Biomedical subjects

Hiroshi Tsuda

Publications and source records attributed to Hiroshi Tsuda.

At least 19 recordsLinked to original sources

PubMed2006

Bmi1 cooperates with Dnmt1-associated protein 1 in gene silencing.

Polycomb group (PcG) proteins are involved in gene silencing through chromatin modifications. Among polycomb repressive complexes (PRCs), PRC1 exhibits H2A-K119 ubiquitin E3 ligase activity. However, the molecular mechanisms underlying PRC1-mediated gene silencing remain largely obscure. In this study, we found that Bmi1 directly interacts with Dnmt-associated protein 1 (Dmap1), which has been characterized to associate with the maintenance DNA methyltransferase, Dnmt1. Bmi1 was demonstrated to form a ternary complex with Dmap1 and Dnmt1 with Dmap1 in the central position. Chromatin immunoprecipitations confirmed the ternary complex formation within the context of the PRC1 at the Bmi1 target loci. Loss of Dmap1 binding to the Bmi1 target loci was tightly associated with derepressed gene expression in Bmi1-/- cells. Dmap1 knockdown exhibited the same impact as Bmi1 knockout did on the expression of Bmi1 targets, including Hox genes. Collectively, our findings suggest that Bmi1 incorporates Dmap1 in polycomb gene silencing.

Animals↗

PubMed2006

A case of polymyositis complicated with myasthenic crisis.

We report a 62-year-old woman who suffered from polymyositis (PM) complicated with myasthenic crisis. Electromyography and muscle biopsy indicated a diagnosis of PM; however, respiratory failure due to respiratory muscle weakness was seen in spite of a normal serum creatine kinase (CK) level. The positive anti-acetylcholine receptor antibody led us to the diagnosis of myasthenic crisis. PM with respiratory muscle weakness is rare. We suggest that the possibility of other neurological disorder complications should be considered when PM patients have respiratory muscle weakness out of proportion to the serum CK level.

Autoantibodies↗

PubMed2006

Differential expression of ABCF2 protein among different histologic types of epithelial ovarian cancer and in clear cell adenocarcinomas of different organs.

Previously, we reported that ABCF2 protein expression is higher in clear cell than serous histotype of ovarian adenocarcinomas and that its expression correlates with chemoresponse in patients with clear cell ovarian cancer. In this study, we examined ABCF2 protein expression in mucinous, endometrioid, and poorly differentiated type of ovarian adenocarcinomas. In addition, ABCF2 expression was evaluated in clear cell adenocarcinomas derived from different organs. A total of 335 epithelial ovarian cancers, 23 clear cell adenocarcinomas of uterine corpus, and 34 clear cell adenocarcinomas of kidney were included in this study. ABCF2 protein expression was determined by immunohistochemistry. The results showed that cytoplasmic ABCF2 expression was significantly higher in clear cell-type ovarian cancer specimens compared with other types (P < .0001). There was a close relationship between nuclear ABCF2 expression levels and age of patients with clear cell ovarian cancer. Multivariate logistic regression model also demonstrated that cytoplasmic ABCF2 expression was associated with clear cell histology (odds ratio, 5.557; 95% confidence interval, 2.694-11.462; P < .0001). In addition, both clear cell adenocarcinomas of the ovary and the uterine corpus showed significantly higher levels of ABCF2 expression, compared with those of the clear cell adenocarcinoma of the kidney (P < .0001). These data suggest that ABCF2 protein may be a candidate marker for clear cell adenocarcinomas of the ovary and the uterine corpus and may be important for the pathogenesis of these diseases.

ATP-Binding Cassette Transporters↗

PubMed2006

Endometrial thickness in Japanese women with hypertension or/and type 2 diabetes mellitus.

