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Y Tomita

Publications and source records attributed to Y Tomita.

At least 19 recordsLinked to original sources
PubMed2006

Absence of Bcl-2 and Fas/CD95/APO-1 predicts the response to immunotherapy in metastatic renal cell carcinoma.

Immunotherapy is the only available treatment for metastatic renal cell cancer (RCC), but the response rate is only about 20% and the treatment is occasionally associated with severe adverse effects. Thus, the selection of patients with a high susceptibility to immunotherapy is needed; however, there is no promising molecular marker that can predict the response to immunotherapy for RCC. This study was carried out to elucidate the potential role of apoptosis-related molecules Bcl-2 and Fas, as well as apoptotic and proliferating indexes (AI, PI) as predictors of the susceptibility of metastatic RCC to immunotherapy. Immunohistochemical examination of tumour tissues from 40 patients with metastatic RCC undergoing postoperative immunotherapy after radical nephrectomy was performed. Patients with progressive disease (PD) after immunotherapy presented with decreased survival (P=0.006). Progressive disease correlated with higher PI in the primary lesion (P=0.0087). All primary tumours of CR or PR patients were negative for Bcl-2, whereas among NC+PD patients, 40.6% were positive for Bcl-2 (P=0.0373). Patients in whom the primary tumours were both Bcl-2- and Fas-negative showed significantly better responses to immunotherapy in comparison with the remaining group (P=0.0022). The Bcl-2 and Fas status of the primary lesion may become useful criteria for the selection of patients with metastatic RCC for immunotherapy.

Adult↗
PubMed2006

Growth hormone therapy and scoliosis in patients with Prader-Willi syndrome.

Growth hormone (GH) therapy for short stature in patients with Prader-Willi syndrome (PWS) has started worldwide, and various favorable effects have been reported. However, the possibility of progression of scoliosis arises as a new problem of the GH therapy. In this study, we analyzed whether 72 patients who have been followed up in our hospital have such a problem. They included 46 males and 26 females (41 patients with the GH therapy and 31 without it) aged from one to 49 years. Consequently, 33 (45.8%) of 72 patients had scoliosis with the Cobb angle of >10 degrees. Twenty (48.8%) of forty-one patients who received a GH therapy and 13 (41.9%) of 31 patients without the therapy had scoliosis, the frequency of scoliosis between the two groups showing no statistical difference (P = 0.56). Height velocity of scoliotic and non-scoliotic patients during the first year of the therapy was 8.59 +/- 1.92 and 10.70 +/- 2.54 cm, respectively, showing a significant difference (P < 0.001). This shows that accelerated height velocity may not induce scoliosis. Comparison of starting age of a GH treatment revealed that non-scoliotic patients received the therapy earlier than scoliotic patients (P = 0.021). Among 20 scoliotic patients who received the GH therapy, the degree of scoliosis progressed during the therapy in six patients, improved in three and fluctuated in one. Many patients showed progression of scoliosis with age irrespective of the use of GH, and some patients improved their scoliosis during the GH therapy. These findings showed that a GH therapy increases height velocity of PWS patients but does not necessarily develop scoliosis, and early start of the therapy may not be an exacerbating factor of scoliosis.

Adolescent↗
PubMed2006

Role of DNA methylation for expression of novel stem cell marker CDCP1 in hematopoietic cells.

CDCP1, a novel stem cell marker, is expressed in hematopoietic cell line K562 but not in Jurkat. When CDCP1 promoter was transfected exogenously, Jurkat showed comparable promoter activity with K562, suggesting that the factor to enhance transcription was present but interfered to function in Jurkat. The reporter assay and si-RNA-mediated knockdown experiment revealed that zfp67, a zinc-finger protein, enhanced CDCP1 transcription. Amount of zfp67 in Jurkat was comparable with K562, but chromatin immunoprecipitation showed that zfp67 bound to CDCP1 promoter in K562 but not in Jurkat. There are CpG sequences around the promoter of CDCP1, which were heavily methylated in Jurkat but not in K562. Addition of demethylating reagent to Jurkat induced CDCP1 expression, and increased the zfp67 binding to CDCP1 promoter. Among normal hematopoietic cells such as CD34+CD38- cells, lymphocytes and granulocytes, inverse correlation between proportion of methylated CpG sequences and CDCP1 expression level was found. Demethylation of CpG sequences in lymphocytes, in which CpG sequences were heavily methylated, induced CDCP1 expression and its expression level further increased through zfp67 overexpression. The methylation of DNA appeared to regulate the cell-type-specific expression of CDCP1 through the control of interaction between chromatin DNA and transcription factors.

