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Biomedical subjects

Y Kodera

Publications and source records attributed to Y Kodera.

At least 91 records · Page 5Linked to original sources

No significant association between HA-1 incompatibility and incidence of acute graft-versus-host disease after HLA-identical sibling bone marrow transplantation in Japanese patients.

We retrospectively examined HA-1 typing with polymerase chain reaction using sequence-specific primers in 120 samples from 60 HLA-A2-positive Japanese bone marrow transplantation recipients who received short-term methotrexate and cyclosporin A for graft-versus-host disease (GVHD) prophylaxis and their HLA-identical sibling donors. HA-1-incompatible pairs were observed in 22% of the samples. The probability of developing acute GVHD (grade II to IV) in HA-1-incompatible and -compatible patients was 0% and 19%, respectively (P = .10). In a comparison between HA-1-incompatible and -compatible patients with standard-risk leukemia, in whom age, patient/donor sex, and use of a total body irradiation-containing regimen were equivalent, the probability of developing acute GVHD (grade II to IV) was 0% and 10%, respectively (P = .38). No evidence of recurrent leukemia was observed in the HA-1-incompatible patients with standard-risk leukemia, compared with 37% in HA-1-compatible patients (P = .11). In conclusion, HA-1 incompatibility may not be a risk factor for grade II to IV acute GVHD in Japanese patients who receive methotrexate and cyclosporin A and undergo bone marrow transplantation from HLA-identical sibling donors.

Adolescent↗

An NMR analysis of ubiquitin recognition by yeast ubiquitin hydrolase: evidence for novel substrate recognition by a cysteine protease.

Yeast ubiquitin hydrolase 1 (YUH1), a cysteine protease that catalyzes the removal of ubiquitin C-terminal adducts, is important for the generation of monomeric ubiquitin. Heteronuclear NMR spectroscopy has been utilized to map the YUH1 binding surface on ubiquitin. When YUH1 was titrated into a sample of ubiquitin, approximately 50% of the (1)H-(15)N correlation peaks of ubiquitin were affected to some degree, as a result of binding to YUH1. It is noteworthy that the amide resonances of the basic residues (Arg42, Lys48, Arg72, and Lys74) were highly perturbed. These positively charged basic residues may be involved in direct interactions with the negatively charged acidic residues on YUH1. In addition to the electrostatic surface, the hydrophobic surfaces on ubiquitin (Leu8, Ile44, Phe45, Val70, Leu71, and Leu73) and YUH1 are also likely to contribute to the binding interaction. Furthermore, the amide resonances of Ile13, Leu43, Leu50, and Leu69, the side chains of which are not on the surface, were also highly perturbed, indicating substrate-induced changes in the environments of these residues as well. These large changes, observed from residues located throughout the five-stranded beta-sheet surface and the C-terminus, suggest that substrate recognition by YUH1 involves a wider area on ubiquitin.

Amino Acid Sequence↗

Influence of habitual smoking on gastric cancer by histologic subtype.

A comparative case-referent study was conducted using data from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center (HERPACC), with the aim of clarifying whether histologic subtypes of gastric cancer exhibit different risk-factor patterns of habitual smoking. Our study comprised 995 histologically confirmed gastric-cancer cases [460 differentiated (intestinal type), 527 non-differentiated (diffuse type) and 8 unclassified], identified via hospital cancer registry and surgical records, and 43,846 non-cancer outpatients at Aichi Cancer Center Hospital over the years 1988-1995. Odds ratios (ORs) were estimated by gender using logistic regression and adjusted for potential confounding factors. In males, a significantly increased OR of gastric cancer was observed for habitual smokers, and this was higher in the differentiated type than the non-differentiated type and in younger than in older age groups. Risk patterns were less clear in females. Our results suggest that habitual smoking is associated more likely with the differentiated type of gastric cancer, particularly in younger cases.

Adult↗

Peritoneal washing cytology: prognostic value of positive findings in patients with gastric carcinoma undergoing a potentially curative resection.

