Biomedical subjects

H Yamanaka

Publications and source records attributed to H Yamanaka.

At least 19 recordsLinked to original sources

PubMed2006

Purification, characterization, and potential applications of formate oxidase from Debaryomyces vanrijiae MH201.

Formate oxidase was found in cell-free extracts of Debaryomyces vanrijiae MH201, a soil isolate. After purification by column chromatography, the preparation showed a protein band corresponding to a molecular mass (MM) of 64 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The MM, estimated by a gel filtration, was 99 kDa. The preparation showed two and three bands on isoelectric focusing under denaturing and native conditions, respectively. These results suggest that the preparation contained three isoforms, each of which might be composed of alphaalpha, alphabeta, and betabeta subunits with apparently similar MM. The preparation acted on formate with K (m) and V (max) values of 11.7 mM and 262 micromol min(-1) mg(-1), respectively, at pH 4.5 and 25 degrees C, but showed no evidence of activity on the other compounds tested. The optimum pH and temperature were pH 4.0 and 35 degrees C, respectively. The preparation showed activities of 85% of the initial activity after storage at pH 6.0 and 4 degrees C for 8 weeks. When 10 mM formaldehyde was reacted with 2.0 U ml(-1) of the enzyme preparation at pH 5.5 and room temperature in the presence of 2.0 U ml(-1) of a microbial aldehyde oxidase and 100 U ml(-1) of catalase for 180 min, neither of formate nor formaldehyde was detected, suggesting that the reaction involved the quantitative conversion of formaldehyde to carbon dioxide.

Aldehyde Oxidase↗

PubMed2006

Increased risk of tuberculosis in patients with rheumatoid arthritis in Japan.

OBJECTIVE: To determine the risk for tuberculosis infection in patients with rheumatoid arthritis before the anti-cytokine era in Japan. PATIENTS AND METHODS: A database of a single-institute-based large observational cohort study for rheumatoid arthritis at the Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan, was analysed. Information on the history of tuberculosis infection was collected by patient self-reporting during April and October 2003. The age-adjusted incidence rate and relative risk for tuberculosis infection were investigated. RESULTS: Among 5044 patients with rheumatoid arthritis, 483 (9.6%) patients claimed to have a history of tuberculosis infection before October 2002. The frequency of history of tuberculosis increased according to the age of the patient. Four cases of new-onset tuberculosis were identified among 5544 patients with rheumatoid arthritis during 1 year. The age-adjusted incidence of tuberculosis was 42.4/100,000 patients. The relative risk for tuberculosis was 3.21 (95% confidence interval (CI) 1.21 to 8.55), and that of men and women was 10.59 (95% CI 3.42 to 32.78) and 1.41 (95% CI 0.2 to 10), respectively. CONCLUSION: There was an increased risk of tuberculosis infection in Japanese patients with rheumatoid arthritis, especially in male patients before the introduction of anti-tumour necrosis factor treatment. These data should form the basis for the risk management of anti-cytokine treatment in Japan.

Adult↗

PubMed2006

Haplotype analysis revealed no association between the PTPN22 gene and RA in a Japanese population.

OBJECTIVE: The protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene is a member of the PTPs that negatively regulate T-cell activation. A missense single nucleotide polymorphism (SNP) in the PTPN22 gene known as R620W was recently reported to be associated with several autoimmune diseases including rheumatoid arthritis (RA). The association was confirmed repeatedly in the populations of North European ancestry. However, the SNP was reported to be non-polymorphic in the Asian populations. Because the gene confers an impact on autoimmune diseases, we attempt to explore an association between PTPN22 gene and RA in a Japanese population without restricting to the SNP, R620W. METHODS: We studied 1128 RA patients and 455 controls. In addition to the SNP, R620W, we selected eight testing SNPs spanning 45 kb over the PTPN22 gene using the International HapMap Project. Genotyping was performed using the TaqMan fluorogenic 5' nuclease assay. Associations between RA and each of the SNPs were estimated by the Fisher's exact test. Haplotype was constructed using the expectation-maximization algorithm. RESULTS: R620W was not polymorphic enough in both the patients and the controls, and was therefore excluded from further analysis. Each allele frequency for the eight other SNPs in both groups was compared and no association was detected. Haplotype analysis also revealed that PTPN22 gene was not associated with RA in a Japanese population. CONCLUSION: We found no association between PTPN22 and RA in a Japanese population. The result suggests that the PTPN22 gene is associated with RA only in a specific ethnic group.

