Biomedical subjects

Y Kodera

Publications and source records attributed to Y Kodera.

At least 127 records · Page 7Linked to original sources

PubMed1998

[FK506 for the prophylaxis of graft-versus-host-disease after bone marrow transplantation from HLA-genotypically mismatched unrelated donor].

Eleven leukemia patients who had undergone bone marrow transplants from HLA-A, B, DR genotypically mismatched unrelated donors received FK506 and short-term methotrexate as prophylaxis for graft-versus-host disease (GVHD). Grade III-IV acute GVHD developed in 2 of the patients, and chronic GVHD developed in 4 of the other patients. Adverse drug reaction included reversible nephrotoxicity, hyperglycemia (all patients) and hypertension (9 patients). Hyperglycemia and hypertension of grade 3 or higher occurred mostly in the patients who were on supplemental steroids. However, severe nephrotoxicity was not observed. Complications included cystitis (4 patients), cytomegalovirus colitis (3 patients), Interstitial Pneumonitis (IP) (3 patients), tuberculosis (1 patient), and thrombotic microangiopathy (1 patient). None of patients relapsed. Although close monitoring of FK506 blood concentration and patient clinical signs are required, we concluded that FK506 is effective for GVHD prophylaxis after bone marrow transplantation from HLA-A, B, DR genotypically mismatched unrelated donors, and that adverse reactions due to FK506 are controllable. To determine the long-term effectiveness of this drug, it will be necessary to conduct prospective randomized studies that compare it wiht cycloporin A as a preventive treatment against GVHD in patients who receive bone marrow transplants from HLA genotypically mismatched unrelated donors.

Adolescent↗

PubMed1997

Overexpression of cyclin E in acute myelogenous leukemia.

Cyclin E is one of the G1 cyclins that play an important role in cell proliferation. Overexpression of cyclin E protein has been reported in several solid tumors, but little is known about the involvement of cyclin E in leukemia. In this study, we analyzed the expression of cyclin E gene product in 85 patients with acute myelogenous leukemia (AML) by Western blot analysis. In 23 of 85 AML samples (27%), cyclin E expression was enhanced in blasts. Among the French-American-British classification of AML, the ratio of the samples with enhanced cyclin E expression was high in M5 and low in M2 and M3. No rearrangements were observed by Southern blot analysis in these AML blasts with enhanced cyclin E expression. Flow cytometric analysis showed no correlation between overexpression of cyclin E and cell cycle distribution. Immunoblot analysis of cyclin D1 showed no correlation between overexpression of cyclin E and that of cyclin D1. Interestingly, p27 expression detected by Western blotting was apparently enhanced in 18 of 23 AML cells with enhanced cyclin E expression but none of 14 AML cells without enhanced cyclin E exhibited enhanced p27 expression. The rates of complete remission and of disease-free survival of the patients with M4 or M5 leukemia blasts with overexpressed cyclin E seemed to be low. Therefore, we suggest the necessity of a larger-scale study to elucidate the contribution of cyclin E overexpression to the phenotype and the prognosis of certain AML.

Adult↗

PubMed1997

CD7+ and CD56+ myeloid/natural killer cell precursor acute leukemia: a distinct hematolymphoid disease entity.

