Biomedical subjects

Tadaichi Kitamura

Publications and source records attributed to Tadaichi Kitamura.

At least 55 records · Page 3Linked to original sources

PubMed2005

DNA hypomethylation on pericentromeric satellite regions significantly correlates with loss of heterozygosity on chromosome 9 in urothelial carcinomas.

PURPOSE: DNA methylation has important roles in genomic stability. Accordingly DNA hypomethylation on pericentromeric satellite regions may induce chromosomal instability through heterochromatin decondensation and chromosomal recombination enhancement. We elucidated the significance of aberrant DNA methylation on pericentromeric satellite regions during urothelial carcinogenesis. MATERIALS AND METHODS: We examined DNA methylation status on satellites 2 and 3 by Southern blotting and determined the allelic status of chromosome 9 using 6 microsatellite markers (D9S775, D9S925, D9S304, D9S303, D9S283 and D9S747) in 27 transitional cell carcinomas of the bladder, ureter or renal pelvis and corresponding noncancerous tissues. RESULTS: DNA hypomethylation on satellites 2 and 3 was detected in 2 (7%) and no (0%) noncancerous tissues, and in 11 (41%) and 12 (44%) urothelial carcinomas, respectively. DNA hypomethylation in urothelial carcinomas significantly correlated with histological grade (p = 0.0012 and 0.0043), invasion depth (p = 0.0055 and 0.0228) and morphological structure (papillary vs nodular, p = 0.0161 and 0.0297) for satellites 2 and 3, respectively. Loss of heterozygosity on at least 1 locus of chromosome 9 was detected in 14 urothelial carcinomas (52%). DNA hypomethylation on satellites 2 (p = 0.0098) and 3 (p = 0.0034) significantly correlated with loss of heterozygosity on chromosome 9. CONCLUSIONS: DNA hypomethylation on pericentromeric satellite regions may participate in the development and progression of urothelial carcinomas by inducing loss of heterozygosity on chromosome 9.

Aged↗

PubMed2005

DNA hypermethylation on multiple CpG islands associated with increased DNA methyltransferase DNMT1 protein expression during multistage urothelial carcinogenesis.

PURPOSE: We elucidated the significance of aberrant DNA methylation on multiple CpG islands and its correlation with DNA methyltransferase DNMT1 protein expression during urothelial carcinogenesis. MATERIALS AND METHODS: We examined the DNA methylation status on multiple CpG islands by methylation specific polymerase chain reaction and combined bisulfite restriction enzyme analysis in 12 specimens of normal urothelium, 23 of noncancerous urothelium showing no remarkable histological changes obtained from patients with bladder cancer (NBC) and 70 of transitional cell carcinoma (TCC). RESULTS: DNA methylation on CpG islands of the p16 (0%, 17% and 21%) and death-associated protein kinase (13%, 33% and 29%) genes, and methylated in tumor-2 (56%, 60% and 76%), 12 (0%, 6% and 30%), 25 (25%, 27% and 35%) and 31 (45%, 56% and 79%) clones was detected in normal urothelium, NBCs and TCCs, respectively. The incidence of concurrent DNA hypermethylation on 3 or more CpG islands in NBCs (38%) was significantly higher than that in normal urothelium (0%, p = 0.0455) and even higher in TCCs (59%, p = 0.0043). The incidence of the CpG island methylator phenotype in nonpapillary carcinomas (nodular invasive carcinomas and their precursors, ie flat carcinoma in situ, 71%) was significantly higher than in papillary carcinomas (40%, p = 0.0143). In all specimens examined concurrent DNA hypermethylation on 3 or more CpG islands significantly correlated with immunohistochemically evaluated DNMT1 protein over expression (p = 0.0167). CONCLUSIONS: DNA hypermethylation on multiple CpG islands in association with DNMT1 protein over expression may participate in multistage urothelial carcinogenesis even at the precancerous stage and particularly in the development of nodular invasive carcinomas of the bladder.

Carcinoma, Transitional Cell↗

PubMed2005

Function of the lower urinary tract in mice lacking alpha1d-adrenoceptor.

