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N Tsuchiya

Publications and source records attributed to N Tsuchiya.

At least 55 records · Page 3Linked to original sources
PubMed2000

Increased risk of prostate cancer and benign prostatic hyperplasia associated with a CYP17 gene polymorphism with a gene dosage effect.

The CYP17 gene (CYP17) codes for the cytochrome P450c17alpha enzyme, which mediates two key steps in the sex steroid synthesis. There is a polymorphism (a T-to-C substitution) in the 5'-untranslated region, which may influence the transcription level of CYP17 mRNA. There is a continuing controversy as to whether the variant allele is associated with a subset of breast cancer or polycystic ovary syndrome. In prostate cancer research, there are contradictory data concerning the CYP17 risk allele. We explored the association between CYP17 polymorphism and a risk of prostate cancer or benign prostatic hyperplasia (BPH) in a Japanese population. This study included 252 prostate cancer patients, 202 BPH patients, and 131 male controls. A 451-bp fragment encompassing the polymorphic site was amplified by PCR, treated with restriction enzyme MspA1, and electrophoresed on an agarose gel. The MspA1-undigested allele with the published sequence and the MspA1-digested variant allele were designated as A1 and A2, respectively. There was a significant difference (P < 0.05) in the genotypes between prostate cancer patients and male controls, and between BPH patients and male controls. Men with the A1/A1 CYP17 genotype had an increased risk of prostate cancer [odds ratio (OR), 2.57; 95% confidence interval (CI) = 1.39-4.78] and BPH (OR, 2.44; 95% CI = 1.26-4.72) compared with those with the A2/A2 genotype. Men with the A1/A2 genotype had an intermediate increased risk of prostate cancer (OR, 1.45; 95% CI = 0.84-2.54) and BPH (OR, 1.60; 95% CI = 0.89-2.87) compared with those with the A2/A2 genotype. The trend of an increasing risk of prostate cancer and BPH with an increasing number of the A1 allele was statistically significant (prostate cancer versus male control, P = 0.003; OR, 1.57; 95% CI = 1.16-2.12; BPH versus male control, P = 0.008; OR, 1.55; 95% CI = 1.12-2.13). There was no significant association between the CYP17 genotype and the tumor status (grade and stage) of prostate cancer. Our results suggest that the A1 allele of the CYP17 polymorphism is associated with an increased risk of prostate cancer and BPH, with a gene dosage effect. However, the CYP17 genotype does not seem to influence the disease status in prostate cancer.

Aged↗
PubMed2000

Molecular characterization of a mouse heterogeneous nuclear ribonucleoprotein D-like protein JKTBP and its tissue-specific expression.

The human DNA- and RNA-binding protein JKTBP is a new member of heterogeneous nuclear ribonucleoproteins (hnRNPs) that are involved in mRNA biogenesis. We cloned and characterized a mouse homolog and studied its expression in mouse tissues. The cDNA encoded a 301-residue polypeptide. There is only a single amino acid difference between the mouse and human sequences. Northern blotting indicated ubiquitous but varied expressions of approximately 1.4 and 2.8kb mRNAs in various tissues. Immunoblotting indicated that the amounts of protein of about 38kDa were higher in the brain and testis than in other tissues. An additional protein of about 53kDa was found in the brain and testis. Germ cell-deficient W/W(v) mutant mice and aged mice had the reduced amounts of JKTBP in the testes. Immunohistochemical staining indicated cell type-specific expression of JKTBP in tissues: neurons and spermatocytes displayed strong signal intensities. The signals were confined to the nucleus. The amount of 38kDa JKTBP was estimated to be approximately 1.3x10(7) molecules per HL-60 cell. These results indicate that JKTBP is an abundant, highly conserved nuclear protein.

Animals↗
PubMed2000

Association of vitamin D receptor gene polymorphism with prostate cancer and benign prostatic hyperplasia in a Japanese population.