Antigens, CD↗
PubMed2006

PDGF isoforms induce and maintain anagen phase of murine hair follicles.

BACKGROUND: It is known that platelet-derived growth factor (PDGF) receptors are expressed in hair follicle (HF) epithelium. OBJECTIVES: The aim of the present study was to clarify the effects of PDGF-AA and -BB on the cyclic growth of HFs. METHODS: PDGF-AA or -BB was injected into the dorsal skin of C3H mice during the second telogen phase once daily for five consecutive days, or PDGF-AA or -BB dissolved in hyaluronic acid was injected only once. In order to confirm the effects of different PDGF isoforms, anti-PDGF-AA antibody or anti-PDGF-BB antibody was injected just after each injection of PDGF-AA or -BB. In addition, anti-PDGF antibodies were injected into the skin of C3H mice during the second anagen phase once daily for 5 days. We studied expression of signaling molecules in the skin where anagen phase had been induced by PDGF injection by real-time RT-PCR. RESULTS: Both PDGF-AA and -BB injection experiments immediately induced the anagen phase of the hair growth cycle at the injection sites. The induction of anagen was interfered by anti-PDGF antibody treatment. Real-time RT-PCR using extracted RNA from the PDGF injected sites of skin samples showed upregulated expression of HF differentiation-related key signaling molecules, Sonic hedgehog (Shh), Lef-1 and Wnt5a. CONCLUSIONS: These results indicate that both PDGF-AA and -BB are involved in the induction and maintenance of the anagen phase in the mouse hair cycle. Local application of PDGF-AA and -BB might therefore prove to be an effective treatment option for alopecia associated with early catagen induction and elongated telogen phase.

Animals↗
PubMed2006

Epigenetic regulation of the expression of the novel stem cell marker CDCP1 in cancer cells.

CDCP1 is a novel stem cell marker that is expressed in several types of cancer. The mechanisms by which CDCP1 expression is regulated, and the clinical implications of this marker, have not been clarified. In this report, we examine the epigenetic regulation of CDCP1 expression in cell lines and clinical samples from patients with breast cancer. Many CpG sequences were localized around the transcription initiation site of CDCP1. These CpG motifs were found to be poorly methylated in cell lines with high levels of CDCP1 expression and heavily methylated in cell lines with low levels of CDCP1 expression. The in vitro methylation of CpG sites decreased CDCP1 promoter activity, and the addition of a demethylating reagent restored activity. In 25 breast cancer samples, an inverse correlation was noted between the CDCP1 expression level and the proportion of methylated to non-methylated CpG sites. Tumours with high-level CDCP1 expression showed higher levels of proliferation, as revealed by immunohistochemical detection of the MIB-1 antigen, than tumours with low-level CDCP1 expression. These findings indicate that the expression of CDCP1 is regulated by methylation of its promoter region in tumours. CDCP1 expression may prove to be useful in the further characterization of cancers.

Adenocarcinoma↗
PubMed2006

Application of chimerism-based drug-induced tolerance to rat into mouse xenotransplantation.