OBJECTIVES: The purpose of this study was: (a) to examine whether the endometrium of postmenopausal women with hypertension (HT) and/or type 2 diabetes mellitus (DM) was thicker than that of healthy controls (HC) and (b) whether endometrial thickness (ET) was associated with endometrial cancer risk factors. STUDY DESIGN: A total of 242 postmenopausal women were included in this study. Thirty women with type 2 DM, 49 women with HT, 23 women with DM and HT and 140 HCs were studied. Clinical evaluation of all women was done using TVS and endometrial cytology. RESULTS: In the 140 HCs, the mean ET of nulliparous women was larger than multiparous women (3.0 mm versus 1.6 mm, p = 0.017). However, there was no significant relationship between ET and other clinical parameters such as a history of sterility or BMI. There was no significant difference in ET amongst the four groups. The relationship between ET, age, pregnancy history, menopause age, BMI and presence of DM or HT were analyzed using stepwise multivariate analysis. There was no significant relationship between these risk factors and ET (p = 0.063). CONCLUSIONS: The risk factors such as age, pregnancy history, menopause age, BMI and presence of DM or HT were not related to ET in Japanese women.

Adult↗

PubMed2006

Immunoadsorption plasmapheresis using a phenylalanine column as an effective treatment for lupus nephritis.

Immunoadsorption plasmapheresis (IAPP) is effective for eliminating pathogenic molecules such as anti-DNA antibody (anti-DNA Ab) and immune complexes from the serum of patients with systemic autoimmune diseases. The purpose of this study was to assess patients with lupus nephritis (LN) treated by IAPP using a phenylalanine column and determine its efficacy with respect to conventional therapies. Six patients (M = 1, F = 5) with histologically proven LN associated with proteinuria and abnormal sedimentation on urinalysis were the subjects for this study. All were treated with oral corticosteroid (prednisolone 1 mg/kg/day) and IAPP (Immusorba PH - 350; 2 L of plasma twice weekly for 2 weeks). Serum anti-DNA Ab and complement, urinary protein, and creatinine clearance were measured over 6 weeks (pretreatment, before and after each of 2 IAPP sessions, and 1 and 4 weeks after the second IAPP session). Clinical efficacy of IAPP was compared with conventional pharmacotherapy regimes by conducting a retrospective review of 23 LN patients treated at our hospital using corticosteroid pulse therapy (CSPT, N = 7, intravenous methylprednisolone 500 mg/day for 3 days), intravenous cyclophosphamide pulse therapy (IVCY, N = 7), or corticosteroid monotherapy (CSMT, N = 9, oral prednisone 1 mg/kg body weight daily, for 4 weeks). Immunosuppressants and anticoagulants were not used. With IAPP, mean urinary protein excretion decreased from 2.2 +/- 1.7 g/day pretreatment to 0.4 +/- 0.6 g/day post-treatment (P < 0.001). Mean serum anti-DNA Ab also decreased from 84.0 +/- 88.1 U/mL pretreatment to 5.8 +/- 5.5 U/mL post-treatment (P < 0.05). In combination with corticosteroid therapy, IAPP would appear to be an effective and safe treatment for LN.

Adult↗

PubMed2006

Fluctuations in peripheral blood leukocyte and platelet counts and leukocyte recruitment with large volume leukocytapheresis in healthy volunteers.

Based on sporadic reports indicating that the effectiveness of leukocytapheresis (LCAP) is proportional to the number of leukocytes removed, it is anticipated that increasing the volume of blood treated, and thus the number of leukocytes removed, will improve the effectiveness of therapy. In advance of its clinical application, the possible clinical usefulness of large volumes of LCAP (pulse LCAP), which treats 5000 mL of blood rather than the usual volume of 3000 mL, was investigated in healthy subjects. As compared with conventional LCAP, pulse LCAP provided comparable safety and enabled the removal of approximately 4.7 times more neutrophils, 1.2 times more lymphocytes, and 1.6 times more monocytes. It also resulted in a more pronounced overshoot phenomenon, as well as lymphocyte and monocyte overshoot, which are not seen with conventional LCAP. The neutrophil overshoot resulted from the recruitment of leukocytes from the bone marrow neutrophil pool as well as from the circulating neutrophil pool and marginal neutrophil pool. Recruitment from the bone marrow pool involved not only recruitment of mature neutrophils but also recruitment from all stages of differentiation and proliferation, including the pluripotent stem cell (CFU-GEMM) fraction; granulocyte-monocyte precursor cell (CFU-GM) fraction; and the fraction of juvenile granulocyte precursors cells capable of cell division, from myeloblasts to myelocytes. Based on the lymphocyte and monocyte overshoot, it was inferred that cells were recruited from mucosal lymphatic tissue, in addition to the lymph nodes, spleen, thymus, and bone marrow. These phenomena might play an important role in the mechanism that underlies the effectiveness of LCAP and the increased effectiveness of pulse LCAP, and it will be necessary to work to elucidate them. Moreover, it appears that investigating the clinical efficacy of pulse LCAP in patients who do not respond to conventional LCAP would be of major significance.