Arthritis, Rheumatoid↗

PubMed2006

Noxious cold stimulation induces mitogen-activated protein kinase activation in transient receptor potential (TRP) channels TRPA1- and TRPM8-containing small sensory neurons.

Two cold-sensitive transient receptor potential (TRP) channels, TRPA1 and TRPM8, have been identified and considered interesting because of their possible roles in thermosensation, nociception and other functions. Recently, we have reported that the phosphorylation of extracellular signal-regulated protein kinase and p38 mitogen-activated protein kinase occurred in primary afferent neurons in response to noxious heat stimulation of the peripheral tissue, i.e. activity-dependent activation of extracellular signal-regulated protein kinase and p38 in dorsal root ganglion neurons. In the present study, we investigated the phosphorylation of extracellular signal-regulated protein kinase, p38, and c-Jun N-terminal kinase in the rat dorsal root ganglion by cold stimulation using immunohistochemistry. Cold stimuli (28-4 degrees C) were applied by immersion of the hind paw into a water bath (six times of 10 s stimulation and 10 s interval, total 2 min). Noxious cold stimulation induced phosphorylated-extracellular signal-regulated protein kinase and phosphorylated-p38, but not phosphorylated-c-Jun N-terminal kinase, in small to medium diameter sensory neurons with a peak at 2 min after stimulation. We found that a cold stimulation at 4 degrees C showed a marked increase in the number of activated neurons. Furthermore, double staining for phosphorylated-extracellular signal-regulated protein kinase and phosphorylated-p38 showed no colocalization in the dorsal root ganglion neurons. We then performed double-labeling experiments for TRPA1 and TRPM8 mRNA and phosphorylation of mitogen-activated protein kinase. The majority of phosphorylated-extracellular signal-regulated protein kinase-positive neurons also expressed TRPM8 mRNA, whereas phosphorylated-p38 heavily colocalized with TRPA1 mRNA after noxious cold stimulation. Our data suggest that the noxious, but not innocuous, cold stimulation in vivo induced differential activation of extracellular signal-regulated protein kinase and p38 pathways in each subpopulation containing TRPA1 or TRPM8 in dorsal root ganglion.

Animals↗

PubMed2006

Raised monocyte chemotactic protein-1 (MCP-1)/CCL2 in cerebrospinal fluid of patients with neuropsychiatric lupus.

BACKGROUND: An imbalance in cytokine homoeostasis is thought to have a key role in the neuropsychiatric syndromes of systemic lupus erythematosus (NPSLE), and recently, a role for chemokines has been noted. OBJECTIVE: To compare concentrations of monocyte chemotactic protein-1 (MCP-1)/CCL2 in cerebral spinal fluid (CSF) of patients with SLE, and with and without neuropsychiatric symptoms. METHODS: CSF was obtained from 185 patients with SLE: 96 with NPSLE and 89 patients with SLE without neuropsychiatric symptoms (non-NPSLE patients). MCP-1/CCL2 concentrations were measured with an ELISA. RESULTS: The average concentration of CSF MCP-1/CCL2 in patients with NPSLE was 1959 pg/ml, and in non-NPSLE patients 712 pg/ml. The average MCP-1/CCL2 concentration was significantly higher in the NPSLE group than in the non-NPSLE group (p<0.001). In one representative patient with NPSLE, MCP-1/CCL2 levels in the CSF decreased in parallel with a decline in neuropsychiatric symptoms. CONCLUSIONS: CSF MCP-1/CCL2 levels are higher in patients with NPSLE than in non-NPSLE patients. MCP-1/CCL2 may have an important role in the expression of NPSLE. These results indicate that CSF MCP-1/CCL2 reflects an inflammatory activity in the brain, suggesting that it might be used as a diagnostic tool and a monitor for therapeutic responses in patients with NPSLE.

Adolescent↗

PubMed2005

The effect of site and type of nerve injury on the expression of brain-derived neurotrophic factor in the dorsal root ganglion and on neuropathic pain behavior.