The current critical shortage of human donor organs has stimulated the feasibility of the xenogenic transplantation, such as swine to primate. We have previously reported the induction of donor-specific tolerance in MHC-disparated recipient mice by using our cyclophosphamide (CP)-induced tolerance conditioning. In this study, we examined the efficacy of our CP-induced tolerance conditioning in xenogenic transplantation model. F344 rats and B10 mice were used as donors and recipients. Recipient mice were treated with donor spleen cells, CP, Busulfan and bone marrow cells, with or without prior NK-cell depletion. Donor mixed chimerism, and the presence of donor reactive T-cell population were analysed by flow cytometry. The survival of the donor skin grafts were observed after the conditioning. Donor mixed chimerism was temporary induced but terminated at 10 weeks after treatments. Donor-specific prolongation of the skin graft survival was observed after the treatments, however, grafts were rejected in the long term. NK-cell depletion, prior to the treatments, did not affect the levels of the mixed chimerism or graft prolongation. The donor-reactive recipient T-cell population was remained the same level as the untreated mice, suggesting the failure of the induction of the central T-cell tolerance. Thus, partial efficacy of our CP-induced tolerance treatments in the rat to mice xenotransplantation was observed. Our results suggested that the additional treatments were required to establish the stable xenogenic tolerance.

Animals↗
PubMed2006

Papillomatosis in a European bison.

Five European bison (Bison bonasus) from three European zoos were shipped to the Bukovské Vrchy Hills (Slovakia) in June 2004 and kept together in an acclimatization enclosure. The European bison were released into the wild in December 2004. At that time, papillomas were found at the medial canthus of the left eye of a 12-yr-old female bison. Cutaneous papillomatosis was confirmed histologically. Negative stain transmission electron microscopic examination revealed papillomavirus in the papillomas, and papillomavirus DNA also was detected using the polymerase chain reaction with FAP59 and FAP64 primers. The amplified 413 bp DNA sequence was identical to that of BAPV2 bovine papillomavirus. This paper is the first report of papillomatosis in European bison.

Animals↗
PubMed2005

Extraskeletal mesenchymal chondrosarcoma: an imaging review of ten new patients.

OBJECTIVE: Extraskeletal mesenchymal chondrosarcoma (EMC) is a rare soft-tissue tumor that most arises in young adults. Because of its rarity, few imaging studies have been reported to date. The purpose of this study was to elucidate the imaging features of this tumor. DESIGN: We conducted a multi-institutional study in cooperation with five referral cancer centers in Japan. Imaging findings of ten new EMC cases, including conventional radiography, computed tomography (CT), and magnetic resonance imaging (MRI), performed at each institute, were reviewed along with clinical features. PATIENTS: Ten patients with EMC, who had been treated at each hospital from 1990 to 2001, participated in this study. RESULTS AND CONCLUSIONS: Soft-tissue masses with well-demarcated, dense and granular calcification were most frequently observed on plain radiographs and CT scans. T2-weighted MR images most clearly depicted a two-component structure composed of calcified and uncalcified areas, and enhanced MRI showed inhomogeneous enhancement in both areas. Although the sensitivity and specificity of these findings are unknown, they might be characteristic and have diagnostic value for this rare tumor.

Adult↗
PubMed2005

Prognostic impact of FAS/CD95/APO-1 in urothelial cancers: decreased expression of Fas is associated with disease progression.

The death receptor Fas (Apo1/CD95) and Fas ligand (FasL) system is recognised as a major pathway for the induction of apoptosis in vivo, and antiapoptosis via its blockade plays a critical role in carcinogenesis and progression in several malignancies. However, the function of Fas-FasL system in urothelial cancer (UC) has not been elucidated. We therefore investigated the expression of Fas, FasL and Decoy receptor 3 for FasL (DcR3) in UC specimens and cell lines, and examined the cytotoxic effect of an anti-Fas-activating monoclonal antibody (mAb) in vitro. Immunohistochemical examinations of Fas-related molecules were performed on 123 UC and 30 normal urothelium surgical specimens. Normal urothelium showed Fas staining in the cell membrane and cytoplasm. In UC, less frequent Fas expression was significantly associated with a higher pathological grade (P < 0.0001), a more advanced stage (P = 0.023) and poorer prognosis (P = 0.010). Fas and the absence thereof were suggested to be crucial factors with which to select patients requiring more aggressive treatment. Moreover, low-dose anti-Fas-activating mAb sensitised resistant cells to adriamycin, and this synergistic effect could be applied in the development of new treatment strategy for UC patients with multidrug-resistant tumours.

