Search PubMed⌕ Search

Biomedical subjects

Tadaichi Kitamura

Publications and source records attributed to Tadaichi Kitamura.

89 records · Page 5Linked to original sources
PubMed2002

Evolution of human Polyomavirus JC: implications for the population history of humans.

The polyomavirus JC virus (JCV), the etiological agent of progressive multifocal leukoencephalopathy, is ubiquitous in the human population, infecting children asymptomatically, then persisting in the kidney. The main mode of transmission of JCV is from parents to children through long-term cohabitation. Twelve JCV subtypes that occupy unique domains in Europe, Africa, and Asia have been identified. Here, we attempted to elucidate the evolutionary relationships among JCV strains worldwide using the whole-genome approach with which a highly reliable phylogeny of JCV strains can be reconstructed. Sixty-five complete JCV DNA sequences, derived from various geographical regions and belonging to 11 of the 12 known subtypes, were subjected to phylogenetic analysis using three independent methods: the neighbor-joining, maximum parsimony, and maximum likelihood methods. The trees obtained with these methods consistently indicated that ancestral JCVs were divided into three superclusters, designated as Types A, B, and C. A split in Type A generated two subtypes, EU-a and -b, mainly containing European and Mediterranean strains. The first split in Type B generated Af2 (the major African subtype). Subsequent splits in Type B generated B1-c (a minor European subtype) and all seven Asian subtypes (B1-a, -b, -d, B2, MY, CY, and SC). Type C generated a single subtype (Af1), consisting of strains derived from western Africa. While the present findings provided a basis on which to classify JCV into types or subtypes, they have several implications for the divergence and migration of human populations.

Base Sequence↗
PubMed2002

JC virus strains indigenous to northeastern Siberians and Canadian Inuits are unique but evolutionally related to those distributed throughout Europe and Mediterranean areas.

Human polyomavirus JC virus (JCV) isolates around the world are classified into more than 10 geographically distinct genotypes (designated as subtypes). Evolutionary relationships among JCV subtypes were recently examined, and the following pattern of JCV evolution was indicated. The ancestral JCV first divided into three superclusters, designated Types A, B, and C. A split in Type A generated two subtypes, EU-a and -b, containing mainly European and Mediterranean isolates. The split in Type B generated Af 2 (the major African subtype), Bl-c (a minor European subtype), and various Asian subtypes. Type C generated a single subtype (Afl), consisting of isolates derived from western Africa. In this study, JCV isolates prevalent among northeastern Siberians and Canadian Inuits were evaluated in the context of the above-described pattern of JCV evolution. The Siberian/Arctic JCV isolates were classified as belonging mainly to Type A, based on the result of a preliminary phylogenetic analysis. We then examined, using the whole-genome approach, the phylogenetic relationships among worldwide Type A isolates. In neighbor-joining and maximum-likelihood analyses, Type A JCVs worldwide consistently diverged into three subtypes, EU-a, -b, and -c, with high bootstrap probabilities. EU-c was constructed only by northeastern Siberian isolates, derived mainly from Nanais living in the lower Amur River region, and was shown to have been generated by the first split in Type A. Most Siberian/Arctic isolates derived from Chukchis, Koryaks, and Canadian Inuits formed a distinct cluster within the EU-a subtype, with a high bootstrap probability. Based on the present findings, we discuss ancient human migrations, accompanied by Type A JCVs, across Asia and to Arctic areas of North America.

Adult↗
PubMed2002

Magnetic stimulation of the sacral roots for the treatment of urinary frequency and urge incontinence: an investigational study and placebo controlled trial.

PURPOSE: We designed an investigational study and placebo controlled trial to evaluate the efficacy of magnetic stimulation of the sacral roots for treating urinary frequency and urge incontinence. MATERIALS AND METHODS: A total of 48 women 43 to 75 years old (mean age 61) with the complaint of urinary frequency and/or urge incontinence were studied. We applied 15 Hz. repetitive magnetic stimulation of the sacral roots with 50% intensity output for 5 seconds per minute for 30 minutes. Urodynamic investigations during magnetic stimulation were performed in 11 cases to evaluate acute effects for lowering urinary tract function. Another 37 women were enrolled in a placebo controlled study to investigate short-term effects. The mean number of voids daily, mean urine volume per void, number of leaks for 3 days and quality of life score were evaluated before and 1 week after stimulation. RESULTS: Urodynamic investigations revealed apparent elevation in mean maximum urethral closure pressure plus or minus standard deviation during stimulation in all 11 cases (8.4 +/- 3.6 cm. water, p = 0.00001) and a significant increase in mean bladder capacity after stimulation (58.2 +/- 50.2 ml., p = 0.003). In the placebo controlled study all parameters significantly improved in the active stimulation group. Intergroup comparison showed that mean urine volume per void, mean number of leaks and mean quality of life score improved more significantly in the active than in the sham stimulation group (23.5 +/- 25.6 ml. versus 6.2 +/- 22.5, p = 0.04, 3.6 +/- 4.1 versus 0.4 +/- 1.4, p = 0.04 and 1.4 +/- 1.3 versus 0.4 +/- 0.8, p = 0.01, respectively). No adverse effects were noted in any patients. CONCLUSIONS: These results suggest that magnetic stimulation of the sacral roots may be useful for treating urinary frequency and urge incontinence.