Adult↗

PubMed2006

Investigation of the clinical effect of large volume leukocytapheresis on methotrexate-resistant rheumatoid arthritis.

Leukocytapheresis (LCAP) is already being used in a clinical setting for the treatment of autoimmune diseases such as inflammatory bowel disease and rheumatoid arthritis, and it has been reported to be effective. However, it is totally or partially ineffective in some patients, which has forced clinicians to rethink therapeutic strategies and concurrent treatment. With the aim of enhancing the therapeutic effect, we carried out large volume leukocytapheresis, with a throughput of 5000 mL instead of the 3000-mL throughput of conventional leukocytapheresis in nine patients with rheumatoid arthritis resistant to methotrexate treatment. Using Cellsorba, the column filled with the unwoven fabric made of the polyethylene phthalate, a leukocyte removal filter, large volume leukocytapheresis was carried out once a week for a total of five sessions. The observation period was the 12-week period following completion of treatment. The American College of Rheumatology (ACR) core set was used for assessment of efficacy. Eight weeks after completion of treatment, a 20% improvement in ACR was observed in 77.8% (7/9) of subjects, a 50% improvement in ACR was seen in 55.6% (5/9) of subjects, and a 70% improvement in ACR was observed in 22.2% (2/9) of subjects. C-reactive protein decreased gradually as treatment progressed, and a significant decrease was observed 4 weeks after completion of treatment. The fact that some subjects had an ACR70 response, few reports of which are observed in the case of conventional leukocytapheresis, and the fact that the effect continued up to 12 weeks after completion of treatment suggests that the degree and duration of the effect of large volume leukocytapheresis might be longer than those of conventional leukocytapheresis.

Aged↗

PubMed2006

Comparison of osteopontin expression in endometrioid endometrial cancer and ovarian endometrioid cancer.

This study compared the DNA, RNA, and protein levels of osteopontin (OPN) in endometrioid endometrial cancer (EEC) and ovarian endometrioid cancer (OEC). In total, 63 cancer cases (EEC: 33, OEC: 30) were included. Of these, 47 (EEC: 26, OEC: 21) were examined by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and 48 (EEC: 25, OEC: 23) were examined by quantitative PCR. OPN expression was detected in 15 (50.0%) of 30 EECs and in 14 (50.0%) of 28 OECs. There was no significant difference in the percentage of positive cytoplasmic OPN staining between the EECs and OECs (12.8 vs 10.4; p = 0.6811). The correlation between relative mRNA and protein expression levels was significant in both the EECs and OECs; however, the correlation between relative DNA and mRNA levels was not significant. There was no significant difference in OPN expression between the EECs and OECs.

Adult↗

PubMed2006

Adjuvant chemotherapy with irinotecan hydrochloride and cisplatin for clear cell carcinoma of the ovary.

Clear cell carcinoma (CCC) of the ovary has distinct characteristics showing resistance to conventional platinum-based regimen. Our aim was to evaluate the effects of combination therapy with irinotecan hydrochloride and cisplatin (CPT-P), comparing to regimen with paclitaxel and platinum (TP). We retrospective reviewed 172 patients with complete surgical staging procedures including lymphadenenctomy. Forty-six patients received CPT-P and 126 patients were treated with TP. Survival of the two groups was compared. Between CPT-P group and TP group, there was no significant difference in median age, performance status, FIGO stage, rate of optimal cytoreduction, and follow-up period. There was no significant difference in progression-free survival of patients with stage I tumors (p=0.95) and suboptimally debulked stage II-IV tumors (p=0.92). Although there was no significant difference of overall survival, progression-free survival of CPT-P group was significantly better than that of TP group in optimally debulked stage II-IV (p=0.03). Multiple regression survival analysis revealed CPT-P regimen (p=0.02) and residual tumor diameter (p<0.01) were both independent prognostic factors in stage II-IV tumors. The combination of CPT-P was shown to have a potential therapeutic benefit for advanced CCC of the ovary, especially for cases with optimal debulking surgery. However, this is a limited retrospective study, therefore we recommend that the CPT-P regimen be evaluated in a larger prospective study.