The disease spectrum of natural killer (NK) cell leukemias and lymphomas has recently been expanding with the continuing evolution in diagnostic concepts. We describe here seven cases of acute leukemia of conceivable myeloid and NK cell precursor phenotype in six men and one woman varying from 19 to 59 years of age (median, 46 years). Striking extramedullary involvement was evident at initial presentation, with peripheral lymphadenopathy and/or mediastinal masses. Two lacked any leukemic cells in the bone marrow at diagnosis. Using cytochemical myeloperoxidase staining, less than 3% of the leukemic cells showed positive reactivity. However, expression of CD7, CD33, CD34, CD56, and frequently HLA-DR, but not other NK, T-cell, and B-cell markers was observed. Cytoplasmic CD3 was detected in three of the cases by flow cytometry and in six by Northern blotting, suggesting an origin from common progenitors between the NK cell and myeloid lineages. All but one presented germline configurations of the T-cell receptor beta and gamma chain genes and Ig heavy chain gene. With regard to morphology, the cells were generally L2-shaped, with variation in cell size, round to moderately irregular nuclei and prominent nucleoli, pale cytoplasm, and a lack of azurophilic granules. Histopathologic examination of biopsied specimens of extramedullary tumors showed a lymphoblast-like morphology, implying the differential diagnostic problem from lymphoblastic lymphomas, especially in cases lacking bone marrow involvement. Three patients were successfully treated with chemotherapy for acute myeloid leukemia (AML), whereas three other patients proved refractory to chemotherapeutic regimens for lymphoid malignancies, although two responded to subsequent AML chemotherapy. However, despite intensive chemotherapy, including allogeneic bone marrow transplantation, most persued fatal courses within 41 months. These data suggested that the CD7+ and CD56+ myeloid/NK cell precursor acute leukemia might constitute a distinct biologic and clinical disease entity. Its recognition appears to be particularly important for the clinicopathologic evaluation of CD56+ hematolymphoid malignancies and the development of therapeutic approaches to such disease.

Acute Disease↗

PubMed1997

Gastric cancer with carcinoma erysipeloides caused by spontaneous thoracic duct rupture: report of a case.

A case of extensive skin metastasis (carcinoma erysipeloides) resulting from spontaneous rupture of the metastasized Virchow lymph node in a 53-year-old woman is herein reported. Imaging evidence attributing this metastasis to spontaneous rupture of the fragile thoracic duct at the supraclavicular fossa is presented. The patient, who had already undergone gastric resection more than 6 years previously because of advanced gastric cancer, died approximately 4.5 months after the occurrence of lymphorrhea in her neck since the anticancer chemotherapy administered demonstrated little or no effect.

Carcinoma↗

PubMed1997

Phase I/II trial of cure-oriented high-dose chemoradiotherapy with transplantation of CD34+ peripheral blood stem cells purified by the immunomagnetic bead method for refractory hematological malignancies. Nagoya CD34+ PBSCT Study Group.

A multicenter phase I/II clinical trial was conducted to evaluate the safety of a device (Isolex System; Baxter Health Corporation, Irvine, Calif., USA) using the immunomagnetic bead method to purify CD34+ stem cells from peripheral blood and to assess the efficacy and toxicity of high-dose chemoradiotherapy with peripheral blood stem-cell transplantation (PBSCT) using purified CD34+ stem cells in patients with refractory hematological malignancies. Patients eligible for the study included those who had T-cell acute lymphoblastic leukemia (T-ALL), lymphoblastic lymphoma (LBL), mantle-cell lymphoma (MCL), high-risk aggressive non-Hodgkin's lymphoma (NHL), and adult T-cell leukemia/lymphoma (ATLL) in first complete remission (CR) and those who had standard-risk aggressive NHL, indolent lymphoma, Hodgkin's disease, or acute promyelocytic leukemia (APL) in second CR or first partial remission (PR) after the completion of first-line chemotherapy and were chemosensitive to salvage chemotherapy, in whom tumor contamination of harvested peripheral blood stem cells (PBSCs) was possible due to bone marrow or peripheral blood involvement. Lack of CD34 expression by tumor cells was an important selection factor. Eight patients with hematological malignancies (six NHL patients, one ATLL patients, and one APL patient) were enrolled; their median age was 41 years (range 26-49 years). After consolidation and mobilization chemotherapy, two or three courses of apheresis were performed in each patient. After high-dose chemo(radio)therapy, in each patient a median of 1.8 x 10(6) cells/kg (range 8.2 x 10(5)-5.1 x 10(6) cells/kg) purified CD34+ PBSCs were infused; granulocyte colony-stimulating factor was given from day 1. Median times to hematopoietic recovery were as follows: WBC of > or = 1,000/microliter, day 11; platelet count of > or = 50,000/microliter, day 19; and reticulocyte count of > or = 10/1000, day 15. Two NHL patients relapsed at 23 and 9 months after PBSCT, respectively; the remaining six patients are alive and in CR. No severe toxicity was observed in any patient. Tumor contamination as measured using a polymerase chain reaction-mediated RNase protection assay at the 10-4 level was detected in the CD34(+)-purified fractions of 2 of the 5 samples analyzed; however, a reduction in contaminating lymphoma cells from the autograft of at least 1,000 to 10,000 orders of magnitude was achieved by CD34+ selection using the immunomagnetic bead method. High-dose chemoradiotherapy with transplantation of CD34+ PBSCs purified by the immunomagnetic bead method was thus shown to be an active and safe therapy for refractory hematological malignancies with bone marrow or peripheral blood involvement. However, it is too early for evaluation of the long-term survival benefit.