Adult↗
PubMed2002

Power Doppler ultrasonography-directed prostate biopsy in men with elevated serum PSA levels: an evaluation of the clinical utility and limitations.

OBJECTIVES: To determine the utility and limitations of power Doppler ultrasonography (PDU)-directed prostate biopsy in patients with elevated serum prostate-specific antigen (PSA) levels. METHODS: A total of 108 men (mean age 67.7 years, range 50 to 86) with serum PSA levels of greater than 4.0 ng/mL were assessed using digital rectal examination (DRE), gray-scale transrectal ultrasonography (TRUS), and PDU. Prostate vasculature identified on PDU was judged using a grading system. Subsequently, these patients underwent systematic six-core transperineal biopsy and additional biopsies for positive sites on DRE, gray-scale TRUS, and PDU. RESULTS: A hypervascular site and prostate cancer on PDU was identified in 43 (40%) and 40 (37%) cases, respectively. PDU-directed and systematic six-core biopsies could independently detect 36 and 30 cancer cases, respectively. The sensitivity of PDU for cancer detection was 90%, specificity 90%, positive predictive value 84%, negative predictive value 94%, and accuracy 90%. High test performance was also observed in 53 cases with serum PSA levels of 4.1 to 10 ng/mL (sensitivity 77%, specificity 88%, positive predictive value 67%, negative predictive value 92%, and accuracy 85%). These values were superior or comparable to those of DRE and gray-scale TRUS. Inflammatory reactions and prostatic calculi were probable major causes of false-positive and false-negative results on PDU, respectively. CONCLUSIONS: PDU can identify appropriate sites for biopsy and improve the cancer detection rate. However, PDU-directed biopsy does not appear to identify prostate cancer with sufficient accuracy to omit the systematic biopsy, and combined use of these methods should be preferable.

Aged↗
PubMed2002

Dendritic cell immunotherapy for patients with metastatic renal cell carcinoma: University of Tokyo experience.

BACKGROUND: Dendritic cells (DC) are the most potent antigen-presenting cells and induce host antitumor immunity through the T-cell response. A clinical study of immunotherapy using cultured DC loaded with tumor antigen, for patients with metastatic renal cell carcinoma (RCC) was performed. METHODS: Dendritic cells were generated by culturing monocytes from peripheral blood for 7 days in the presence of granulocyte-macrophage colony-stimulating factor and interleukin-4. On day 6 the DC were pulsed with lysate from autologous tumor as the antigen and with keyhole limpet hemocyanin (KLH) as immunomodulator. The patients were given four doses of lysate-pulsed DC by intradermal injection with a 2-week interval between doses. Clinical effect and immune response were, respectively, evaluated by radiological examination and delayed-type hypersensitivity (DTH) test. RESULTS: Three patients were enrolled and the immunotherapy was well tolerated without significant toxicity. The vaccination induced a positive DTH reaction to tumor lysate in two patients and to KLH in all patients. Clinical responses consisted of one case of no change and two cases of progression of disease. However, we did not see a significant reduction of tumor volume in any case. CONCLUSION: Dendritic cell vaccination can safely induce an immunological response against RCC. Further trials are needed to fully evaluate its efficacy.

Adult↗
PubMed2002

Promoter methylation of TSLC1 and tumor suppression by its gene product in human prostate cancer.

We recently identified TSLC1, a tumor suppressor gene in human lung cancer. Gene silencing by promoter methylation has been observed frequently in adenocarcinoma of the lung, liver, and pancreas. Here, we demonstrate that TSLC1 expression is also absent or markedly reduced in 3 of 4 prostate cancer cell lines. Promoter sequences of TSLC1 were heavily methylated in PPC-1 cells that lacked TSLC1 expression, supporting the idea that promoter methylation is strongly correlated with complete loss of gene expression. Promoter sequences of TSLC1 were also methylated significantly in 7 of 22 (32%) primary prostate cancers. Hypermethylation of the promoter occurred not only in advanced tumors, but also in relatively early-stage tumors. Restoration of TSLC1 expression substantially suppressed tumor formation of PPC-1 cells in nude mice. These findings indicate that alteration of TSLC1 is involved in prostate cancer.

Animals↗
PubMed2002

Asian genotypes of JC virus in Japanese-Americans suggest familial transmission.