Adenocarcinoma, Clear Cell↗

PubMed2005

Fiber optic liquid leak detection technique with an ultrasonic actuator and a fiber Bragg grating.

We present a technique for liquid leak detection in which ultrasonic and optical waves are introduced into a fiber simultaneously. The system is based on an ultrasonic technique using an ultrasonic actuator and a fiber Bragg grating receiver. A fiber-guided ultrasonic wave is utilized to stress the fiber Bragg grating, which is remote from the ultrasonic transmitter. When the traveling ultrasonic wave encounters a liquid, part of the wave will leak out from the fiber, which results in an ultrasonic strain decrease in the fiber Bragg grating. The ultrasonic wave and its attenuation are detected by the light variation of a narrowband laser source reflected and transmitted from the fiber Bragg grating, and the amplitude variation of the ultrasound can eventually be correlated with the fiber area coupled with the liquid.

Journal Article↗

PubMed2005

PTEN expression in clear cell adenocarcinoma of the ovary.

OBJECTIVES: In this study, we analyzed the PTEN expression in a large collection of clear cell adenocarcinomas of the ovary. Furthermore, we analyzed the expression of cyclin D1 and p27, and investigated the correlation among all these variables. METHODS: Totally, 40 clear cell adenocarcinomas were included in this study. The protein expression of PTEN, cyclin D1 and p27 was investigated by immunohistochemistry. RESULTS: Of 40 clear cell adenocarcinomas, 15 (37.5%) lost all PTEN immunoreactivity. There was no significant correlation between PTEN expression and clinical stage. Cyclin D1 expression and loss of p27 expression were detected in 16/40 (40.0%) and 14/40 (35.0%) clear cell adenocarcinoma cases. There was no significant correlation between PTEN expression and cyclin D1 or p27 protein expression. CONCLUSIONS: Loss of PTEN expression is relatively common and both cyclin D1 and p27 expressions are not related with PTEN inactivation in clear cell adenocarcinoma of the ovary.

Adenocarcinoma, Clear Cell↗

PubMed2005

Identification of overexpression and amplification of ABCF2 in clear cell ovarian adenocarcinomas by cDNA microarray analyses.

PURPOSE: Patients with ovarian clear cell adenocarcinoma generally have a poor response to combination chemotherapy and have overall poorer prognosis than patients with other histologic types of ovarian cancer. Genetic changes in this group of cancer have not been thoroughly explored. Identification of these changes may provide us new therapeutic targets to treat this disease. EXPERIMENTAL DESIGN: Genomic and expression array analyses were applied on 30 clear cell ovarian cancer cases and 19 serous cases using a 10,816-element cDNA microarray platform. Further validation and clinical correlation studies were done on differentially expressed genes that are related to chemoresistance. RESULTS: Based on array analyses, 12 genes showed a significant increase in DNA and mRNA copy number and 5 genes showed a significant decrease in DNA and RNA copy number in clear cell tumors compared with those in the serous type. One of the genes was ABCF2, which belongs to the ATP-binding cassette gene superfamily and has been shown to amplify in other tumor types. Validation studies were done using real-time quantitative PCR and immunohistochemistry. The results showed significantly higher ABCF2 DNA and mRNA copy number and protein levels in clear cell cases compared with those in serous cases. Furthermore, in 20 clear cell cases with chemo-response data available, ABCF2 cytoplasmic staining was significantly higher in nonresponders than that in the responders (60.0% versus 28.5%; P = 0.0002). CONCLUSIONS: These data suggest that ABCF2 protein may be a prognostic marker for ovarian clear cell ovarian adenocarcinoma.