BACKGROUND AND OBJECTIVES: Free cancer cells in the abdominal cavity exfoliated from a tumor are considered to be responsible for peritoneal dissemination, the most frequent pattern of failure in gastric carcinoma patients treated with curative surgery. METHODS: A prospective survival analysis was performed with 91 gastric carcinoma patients treated by potentially curative resection. Cytology was performed for all the patients. The method of Kaplan and Meier was used to construct curves with diagnosis of peritoneal dissemination and cancer death as the end points. Multivariate analysis by Cox's proportional hazards model was performed to identify independent prognostic factors of significance. RESULTS: Patients with a positive cytology result were confirmed to have a greater risk for recurrence in the pattern of peritoneal carcinomatosis and hence a significantly inferior prognosis. Positive cytology was the only significant independent prognostic factor among the curatively resected patients with advanced gastric carcinoma. CONCLUSIONS: Peritoneal lavage cytology should be employed for all advanced cancer undergoing potentially curative resection for added accuracy in the stage classification. The results should also reflect the eligibility of the patients for future clinical trials involving perioperative intraperitoneal chemotherapy.

Ascitic Fluid↗

Isolation of Biopterin-alpha-glucoside from Spirulina (Arthrospira) platensis and Its Physiologic Function.

: A fluorescent substance was isolated from the cyanobacterium with a yield of 4.5 mg per 10 g of dried Spirulina (Arthrospira) platensis cells by gentle extraction and ethanol fractionation followed by column chromatography. The fluorescent substance, which has absorption maxima at 256 nm and 362 nm (pH 8.4), was identified as biopterin-alpha-glucoside by spectrophotometry and nuclear magnetic resonance spectroscopy. Biopterin-alpha-glucoside prevented decolorization of the photosynthetic pigments, chlorophyll a, phycocyanin, and carotenoids in photosynthetic vesicles of Spirulina platensis cells, by ultraviolet irradiation.

Journal Article↗

Molecular diagnostic detection of free cancer cells in the peritoneal cavity of patients with gastrointestinal and gynecologic malignancies.

Free cancer cells exfoliated from cancer-invaded serosa contribute to peritoneal dissemination, the most frequent pattern of recurrence in patients with gastric and ovarian cancers. This study was designed to evaluate the prognostic significance of free cancer cells in peritoneal washes detected using the reverse transcriptase-polymerase chain reaction (RT-PCR) and cytology. RT-PCR analysis with primers specific for the carcinoembryonic antigen (CEA) gene was found to be more sensitive than cytology for detection of free tumor cells in the peritoneal washes, collected at laparotomy from 199 gastric carcinoma patients, with higher detection rates for each of the T-categories in the TNM classification. Six patients with synchronous and 5 with recurrent peritoneal dissemination were found among 25 advanced cancer patients with positive PCR and negative cytology results. Positive PCR results were significantly associated with poor survival of curatively resected advanced gastric carcinoma patients (P < 0.001). A rapid method for detecting CEA mRNA using the LightCycler and the dsDNA binding dye SYBR green I was also developed. The results obtained using this technique were essentially the same as those obtained using the conventional RT-PCR method. Furthermore, RT-PCR analysis with primers specific for MUC1 epithelial mucin were performed on peritoneal washes from patients with ovarian cancer. Peritoneal washes from 21 of 25 ovarian carcinoma patients, including all 17 with positive cytology results, were positive for MUC1 mRNA, again indicating a higher sensitivity using this method than conventional cytology. Highly sensitive and rapid detection of free cancer cells in peritoneal washes, most reliably by RT-PCR, is a powerful technique to predict peritoneal dissemination in patients with gastric and ovarian cancers.

Animals↗

Adenocarcinoma of the gastroesophageal junction in Japan: relevance of Siewert's classification applied to 177 cases resected at a single institution.

BACKGROUND: There had been a lack of international consensus about the definition of cancer of the gastric cardia until Siewert's classification was approved at a consensus conference during the second International Gastric Cancer Congress held in 1997. STUDY DESIGN: A review of the prospective gastric cancer database at Aichi Cancer Center from 1983 to 1992 identified 1,913 gastric carcinoma patients who underwent gastrectomy. These patients were classified retrospectively according to the Siewert classification, and 177 patients who fell into one of the three types form the basis of this study. Survival analyses were performed after stratifying patients by clinicopathologic variables. RESULTS: There were 33 patients with type II and 144 with type III, although none had type I, a type frequently observed in the west. No evidence of a change in the frequency of types II or III cancers (approximately 9.3% overall) among gastric carcinoma patients was observed over the 10-year period. Clinical staging of gastric carcinoma by the TNM classification was found to reflect accurately the prognosis of these patients. There were no longterm survivors among the few patients with metastasis to the perigastric nodes of the distal stomach. CONCLUSIONS: A striking difference in the distribution of types of adenocarcinoma of the gastroesophageal junction was observed in Japan compared with previously reported western data. A subgroup of carcinoma of the proximal stomach identified as types II and III may not require proximal gastrectomy from the viewpoint of sufficient lymphadenectomy.

