Biomedical subjects

Y Kodera

Publications and source records attributed to Y Kodera.

At least 73 records · Page 4Linked to original sources

PubMed2000

Successful ribavirin therapy for severe adenovirus hemorrhagic cystitis after allogeneic marrow transplant from close HLA donors rather than distant donors.

Intravenous ribavirin was given to nine patients who had developed severe adenovirus-induced hemorrhagic cystitis (AD-HC) which was resistant to conventional therapy or where there was involvement of other organs after allogeneic BMT. Three patients recovered completely from AD-HC, two of whom had been resistant to vidarabine. All three had received sibling BMTs (2 HLA matched, 1 HLA mismatched). Five patients who received BMTs from related (2 HLA mismatched) or unrelated (1 HLA matched, 2 HLA mismatched) showed an improvement in symptoms but had recurrent AD-HC after discontinuation of ribavirin. Improvement in clinical symptoms and termination of virus excretion were well correlated. The last patient who received a mismatched unrelated BMT died during ribavirin therapy. Ribavirin was notably more effective among patients receiving BMTs from siblings in contrast to patients receiving BMTs from alternative donors (<0.05). One patient experienced severe pancytopenia during the second treatment with ribavirin after HC recurrence and recovered after ceasing ribavirin. Thus, ribavirin seems to be very effective for severe AD-HC for some recipients who receive transplants from a genetically close donor. Bone Marrow Transplantation (2000) 25, 545-548.

Adenoviridae Infections↗

PubMed2000

Cord blood transplantation and cord blood bank in Japan.

The first cord blood transplantation (CBT) was performed in a 5-year-old boy with acute myelogenous leukemia from his HLA-identical sibling donor in 1994. Since then there have been 17 related and 131 unrelated CBTs in Japan. Overall survival and disease-free survival (DFS) were over 70% in sibling donor CBT. DFS of unrelated CBT in leukemia and other hematological malignancies was 43%, and OS of UCBT in non-malignant diseases was 63%. HLA disparity between the donor and the recipient did not affect the incidence and severity of acute graft-versus-host disease (GVHD) or survival. Cell dose was the most important factor for engraftment and survival both in malignant and in non-malignant diseases. The Japanese government has recently established the nationwide cord blood bank network, and eight local cord blood banks are financially supported by the government. 20,000 units of CB are planned to be collected and stored in the next 5 years by this network.

Blood Banks↗

PubMed2000

Donor leukocyte infusion for Japanese patients with relapsed leukemia after allogeneic bone marrow transplantation: lower incidence of acute graft-versus-host disease and improved outcome.

To clarify the role of donor leukocyte infusion (DLI) in the treatment of leukemia relapsing after allo-BMT, data from 100 patients were collected from 46 facilities in Japan and analyzed with respect to the efficacy and adverse effects of donor leukocyte infusion. Complete remission was achieved in 11 of 12 (91%) patients with relapsed chronic myelogenous leukemia (CML) in chronic phase, three of 11 (27%) with CML in the acute phase, eight of 21 (38%) with acute myelogenous leukemia (AML), six of 23 (25%) with acute lymphoblastic leukemia (ALL) and five of 11 (45%) with myelodysplastic syndrome (MDS). The probability of remaining in CR at 3 years was 82% in CML patients in the chronic phase, but 0% in those with CML in the acute phase, 7% in those with AML, 0% with ALL and 33% with MDS. Acute GVHD (>/=2) developed in 31 of 89 (34%) patients with HLA-identical related donors and was fatal for seven (7%). Cytopenia developed in 21 of 94 (22%) with no associated fatalities. When the outcome of patients with CML in CP and MDS was analyzed, development of GVHD, cytopenia, or both, was associated with a higher GVL effect (15 of 16, 93%) than in those without adverse affects (one of 6, 17%). A leukocyte dose of 5 x 107/kg of recipient body weight appeared to be optimal as an initial dose of DLI. Given the relatively low incidence of acute GVHD and the similar GVL effect, DLI may be more beneficial to patients in Japan with recurrent leukemia than to those in Western countries. Bone Marrow Transplantation (2000) 26, 769-774.

Acute Disease↗

PubMed2000

Allogeneic hematopoietic transplantation of CD34+ selected cells from an HLA haplo-identical related donor. A long-term follow-up of 135 patients and a comparison of stem cell source between the bone marrow and the peripheral blood.