A number of rat neuropathy models have been developed to simulate human neuropathic pain conditions, such as spontaneous pain, hyperalgesia, and allodynia. In the present study, to determine the relative importance of injury site (proximal or distal to the primary afferent neurons) and injury type (motor or sensory), we examined pain-related behaviors and changes of brain-derived neurotrophic factor expression in the dorsal root ganglion in sham-operated rats, and in the L5 dorsal rhizotomy, L5 ventral rhizotomy, L5 dorsal rhizotomy+ventral rhizotomy, and L5 spinal nerve transection models. L5 ventral rhizotomy and spinal nerve transection produced not only mechanical and heat hypersensitivity, but also an increase in brain-derived neurotrophic factor mRNA/protein in the L5 dorsal root ganglion at 7 days after surgery. In contrast, rats in the L5 dorsal rhizotomy and dorsal rhizotomy+ventral rhizotomy groups did not show both pain behaviors at 7 days after surgery, despite brain-derived neurotrophic factor upregulation in medium- and large-size neurons in the L5 dorsal root ganglion. On the other hand, L5 spinal nerve transection, but not dorsal rhizotomy, dorsal rhizotomy+ventral rhizotomy or ventral rhizotomy, increased the expression of brain-derived neurotrophic factor in the L4 dorsal root ganglion at 7 days after surgery. Taken together, these findings suggest that the upregulation of brain-derived neurotrophic factor expression in the L4 and L5 dorsal root ganglion neurons may be, at least in part, involved in the pathophysiological mechanisms of neuropathic pain and that the selective nerve root injury models may be useful for studying the underlying mechanisms of chronic pain after nerve injury.

Animals↗

PubMed2005

Supportive evidence for a genetic association of the FCRL3 promoter polymorphism with rheumatoid arthritis.

BACKGROUND: An association between susceptibility to rheumatoid arthritis and the Fc receptor-like 3 gene (FCRL3) has been reported in a Japanese population. A case-control study showed that the strongest evidence of the association was derived from a polymorphism in the promoter region of FCRL3, which has a regulatory effect on the expression of the gene. OBJECTIVE: To validate the findings of this previous report by examining the -169C-->T single nucleotide polymorphism (SNP) in a large cohort. METHODS: 752 unrelated cases and 940 controls were genotyped. All the samples were from the same ethnic background as the original study. Genotyping was done using 5' allelic discrimination assays. Association between susceptibility to rheumatoid arthritis and -169C-->T SNP was examined by chi(2) testing. RESULTS: As in the previous study, the SNP showed significant differences between cases and controls (p = 0.022, odds ratio = 1.18, 95% confidence interval 1.02 to 1.35). CONCLUSIONS: This result supports a genetic association of the FCRL3 promoter polymorphism with rheumatoid arthritis.

Arthritis, Rheumatoid↗

PubMed2005

Insulin-like growth factor binding protein-6 inhibits prostate cancer cell proliferation: implication for anticancer effect of diethylstilbestrol in hormone refractory prostate cancer.

Diethylstilbestrol (DES) is a synthetic oestrogen, and its anticancer effects are exerted in androgen-dependent prostate cancer. The administration of DES decreases serum testosterone to castration levels. However, in androgen-independent prostate cancer patients, who are already orchiectomised, the administration of DES improves symptoms and decreases prostate-specific antigen (PSA). The mechanisms responsible for these direct inhibitory effects have been explained as biological actions not mediated by oestrogen receptors. We assessed the gene expression profiles of prostate cancer cells treated with DES, and investigated direct inhibitory effects of DES. DES inhibited the proliferation of LNCaP and PC-3 cells. cDNA microarray analysis showed that expression of many genes was downregulated by DES. However, insulin-like growth factor binding protein 6 (IGFBP-6) gene expression levels were upregulated in PC-3 cells. IGFBP-6 gene expression and protein levels significantly increased after DES treatment. Recombinant IGFBP-6 inhibited cell proliferation, and the inhibitory effect of DES was neutralised by anti-IGFBP-6 antibody. From the immunohistochemical analysis of IGFBP-6 using biopsy samples from androgen-independent prostate cancer, we found IGFBP-6 expression in androgen independent prostate cancer, and that DES treatment increased the IGFBP-6 staining intensity of the cancer cells in one sample. These findings suggested that DES induces IGFBP-6, which inhibits cell proliferation in an androgen-independent prostate cancer cell line, PC-3. IGFBP-6 therefore might be involved in the direct effects of DES in androgen-independent prostate cancer.

