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Tadaichi Kitamura

Publications and source records attributed to Tadaichi Kitamura.

At least 37 records · Page 2Linked to original sources

Acute pericarditis as a result of unusual metastasis of the visceral pleura in a patient with testicular seminoma.

A 30-year-old man with a left testicular swelling was referred to our hospital. We performed a left high orchiectomy based on a diagnosis of clinical stage II testicular cancer. Pathological specimens of the left testis showed seminoma. The patient underwent three courses of combined chemotherapy. The retroperitoneal lymph nodes were dissected and there were no viable cancer cells. Twelve years later a right testicular tumor was discovered. The patient underwent a right high orchiectomy. Pathological specimens of the testis showed seminoma, and the patient was treated with prophylactic irradiation. One year after discharge a metastasis was found at a left supraclavicular fossa. The patient was treated with combined chemotherapy and irradiation. Six months after the treatment he complained of dyspnea. We diagnosed the condition as pleuritis carcimatosa. Two days after irradiation to the left thorax the patient suffered a sudden and fatal cardiac arrest. Autopsy survey revealed pericarditis as a result of a direct invasion of visceral pleural metastasis.

Adult↗

Tubulovillous adenoma developing after urinary reconstruction using ileal segments.

A case of tubulovillous adenoma arising in an augmented bladder is described. Ureteroileal substitution and ileocystoplasty was performed when the patient was 18 years old. She noticed gross hematuria 44 years after the surgery. Cystoscopy revealed a non-papillary multiple tumor at the site of ileovesical anastomosis and transurethral resection biopsy was performed. Histopathological examination revealed a tubulovillous adenoma. A tubulovillous adenoma developing at the augmented bladder is rare. To our knowledge, this is the second case in which a tubulovillous adenoma developed in an augmented bladder.

Adenoma, Villous↗

Predictors of seminal vesicle invasion before radical prostatectomy.

AIM: To predict whether or not seminal vesicle invasion is present before radical prostatectomy, the relationships between clinical parameters and seminal vesicle invasion were analyzed. METHODS: A review was conducted of 187 patients who had been clinically diagnosed with stages A(2), B(0), B(1), B(2) or C prostate cancer and who had undergone radical prostatectomy without neoadjuvant therapy. The parameters analyzed for potential predictors of seminal vesicle invasion before radical prostatectomy included age, clinical stage, serum prostate-specific antigen (PSA) level at biopsy, tumor differentiation of biopsy specimens and percentage of cancer positive cores by biopsy. For percentage of cancer positive cores by biopsy, 143 of 187 patients who underwent transrectal sextant biopsy or more than six transrectal ultrasound guided core biopsies were evaluated. These parameters were subjected to univariate and multivariate logistic regression analyses to identify predictors for seminal vesicle invasion. RESULTS: The median age was 66.8 years (range 51-77 years). Of 187 patients, 27 (14.4%) had seminal vesicle invasion confirmed pathologically. There were significant differences in all parameters except for age between patients with positive and negative seminal vesicle invasion on univariate analysis. Multivariate analysis revealed that serum PSA level, tumor differentiation of biopsy specimens and percentage of cancer positive cores were significant independent predictors of seminal vesicle invasion. CONCLUSIONS: The results showed serum PSA level, tumor differentiation of biopsy specimens and percentage of cancer positive cores by biopsy before radical prostatectomy may be useful predictors for seminal vesicle invasion.

Aged↗

Neutralization of interleukin-2 retards the growth of mouse renal cancer.