Recent studies have suggested that vitamin D is an important determinant of prostate cancer risk and inherited polymorphisms in the 3'-untranslated region (3'UTR) of the vitamin D receptor (VDR) gene are associated with the risk and progression of prostate cancer. This study was conducted to explore the association of VDR gene polymorphisms with prostate cancer risk in Japanese men who are considered to be much less influenced by environmental risk factors for prostate cancer. We studied 222 prostate cancer patients, 209 benign prostatic hyperplasia (BPH) patients, 128 male controls who were over 60 years old and without any evidence of prostate cancer or BPH, and 198 female controls. A PCR-RFLP method was used to determine three VDR gene polymorphisms in the 3'UTR characterized by restriction enzymes BsmI, ApaI and TaqI. In the BsmI polymorphism, heterozygosity or homozygosity for the absence of the BsmI restriction site was associated with one-third the risk of prostate cancer (P < 0.0001; odds ratio, 3.31; 95% confidence interval, 2.05-5.32) and with one-half the risk of BPH (P < 0.005; odds ratio, 2.07; 95% confidence interval, 1.33-3.22) compared with the male controls. The TaqI and ApaI polymorphisms did not show any significant association with either prostate cancer or BPH. The results indicate that the BsmI polymorphism in the VDR gene plays a significant role in protection against prostate cancer and BPH. Because of the racial difference in the strength of the linkage disequilibrium between the three polymorphisms, additional studies are required to apply the present results to other racial-ethnic groups.

3' Untranslated Regions↗
PubMed2000

Tumor necrosis factor alpha 5'-flanking region, tumor necrosis factor receptor II, and HLA-DRB1 polymorphisms in Japanese patients with rheumatoid arthritis.

OBJECTIVE: New polymorphisms affecting transcriptional activity were recently reported within the 5'-flanking region of the tumor necrosis factor alpha gene (TNFalpha). In addition, genome-wide linkage screening indicated 1p36 as one of the candidate chromosomal regions where the TNF receptor II gene (TNFR2) is located. In the present study, HLA-DRB1, TNFalpha promoter, and TNFR2 genotypes were determined to examine whether these polymorphisms are associated with rheumatoid arthritis (RA), either independently or in combination. METHODS: Genotypes of HLA-DRB1, TNFalpha upstream promoter, and TNFR2 codon 196 were determined in 545 Japanese patients with RA and 265 healthy controls. Association of these genes with susceptibility to RA was analyzed both independently and after stratification by one of the genotypes. RESULTS: As expected, the HLA-DRB1 shared epitope was strongly associated with RA. In addition, a significant negative association of DRB1*1405 and 1302 was observed. Furthermore, DRB1*1405 was suggested to possess a protective role for the development of RA in DRB1*0405-positive individuals. A significant increase in TNFalpha-U02 in RA was detected, which was not independent of DRB1*0405. A significant association was not observed between TNFR2-196M/R polymorphism and RA. CONCLUSION: Among the 3 genes examined in this study, HLA-DRB1 was considered to be most strongly associated with RA.

Antigens, CD↗
PubMed2000

Single nucleotide polymorphisms in the coding regions of human CXC-chemokine receptors CXCR1, CXCR2 and CXCR3.

Chemokines and their receptors have critical roles in inflammatory and immunological responses, and thus their genetic contribution to various human disorders needs investigation. In this study, systematic variation screening of the entire coding regions of CXCR1 (IL8RA), CXCR2 (IL8RB) and CXCR3 was carried out, using genomic DNA from a large number of Japanese healthy individuals and patients with rheumatic diseases. In addition to the previously reported variations in CXCR1 and in CXCR2, two non-synonymous, two synonymous substitutions and one nonsense mutation of CXCR1, one non-synonymous and two synonymous substitutions of CXCR2, two non-synonymous substitutions of CXCR3 were newly identified. The common single nucleotide polymorphisms (SNPs) at CXCR1 codon 827 and CXCR2 codon 786 were in strong linkage disequilibrium. In addition, familial analysis indicated that human CXCR3 is located on chromosome X. No significant association was observed between the variations and the tested rheumatic diseases. However, CXCR variations identified in this study will provide valuable information for the future studies in medical sciences as well as in human genetics.

Alleles↗
PubMed2000

Independent contribution of HLA-DRB1 and TNF alpha promoter polymorphisms to the susceptibility to Crohn's disease.