Antineoplastic Agents, Hormonal↗

PubMed2005

Induction of plasminogen activator inhibitor-1 and -2 in dorsal root ganglion neurons after peripheral nerve injury.

We have previously found that tissue type and urokinase type plasminogen activators (tPA and uPA) are induced in dorsal root ganglia (DRG) neurons after peripheral axotomy and that tPA plays crucial roles in generating neuropathic pain. Here we examined whether the plasminogen activator inhibitor-1 and -2 (PAI-1 and PAI-2) mRNA, endogenous inhibitors of tPA and uPA, are induced in the DRG following sciatic nerve transection. L4 and L5 DRG sections were examined using in situ hybridization histochemistry. The results showed that both PAI-1 and PAI-2 mRNA were up-regulated in DRG neurons within 1 day, and peaked at 1-3 days, after injury. Reduction of these mRNA was observed from 7 days after injury. The precise expression patterns of PAI-1 and PAI-2 mRNA at 3 days after axotomy revealed that PAI-1 mRNA was observed in predominantly small neurons, while much of the PAI-2 mRNA was expressed in large neurons. Double-labeling analysis of these mRNAs with activated transcription factor 3, known as an injury marker, revealed that most PAI-1 and PAI-2 mRNAs was induced in injured neurons. Co-expression of PAI-1, 2 with tPA and uPA in DRG neurons suggests that these inhibitors may act in an autocrine manner to modulate extracellular proteolytic activity after nerve injury.

Activating Transcription Factor 3↗

PubMed2005

Single nucleotide polymorphisms in the gene encoding the major histocompatibility complex class II transactivator (CIITA) in systemic lupus erythematosus.

BACKGROUND: The major histocompatibility complex (MHC) class II transactivator (CIITA) is a master switch of antigen presentation and activates expression of the MHC II gene. Insufficient up regulation of MHC class II molecules is reported to be one of the major immunological mechanisms in systemic lupus erythematosus (SLE). OBJECTIVE: To examine the association between single nucleotide polymorphisms (SNPs) in the human CIITA gene (MHC2TA) and SLE. METHODS: Promoters and coding regions of MHC2TA were evaluated for polymorphisms in 100 patients with SLE and 100 healthy donors. Eight oligonucleotide primer sets that covered the coding region and each promoter region were used for genomic analysis of SNPs. RESULTS: Allele frequencies of previously reported SNPs did not differ between healthy donors and patients with SLE. Additionally, a new polymorphism in an intronic region at nt 485 (A-->A/G) was identified, which is close to the polymorphism at nt 474 that has been associated with one of the disease causing CIITA cDNA mutations in bare lymphocyte syndrome. This SNP was found in 11% of patients with SLE and in 3% of healthy donors, suggesting it may have a role in the pathogenesis of SLE. CONCLUSIONS: A newly identified polymorphism in an intronic region at nt 485 (A-->A/G) may have an important role in the pathogenesis of SLE.

Adolescent↗

PubMed2005

[Analysis of acute exacerbation from focal usual interstitial pneumonia following to lung cancer resection].

To evaluate the susceptibility of patient with focal interstitial pneumonia (IP) to postoperative acute exacerbation, and to determine whether measuring serum level of several markers is useful for early detection of postoperative IP or not, we analyzed a total of 753 patients with primary lung cancer underwent thoracotomy. Twelve (1.6%) had postoperative IP. Eight of the 12 died due to IP and 9 of the 12 had focal IP findings on chest computed tomography (CT). Chest CT of 477 patients were reviewed retrospectively, and 51 (10.7%) had IP findings (diffuse 2.1%, focal 8.6%). Postoperative IP occurred in 17.6% of patients with IP findings, but only in 0.7% without such findings (p<0.01). Values of serum KL-6 decreased after lung resection. There were no changes in the value of serum TNF-alpha, IL-1beta, thrombomodulin and sICAM-1 after surgery. We conclude that focal IP is a risk factor of postoperative IP, and that it is not useful to measure serum markers for early detection of postoperative IP.

Aged↗

PubMed2005

[Extended sleeve lobectomy including carinaplasty for locally advanced lung cancer].