PURPOSE: alpha1-Adrenoceptor (AR) blockers are known to relieve not only voiding symptoms, but also storage symptoms in elderly men. We investigated lower urinary tract function in mice lacking alpha1d-AR using frequency/volume analysis and filling cystometry. MATERIALS AND METHODS: A total of 10, 12-week-old female alpha1d-knockout (KO) mice and 10 age matched female wild-type (WT) mice were studied. Each mouse was placed in a metabolic cage connected to a digital scale and personal computer. Under a 12/12-hour dark/light photocycle voiding frequency and volume were recorded for 48 hours. After frequency/volume analysis filling cystometry was performed with the mice awake and without restraint. The expression of alpha1-AR subtype mRNA in the bladder of mice in each group was quantified using real-time polymerase chain reaction. RESULTS: Mean daily voiding frequency +/- SD in alpha1d-KO mice was 9.0 +/- 2.1, significantly lower than 15.9 +/- 5.2 in WT mice (p = 0.0048). Mean volume per void in alpha1d-KO mice was significantly larger than in WT mice (0.24 +/- 0.02 vs 0.16 +/- 0.03 ml, p = 0.0096). Similarly cystometric analysis demonstrated larger bladder capacity (140%, p = 0.0008) and voided volume (146%, p = 0.0048) in alpha1d-KO mice compared with those in WT mice. No significant difference in maximum pressure at void was observed between the 2 groups. In WT mice the amount of alpha1a, alpha1b and alpha1d-AR subtype mRNA in the bladder was 5.2 +/- 0.7, 1.0 +/- 0.1 and 6.3 +/- 0.7 gene copies per ng total RNA, respectively. In contrast, alpha1d-AR transcript was not detectable in alpha1d-KO mice but alpha1a and alpha1b-AR expression was similar to that in WT mice. CONCLUSIONS: The results demonstrate that the alpha1d-AR subtype has an important role in regulating bladder function. They theoretically support a clinical finding that alpha1-blockers with significant affinity for alpha1d-AR are effective for treating storage symptoms associated with benign prostatic obstruction.

Animals↗

PubMed2005

New sequence polymorphisms in the outer loops of the JC polyomavirus major capsid protein (VP1) possibly associated with progressive multifocal leukoencephalopathy.

JC polyomavirus (JCPyV) causes progressive multifocal leukoencephalopathy (PML) in patients with decreased immune competence. To elucidate genetic changes in JCPyV associated with the pathogenesis of PML, multiple complete JCPyV DNA clones originating from the brains of three PML cases were established and sequenced. Although unique rearranged control regions occurred in all clones, a low level of nucleotide variation was also found in the coding region. In each case, a parental coding sequence was identified, from which variant coding sequences with nucleotide substitutions would have been generated. A comparison between the parental and variant coding sequences demonstrated that all 12 detected nucleotide substitutions gave rise to amino acid changes. Interestingly, seven of these changes were located in the surface loops of the major capsid protein (VP1). Finally, 16 reported VP1 sequences of PML-type JCPyV (i.e. derived from the brain or cerebrospinal fluid of PML patients) were compared with their genotypic prototypes, generated as consensus sequences of representative archetypal isolates belonging to the same genotypes; 13 VP1 proteins had amino acid changes in the surface loops. In contrast, VP1 proteins from isolates from the urine of immunocompetent and immunosuppressed patients rarely underwent mutations in the VP1 loops. The present findings suggest that PML-type JCPyV frequently undergoes amino acid substitutions in the VP1 loops. These polymorphisms should serve as a new marker for the identification of JCPyV isolates associated with PML. The biological significance of these mutations, however, remains unclear.

Adult↗

PubMed2005

Single-nucleotide polymorphisms in the 17beta-hydroxysteroid dehydrogenase genes might predict the risk of side-effects of estramustine phosphate sodium in prostate cancer patients.