OBJECTIVE: To examine the significance of the thymus and the neutralization of interleukin-2 (IL-2) in treating renal cancer, as the involvement of immunoregulatory cells in tumour development in vivo is well known, naturally occurring CD25+ CD4+ T cells possess potent immunoregulatory functions, and they are of thymic origin dependent on IL-2. MATERIALS AND METHODS: We first tested activity against mouse renal cell carcinoma (RENCA) cells by adoptively transferring splenocytes of euthymic Balb/c mice depleted of CD25+ cells into athymic Balb/c nude mice bearing established macroscopic RENCA tumours. Second, we tested the anti-RENCA activity in euthymic mice bearing macroscopic RENCA tumours by neutralizing IL-2. RESULTS: The intravenous administration of CD25+ cell-depleted splenocytes of euthymic Balb/c mice initiated the retardation of macroscopic RENCA tumours subcutaneously established in athymic Balb/c mice. The tumour site showed massive lymphocyte infiltration of mainly CD4+ T cells. By eliminating either the CD4+ cells, CD8+ cells, or natural killer (NK) cells with antibodies after the adoptive transfer of CD25+ cell-depleted splenocytes of euthymic Balb/c mice, macroscopic RENCA tumour retardation was abrogated. The growth of macroscopic RENCA tumour established in euthymic Balb/c mice was also retarded with IL-2 neutralization alone by anti-IL-2 monoclonal antibody (mAb), as well as co-administration of anti-IL-2 mAb and anti-CD25 mAb compared with that of the controls given vehicle. After tumour inoculation, peri- and intratumoral infiltration of CD4+ and CD8+ T cells was very prominent in RENCA tumours in hosts given anti-IL-2 mAb, regardless of the administration of anti-CD25 mAb. Two x 10(5) units of recombinant human IL-2 reverted the retardation of RENCA tumour growth caused by the anti-IL-2 mAb. IL-2 neutralization alone in euthymic Balb/c mice with no tumour inoculation did not suppress splenic CD25+ CD4+ T cells. CONCLUSION: Both the intravenous administration of CD25+ cell-depleted splenocytes of euthymic Balb/c mice into athymic Balb/c nude mice and IL-2 blocking with anti-IL-2 mAb in euthymic Balb/c mice retarded the growth of macroscopic RENCA tumours in vivo.

Animals↗

Disruption of spermatogenic cell adhesion and male infertility in mice lacking TSLC1/IGSF4, an immunoglobulin superfamily cell adhesion molecule.

TSLC1/IGSF4, an immunoglobulin superfamily molecule, is predominantly expressed in the brain, lungs, and testes and plays important roles in epithelial cell adhesion, cancer invasion, and synapse formation. We generated Tslc1/Igsf4-deficient mice by disrupting exon 1 of the gene and found that Tslc1(-/-) mice were born with the expected Mendelian ratio but that Tslc1(-/-) male mice were infertile. In 11-week-old adult Tslc1(-/-) mice, the weight of a testis was 88% that in Tslc1(+/+) mice, and the number of sperm in the semen was approximately 0.01% that in Tslc1(+/+) mice. Histological analysis revealed that the round spermatids and the pachytene spermatocytes failed to attach to the Sertoli cells in the seminiferous tubules and sloughed off into the lumen with apoptosis in the Tslc1(-/-) mice. On the other hand, the spermatogonia and the interstitial cells, including Leydig cells, were essentially unaffected. In the Tslc1(+/+) mice, TSLC1/IGSF4 expression was observed in the spermatogenic cells from the intermediate spermatogonia to the early pachytene spermatocytes and from spermatids at step 7 or later. These findings suggest that TSLC1/IGSF4 expression is indispensable for the adhesion of spermatocytes and spermatids to Sertoli cells and for their normal differentiation into mature spermatozoa.

Animals↗

Extracellular matrix dermatopontin modulates prostate cell growth in vivo.

Dermatopontin is a tyrosine-rich acidic extracellular matrix protein of 22 kDa with possible functions in cell-matrix interactions and matrix assembly. We have previously isolated mRNAs expressed in hormone-refractory, but not in hormone-sensitive, mouse mammary cancer by comparing the mRNAs expressed in either tumor. A partial mRNA sequence isolated was later proven to be a part of mouse dermatopontin mRNA sequence. Transfectants of mouse dermatopontin cDNA into PC-3 human prostate cancer cells enhanced tumor growth when those were implanted subcutaneously in nude mice compared with the controls. Those transfectants showed a prominent stroma compared with the controls. Localization of the targets of a fusion protein of mouse dermatopontin and alkaline phosphatase was in the stroma of the PC-3 tumor tissues, but not in the tumor cells themselves. Additionally, we have established mouse dermatopontin transgenic mice under the control of the rat probasin promoter. The prostatic dorsal lobes of dermatopontin transgenic mouse showed prostate intra-epithelial neoplasia at the age of 11 months, but the control littermates did not. Epithelium of other prostatic lobes was not markedly different from that of the controls. In conclusion, dermatopontin may be involved in the pathogenesis and growth of the prostate cancer.