Because pneumonectomy causes a high-risk of perioperative mortality and morbidity, we have tried extended sleeve lobectomy (ESL) for patients with locally advanced lung cancer. The purpose of this study is to analyze the risk of complications and local relapses of ESL. Twelve patients underwent ESL, one-lobe and segment resection for 7, bi-lobe resection for 4, and bi-lobe and segment resection for 1. There was no hospital death. Two of 12 patients (17%) had an anastomosis complication. One (8%) had a staple line relapse. We conclude that ESL is a practicable technique for locally advanced lung cancer to avoid pneumonectomy.

Aged↗

PubMed2004

Carcinogenic potential of tobacco tar-resistant Staphylococcus aureus in buccal cavity.

PURPOSE: The effects of cigarette smoking on the association between inflammation and cancer were studied, since some bacteria induce the production of tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine and endogenous tumor promoter, in cells. METHODS: Bacteria from a gargled solution from the buccal cavity of 20 individuals were cultured in the presence of 4 mg/ml cigarette-smoke condensates. Although cigarette-smoke condensates inhibited growth of Staphylococcus aureus strongly and that of Staphylococcus warneri weakly, tobacco tar-resistant S. aureus and S. warneri were obtained. RESULTS: One tobacco tar-resistant S. aureus strain (Sa-TA10) induced expression of the TNF-alpha gene in both Bhas 42 cells (v-Ha-ras transfected BALB/3T3 cells) and human lung cancer cell line H226B, while one tobacco tar-resistant S. warneri (Sw-TA75) did not induce it significantly. Moreover, Sa-TA10 induced formation of transformed foci and soft-agar colony in Bhas 42 cells in cooperation with the v-Ha-ras gene. The results suggested that Sa-TA10 has carcinogenic potential, whereas Sw-TA75 does not. CONCLUSION: These data suggest that tobacco tar-resistant S. aureus, with carcinogenic potential, is present in the buccal cavity of some individuals, and that cigarette smoking simultaneously inhibits growth of most of the bacteria and selects carcinogenic bacteria.

3T3 Cells↗

PubMed2004

Pharmacogenetics of disease-modifying anti-rheumatic drugs.

The outcome of treatment with disease-modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis (RA) patients is considerably variable and is also unpredictable. It would be useful clinically if physicians were able to predict responses to DMARDs prior to their administration. One possible cause of differences in efficacy and adverse drug reactions is genetic variation in how individuals metabolize drugs. Based on pharmacogenetics, tailor-made drug therapy, also called personalized drug therapy or individual drug therapy, will be possible with analysis of genetic polymorphism, such as single nucleotide polymorphism (SNP), and analysis of haplotype and diplotype configuration. Several studies of the correlation between the genetic polymorphism of enzymes metabolizing several DMARDs and efficacy or adverse drug reactions have already been reported, suggesting that pharmacogenetics will be applicable to the treatment of RA in the near future.

Antirheumatic Agents↗

PubMed2004

Activation of extracellular signal-regulated protein kinase in the dorsal root ganglion following inflammation near the nerve cell body.

Inflammation of the primary afferent proximal to the dorsal root ganglion (DRG) and the DRG itself is known to produce radicular pain. Here, we examined pain-related behaviors and the activation of extracellular signal-regulated protein kinase (ERK) in the DRG after inflammation near the DRG somata. Inflammation of the L4/5 nerve roots and DRG induced by complete Freund's adjuvant (CFA) produced mechanical allodynia on the ipsilateral hindpaw and induced an increase in the phosphorylation of ERK, mainly in tyrosine kinase (trk) A-expressing small- and medium-size neurons. This CFA-induced increase in ERK phosphorylation was mediated through trk receptors, because intrathecal treatment with the tyrosine kinase inhibitor, K252a, reduced the activation of ERK. On the other hand, an increase in brain-derived neurotrophic factor (BDNF) mRNA/protein in the DRG concomitant with the ERK activation was also observed. Furthermore, we found that nerve growth factor (NGF) injection directly into the L4/5 nerve roots and DRG produced mechanical allodynia, and an increase in the phosphorylation of ERK and BDNF expression in the DRG, but the mitogen-activated protein kinase (MAPK) kinase1/2 inhibitor, U0126, inhibited the effects induced by NGF. Therefore, we suggest that after inflammation near the cell body, NGF synthesized within the nerve root and DRG induces BDNF expression through trkA receptors and intracellular ERK-MAPK. The activation of MAPK in the primary afferents may be involved in the pathophysiological mechanisms of inflammation-induced radiculopathy and MAPK pathways in the primary afferents may be potential targets for pharmacological intervention for neuropathic pain produced by inflammation near the DRG somata.