BACKGROUND: Estramustine phosphate sodium (EMP) frequently causes side-effects such as gastrointestinal discomfort, nausea, and edema in extremities. We analyzed single nucleotide polymorphisms (SNP) in the 17beta-hydroxysteroid dehydrogenase (HSD17B) genes, which are involved in the metabolism of EMP, to predict the risk of EMP side-effects in prostate cancer patients. METHODS: We performed genotyping of SNP in the HSD17B genes of 44 Japanese patients with newly diagnosed prostate cancer. The association of SNP and individual EMP side-effects was evaluated. RESULTS: Peripheral edema occurred more frequently in patients with C/C genotype of IMS-JST123219 than in those with C/G genotype (OR: 5.47, 95% CI: 1.27-23.64). Haplotype analysis showed that appetite loss was associated with the G allele of IMS-JST123219 and the T allele of IMS-JST123218 (OR: 9.13, 95% CI: 1.15-72.76). CONCLUSIONS: These preliminary data demonstrated that analyses of SNP in the HSD17B genes might predict the occurrence of side-effects from EMP.

17-Hydroxysteroid Dehydrogenases↗

PubMed2005

Different transformation of mature teratoma in a patient with mixed germ cell tumor of the testis.

A 44-year-old male was referred with a left supraclavicular lymphadenopathy. A biopsy of the lymph node showed metastatic embryonal carcinoma. Tumor markers were present at high levels: alpha-fetoprotein 253.9 ng/mL, beta-human chorionic gonadotrophin 62 ng/mL. Computed tomography (CT) showed retroperitoneal adenopathy. High orchiectomy was done. The patient was treated with three cycles of etoposide plus cisplatin, achieved normalization of the serum tumor markers and underwent retroperitoneal lymph node dissection. Pathological findings of multiple lymph nodes showed teratomatous glands without viable cells. At follow-ups performed every 3 months, tumor markers remained within normal limits and no evidence of recurrence was observed. Eight years after first admission a CT scan revealed a cystic tumor 1 cm in diameter in the para-aortic region. The cystic tumor continued to slowly grow, expanding by 1 cm in diameter per year without elevation of tumor markers. The para-aortic tumor had grown to 4 cm in diameter and a left supraclavicular lymphadennopathy recurred. A resection of the supraclavicular cystic tumor showed mucinous cystadenocarcinoma, but a cystic tumor in the para-aortic region revealed mature teratoma. Here we report a case of mature teratoma with metastases at supraclavicular and para-aortic lymph nodes which had different transformations in spite of both regions consisting of cystic tumors.

Adult↗

PubMed2005

Hemiresective reconstruction of a redundant ileal conduit with severe bilateral ileal conduit-ureteral re fl ux.

A 58-year-old man was referred to our hospital with high fever and anuria. Since undergoing a total pelvic exenteration due to bladder-invasive sigmoid colon cancer, urinary tract infections had frequently occurred. We treated with the construction of a bilateral percutaneous nephrostomy (PCN), and chemotherapy. Although we replaced the PCN with a single J ureteral catheter after an improvement of infection, urinary infection recurred because of an obstruction of the catheter. Urological examinations showed that an ileal conduit-ureteral reflux caused by kinking of the ileal loop was the reason why frequent pyelonephritis occurred. We decided to resect the proximal segment to improve conduit-ureteral reflux for the resistant pyelonephritis. After the surgery, the excretory urogram showed improvement and the urinary retention at the ileal conduit disappeared. Three years after the operation, renal function has been stable without episodes of pyelonephritis. Here we report a case of open repair surgery of an ileal conduit in a patient with severe urinary infection.

Humans↗

PubMed2005

Proteus syndrome with giant myelolipoma in the pelvis.

Proteus syndrome is a very rare and complex disorder with malformations and overgrowth of multiple tissues. This disorder was designated Proteus syndrome by Wiedemann et al. to denote its variable clinical expression. Our patient presented with macrodactyly, cerebriform appearance and a huge abdominal mass. A biopsy under laparotomy was performed, and histopathological examination revealed myelolipoma. Tumor resection was performed. To our knowledge, no case of Proteus syndrome presenting a myelolipoma in the retroperitoneal cavity has been reported before.

Humans↗

PubMed2005

Transrectal high-intensity focused ultrasound in the treatment of localized prostate cancer: a multicenter study.