ATP-Binding Cassette Transporters↗

PubMed2005

The AXH domain of Ataxin-1 mediates neurodegeneration through its interaction with Gfi-1/Senseless proteins.

Spinocerebellar ataxia type 1 (SCA1) is a neurodegenerative disease caused by an expanded glutamine tract in human Ataxin-1 (hAtx-1). The expansion stabilizes hAtx-1, leading to its accumulation. To understand how stabilized hAtx-1 induces selective neuronal degeneration, we studied Drosophila Atx-1 (dAtx-1), which has a conserved AXH domain but lacks a polyglutamine tract. Overexpression of hAtx-1 in fruit flies produces phenotypes similar to those of dAtx-1 but different from the polyglutamine peptide alone. We show that the Drosophila and mammalian transcription factors Senseless/Gfi-1 interact with Atx-1's AXH domain. In flies, overexpression of Atx-1 inhibits sensory-organ development by decreasing Senseless protein. Similarly, overexpression of wild-type and glutamine-expanded hAtx-1 reduces Gfi-1 levels in Purkinje cells. Deletion of the AXH domain abolishes the effects of glutamine-expanded hAtx-1 on Senseless/Gfi-1. Interestingly, loss of Gfi-1 mimics SCA1 phenotypes in Purkinje cells. These results indicate that the Atx-1/Gfi-1 interaction contributes to the selective Purkinje cell degeneration in SCA1.

Animals↗

PubMed2005

Photodynamic therapy for cervical intraepithelial neoplasia.

OBJECTIVES: Photodynamic therapy (PDT) is a minimally invasive treatment for cervical intraepithelial neoplasia (CIN). We report the effectiveness of PDT in 105 cases of CIN. METHODS: All patients received photofrin (PHE) 2 mg/kg intravenously and, 48-60 h later, phototherapy was performed using the Excimer dye laser or a YAG-OPO laser with an irradiation dose of 100 J/cm(2) using 630 nm wavelength. RESULTS: Mild photosensitivity occurred in 48% (50/105) of patients. The complete response (CR) rate was 90% (94/105) at 3 months following treatment. In the remaining 11 patients, 5 patients had CIN1, 2 patients had CIN2, and 4 patients had mild cytologic findings. However, in 9 of these 11 patients, CR was achieved 6 months after PDT. In 69 patients, human papilloma virus (HPV) typing was performed before and after PDT therapy. Pre-treatment, 64 of 69 patients (93%), were HPV-positive including 30 cases of high-risk HPV (43%). Testing performed 3, 6 and 12 months following PDT revealed no HPV-DNA in 75% (52/69), 74% (48/65) and 72% (41/57) of patients. At present, the median follow-up period is 636 days (90-2,232 days). In 3 patients, recurrence requiring surgical treatment was identified at 646, 717 and 895 days after PDT. CONCLUSIONS: PDT is an effective and minimally invasive treatment for CIN, which also appears to eradicate HPV infection.

Adult↗

PubMed2005

Transvaginal ultrasonography of the endometrium in postmenopausal Japanese women.

AIMS: To determine the cut-off level of endometrial thickness for detecting endometrial disease on a large scale of screening and to examine the usefulness of transvaginal ultrasonography (TVS) for endometrial disease screening in asymptomatic postmenopausal Japanese women. METHODS: The study involved 1,400 postmenopausal women in whom endometrial thickness was measured with TVS, and then compared with the histopathological diagnosis of endometrial specimens. RESULTS: The prevalence of endometrial disease in asymptomatic and symptomatic cases was 2.3 and 21%. In symptomatic cases, at a cut-off limit of 3 mm for endometrial thickness, the sensitivity for detecting endometrial disease was 94%, specificity 70% and positive predictive value 46%. With an endometrial thickness < or = 3 mm, the probability that endometrial disease would be overlooked was 0.025. In asymptomatic cases, the corresponding figures at a cut-off limit of 3 mm were 90, 84, 12% and 0.003. CONCLUSIONS: TVS does not appear to be an effective screening method in asymptomatic postmenopausal Japanese women because of the low prevalence of endometrial disease in this population. We recommend a normal cut-off level for endometrial thickness of 4 mm in symptomatic postmenopausal Japanese women.