We studied the outcome of allogeneic transplants in 135 patients who received selected BM and/or PBSC CD34+ cells from HLA haplo-identical related donors. Donor engraftment was achieved in 108 of 128 evaluable transplants. Engraftment failure occurred more often in non-malignant than in malignant diseases (10 of 25 vs 17 of 103, P = 0.010). The CD34+ cell dose was associated with the speed of neutrophil and platelet recovery, but the cell source was not. Acute GVHD (> or = grade II) developed in 21.0 +/- 3.7%. Chronic GVHD occurred more frequently in malignancies than in non-malignancies (44.1 +/- 7.6% vs 0.0%, P = 0.0075), and more in PBSC recipients than in BM recipients (53.6 +/- 9.4% vs 17.4 +/- 9.3%, P = 0.0054). Relapse rate was higher in high risk patients than in standard risk patients (78.7 +/- 7.1% vs 22.1 +/- 10.0%, P = 0.0001). Probabilities of disease-free survival (DFS) were 14.2 +/- 3.5% in malignancies and 25.7 +/- 9.2% in non-malignancies. Probabilities of DFS in standard and high risk patients were 39.4 +/- 9.2% and 5.7 +/- 2.8% (P = 0.0001). A high incidence of graft failure, infection and relapse was observed and resulted in high mortality.

Actuarial Analysis↗

PubMed2000

Cytomegalovirus pneumonitis, activated prothrombin time prolongation and subacute thyroiditis after unrelated allogeneic bone marrow transplantation.

A 22-year-old female with acute myeloid leukemia (AML) in complete remission received a conditioning regimen containing antithymocyte globulin for an unrelated bone marrow transplant (BMT). After BMT, the patient suffered from cytomegalovirus (CMV) pneumonitis with markedly high levels of CMV antigenemia, activated prothrombin time (APTT) prolongation, and subacute thyroiditis. Recovery of CD4+ cells was delayed as long as 1 year after BMT. An association between these three episodes and viral infection due to the delayed recovery of CD4+ cells is suggested.

Acute Disease↗

PubMed2000

Prognostic significance of the cell cycle inhibitor p27Kip1 in acute myeloid leukemia.

There are few molecular biologic determinants that are prognostic for patients with acute myeloid leukemia (AML). Hence, we examined whether cellular levels of the cyclin-dependent kinase inhibitor p27Kip1 in acute myeloid leukemia could be used to predict clinical outcome in AML. Using immunoblot analysis, levels of p27 were assessed in blast cells from 72 AML patients who were registered and treated by the identical chemotherapy protocol. AML cases were classified into three groups on the basis of the percentage of the expression level of p27 compared to a control cell line. AML cases exhibiting p27 expression at low, moderate, and high levels were 43, 9, and 20 cases, respectively. No significant differences in the rates of complete remission (CR) were observed among the three groups. Although the level of p27 expression was not correlated with any other possible prognostic markers, such as age, white blood cell count, chromosome abnormalities, and FAB subclasses, patients with high p27 expression had a significantly increased disease-free survival (DFS) (78% vs 19%, P = 0.004). We further examined the expression of cyclin E at the protein level in all 72 AML cases. We observed a statistically significant correlation between a high cyclin E level and a high p27 level (P < 0.005). However, we failed to find any correlation between the rates of CR or DFS and cyclin E expression. The present study reveals that levels of p27 expression can be one of the useful prognostic molecular markers for AML. Leukemia (2000) 14, 28-33.

Acute Disease↗

PubMed2000

Absence of mutations in the granulocyte colony-stimulating factor (G-CSF) receptor gene in patients with myelodysplastic syndrome/acute myeloblastic leukaemia occurring after treatment of aplastic anaemia with G-CSF.

The development of myelodysplastic syndrome/acute myeloblastic leukaemia (MDS/AML) has been reported in patients with aplastic anaemia (AA) after administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF). Similarly, patients with severe congenital neutropenia (SCN) have an increased risk of developing MDS/AML after treatment with rhG-CSF. Point mutations in the G-CSF receptor gene are found in about 20% of SCN patients who are predisposed to MDS/AML. We investigated the occurrence of mutations in the G-CSF receptor in eight patients with AA who developed MDS/AML. No mutations were detected around the cytoplasmic domain of the gene in our patients, indicating that the mechanisms of clonal evolution to MDS/AML in patients with AA might be different from those with SCN.

Adult↗

PubMed2000

Clinical significance of major and minor bcr/abl chimeric transcripts in essential thrombocythemia.