We report a multicenter trial with transrectal high-intensity focused ultrasound (HIFU) in the treatment of localized prostate cancer. A total of 72 consecutive patients with stage T1c-2NOM0 prostate cancer were treated using the Sonablate 500TM HIFU device (Focus Surgery, Indianapolis, USA). Biochemical recurrence was defined according to the criteria recommended by the American Society for Therapeutic Radiology and Oncology Consensus Panel. The median age and prostate specific antigen (PSA) level were 72 years and 8.10 ng/ml, respectively. The median follow-up period for all patients was 14.0 months. Biochemical disease-free survival rates in all patients at 1 and 2 years were 78% and 76%, respectively. Biochemical disease-free survival rates in patients with stage T1c, T2a and T2b groups at 2 years were 89, 67% and 40% (p = 0.0817). Biochemical disease-free survival rates in patients with Gleason scores of 2-4, 5-7 and 8-10 at 2 years were 88, 72% and 80% (p = 0.6539). Biochemical disease-free survival rates in patients with serum PSA of less than 10 ng/ml and 10-20 ng/ml were 75% and 78% (p = 0.6152). No viable tumor cells were noted in 68% of patients by postoperative prostate needle biopsy. Prostatic volume was decreased from 24.2 ml to 14.0 ml at 6 months after HIFU (p < 0.01). No statistically significant differences were noted in International Prostate Symptom Score, maximum urinary flow rate and quality of life analysis with Functional Assessment of Cancer Therapy. HIFU therapy appears to be minimally invasive, efficacious and safe for patients with localized prostate cancer with pretreatment PSA levels less than 20 ng/ml.

Adult↗

PubMed2004

BMP signals inhibit proliferation and in vivo tumor growth of androgen-insensitive prostate carcinoma cells.

Prostate cancer is one of the most common cancers in men. Several lines of evidence have suggested that bone morphogenetic protein (BMP) signals play important roles in the generation and progression of prostate cancers. In the present study, we show that BMP-7 inhibits the proliferation of androgen-insensitive PC-3 and DU-145 prostate cancer cells in a medium containing 1% fetal bovine serum, observed as decreased incorporation of [(3)H]thymidine and decreased cell number. Cell cycle analysis by flow cytometry showed an increased fraction of cells in the G1 phase and subsequent decrease in both S and G2/M phase after BMP-7 stimulation. BMP-7 caused an upregulation of the cyclin-dependent kinase inhibitor (CDKI) p21(CIP1/WAF1), and decreased the activity of Cdk2, leading to hypophosphorylation of Rb proteins. Furthermore, in order to evaluate the impact of BMP signals on prostate tumor growth, we generated the PC-3 cell lines expressing a constitutively active BMP type I receptor (constitutively active (c.a.) activin receptor-like kinase (ALK)-6) in a tetracycline (Tet)-regulated manner. Tet/doxycycline-regulated expression of c.a.ALK-6 resulted in the inhibition of in vitro cell proliferation and reduction of the size of tumors derived from the PC-3 cells subcutaneously injected into immune-deficient mice. Collectively, these findings suggest that BMP signals inhibit growth and proliferation of prostate tumor cells through induction of CDKI. Furthermore, this is the first report of a role for BMP signaling in reducing growth kinetics of androgen-insensitive prostate tumors.

Androgens↗

PubMed2004

Two alpha1-adrenergic receptor subtypes regulating the vasopressor response have differential roles in blood pressure regulation.