Although a number of studies reported the association of HLA-DRB1 and Crohn's disease (CD), the actual alleles associated with CD are considerably variable among populations. On the other hand, the relevance of tumor necrosis factor alpha (TNF alpha) in the pathogenesis of CD is established through experimental as well as clinical studies, raising the possibility that TNFA polymorphism is primarily or independently contribute to the association of HLA region genes with CD. New polymorphisms which may affect the transcriptional activity were recently reported within the upstream promoter region of TNFA gene. In the present study, we compared HLA-DRB1, TNFA promoter and TNF receptor 2 (TNFR2) genotypes in 154 Japanese patients with CD and 265 unrelated healthy controls to evaluate the individual contribution of these genes to the genetic predisposition to CD. Significant positive association was observed in HLA-DRB1*0405 (P = 0.001, odds ratio (OR) = 2.02) and 0410 (P = 0.002, OR = 4.79). Among the TNFA promoter haplotypes, TNFA-U03 (-1031C, -863A, -857C) was significantly increased (P = 0.008, OR = 1.64), while TNFA-U04 (-1031C, -863C, -857C) was significantly decreased (P = 0.014, OR = 0.12), in CD. The association with TNFA-U03 was independent of that with DRB1*0405 and 0410, and apparent additive or multiplicative effect was not observed between these susceptibility alleles. No association was observed between TNFR2-196M/R polymorphism and CD. These results indicated that both of HLA-DRB1 and TNFA promoter polymorphisms contribute to the susceptibility to CD in an independent manner.

Adult↗
PubMed2000

New single nucleotide polymorphisms in the coding region of human TNFR2: association with systemic lupus erythematosus.

We recently reported the association of the allele coding for Arg at the position 196 (196R: nucleotide [nt] 587G) of tumor necrosis factor receptor 2 (TNFR2, TNF-R75) with systemic lupus erythematosus (SLE) in Japanese. In the present study, we completed the variation screening of the entire coding region of TNFR2. Three new single nucleotide polymorphisms within the coding sequence (cSNPs), as well as several variations within the promoter, introns and 3'-untranslated region (3' UTR), were identified. Among the new SNPs, nt168G, a synonymous substitution (K56K), was in tight linkage disequilibrium with nt587G. Two other cSNPs, nt543 (C-->T) (P181P) and nt694 (G-->A) (E232K), were not significantly associated with SLE. Thus, among the non-synonymous cSNPs, only nt587 (T-->G) (M196R) was found to be significantly associated with SLE in Japanese.

Alleles↗
PubMed2000

New polymorphisms of human CD80 and CD86: lack of association with rheumatoid arthritis and systemic lupus erythematosus.

The crucial role of costimulatory molecules, CD28, CTLA-4, CD80 and CD86, for T cell activation and inhibition has been established. In the previous study, we reported the results of a polymorphism screening of human CTLA-4 gene. In this study, we screened for polymorphisms of human CD28, CD80 and CD86 genes, and detected that polymorphisms were tested for the association with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Variations were identified in the coding regions of CD80 (452G/A, 614C/G and 864A/G) and CD86 (1057A/G), while no variation was observed in the coding region of CD28. The variations at CD80 position 452 and CD86 position 1057 were present in a substantial proportion of the Japanese population, and were considered to be single nucleotide polymorphisms within the coding sequence (cSNPs). CD80 864 (G-->A) leads to the amino acid substitution N186D, and CD86 1057 (A-->G) results in A304T substitution. Furthermore, in the analysis of CD80 5'-flanking region, six SNPs, -454C/A, -387T/C, -232G/A, -79G/C, -7T/C and /A, and one insertion, -558ins (CATGA), were identified. The combination of these variations was found to constitute four promoter alleles of CD80. None of the observed variations was significantly associated with RA or SLE. Further studies will be of particular interest to examine the functional difference of the promoter alleles for the transcriptional activity of CD80, as well as the evolutionary pathway of the four alleles.

Alleles↗
PubMed2000

New variations in human OX40 ligand (CD134L) gene.