BACKGROUND: Contradictory results have been reported in terms of detecting bcr/abl transcripts in patients with essential thrombocythemia. The aim of this study was to investigate whether the bcr/abl transcript could be found in patients with essential thrombocythemia (ET). METHODS: The bcr/abl transcript was amplified by the RT-nested PCR method using RNA extract from leukocytes taken from 14 essential thrombocythemia patients. The amplified DNAs were electrophoresed in 1% agarose and visualized with ethidium bromide. The DNA bands associated with the bcr/abl transcript were then extracted and followed by DNA sequence analysis. RESULTS: Major bcr/abl transcripts of the b3a2 type and minor ones of the e1a2 type were found in one and two ET patients, respectively. The incidence of bcr/abl transcripts was 21.4% (three of 14 patients). CONCLUSION: Our experiments confirmed that bcr/abl transcripts are present in some patients with essential thrombocythemia.

Adult↗

PubMed2000

A case of cancerous familial adenomatous polyposis in urinary bladder due to migration of colonic mucosa through rectovesical fistula.

The patient was a 50-yr-old man who had undergone low anterior resection for rectal cancer at the age of 24 yr in 1966. At that time, gastric and colonic polyposis were indicated. Postoperative anastomotic dehiscence occurred and, by 1985, a rectovesical fistula had formed. In 1986, when the patient was 44 yr old, he was examined at our hospital for constriction of the rectum due to the rectovesical fistula. Abdominoperineal excision of rectum and surgical closure of the fistula were performed, and the patient was kept under observation because of a diagnosis of familial adenomatous polyposis. In 1988, when the patient was 46 yr old, early ascending colon cancer was discovered and total colectomy was performed. Then, in December, 1991, gross hematuria was found. Further examination revealed a tumor on the posterior wall of the urinary bladder lumen, and biopsy showed adenocarcinoma. Pelvic recurrence of the rectal cancer was diagnosed, and total pelvic exenteration was performed. There were no distant metastases; histologically, the tumor of the bladder was thought to be due to colonic mucosa of familial adenomatous polyposis that had migrated to the bladder lumen via the rectovesical fistula and had become cancerous.

Adenomatous Polyposis Coli↗

PubMed2000

Immune tolerance induced by polyethylene glycol-conjugate of protein antigen: clonal deletion of antigen-specific Th-cells in the thymus.

Polyethylene glycol (PEG) conjugates of protein antigens induce antigen-specific immune tolerance of helper T (Th)-cells. However, the mechanism of this Th-cell tolerance has remained unelucidated. Using transgenic mice with ovalbumin (OVA)-specific T-cell receptor (TCR) genes, we examined the response of OVA-specific Th-cells towards tolerogenic PEG-conjugate of OVA in vitro and in vivo. When stimulated with PEG--OVA in vitro, transgenic OVA-specific Th-cells proliferated and produced interleukin 2, the levels of which were comparable to those induced by unmodified OVA. In contrast, PEG--OVA administered into the circulation of transgenic mice induced unresponsiveness in peripheral OVA-specific Th-cells. Moreover, in the thymus of these transgenic mice, the frequency of immature CD4+CD8+ (double positive) thymocytes was reduced. A similar phenomenon was not observed in transgenic mice treated with unmodified OVA. As autoreactive T-cells are known to be clonally deleted at the immature double positive stage in the thymus. Th-cell tolerance induced by PEG--protein antigens is at least in part mediated by central tolerance in the thymus, and is likely caused by the markedly enhanced stability of PEG--protein conjugates in the circulatory system.

Animals↗

PubMed2000

Effects of dietary, drinking, and smoking habits on the prognosis of gastric cancer.

Although it has been clarified that dietary, drinking, and smoking habits contribute to the onset of gastric cancer, little is known about their impact on prognosis of gastric cancer. To examine this question, a prognostic analysis was conducted using data from Aichi Cancer Center Research Institute and Hospital. From January 1988 to December 1994, information on 877 gastric cancer patients (578 men and 299 women) regarding habitual smoking and drinking, food consumption, histological grade, and clinical stage of tumor as well as follow-up results were collected. Survival status of all patients was followed up until December 1998, and the survival function was estimated by the Kaplan-Meier method. Proportional hazard analysis was used to test the effect of each lifestyle item on gastric cancer death. After controlling for age, gender, histological grade, and stage of disease, hazard ratios (HR) were calculated. Values for consumption of raw vegetables [HR = 0.74, 95% confidence interval (CI) = 0.56-0.98], tofu (HR = 0.65, 95% CI = 0.42-0.99), and chicken meat (HR = 0.61, 95% CI = 0.39-0.95) more than three times per week demonstrated significantly decreased risk. However, the risk ratio was 2.53 (95% CI = 1.22-5.29) for habitual smokers, and an inverse dose-response relationship was also found between ever smoking and gastric cancer patient survival. Therefore, this study suggested that frequent intake of raw vegetables and tofu is favorable, whereas habitual smoking is an adverse prognostic factor for gastric cancer. Our study implies that an improvement of survival of Japanese gastric cancer might be achieved by lifestyle improvement.