Animals↗

[Prostate cancer].

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Androgen Antagonists↗

Ghrelin improves renal function in mice with ischemic acute renal failure.

Growth hormone and IGF-1 have been suggested to have tissue-protective effects. Ghrelin is a stomach-derived growth hormone secretagogue. The effects of ghrelin on ischemia/reperfusion-induced renal failure in mice were examined. Ischemic acute renal failure was induced by bilateral renal artery clamping for 45 min and reperfusion for 24 h. Ghrelin (100 microg/kg mouse) or vehicle was injected subcutaneously six times before surgery and three times after surgery every 8 h. Twenty-four hours after reperfusion, the right kidney was isolated and perfused. Acetylcholine (ACh)- and adrenomedullin-induced endothelium-dependent vasorelaxation of renal vessels significantly improved in ghrelin-pretreated mice (%Delta renal perfusion pressure by 10(-7) M ACh -63.5 +/- 3.7 versus -41.2 +/- 5.5%; P < 0.05). This change was associated with significant increases of nitric oxide release in the kidneys of ghrelin-treated mice (10(-7) M ACh 35.5 +/- 5.8 versus 16.9 +/- 3.5 fmol/g kidney per min; P < 0.05). Serum concentration of urea nitrogen (53 +/- 7 versus 87 +/- 15 mg/dl; P < 0.05) and renal injury score were significantly lower in the ghrelin group (2.5 +/- 0.8 versus 5.3 +/- 1.5; P < 0.01). Tubular apoptotic index was significantly lower in the ghrelin group (5 +/- 5 versus 28 +/- 4; P < 0.05). Furthermore, the survival rate after the 60-min ischemic period was higher in the ghrelin group (80 versus 20%; P < 0.05). Ghrelin treatment significantly increased the serum level of IGF-1. However, such renal protective effects of ghrelin on ischemia/reperfusion injury were not observed in insulin receptor substrate-2 knockout mice. These results suggest that ghrelin may protect the kidneys from ischemia/reperfusion injury and that this effect is related to an improvement of endothelial function through an IGF-1-mediated pathway.

Acute Kidney Injury↗

A quantitative matrigel assay for assessing repopulating capacity of prostate stem cells.

Homeostasis of prostate tissue is maintained by stem cells, although such cells have not been well characterized. Here, we report establishment of such a method using matrigel. Matrigel containing a single-cell suspension from adult prostatic cells was subcutaneously grafted into the flank of nude mice. Prostatic duct-like structures derived from donor tissue were observed in the gel 2 weeks after transplantation. Luminal and basal cells observed in the gel expressed several markers characteristic of prostatic and/or epithelial cells. When a mixture with both EGFP-positive and negative prostate cells was transplanted, prostatic ducts consisted of either EGFP-positive or negative cells and chimeric patterns were rarely observed, suggesting that ducts were reconstituted from a single cell. Stem cell number and function were also evaluated by competition with control cells. Overall this method revealed that cells localized in the proximal portion in prostate ducts had higher reconstitution capacity than those in the distal portion. We conclude that prostate stem/progenitor cells exist and that our method is applicable to analysis of prostate stem cells, epithelial mesenchyme interactions, and prostate cancer stem cells.

Animals↗

Characterization of the VP1 loop mutations widespread among JC polyomavirus isolates associated with progressive multifocal leukoencephalopathy.