Animals↗

PubMed2004

Pilot study of the optimum hematocrit for patients in the predialysis stage after renal transplantation.

Anemia is a common complication in patients with chronic kidney diseases including posttransplant patients. Guidelines for the treatment of anemia in chronic kidney disease published by NHF-K/DOQI recommend the target hemoglobin and hematocrit (Hb and Ht) levels to be in the 11 to 12 g/dL and 33% to 36% ranges, respectively, which are somewhat higher than those recommended in Japan (Ht = 30%). However, these guidelines were established mainly from the data on hemodialysis patients with only limited information available as to the impact of anemia control in posttransplant patients. The aim of the present study was to evaluate cardiac function and quality of life (QOL) when the Ht was raised to about 36% by administration of recombinant-human-erythropoietin (rHuEPO) to patients with mild impairment of renal function (s-Cre < 2.0 mg/dL) after renal transplantation. Twenty-five patients were analyzed for cardiac function, blood data, and QOL in a prospective study encompassing 8 months of rHuEPO treatment. Using a once weekly subcutaneous dose of 6000 IU of Epoetin-beta, the Ht became 33% to 36% and Hb was 11 to 12 g/dL. Among the cardiac function tests, left ventricular end-diastolic diameter and left ventricular mass index decreased significantly. QOL did not show any significant changes after administration of rHuEPO. In conclusion, we demonstrated a potential benefit of using rHuEPO to maintain the Hb between 11 and 12 g/dL and the Ht between 33% and 36% in posttransplant patients with regard to the prevention of cardiovascular complications. Further study is required to establish the benefits of correcting anemia by rHuEPO on the outcome of posttransplant patients.

Anemia↗

PubMed2004

Pharmacokinetics and pharmacodynamics of febuxostat (TMX-67), a non-purine selective inhibitor of xanthine oxidase/xanthine dehydrogenase (NPSIXO) in patients with gout and/or hyperuricemia.

The diurnal change of sUA and the effect of febuxostat on this change were investigated in 10 patients with gout and/or hyperuricemia. The diurnal sUA change after the last dose during the 4-week treatment phase (20 mg, QD) was almost the same as the pre-treatment value. Considering the dose, the AUC(obs) and Cmax of unchanged drug in patients with gout and/or hyperuricemia were estimated to be similar to those of healthy male adults. The results show that a 6-week treatment with febuxostat is safe and well-tolerated in the target patient population for this drug.

Area Under Curve↗

PubMed2003

Role of genetic polymorphisms of the RNASEL gene on familial prostate cancer risk in a Japanese population.

The RNASEL gene on chromosome 1q25 has been identified as a prostate cancer susceptibility gene. We screened for RNASEL germline mutations in familial prostate cancer patients, and performed a case-control study to examine the association of specific variants with prostate cancer risk in the Japanese. Three variants within the RNASEL gene, G282A, G1385A and T1623G were identified. G1385 and T1623G variants result in previously reported Arg462Gln and Asp541Glu variants, respectively. The novel G282A variant does not cause amino-acid substitution. A case-control study consisting of 101 familial prostate cancer cases and 105 noncancer controls showed that the Gln/Gln genotype of codon462 was observed in 7.6% of controls. However, the Gln/Gln genotype was not observed in cases, and reduced prostate cancer risk (odds ratio (OR)=0.061, P=0.014). The Asp/Asp genotype of codon541 increased the familial prostate cancer risk (OR=7.37, P=0.0004). In subset analysis, a significant association was observed in patients with more than two affected members (OR=3.15, P=0.028), and weak associations were found in patients with metastatic disease (OR=2.40, P=0.11) and high-grade disease (Gleason score >or=7) (OR=3.07, P=0.14). These findings suggested that the polymorphic changes within the RNASEL gene may be associated with familial prostate cancer risk in a Japanese population.

Adult↗