Adenocarcinoma↗

PubMed2000

Development of a digital image database for chest radiographs with and without a lung nodule: receiver operating characteristic analysis of radiologists' detection of pulmonary nodules.

OBJECTIVE: We developed a digital image database (www.macnet.or.jp/jsrt2/cdrom_nodules.html ) of 247 chest radiographs with and without a lung nodule. The aim of this study was to investigate the characteristics of image databases for potential use in various digital image research projects. Radiologists' detection of solitary pulmonary nodules included in the database was evaluated using a receiver operating characteristic (ROC) analysis. MATERIALS AND METHODS: One hundred and fifty-four conventional chest radiographs with a lung nodule and 93 radiographs without a nodule were selected from 14 medical centers and were digitized by a laser digitizer with a 2048 x 2048 matrix size (0.175-mm pixels) and a 12-bit gray scale. Lung nodule images were classified into five groups according to the degrees of subtlety shown. The observations of 20 participating radiologists were subjected to ROC analysis for detecting solitary pulmonary nodules. Experimental results (areas under the curve, Az) obtained from observer studies were used for characterization of five groups of lung nodules with different degrees of subtlety. RESULTS: ROC analysis showed that the database included a wide range of various nodules yielding Az values from 0.574 to 0.991 for the five categories of cases for different degrees of subtlety. CONCLUSION: This database can be useful for many purposes, including research, education, quality assurance, and other demonstrations.

Adult↗

PubMed2000

[Peroxisome proliferator-activated receptor(PPAR)--structure, function, tissue distribution, gene expression].

Peroxisome proliferator-activated receptors(PPARs, alpha, beta/delta, and gamma) are members of the nuclear receptor superfamily of ligand-activated transcription factors. PPAR has been shown to be regulated the expression of genes involved in lipid metabolism by various compounds such as fibrates, thiazolidinediones, prostaglandins, and fatty acids that is important in adipocyte differentiation and glucose homeostasis. PPARs form a heterodimer with the retinoid X receptor(RXR) and bind to specific DNA sequences located upstream of peroxisome proliferator responsive genes and interact with co-activators, including SRC-1 family, CBP/p300 or TRAP/DRIP complex by ligand dependent way. It is suggested that the selective interactions of PPAR with coactivators induced by PPAR's compounds specify the biological activities of the its compounds. Such differential combinations of transcription factors/coactivators are believed to activate only particular sets of target gene promoters.

Animals↗

PubMed2000

Protein expression and constitutive phosphorylation of hematopoietic transcription factors PU.1 and C/EBP beta in acute myeloid leukemia blasts.

The transcriptional activity of transcription factors is regulated by phosphorylation. The uncontrolled expression and constitutive activation of transcriptional regulators have been reported to cause malignant diseases. However, little is known about the phosphorylation status of tissue-specific transcription factors in human primary malignancies. Here we present the first insights into both protein expression and phosphorylation of transcription factors in a large-scale study of patients with acute myeloid leukemia (AML). We examined the expression and phosphorylation status of hematopoietic transcription factors PU.1 and C/EBP beta detected by the retarded mobility of the phosphorylated forms of the proteins. The rate of protein expression differed among French-American-British (FAB) subclasses. The expression of C/EBP beta and PU.1 were detectable in 77% and 61%, respectively, of 90 AML samples examined. The expressed PU.1 and C/EBP beta was always accompanied with both phosphorylated and unphosphorylated forms of PU.1 and C/EBP beta, respectively. Statistical significance was observed between PU.1 expression (phosphorylation) and FAB classification (M0, M4, or M5 versus M2 or M3, P < .0001). PU.1 and C/EBP beta were simultaneously detected in all M0, M4, M5 and peripheral blood monocytes, whereas in M2 and M3, the expression of the 2 transcription factors varied among samples. Examination of protein expression and phosphorylation of these lineage-specific molecules may help us to understand the functional characteristics of AML.

Acute Disease↗

PubMed2000

Polyethylene glycol-modified concanavalin A as an effective agent to stimulate anti-tumor cytotoxicity.