Recently, we found that JC polyomavirus (JCPyV) associated with progressive multifocal leukoencephalopathy (PML) frequently undergoes amino acid substitutions (designated VP1 loop mutations) in the outer loops of the major capsid protein, VP1. To further characterize the mutations, we analyzed the VP1 region of the JCPyV genome in brain-tissue or cerebrospinal fluid samples from 20 PML patients. VP1 loop mutations occurred far more frequently than silent mutations. Polymorphic residues were essentially restricted to three positions (55, 60, and 66) within the BC loop, one (123) within the DE loop, and three (265, 267, and 269) within the HI loop. The mutations at most polymorphic residues showed a trend toward a change to specific amino acids. Finally, we presented evidence that the VP1 loop mutations were associated with the progression of PML. These findings should form the basis for elucidating the biological significance of the VP1 loop mutations.

Autopsy↗

The Val158Met polymorphism of the catechol-O-methyltransferase gene is associated with the PSA-progression-free survival in prostate cancer patients treated with estramustine phosphate.

OBJECTIVE: The aim of our study is to find out the good responders for estramustine phosphate (EMP) therapy in patients with prostate cancer. We have focused on the metabolism of EMP and studied the association between a functional single-nucleotide polymorphism in the catechol-O-methyltransferase gene (Val158Met of COMT) and PSA-progression-free survival in Japanese patients with prostate cancer treated by EMP. METHODS: Seventy-two Japanese patients with previously untreated prostate cancer who were found to be eligible for low-dose EMP therapy were enrolled in the study. Genotyping of the Val158Met polymorphism of COMT was conducted by both the polymerase chain reaction-based restriction fragment length polymorphism method and TaqMan assay. RESULTS: Patients with the Val/Val genotype of COMT had a significantly higher PSA-progression-free rate as compared to those with the Val/Met or Met/Met genotype (p=0.027). The adjusted hazard ratio of biochemical PSA failure for the Val158Met genotype of COMT was 2.164 (95% CI, 1.111 to 5.525). CONCLUSIONS: The Val158Met polymorphism of COMT is associated with the PSA-progression-free rate of EMP-treated patients in prostate cancer.

Aged↗

Estrogen receptor-binding fragment-associated antigen 9 is a tumor-promoting and prognostic factor for renal cell carcinoma.

The estrogen receptor-binding fragment-associated antigen 9 (EBAG9) has been identified as a primary estrogen-responsive gene in human breast cancer MCF7 cells. A high expression of EBAG9 has been observed in invasive breast cancer and advanced prostate cancer, suggesting a tumor-promoting role of the protein in malignancies. Here we show that intratumoral (i.t.) administration of small interfering RNA against EBAG9 exerted overt regression of tumors following s.c. implantation of murine renal cell carcinoma (RCC) Renca cells. Overexpression of EBAG9 did not promote the proliferation of culture Renca cells; however, the inoculated Renca cells harboring EBAG9 (Renca-EBAG9) in BALB/c mice grew faster and developed larger tumors compared with Renca cells expressing vector alone (Renca-vector). After renal subcapsular implantation, Renca-EBAG9 tumors significantly enlarged compared with Renca-vector tumors in BALB/c mice, whereas both Renca-EBAG9 and Renca-vector tumors were developed with similar volumes in BALB/c nude mice. No apparent difference was observed in specific cytotoxic T-cell responses against Renca-EBAG9 and Renca-vector cells; nonetheless, the number of infiltrating CD8+ T lymphocytes was decreased in Renca-EBAG9 subcapsular tumors. Furthermore, immunohistochemical study of EBAG9 in 78 human RCC specimens showed that intense and diffuse cytoplasmic immunostaining was observed in 87% of the cases and positive EBAG9 immunoreactivity was closely correlated with poor prognosis of the patients. Multivariate analysis revealed that high EBAG9 expression was an independent prognostic predictor for disease-specific survival (P = 0.0485). Our results suggest that EBAG9 is a crucial regulator of tumor progression and a potential prognostic marker for RCC.

Adult↗

Genetic diversity of JC virus in the Saami and the Finns: implications for their population history.