Adenocarcinoma↗

Inhibition of Df-protease associated with allergic diseases by polyphenol.

It was reported that Df-protease from house dust mite (Dermatophagoides farinae) catalyzes the activation of the kallikrein-kinin system in human plasma and is closely associated with mite-induced allergy. Therefore, to prevent the release of kinin by Df-protease, the inhibitory activity of polyphenols including catechins and flavonols was tested in vitro and in vivo. Among them, myricetin and epigallocatechin gallate (EGCg) effectively inhibited the amidase activity of Df-protease with K(i) values of 1 x 10(-)(8) and 6 x 10(-)(4) M, respectively. The kinin release in human plasma was extensively inhibited by the addition of EGCg in comparison with myricetin. Enhancement of vascular permeability in guinea pigs caused by Df-protease was markedly suppressed by EGCg.

Animals↗

Human platelet alloantigen (HPA)-5a/b mismatch decreases disease-free survival in unrelated bone marrow transplantation.

Matching of human platelet alloantigen (HPA) systems 2-6 was retrospectively investigated in 715 unrelated bone marrow transplantations. Of the five HPA systems studied, HPA-5 mismatching was found to have a significant effect on the disease-free survival rate of recipients following transplantation in the HLA-A, -B, -C, and -DR allele-matched donor-recipient pairs. The effect of the HPA-5 mismatch was most significant in the recipient group possessing the HLA haplotype A*2402-B*5201, which is a highly frequent haplotype among the Japanese population. However, the probability of development of acute graft-versus-host disease (GVHD) was not increased significantly by the HPA-5 mismatching. These findings suggest that the HPA-5 mismatching decreases the recipient's survival by a mechanism different from that in the case of mismatching of minor antigens found often in transplant recipients developing GVHD.

Antigens, Human Platelet↗

Analysis of 500 bone marrow transplants from unrelated donors (UR-BMT) facilitated by the Japan Marrow Donor Program: confirmation of UR-BMT as a standard therapy for patients with leukemia and aplastic anemia.

In December 1991, the Japan Marrow Donor Program (JMDP) was established with the cooperation of the Japanese Red Cross and Japan Marrow Donor Foundation under the auspices of the Ministry of Health and Welfare in Japan. By December 1998, 122365 HLA-A,B typed volunteer marrow donors and 7207 patients had been cumulatively registered in the JMDP. The results of HLA-matching between donors and patients revealed that 5684 out of 7207 (78.9%) patients could have at least one HLA-A,B,DR serologically matched donor. Among these matched pairs, 1829 unrelated bone marrow transplants (UR-BMT) were performed. The initial 500 UR-BMT transplanted from January 1993 to October 1995 were analyzed as of July 1998. Engraftment was achieved in 95% of cases. Probability of the occurrence of grade III and IV acute GVHD was 18.4%. The rate of disease-free survival (DFS) of the patients who had standard-risk leukemia and did not suffer from grade III or IV acute GVHD (n = 154) was 60-71% and the rate of survival of patients with aplastic anemia was 56%. It can be stated that UR-BMT is a modality of treatment which is as effective as related BMT if the occurrence of grade III or IV acute GVHD is predicted and prevented.

Acute Disease↗

Peripheral blood stem cell mobilization and apheresis: analysis of adverse events in 94 normal donors.

Adverse events were analyzed in 94 normal donors who underwent PBSC harvest with G-CSF. The median dose of G-CSF was 9.7 microg/kg/day (range, 2.0-16.7), and the duration of administration was 4-6 days. Frequent symptoms were bone pain (71%), general fatigue (33%), headache (28%), insomnia (14%), anorexia (11%), nausea and/or vomiting (11%). One donor (1%) developed grade 3 toxicity bone pain (WHO criteria). WBC counts and ANC increased during G-CSF administration. After leukapheresis, three donors (3%) developed grade 3 toxicity neutropenia. Platelet counts decreased after leukapheresis. Three donors (3%) developed grade 3 thrombocytopenia. The means of both ALP and LDH increased approximately 1.9-fold compared with pretreatment levels. In one pediatric donor (1%), ALP was elevated to the grade 3 toxicity level. From multivariate analysis, the incidence of bone pain increased when G-CSF was given at a dose of 8.8 microg/kg/day or more, headaches were frequent in donors younger than 35 years, and the incidence of nausea and/or vomiting was high in female donors. The peak levels of WBC counts and ANC and post-treatment level of LDH increased in correspondence with the escalation of G-CSF dose. All adverse events normalized on follow-up evaluation. In conclusion, although PBSC harvest for normal donors is acceptable, care must be taken for all donors in terms of their sex and age as well as the G-CSF dose. We recommend less than 8.8 microg/kg/day as the G-CSF dose for PBSC mobilization in normal donors.