The jack bean lectin, concanavalin A (Con A), was modified with 2,4-bis[O-methoxypoly(ethylene glycol)]-6-chloro-s-triazine, activated PEG2, to form PEG-Con A. The immunoreactivity of PEG-Con A towards anti-Con A antibodies was reduced by increasing the degree of modification of amino groups in the Con A molecule. PEG-Con A had a complete reduction of the immunogenicity in mice and prolonged the clearance-time in blood. Although the mitogenic activity of Con A towards murine spleen cells was reduced by the conjugation with activated PEG2, the administration of PEG-Con A to mice enhanced the anti-tumor cytotoxicity of peripheral lymphocytes against melanoma B16 cells.

Animals↗

PubMed2000

Quality of life in adult patients after stem cell transplantation.

Many articles pertaining to quality of life (QOL) following stem cell transplantation have been published in the US and western Europe. However, since the actions of health insurance systems and overall cultural aspects are strongly associated with QOL, investigations into QOL should be carried out within all countries. Therefore, we have investigated the QOL of adult patients following stem cell transplantation at 31 hospitals in Japan. The survivors, who were surveyed by mail questionnaire, were 20 years or older at the time of this study. The underlying diseases were acute lymphoblastic leukemia, acute myelogenous leukemia, chronic myelogenous leukemia, non-Hodgkin's lymphoma, Hodgkin's disease, myelodysplastic syndrome, and multiple myeloma. Median age at the time of the study was 36 years, and median interval after transplantation was 35.3 months. Of 383 patients surveyed, 282 (73.6%) responded to the questionnaire. One hundred and ninety-two patients were treated with an allogeneic-related transplantation, 52 with allogeneic-unrelated, and 38 with an autologous transplantation. Our data revealed that the length of time since transplantation and the diagnosis of chronic GVHD were associated with QOL. When unrelated and related transplantation recipients were compared, ratings on relief from pain, stability in weight, and confidence in dealing with daily life were lower among unrelated transplantation patients.

Adolescent↗

PubMed2000

Effective and safe interferon treatment for Japanese patients with chronic myelogenous leukemia relapse after bone marrow transplantation. The Nagoya Blood and Marrow Transplantation Group.

The purpose of this study was to assess the efficacy and safety of interferon (IFN) treatment in patients with a relapse of chronic myelogenous leukemia (CML) after bone marrow transplantation in Japan. Accordingly, we retrospectively analyzed the results obtained from 8 patients treated with IFN by the Nagoya Blood and Marrow Transplantation Group. One of 3 patients with hematologic relapse and all 5 patients with cytogenetic relapse achieved complete cytogenetic response (CCR). The median time to achieve CCR was 8 months (range, 3-16 months). One patient relapsed 9 months after starting IFN and died of blast crisis. CCR was maintained for a median duration of 47 months (range, 9-79 months) in the remaining 5 patients. The median duration of survival of these 5 patients after starting IFN was 58 months (range, 12-89 months). At the time of this report, 2 patients who did not attain CCR have survived for 81 months and 142 months after starting IFN, respectively. During IFN treatment, 1 patient showed a transient deterioration of chronic graft-versus-host disease, and no treatment-related deaths were observed. These results suggest that treatment with IFN for CML patients who relapse after bone marrow transplantation is effective and safe. A prospective study to compare IFN with donor lymphocyte infusion is necessary to establish the optimal strategy for the treatment of CML patients who relapse after bone marrow transplantation.

Adult↗

PubMed2000

Analysis of genetic polymorphism in NQO1, GST-M1, GST-T1, and CYP3A4 in 469 Japanese patients with therapy-related leukemia/ myelodysplastic syndrome and de novo acute myeloid leukemia.

Several genetic polymorphisms in metabolic activation or detoxification enzymes have been associated with susceptibility to therapy-related leukemia and myelodysplastic leukemia (TRLIMDS). We analyzed gene polymorphisms of NAD(P)H:quinone oxidoreductase (NQOl), glutathione S-tranferase (GST)-MI and -TI, and CYP3A4, the enzymes of which are capable of metabolizing anticancer drugs, in 58 patients with TRL/MDS and in 411 patients with de novo acute myeloid leukemia (AML). Homozygous Ser/Ser genotype of NQOl at codon 187, causing loss of function, was more frequent in the patients with TRLIMDS (14 of 58, 24.1%; OR = 2.62) than in those with de novo AML (64 of 411, 15.6%), and control (16 of 150, 10.6%; P = 0.002). Allelic frequencies of NQOJ were different between TRL/ MDS and de novo AML (P = 0.01). In GST-MJ and -Ti, the incidence of homologous deletion was similar among the three groups. The polymorphism of the 5' promoter region of CYP3A4 was not found in persons of Japanese ethnicity. These results suggest that the NQOJ polymorphism is significantly associated with the genetic risk of TRLIMDS.

Adult↗