The JC virus (JCV) genotyping method was used to gain insights into the population history of the Saami and the Finns, both speaking Finno-Ugric languages and living in close geographic proximity. Urine samples from Saami and Finns, collected in northern and southern Finland, respectively, were used to amplify a 610-bp JCV-DNA region containing abundant type-specific mutations. Based on restriction site polymorphisms in the amplified fragments, we classified JCV isolates into one of the three superclusters of JCV, type A, B, or C. All 15 Saami isolates analyzed and 41 of 43 Finnish isolates analyzed were classified as type A, the European type, and two samples from Finns were classified as type B, the African/Asian type. We then amplified and sequenced a 583-bp JCV-DNA region from the type A isolates of Saami and Finns. According to type-determining nucleotides within the region, we classified type A isolates into EU-a1, -a2, or -b. Most type A isolates from Saami were classified as EU-a1, while type A isolates from Finns were distributed among EU-a1, EU-a2, and EU-b. This trend in the JCV-genotype distribution was statistically significant. On a phylogenetic tree based on complete sequences, most of the type A isolates from Saami were clustered in a single clade within EU-a1, while those from Finns were distributed throughout EU-a1, EU-a2, and EU-b. These findings are discussed in the context of the population history of the Saami and the Finns. This study provides new complete JCV DNA sequences derived from populations of anthropological interest.

Adult↗

JC virus genotyping using formalin-fixed, paraffin-embedded renal tissues.

Recently genotyping of JC virus (JCV) DNA in renal tissue was reported to be useful to identify the geographic origin of unidentified cadavers. In the above study, autopsied tissue samples without storage or stored in a frozen state were used. This study examined JCV DNA sequence modifications caused by formalin-fixation, in an attempt to elucidate whether formalin-fixed, paraffin-embedded tissue samples can also be used to determine the genotypes of JCV DNA in the kidney. In four cases, a 610 bp typing region of the JCV genome was PCR-amplified from renal tissues stored for 1 year in three different states: frozen at -80 degrees C [Amaker, B.H., Chandler, F.W., Huey, L.O., Colwell, R.M., 1997. Molecular detection of JC virus in embalmed, formalin-fixed, paraffin-embedded brain tissue. J. Forensic Sci., 1157-1159], formalin-fixed, paraffin-embedded [Ault, G.S., Stoner, G.L., 1992. Two major types of JC virus defined in progressive multifocal leukoencephalopathy brain by early and late coding region DNA sequences. J. Gen. Virol. 73, 2669-2678], and soaked in 5% formalin [Baksh, F.K., Finkelstein, S.D., Swalskey, P.A., Stoner, G.L., Ryschkewitsch, C.F., Randhawa, P.R., 2001. Molecular genotyping of BK and JC virus in human polyomavirus-associated interstitial nephritis after renal transplantation. Am. J. Kidney Dis. 38 (2), 354-365]. The amplified fragments were cloned, and the resultant clones were sequenced. In frozen samples, single sequences ('original' sequences) were detected in all cases. In formalin-fixed, paraffin-embedded samples, not only the original sequences but also those with 1-6 base substitutions were detected. From formalin-soaked samples, the original sequences and those with 1-5 and 10-13 substitutions were detected. The genotyping of JCV DNA was not hampered by the presence of 1-6 substitutions, but a shift in JCV genotypes was observed in sequences with 10-13 substitutions. Thus, it was concluded that the genotypes of JCV DNA in the kidney can be determined only with specimens stored in a frozen state or formalin-fixed for a short time.

Adult↗

Correlation between vasoconstrictor roles and mRNA expression of alpha1-adrenoceptor subtypes in blood vessels of genetically engineered mice.