Adult↗
PubMed2005

Human papillomaviruses of the mucosal type are present in some cases of extragenital Bowen's disease.

BACKGROUND: Bowen's disease in the genital area is generally considered to be caused by mucosal high-risk human papillomaviruses (HPVs). However, the detection rate and spectrum of HPVs in extragenital Bowen's disease are various and it is not clear to what extent HPV is involved in its pathogenesis. OBJECTIVES: To assess the degree of association of HPV in extragenital cases by examining detection rates, types, quantities and localization of HPV. METHODS: A polymerase chain reaction (PCR) approach that we had previously established, which can give sensitive detection of a broad range of HPVs from cutaneous [including epidermodysplasia verruciformis-related HPVs (EV-HPVs)] to mucosal HPVs, was applied to samples from 41 patients with extragenital Bowen's disease and normal skin samples from 48 individuals. Semiquantitative L1-PCR and tyramide-based in situ hybridization (ISH) were also employed for positive cases. RESULTS: HPVs belonging to the mucosal high-risk group were detected in three patients with Bowen's disease (7%; two HPV 16 and one HPV 33), with 10(1)-10(3) copy equivalents per diploid amount of cellular DNA. They were distributed among most nuclei of tumour cells but in none of the cells of adjacent normal skin. HPVs belonging to the cutaneous group were detected in two patients (5%; HPV 27 and HPV 76) at 10(-2)-10(-3) copy equivalents, the same level as in a normal skin specimen positive for type 23 EV-HPV. No positive signals were observed by ISH. CONCLUSIONS: HPVs belonging to the mucosal high-risk group may participate in the development of extragenital Bowen's disease.

Aged↗
PubMed2005

Efficacy and limitations of cyclophosphamide-induced tolerance against alphaGal antigen.

In the present study, we have elucidated the efficacy of two cyclophosphamide (CP)-induced tolerance protocols for the induction of B-cell tolerance against Galalpha1-3Galbeta1-4GlcNAc (alphaGal) antigens. alpha1,3-galactosyltransferase-deficient (GalT-/-; H-2(b/d)) mice received with 1 x 10(8) AKR (alphaGal+/+ H-2k) spleen cells (SC) followed by 200 mg/kg CP, or alternatively followed by 200 mg/kg CP, 30 mg/kg Busulfan (BU) and 1 x 10(8) T-cell-depleted AKR bone marrow cells (BMC). The generation of both anti-alphaGal and anti-donor antibodies were completely suppressed, but normal antibody production against third party antigens was observed after BALB/c skin grafting in both groups of GalT-/- mice. In GalT-/- mice, treated with SC and CP, mixed chimerism was not observed. Cellular rejection was observed in grafted donor AKR hearts with an absence of humoral rejection, whereas humoral rejection was observed in untreated GalT-/- mice. On the other hand, long-term mixed chimerism and permanent acceptance of donor AKR skin graft and heart graft were achieved in GalT-/- mice treated with SC, CP, BU and BMC. These results demonstrate the efficacy of classical drug-induced tolerance in the induction of B-cell tolerance against alphaGal antigens. However, induction of stable mixed chimerism was required for the suppression of cellular rejection.

Animals↗
PubMed2004

Integration-plot test for peri-stimulus time histograms in human motor units.

A statistical test is proposed for peri-stimulus time histograms in human motor units for the case where a test stimulus is delivered at a constant interval after a previous discharge. This mathematically described test included the notion of the multiple comparison and thus achieved higher sensitivity than the previously proposed method. With regard to data acquisition, the interval from a sham stimulus to the next discharge was acquired as a control, and the total number of samples was set to be four times as large as that in the test situation to reduce the statistical scattering noise. A newly defined statistical object, the integration plot (timewise accumulation of the test histogram without control subtraction) was used for this statistical test. The integration plot had less noise than the cumulative sum (CUSUM) plot (1/square root(2) in theory) and thus represented the neural effect. To compare this integration-plot test with that of the CUSUM, a simulation experiment that compared two sample histograms (one of which had a faint structural change from 20 ms) was conducted. As a result, the present test succeeded in detecting the onset of the change point earlier (23 ms on average) than the CUSUM test (27 ms on average), and the detection probability was also higher (9 out of 10) than the CUSUM (6 out of 10). It was therefore confirmed experimentally that the present statistical test had higher sensitivity than that of the CUSUM proposed previously.