To study the functional role of individual alpha1-adrenergic (AR) subtypes in blood pressure (BP) regulation, we used mice lacking the alpha1B-AR and/or alpha1D-AR with the same genetic background and further studied their hemodynamic and vasoconstrictive responses. Both the alpha1D-AR knockout and alpha1B-/alpha1D-AR double knockout mice, but not the alpha1B-AR knockout mice, had significantly (p < 0.05) lower levels of basal systolic and mean arterial BP than wild-type mice in nonanesthetized condition, and they showed no significant change in heart rate or in cardiac function, as assessed by echocardiogram. All mutants showed a significantly (p < 0.05) reduced catecholamine-induced pressor and vasoconstriction responses. It is noteworthy that the infusion of norepinephrine did not elicit any pressor response at all in alpha1B-/alpha1D-AR double knockout mice. In an attempt to further examine alpha1-AR subtype, which is involved in the genesis or maintenance of hypertension, BP after salt loading was monitored by tail-cuff readings and confirmed at the endpoint by direct intra-arterial recording. After salt loading, alpha1B-AR knockout mice developed a comparable level of hypertension to wild-type mice, whereas mice lacking alpha1D-AR had significantly (p < 0.05) attenuated BP and lower levels of circulating catecholamines. Our data indicated that alpha1B- and alpha1D-AR subtypes participate cooperatively in BP regulation; however, the deletion of the functional alpha1D-AR, not alpha1B-AR, leads to an antihypertensive effect. The study shows differential contributions of alpha1B- and alpha1D-ARs in BP regulation.

Animals↗

PubMed2004

Endothelial dysfunction and hypercontractility of vascular myocytes are ameliorated by fluvastatin in obese Zucker rats.

To study the mechanisms of vascular dysfunction in diabetes mellitus, we examined the responses of the aorta to adrenomedullin (AM) and ANG II in obese Zucker (OZ), lean Zucker (LZ), and OZ rats administered fluvastatin (OZ + Flu). AM-induced endothelium-dependent vasorelaxation was impaired in OZ rats compared with LZ rats, and fluvastatin restored AM-induced, endothelium-dependent vasorelaxation (%Deltatension at 10(-7) mol/l AM; LZ, -85.1 +/- 3.1%; OZ, -50.7 +/- 2.5%; OZ + Flu, -75.6 +/- 2.7%). Expression of endothelial nitric oxide synthase (eNOS) and Akt phosphorylation in response to AM (10(-7) mol/l) were also diminished in OZ rats. Fluvastatin restored the eNOS expression and Akt phosphorylation [eNOS expression (relative intensity): LZ, 2.3 +/- 0.4; OZ, 1.0 +/- 0.2; OZ + Flu, 1.8 +/- 0.3; Akt phosphorylation (relative intensity): LZ, 2.3 +/- 0.2; OZ, 1.0 +/- 0.3; OZ + Flu, 1.9 +/- 0.2]. ANG II-induced vasoconstriction was enhanced in the aortic rings of OZ rats compared with LZ rats, and this enhanced vasoconstriction was partially normalized by fluvastatin and was abolished when the aorta of OZ rats was preincubated with the Rho kinase inhibitor Y-27632. GTPgammaS-induced contraction of permeabilized aortic smooth muscle cells, which is an indicator of the Rho-dependent Ca(2+) sensitization of contraction, was enhanced in OZ rats compared with LZ rats, and this enhanced contraction was suppressed in OZ + Flu rats. These results suggested that endothelium-dependent vasorelaxation was impaired, Ca(2+) sensitization of contraction was augmented in blood vessels of OZ rats and that fluvastatin restored vascular function by activating the Akt-dependent pathway and inhibiting the Rho-dependent pathway.

Adrenomedullin↗

PubMed2004

14-3-3sigma is down-regulated in human prostate cancer.

The 14-3-3sigma is a negative regulator of the cell cycle, which is induced by p53 in response to DNA damage. It has been characterized as an epithelium-specific marker and down-regulation of the protein has been shown in breast cancers, suggesting its tumor-suppressive activity in epithelial cells. Here we demonstrate that 14-3-3sigma protein is down-regulated in human prostate cancer cell lines, LNCaP, PC3, and DU145 compared with normal prostate epithelial cells. Immunohistochemical analysis of primary prostate cells shows that the expression of 14-3-3sigma protein is epithelial cell-specific. Among prostate pathological specimens, > 95% of benign hyperplasia samples show significant and diffuse immunostaining of 14-3-3sigma in the cytoplasm whereas < 20% of carcinoma samples show positive staining. In terms of mechanisms for the down-regulation of 14-3-3sigma in prostate cancer cells, hypermethylation of the gene promoter plays a causal role in LNCaP cells as 14-3-3sigma mRNA level was elevated by 5-aza-2'-deoxycytidine demethylating treatment. Intriguingly, the proteasome-mediated proteolysis is responsible for 14-3-3sigma reduction in DU145 and PC3 cells, as 14-3-3sigma protein expression was increased by treatment with a proteasome inhibitor MG132. Furthermore, tumor necrosis factor-related apoptosis-inducing ligand enhances 14-3-3sigma gene and protein expression in DU145 and PC3 cells. These data suggest that 14-3-3sigma expression is down-regulated during the neoplastic transition of prostate epithelial cells.