Adolescent↗

Selective usage of D-type cyclins in lymphoid malignancies.

Three D-type cyclins, cyclin D1, D2 and D3, belong to the G1 cyclin, which regulates the G1/S transition of the cell cycle, and feature highly homologous amino acid sequences. The cyclin D1 gene was found to be transcriptionally activated in B-lymphoid malignancies with t(11;14), but available information is limited regarding expression of cyclin D2 and D3 in hematopoietic malignancies. We examined the expressions of three D-type cyclins to investigate how these homologous genes are differentially used. Northern blot hybridization with densitometric analyses was performed to examine 64 cell lines and 159 patients with various hematopoietic malignancies. Among lymphoid malignancies, cyclin D1 overexpression was exclusively detected in B cell malignancies accompanied by a genetic event consisting of 11q13 chromosomal translocation, consisting of 13 of 19 (68%) patients with mantle cell lymphoma, two of 11 (18%) with B-chronic lymphocytic leukemia, and one of six (17%) with multiple myeloma. The cyclin D2 expression was significantly higher in T cell malignancies than in B cell malignancies (P = 0.003 for cell lines and P < 0.0001 for patient samples, respectively). In the T cell malignancies, cyclin D2 overexpression was predominantly recognized in those with mature phenotype. Furthermore, cyclin D2 expression was upregulated by phytohemagglutinin (PHA) stimulation of normal T-lymphocytes, suggesting that this simply represents the proliferation status of mature T cells. Although cyclin D3 was ubiquitously expressed, its expression was reduced in lymphoid malignancies with cyclin D1 or D2 overexpression. In myeloid leukemias, although three D-type type cyclins were differentially expressed, no preference for particular D-type cyclins was found. This selective usage of D-type cyclins in lymphoid malignancies suggests an existence of a regulatory mechanism among three D-type cyclins.

Cell Lineage↗

Molecular and immunological dissection of diffuse large B cell lymphoma: CD5+, and CD5- with CD10+ groups may constitute clinically relevant subtypes.

Diffuse large B cell lymphoma (DLBL) constitutes the greatest percentage of adult non-Hodgkin's lymphomas and represents a diverse spectrum of lymphoid neoplasms. Clinicopathologic, phenotypic and genotypic findings were correlated and compared for 63 DLBL cases to investigate whether they represent clinically relevant subtypes. They were all cyclin D1 negative and were phenotypically divided into three groups, ie group I (CD5+ type, n=11), group II (CD5- CD10+ type, n=19), and group III (CD5- CD10- type, n=33). Data were correlated by observing the respective gene rearrangement and expression of BCL2 and BCL6. In clinical aspects, the group I cases demonstrated a significantly inferior survival than those of the other two groups (log-rank test, P = 0.016). Although rearrangement of BCL2 and BCL6 did not show any inclination to a specific subgroup, the immunohistochemical detection of BCL2 was less frequent, at a statistically significant level (P=0.011), in group II (50%) than in group I (82%) and III (82%) cases. This appears to confirm the unique aspect of the CD5- CD10+ type DLBL, indicating a certain relationship with the normal germinal center cells which usually lack BCL2 expression. The BCL6 protein expression was detected in most of the present DLBL cases (92%) irrespective of this grouping. These data suggest that the phenotypic delineation by the detection of CD5 and CD10 will improve our understanding of DLBL and be helpful in a future subgrouping of DLBL.

Adult↗

A new preconditioning regimen with melphalan, busulphan and total body irradiation followed by low-dose immunosuppressant in allogeneic haemopoietic stem cell transplantation.