We found three new variations in the OX40 ligand (OX40L, CD134L) gene and its 5' upstream region. -921 (G-->A) at 5' upstream region, -19 (C-->G) at 5' untranslated region, and 202 + 25 (G-->T) at intron 2 were identified. -921 (G-->A) and 202 + 25 (G-->T) were detected in a substantial proportion of healthy Japanese individuals and were considered to be single nucleotide polymorphisms (SNPs). -19 (C-->G) was detected in only one healthy individual. There was no association between these variations and the presence of rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE).

Arthritis, Rheumatoid↗
PubMed2000

An accessory spleen mimicking a nonfunctional adrenal tumor: a potential pitfall in the diagnosis of a left adrenal tumor.

We describe a case of accessory spleen mimicking a left adrenal tumor. A 66-year-old woman was referred to our hospital because of a suspected left adrenal mass detected by US. A laparoscopic adrenalectomy was performed, and examination of the surgical specimen revealed that the resected adrenal gland contained no tumorous lesion. A further investigation of the intraperitoneal space revealed an accessory spleen. This indicates that urologists should be aware of the possible existence of accessory spleens when left adrenal tumors are suspected on CT and MRI.

Adrenal Gland Neoplasms↗
PubMed2000

[A case of acupuncture needle dermatitis].

A 65-year-old female visited our clinic with painful red vesicular dermatitis of the forehead and around the left eye. She had received acupuncture for headache and shoulder stiffness 6 days before visiting our clinic. A patch test with nickel sulfate gave positive results. We treated her with the greater occipital nerve block and trigger point injection which relieved her pain. We reached the diagnosis of greater occipital trigeminal syndrome with contact dermatitis from the acupuncture needle.

Acupuncture Therapy↗
PubMed2000

Cardiac troponin I level correlates with chronic-phase left ventricular function after successful direct percutaneous transluminal coronary angioplasty in patients with acute myocardial infarction.

OBJECTIVES: The relationships between cardiac troponin I, various biochemical markers, and chronic-phase left ventricular ejection fraction (LVEF) after successful direct percutaneous transluminal coronary angioplasty (PTCA) were examined in 36 patients with acute myocardial infarction. METHODS: Biochemical markers were measured on admission, immediately after, and from 6 hours to 9 days after PTCA. RESULTS: The time to peak values were: creatine kinase-MB 9.7 hours, cardiac troponin I 9.8 hours, myoglobin 10.7 hours, creatine kinase 10.6 hours, cardiac troponin T 18.6 hours, and myosin light chain 68.9 hours. Cardiac troponin T, cardiac troponin I and myosin light chain levels were elevated over 9 days after successful direct PTCA. Chronic-phase LVEF inversely correlated with peak values of creatine kinase-MB (r = -0.519, p < 0.01), cardiac troponin T (r = -0.500, p < 0.01), cardiac troponin I (r = -0.441, p < 0.05) and creatine kinase (r = -0.411, p < 0.05). The values of cardiac troponin I, cardiac troponin T, creatine kinase and creatine kinase-MB at each sampling point were significantly inversely related to chronic-phase LVEF. The value of cardiac troponin I at each time point for 7 days correlated well with chronic-phase LVEF. CONCLUSIONS: Cardiac troponin I has high specificity for predicting long-term cardiac function after successful direct PTCA when early values are unavailable.

Adult↗
PubMed1999

Two forms of expression and genomic structure of the human heterogeneous nuclear ribonucleoprotein D-like JKTBP gene (HNRPDL).

The human DNA- and RNA-binding protein JKTBP is a member of a 2xRNA-binding domain (RBD)-glycine family of heterogeneous nuclear ribonucleoproteins that are involved in mRNA biogenesis. Northern and Western blottings revealed that mRNAs of approx. 1.4 and 2.8kb and proteins of approx. 38 and 53kDa were present in HL-60 cells and various tissues. Cloning and characterization of a previously unknown cDNA for the 2.8kb mRNA indicated that the cDNA encodes a 420 amino acid JKTBP polypeptide. Isolation and characterization of the genomic DNA showed that the gene (HNRPDL) had nine exons and had two separate transcription start sites for the two transcripts. The features of the 5' flanking sequences of these sites showed that the gene is a housekeeping gene. Fluorescence in situ hybridization mapped the gene to 4q13-q21. From its gene organization, the JKTBP seems to be most closely related to hnRNP D/AUF1.

Amino Acid Sequence↗