Adult↗

PubMed2005

Length variation of CAG/CAA triplet repeats in 50 genes among 16 inbred mouse strains.

CAG repeats coding for poly-glutamines have been studied by many groups as repeat length variations contributes to differences in protein function and disease outcome. In this study, we systematically searched public databases for genes carrying CAG repeats. For the genes obtained, we experimentally analyzed variations of length and the purity of the repeats in 62 loci among 16 inbred mouse strains, including wild-derived and laboratory strains. We found that length was conserved in 50% of the loci, especially among wild-derived strains. Of 496 polymorphic repeat alleles, 78% were uninterrupted and 22% were interrupted with non-CAG codons. Interruptions tended to occur in longer repeats and all repeats of greater length than 23 were interrupted. Although interruptions can act as suppressors for the expansion of CAG repeats, we found that the occurrence of the interruptions depended on the length of the CAG repeats. Furthermore, most poly-glutamines examined in this study existed in human orthologous genes, reflecting the functional significance of poly-glutamines in proteins.

Alleles↗

PubMed2005

The relationship between initial clinical manifestation and long-term prognosis of patients with systemic lupus erythematosus.

The relationship between clinical manifestations and prognosis was examined and evaluated among systemic lupus erythematosus (SLE) patients. A total of 542 patients with SLE were selected and divided into nine groups according to their main clinical manifestation at the time of initial diagnosis. The relationship between these clinical manifestations and long-term prognosis was evaluated in respect to the survival, remission, relapse rates, the development of a new clinical manifestation, and/or damage index. Patients with neuropsychiatric SLE (NPSLE), accompanied with acute confusional state/seizure disorder, cerebral vascular disease, or pneumonitis had poor survival rates with cause of death related to their major organ involvement. Patients with nephropathy or leukopenia had lower remission rates, and an increase in relapse rates was frequently recognized in patients with pneumonitis. Body damage (damage index) was higher in patients with lupus psychosis, pneumonitis, and/or arthritis. The translation of the main manifestations after diagnosis was confirmed in 64 patients (11.8%), and often observed in patients with autoimmune hemolytic anemia and arthritis. The majority of these manifestations were nephropathy, NPSLE, thrombocytopenia, and pneumonitis, and the prognosis of patients with nephropathy and thrombocytopenia as a new main manifestation had a poor outcome. The results of long-term prognosis in SLE greatly differed with respect to the initial clinical manifestation at the time of diagnosis.

Journal Article↗

PubMed2005

Study of plasma levels of soluble CD40 ligand in systemic lupus erythematosus patients who have undergone plasmapheresis.

We studied whether soluble CD40 ligands (sCD40L) are removed by means of double filtration plasmapheresis (DFPP), and the removal may help decrease activity of systemic lupus erythematosus (SLE). We studied 10 female patients with active SLE. Double filtration plasmapheresis was conducted one or two times per week. Plasma sCD40L levels were measured before and after each round of DFPP and throughout the treatment course. The plasma sCD40L level of SLE patients was significantly higher (14.09 +/- 18.88 ng/mL) than that of healthy individuals (0.19 +/- 0.20 ng/mL; P < 0.0001). In the SLE patients, plasma sCD40L levels were significantly lower following DFPP (P = 0.0251). The plasma waste from DFPP of an SLE patient was subjected to gel filtration, and the sCD40L concentration in each fraction was measured. We observed a peak in the fraction corresponding to > or =60 kDa. These results indicate that trimers and higher order complexes of sCD40L are removed during DFPP. Plasma sCD40L level and SLE disease activity index (SLEDAI) were decreased following the treatment course (mean 9.3 months). sCD40L exists as both a monomer and trimer in the plasma of SLE patients. The trimer as well as higher-order compounds can be removed via DFPP. It was thought that removal of sCD40L via DFPP may be useful for improving the overall condition of SLE.

Adult↗