To examine the mode of JC virus (JCV) transmission, we collected urine samples from second- and third-generation Japanese-Americans in Los Angeles, Calif., whose parents and grandparents were all Japanese. From the urine samples of these Japanese-Americans, we mainly detected two subtypes (CY and MY) of JCV that are predominantly found among native Japanese. This finding provides support for the hypothesis that JCV is transmitted mainly within the family through long-term cohabitation.

Asian↗
PubMed2002

Habitual intake of lactic acid bacteria and risk reduction of bladder cancer.

INTRODUCTION: A kind of lactic acid bacteria, Lactobacillus casei strain Shirota, shows antitumor activity in experimental animals. One clinical trial using L. casei showed a significant decrease in the recurrence of superficial bladder cancer. So, to assess the preventive effect of the intake of L. casei, widely taken as fermented milk products in Japan, against bladder cancer, we conducted a case-control study. METHODS: A total of 180 cases (mean age: 67 years, SD 10) were selected from 7 hospitals, and 445 population-based controls matched by gender and age were also selected. Interviewers asked them 81 items. The conditional logistic regression was used to estimate adjusted odds ratios (OR). RESULTS: The OR of smoking was 1.61 (95% confidence interval: 1.10-2.36). Those of previous (10-15 years ago) intake of fermented milk products were 0.46 (0.27-0.79) for 1-2 times/week and 0.61 (0.38-0.99) for 3-4 or more times/week, respectively. CONCLUSION: It was strongly suggested that the habitual intake of lactic acid bacteria reduces the risk of bladder cancer.

Aged↗
PubMed2002

EMP combination chemotherapy and low-dose monotherapy in advanced prostate cancer.

Many chemotherapeutic regimens combined with estramustine phosphate (EMP) have been elaborated for the treatment of hormone-refractory prostate cancer over 30 years. However, older EMP-based combination chemotherapies with vinblastine, vinorelbine, doxorubicin or cyclophosphamide showed relatively low PSA response rate (25-58%) accompanied with high toxicities. On the other hand, newly developed EMP-based combination regimens with etoposide, pacitaxel, carboplatin or docetaxel demonstrated promising PSA response rate (43-77%) with moderate to severe toxicity in the rate of thromboembolic event (5-18%) and of neutropenia (9-41%). Treatment-related death was less in the latter combination group (5/615, 0.8%) than that in the former group (3/234, 1.3%). Of note, in the docetaxel combination with EMP, PSA response rate is as high as 77% with high rate (41%) of neutropenia but no treatment-related death was observed. Docetaxel combination with EMP seems to be the best regimen, though not completely justified by randomized trials, to be selected in the modern era, which will be followed by paclitaxel, carboplatin and EMP combination with PSA response rate of 71%. In addition, an interim report in 83 patients was presented. They were not consecutively enrolled but were treated on low-dose EMP monotherapy for previously untreated advanced prostate cancer in Department of Urology of Tokyo University and our 21 affiliated hospitals. Overall PSA response rate was as high as 93.4% out of 76 assessable patients. However, overall toxicity rate was abnormally high (39.5%) with drug discontinuation rate of 32.1%. The reason of low drug compliance may be attributed to gastrointestinal symptoms. To overcome the low drug compliance, appropriate patients for EMP administration should be selected by using gene analysis on the basis of sophisticated tailor-made medicine.

Aged↗
PubMed2002

[Surgical outcomes of nephron-sparing surgery for renal tumors].

PURPOSE: We retrospectively assessed the surgical outcomes of nephron-sparing surgery (NSS) for patients with renal tumors. PATIENTS AND METHODS: From 1985 to March 2001, a total of 99 NSSs were performed on 94 patients with renal tumors. The patients were divided into three groups. Group I comprised of 22 patients who underwent imperative surgeries for renal cell carcinoma (RCC). The tumors were found in 18 patients bilaterally (including 8 patients with von Hippel-Lindau disease), in 3 with solitary kidney, and in 1 with chronic renal failure. The mean +/- standard deviation of patient age and tumor diameter was 46 +/- 23 years and 36 +/- 23 mm, respectively. Twenty-three in situ NSSs were performed on 18 patients in Group I, and the remaining 4 patients were treated with 3 simultaneous operations for bilateral renal tumors with or without 2 ex vivo surgeries. Group II consisted of 49 patients who had small RCCs with the normal contralateral kidney and underwent NSSs (elective indication). The mean age and tumor diameter was 54 +/- 10 years and 28 +/- 11 mm, respectively. Group III consisted of 23 patients with non-RCC tumor (10 angiomyolipomas, 8 cystic tumors, 2 adenomas, 2 metastatic tumors, and 1 degenerative lesion), all of whom were treated with NSS. The mean age and tumor diameter was 47 +/- 14 years and 41 +/- 29 mm, respectively. RESULTS: In Group I, 3 patients died of cancer including 2 patients who had had multiple lung metastases preoperatively. The five-year tumor specific survival rate was 87.3% with a postoperative follow-up of 49 +/- 36 months. In Group II, there were few peri-operative complications or no local recurrence at follow-up of 52 +/- 38 months. A patient developed lung metastasis, which was removed surgically with no evidence of recurrence at 159 months after NSS. Postoperative renal scintigraphy on 35 patients showed well-preserved renal function of the operated kidney. Improvement in surgical techniques resulted in less-invasive surgery in 22 operations during the last 4 years. The patients of Group III were also operated uneventfully, although 1 experienced postoperative bleeding. In 12 patients with solitary kidney (11 in Group I and 1 in Group III) serum creatinine level increased transiently, decreased to 1.3 times of preoperative values within 3 months, and almost recovered at 1-year follow-up. CONCLUSION: Excellent outcomes in cancer control and preservation of renal function support the validity of nephron-sparing surgery to treat renal tumors. The candidate patients may include those with bilateral kidney tumors, tumor occuring in the solitary kidney or small renal cell carcinomas with the normal contralateral kidney. Earlier detection of small lesions and less invasive surgical techniques will facilitate a wider indication of NSS.