14-3-3 Proteins↗

PubMed2004

Keratinocyte-specific POU transcription factor hSkn-1a represses the growth of cervical cancer cell lines.

The POU transcription factor human Skn-1a (hSkn-1a) specifically promotes the proliferation of keratinocytes and enhances their differentiation. We examined the effects of hSkn-1a on cervical cancer cell lines of epithelial origin, in which the differentiation program is interrupted. From HeLa/Tet-On, a clone that can be induced to make hSkn-1a by doxycycline (HeLa/hSkn-1a) was prepared and characterized. Shortly after the induction, the cells expressed cytokeratin 10 (K10), a major marker protein in differentiating keratinocytes. While maintained for several days in the presence of doxycycline, the HeLa/hSkn-1a cells showed a slightly prolonged time of population doubling, the occasional appearance of flat cells with lowered DNA synthesis, and a low level of apoptotic DNA fragmentation. In SiHa and HeLa S3 cultures, K10 mRNA and apoptotic DNA fragmentation were detected at 48 h after infection with an adenoviral vector capable of expressing hSkn-1a. A colony inhibition assay showed that the growth of HeLa S3, SiHa, CaSki, and C-33A cells was repressed, as seen from the decreased number and average size of the drug-resistant colonies at 2 or 3 weeks after transfection with a plasmid that can express hSkn-1a and neomycin resistance gene. These results suggest that the expression of hSkn-1a represses the growth of the cervical cancer cells through the partial resumption of the differentiation pathway followed by slow suppression of cell replication and apoptosis.

Apoptosis↗

PubMed2004

Promotion of carcinogenesis and oxidative stress by dietary cholesterol in rat prostate.

The association between prostate cancer risk and dietary fat consumption is well documented and explained partly by accelerated lipid peroxidation. We explored the possible effects of high dietary cholesterol on carcinogenesis and oxidative stress in the prostate of ACI/Seg rats. The rats develop prostate cancer spontaneously late in the life, providing an appropriate model to explore prolonged dietary conditions. Two groups of 20-week-old male rats, 28 each, were fed either a basal diet or a basal diet supplemented with 1% cholesterol (high cholesterol diet), and killed at 100 weeks of age. Rats on the high cholesterol diet developed adenocarcinoma in the ventral prostate more frequently (26 versus 4%, P = 0.023). In the repeat study, 26 rats each were treated similarly and killed at 80 weeks for histology and oxidative stress assay. Oxidative stress was assessed by measuring the plasma and intra-prostatic levels of vitamin E, vitamin C, uric acid and the oxidized and reduced forms of coenzyme Q(9). The relative amount of oxidized form of coenzyme Q(9) is a sensitive marker of oxidative stress. Rats on the high cholesterol diet demonstrated a higher incidence of atypical prostatic hyperplasia (24 versus 4%, P = 0.049). Also, the prostate showed a 2-fold increase (203% of the control) in the relative amounts of the oxidized form of coenzyme Q(9) and reciprocal reduction of vitamin C (9.5% of the control) and uric acid (46% of the control) levels (P < 0.01), with a minimal change in vitamin E. The plasma levels of these compounds were not affected by dietary conditions. These results indicated that long-term feeding of a 1% cholesterol diet promoted carcinogenesis and tissue oxidative stress in rat prostate. The role of dietary fat and oxidative stress in prostate carcinogenesis needs further investigation.

Animals↗

PubMed2004

Engineered FGF-2 expression induces glandular epithelial hyperplasia in the murine prostatic dorsal lobe.