We examined the contribution of each alpha(1)-adrenoceptor (AR) subtype in noradrenaline (NAd)-evoked contraction in the thoracic aortas and mesenteric arteries of mice. Compared with the concentration-response curves (CRCs) for NAd in the thoracic aortas of wild-type (WT) mice, the CRCs of mutant mice showed a significantly lower sensitivity. The pD(2) value in rank order is as follows: WT mice (8.21) > alpha(1B)-adrenoceptor knockout (alpha(1B)-KO) (7.77) > alpha(1D)-AR knockout (alpha(1D)-KO) (6.44) > alpha(1B)- and alpha(1D)-AR double knockout (alpha(1BD)-KO) (5.15). In the mesenteric artery, CRCs for NAd did not differ significantly between either WT (6.52) and alpha(1B)-KO mice (7.12) or alpha(1D)-KO (6.19) and alpha(1BD)-KO (6.29) mice. However, the CRC maximum responses to NAd in alpha(1D)- and alpha(1BD)-KO mice were significantly lower than those in WT and alpha(1B)-KO mice. Except in the thoracic aortas of alpha(1BD)-KO mice, the competitive antagonist prazosin inhibited the contraction response to NAd with high affinity. However, prazosin produced shallow Schild slopes in the vessels of mice lacking the alpha(1D)-AR gene. In the thoracic aorta, pA(2) values in WT mice for KMD-3213 and BMY7378 were 8.25 and 8.46, respectively, and in alpha(1B)-KO mice they were 8.49 and 9.13, respectively. In the mesenteric artery, pA(2) values in WT mice for KMD-3213 and BMY7378 were 8.34 and 7.47, respectively, and in alpha(1B)-KO mice they were 8.11 and 7.82, respectively. These pharmacological findings were in fairly good agreement with findings from comparison of CRCs, with the exception of the mesenteric arteries of WT and alpha(1B)-KO mice, which showed low affinities to BMY7378. We performed a quantitative analysis of the mRNA expression of each alpha(1)-AR subtype in these vessels in order to examine the correlation between mRNA expression level and the predominance of each alpha(1)-AR subtype in mediating vascular contraction. The rank order of each alpha(1)-AR subtype in terms of its vasoconstrictor role was in fairly good agreement with the level of expression of mRNA of each subtype, that is, alpha(1D)-AR > alpha(1B)-AR > alpha(1A)-AR in the thoracic aorta and alpha(1D)-AR > alpha(1A)-AR > alpha(1B)-AR in the mesenteric artery. No dramatic compensatory change of alpha(1)-AR subtype in mutant mice was observed in pharmacological or quantitative mRNA expression analysis.

Adrenergic alpha-Antagonists↗

Xanthoma of the urinary bladder.

A 55-year-old male presented with asymptomatic macroscopic hematuria. A diagnosis of xanthoma of the urinary bladder was made histologically. Xanthoma of the urinary bladder is a rare condition. Its etiology, diagnosis and treatment are discussed.

Biopsy↗

Combination chemotherapy of docetaxel, ifosfamide and cisplatin (DIP) in patients with metastatic urothelial cancer: a preliminary report.

OBJECTIVE: The aim of this study was to evaluate the efficacy and toxicity of a new combination chemotherapy of docetaxel, ifosfamide and cisplatin (DIP) in the treatment of metastatic urothelial cancer. METHODS: Fourteen patients (nine male and five female; aged 59-82 years) with metastatic urothelial carcinoma, including five patients who have a history of methotrexate, vinblastine, doxorubicin and cisplatin (MVAC) chemotherapies, received the combination of docetaxel 60 mg/m(2) on day 1, and ifosfamide 1.0 g/m(2) and cisplatin 20 mg/m(2) on days 2-6 and repeated every 21 days, to a maximum of six cycles. Eligibility criteria included performance status (World Health Organization) 0-3; normal bone marrow and liver function; and no symptomatic peripheral neuropathy. RESULTS: Ten of the 14 patients (72%) demonstrated a partial response (PR), with durations of response ranging from 3 to 12 months [median 6.5 months; 95% confidence interval (CI), 4.1-8.7 months]. The response rate of the five patients with MVAC-refractory cancer was 80% with median duration of response 5.5 months, comparable with that of the cases without previous MVAC therapies. Grade 3-4 granulocytopenia occurred in 10 cases (71%), resulting in three episodes (21%) of febrile neutropenia. Grade 3 thrombocytopenia was observed in five cases (36%). No toxic death was observed. Grade 2 peripheral neuropathy was identified in one case. CONCLUSIONS: This pilot study demonstrated that DIP is an effective regimen for the treatment of metastatic urothelial cancer, and warrants further investigation.

Aged↗