Adult↗
PubMed2004

New method using multi-regression analysis on evoked electromyography during movement to adjust stimulation conditions.

A new method of stimulation of the lower extremities was devised that automatically adjusts the stimulation conditions at any angle of the knee joint. An M-wave is considered to indicate the stimulation conditions, because it is the waveform that results from direct stimulation to the axon of the alpha motor neuron. The present device adjusted the stimulation intensity, using multi-regression analysis to evoke an M-wave of preset amplitude. Participants included five people without any neuromuscular impairment. The subjects sat on a chair during the test. The hip joint was fixed at a flexion angle of 90 degrees, and the ankle joint was fixed at the midposition. During passive knee joint movement ranging from 0 degrees to 135 degrees, M-waves were measured. Electrodes were attached at the popliteal fossa and the patella to stimulate the tibial nerve. Ag-AgCl electrodes were put on the belly of the right soleus muscle for the M-wave measurement. The device was set to give M-waves close to the preset value, 10% Mmax. According to previous research, the allowable limit of M-wave amplitude deviations was reported to be about 5% Mmax. The M-wave amplitudes evoked by the device were in the allowable range (9.2 +/- 2.5% Mmax). The device enabled control of the M-wave amplitude over the entire range of motion of the joint. Using this device, it was possible to examine the excitability of the alpha motor neuron pool more precisely.

Adult↗
PubMed2004

Expression level of valosin-containing protein (VCP) as a prognostic marker for gingival squamous cell carcinoma.

BACKGROUND: Valosin-containing protein (VCP) is associated with anti-apoptotic function and metastasis via activation of the nuclear factor-kappaB signaling pathway. In the present study, association of VCP expression with prognosis of gingival squamous cell carcinoma (GSCC) was examined. PATIENTS AND METHODS: VCP expression in 74 patients with GSCC (34 males and 40 females) with ages ranging from 42 to 85 (median 66) years was evaluated by immunohistochemistry, in which staining intensity in tumor cells was categorized as either weaker (level 1) or equal to/stronger (level 2) than that in the endothelial cells. RESULTS: Twenty-four (32.4%) cases showed level 1 and 50 (67.6%) level 2 VCP expression. Patients with level 1 GSCC showed a significantly better 5-year survival rate than those with level 2 GSCC (5-year overall survival: 100% versus 84.9%, P < 0.05). Multivariate analysis revealed VCP expression level, lymph node metastasis and pT(TNM) to be independent factors for overall survival. Patients with GSCC at stages I and II showed favorable prognosis regardless of VCP expression status, whereas at stages III and IV, patients with level 1 VCP expression showed better survival rates than those with level 2 expression. CONCLUSION: Prognostic significance of VCP expression level in GSCC was demonstrated.

Adenosine Triphosphatases↗
PubMed2004

Detection of human papillomavirus type 56 DNA, belonging to a mucous high-risk group, in hair follicles in the genital area of a woman no longer suffering from viral warts.

BACKGROUND: Human papillomaviruses (HPVs) parasitize human epithelium, but it is not clear where they reside when they do not cause apparent infection. Hair follicles are important candidates as reservoirs. OBJECTIVES: A patient reported previously by us as having perianal warts caused mainly by HPV 56, demonstrated hair follicles in her genital area which bulged a little from the surface and appeared somewhat enlarged. We therefore examined whether DNA of HPV 56, a member of the mucous high-risk group, might be detectable in these structures. METHODS: We obtained plucked hairs and performed an examination by polymerase chain reaction and subsequent reverse-phase dot blot hybridization (PCR-RDBH) and in situ hybridization (ISH). RESULTS: Strong positive signals were obtained not only with PCR-RDBH but also with ISH. CONCLUSIONS: Hair follicles in the genital area might serve as reservoirs for HPVs belonging to the mucous high-risk group.

Adult↗