemorrhagic cystitis resulting from radiation to pelvic visceral malignant lesions often might be incurable and there have been established no definitive treatment. We experienced 2 cases with radiation-induced severe hemorrhagic cystitis refractory to conventional therapy. The treatment with hyperbaric oxygen to control hematuria was performed and obtained successful results. Gross hematuria was disappeared and cystoscopic figure was remarkably improved. No remarkable side-effect was observed in both patient. This experience suggested that hyperbaric oxygen could be considered the primary treatment for patient with radiation-induced hemorrhagic cystitis instead of usual treatment.