Adult↗
PubMed2002

Significance of nocturia in the International Prostate Symptom Score for benign prostatic hyperplasia.

PURPOSE: We studied the relationship of nocturia with the International Prostate Symptom Score in men with lower urinary tract symptoms due to benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: Baseline symptom score and the change in the score by treatment were analyzed in 219 consecutive Japanese men with BPH using basic statistics, and correlation, cluster and principal component analyses. RESULTS: The average nocturia score was the middle of that of the 7 symptoms at baseline and by far the highest after treatment. Hence, the score change was the smallest. Analysis of baseline scores demonstrated that all symptoms were the initial component in principal component analysis with individual symptom scores correlating with the total symptom score and quality of life index. However, the correlation was least for nocturia. Observations were similar when analyzing the score change by treatment. These results indicate that the nocturia score is least specific to symptoms associated with BPH or least sensitive to the therapeutic effect on symptoms. This finding may be related to the high nocturia score in the age matched control population. CONCLUSIONS: The nocturia score of the International Prostate Symptom Score behaves differently in the symptom complex of BPH in Japanese men, partially because it is most confounded by the aging factor.

Aged↗
PubMedDate not supplied

JC virus genotyping offers a new paradigm in the study of human populations.

A small DNA virus, named JC virus (JCV) and belonging to the Polyomaviridae, is attracting the attention of anthropologists worldwide, as JCV genotyping appears to be a novel means of elucidating human migrations and the origins of various ethnic groups. The basic properties of JCV, the regional distributions of JCV genotypes, and the phylogenetic relationships among various JCV genotypes are described. Then, a study is described in which the origin of the modern Japanese was extensively investigated using the JCV genotyping method. Based on JCV genotypes in neighboring areas, the origins of people who carried JCV genotypes to the Japanese Archipelago are discussed. Finally, the relationships between JCV genotypes and Y-chromosome haplogroups are examined, as genetic variation on the Y chromosome has recently been examined in detail to investigate ancient human migrations and the population structures of human groups.

Chromosomes, Human, Y↗
PubMedDate not supplied

Treatment of patients with superficial bladder cancer by intravesical instillation of anticancer drugs plus oral chemotherapy following TUR-Bt: a randomized controlled trial.

We conducted a randomized controlled trial to compare local recurrence rate after transurethral resection of superficial bladder cancer treated by either intravesical instillation of an anticancer drug alone (method A) and the intravesical instillation plus oral chemotherapy (doxifluridine, 5'-DFUR, an intermediate metabolite of capecitabine) (method B). Results between groups showed no difference in recurrence-free survival curves in 196 patients subjected to primary analysis. However, patients subjected to secondary analysis (method B, over 3 months administration of 5'-DFUR) showed a significantly better prognosis than method A (p=0.0244, Wilcoxon). Regarding correlation between thymidine phosphorylase (TP, an enzyme to convert 5'-DFUR to 5-fluorouracil) level and prognosis, method A patients showed poorer prognosis in higher TP level cases than in lower TP levels. However, there was no significant difference in prognosis between those with higher and lower TP levels. In method B patients, there was no difference in prognosis between those with higher and lower TP levels. Method A patients tended to show a slightly better prognosis than those with lower TP levels, while method B patients tended to have a slightly better prognosis with higher TP levels, but no significant difference was observed. These findings suggested 5'-DFUR showed a mild efficacy in patients with higher TP levels and that patients with higher TP levels resulted in poorer prognosis.

Administration, Intravesical↗