OBJECTIVE: It is known that androgens and stromal-epithelial interactions are required for the formation and growth of the prostate. FGF-2 is overexpressed in prostatic stromal cells in benign prostatic hypertrophy (BPH)/prostate cancer. This supports the paracrine/autocrine growth of prostatic epithelial/stromal cells in the pathogenesis of BPH and invasive prostate cancer. METHODS: We established transgenic mice expressing FGF-2 under the control of a short rat probasin promotor. FGF-2 transgenic founder mice expressing FGF-2 in the prostate were infertile. Thus, male founder mice were sacrificed for histological analysis. RESULTS: FGF-2 was expressed in epithelial cells in glands of the dorsal, lateral, and ventral prostatic lobes of two FGF-2 transgenic founder mice, but not in the anterior lobe of transgenic mice or in any lobe of non-transgenic control littermates. Acinar epithelial glands in dorsal prostatic lobes of FGF-2 transgenic mice expressing FGF-2 were more dense and showed simple papillary hyperplasia of epithelial cells compared with those of control littermate mice. Glandular and luminal enlargement without epithelial growth was observed in the ventral lobe of FGF-2 transgenic mice compared with the controls. CONCLUSION: In conclusion, FGF-2 transgenic mice under the control of rat probasin promoter showed simple epithelial hyperplasia in glands of the prostatic dorsal lobe and glandular enlargement without epithelial growth in the prostatic ventral lobe.

Animals↗

PubMed2004

Regional distribution of two related Northeast Asian genotypes of JC virus, CY-a and -b: implications for the dispersal of Northeast Asians.

JC virus (JCV) is a useful marker to trace human dispersal. Two genotypes of JCV (MY and CY) are mainly distributed in Northeast Asia. The population history of people carrying MY has been studied in some detail but that of people carrying CY remains poorly understood. To gain insights into the population history of Northeast Asians carrying CY we analyzed the genetic variation in CY isolates. We constructed a neighbor-joining phylogenetic tree from 28 complete CY DNA sequences: on the resultant tree the CY DNA sequences diverged into two clades, designated CY-a and -b, each clustered with a high bootstrap probability. The split into CY-a and -b was estimated to have occurred about 10 000 years ago, based on K(s) values (synonymous substitutions per synonymous site) and the suggested rate of synonymous nucleotide substitutions. Comparison of the 28 complete CY sequences revealed six nucleotide mismatches between CY-a and -b, one of which showed a restriction fragment length polymorphism (RFLP). We then PCR-amplified a region of the genome containing this polymorphic site from many CY isolates in various Northeast Asian populations and classified the isolates into CY-a or -b according to the RFLP analysis. CY-a was more abundant than CY-b in various Chinese and Japanese populations but CY-b was more abundant than CY-a in South Koreans. On the basis of the present findings we inferred the population history in East Asians carrying CY.

Asia↗

PubMed2004

Detection of the archetypal regulatory region of JC virus from the tonsil tissue of patients with tonsillitis and tonsilar hypertrophy.

The regulatory regions of JC virus (JCV) DNAs in the brain of patients with progressive multifocal leukoencephalopathy (PML) (designated as PML-type regulatory regions) are hypervariable, whereas those in the urine and renal tissue of individuals without PML have the same basic structure, designated as the archetype. It is thought that JCV strains with the archetypal regulatory region circulate in the human population. Nevertheless, Monaco et al (J Virol 70: 7004-7012, 1996) reported that PML-type regulatory regions occur in human tonsil tissue. The purpose of this study is to confirm their findings. Using nested polymerase chain reaction (PCR), the authors detected the regulatory region of JCV DNA in the tonsil tissue from 14 (44%) of 32 donors with tonsillitis and tonsilar hypertrophy. Sequencing of the detected regulatory regions indicated that they were identical with the archetypal regulatory regions detected previously or, in a few cases, slightly deviated from the archetype. This finding suggests not only that tonsil tissue is the potential site of initial JCV infection but also that archetypal JCV strains circulate in the human population.

Adult↗