Twenty adult patients with high-risk leukaemia underwent allogeneic haemopoietic stem cell transplantation after melphalan, busulphan and total body irradiation followed by short-term methotrexate and low-dose cyclosporine or tacrolimus. Three patients developed veno-occlusive disease and no patient developed renal dysfunction. Seven patients experienced grade II-IV acute graft-versus-host disease (aGVHD) and five patients experienced grade III-IV. The 3-year probabilities of relapse and leukaemia-free survival were 22 +/- 11% (95% confidence interval) and 50 +/- 11%, respectively. These data suggest that this preconditioning regimen followed by a low-dose immunosuppressant provided a more anti-leukaemic effect without increased regimen-related toxicity and aGVHD.

Adult↗

Positive and negative regulations of the renal 25-hydroxyvitamin D3 1alpha-hydroxylase gene by parathyroid hormone, calcitonin, and 1alpha,25(OH)2D3 in intact animals.

Reflecting the prime role of 1alpha,25(OH)2D3 in calcium homeostasis, the activity of 25-hydroxyvitamin D3 1alpha-hydroxylase, a key enzyme for 1alpha,25(OH)2D3 biosynthesis, is tightly regulated by 1alpha,25(OH)2D3, PTH and calcitonin. Its significant activity is found in kidney, though the enzymatic activity is also reported in extra-renal tissues. In the present study, we found that the 1alpha-hydroxylase gene abundantly expresses in kidney, and at low levels in other tissues and in some cell lines. Positive and negative regulations of 1alpha-hydroxylase gene by PTH, calcitonin, or 1alpha,25(OH)2D3 were observed at transcriptional levels in kidneys of animals and in a mouse proximal tubule cell line. Moreover, the protein kinase A inhibitor abrogated the PTH-mediated positive regulation. In mice lacking the vitamin D receptor, the 1alpha-hydroxylase gene expression was overinduced, and the inducible effect of either PTH or calcitonin, but not the repression by 1alpha,25(OH)2D3, was evident. Thus, vitamin D receptor is essential for the negative regulation by 1alpha,25(OH)2D3. Moreover, we demonstrate that renal 1alpha-hydroxylase gene expression in chronic renal failure model rats was decreased and the positive effect by PTH and calcitonin was diminished. The present study demonstrates that PTH and calcitonin positively regulate renal 1alpha-hydroxylase gene expression via PKA-dependent and independent pathway, respectively, and that 1alpha,25(OH)2D3 negatively regulates it mediated by vitamin D receptor. Furthermore, in a moderate state of chronic renal failure, renal cells expressing the 1alpha-hydroxylase gene appear to have diminished potential in response to PTH and calcitonin.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗

Immune response of post-transplant peripheral lymphocytes against the patient pre-B cell line, NAGL-1.

We have established a pre-B acute lymphoblastic leukemia (ALL) cell line, NAGL-1, from the bone marrow of a patient diagnosed with pre-B ALL. The patient has been disease-free for the 4 years since allogeneic bone marrow transplantation from her HLA-genotypically identical sister. NAGL-1 showed a pre-B cell phenotype (CD19+, CD10+, c mu+, s mu-) mostly identical to freshly isolated leukemic cells from the patient. This cell line strongly expressed HLA class I and HLA-DR molecules, as well as the costimulatory molecules CD54, CD40, and CD86. Cytotoxic T-lymphocyte (CTL) lines were generated by stimulating the donor-derived peripheral blood mononuclear cells with either irradiated leukemic cells or NAGL-1. Both CTL lines showed specific lysis against NAGL-1 in 51Cr release assays. Lytic activity was partially inhibited by anti-CD8 and anti-HLA class I monoclonal antibodies. Treatment of NAGL-1 with TNF-alpha increased its susceptibility to the CTL line. One CD8+ T cell clone derived from the CTL line killed both the patient phytohemagglutinin (PHA) blasts and NAGL-1 but not the donor PHA blasts, suggesting that the clone recognized the patient-specific minor antigen presented on both PHA blasts and NAGL-1. Utilization of leukemic cell lines could be a useful model for the development of CTL lines and clones for immunological study and potential immunotherapy.

Adolescent↗

[The current status and future aspects of umbilical cord blood banking system in Japan].

Since 1995, when the first, non-governmental umbilical cord blood bank (CB bank) was created in Kanagawa prefecture, 9 local CB banks have been established in Hokkaido, Kanto, Tokai, Kinki and Kyusyu district. According to the experiences of organizing these local banks and of collecting the data of cord blood cell transplantation by 2 grant study groups, The Ministry of Health and Welfare is now creating national cord blood banking system, which will be opened in the coming April.

Blood Banks↗