Adolescent↗

PubMed1997

Broncho-bronchiolitis obliterans as a complication of bone marrow transplantation: a clinicopathological study of eight autopsy cases. Nagoya BMT Group.

We identified eight patients with bronchiolitis obliterans (BO) in the autopsies of 81 bone marrow transplant (BMT) recipients. Rapidly progressive dyspnoea and cough were the main presenting symptoms in all eight patients, associated with overinflation and/or infiltrative opacity seen on chest X-ray and obstructive disorder revealed by pulmonary function tests. Early lesions were characterized by epithelial loss and an inflammatory infiltrate containing foamy histiocytes with mild luminal narrowing. Partial or total occlusion of the bronchiolar lumina by fibrous connective tissue was the feature of late lesions. Both changes were coexistent in all cases. In one case, small bronchi with cartilage were also affected by the obstructive process, showing bronchitis obliterans. All eight patients showed non-obstructive broncho-bronchiolitis characterized by denuding of respiratory epithelium, mural oedema and an inflammatory infiltrate in addition to BO, and these changes were also seen in 18 patients without BO. The submucosal glands of large bronchi and the trachea showed mucous retention and a mild inflammatory infiltrate in four of the eight patients. Coexistent infectious processes were seen in all cases, cytomegalovirus and Aspergillus being the most frequent organisms. BO probably develops as an immunopathological event related to graft-versus-host disease (GVHD) during the impaired immune status phase of the post-BMT period, possibly initiated by infection. Bronchial gland involvement in chronic GVHD is one of the factors responsible for this abnormal immune status.

Adolescent↗

PubMed1997

Unrelated bone marrow transplantation from the National Marrow Donor Program.

Between November 1992 and December 1996, we carried out bone marrow transplantation through the National Marrow Donor Program (NMDP) for 11 patients who lacked an appropriate donor among their family members and the Japan Marrow Donor Program (JMDP). They accounted for 11% of 101 patients who had registrated to the NMDP Transplant Center Office in Japan. The median time required from the initiation of preliminary search to transplant for these 11 patients was 198 days. The 11 donors included four Caucasians, one Native American and the others were Asian/Pacific islanders. A median of 17 h was required to transport bone marrow from harvest institutes to our hospital and their viability determined in our laboratory had a median of 96%. Engraftment was observed in all recipients and the incidence of grade III-IV acute graft-versus host disease was 27%. Of four patients three (75%) with chronic myelogenous leukemia in chronic phase (standard-risk) and two (29%) of seven patients in progressive state of the disease (high-risk), are alive at present. Cooperation between the JMDP and the NMDP, which began in April 1997, could shorten the time for donor search and allow transplantation to more patients with more appropriate timing.

Adolescent↗

PubMed1997

Prolonged selective neutropenia after allogeneic bone marrow transplantation: possible effect of presensitization by donor lymphocytes prior to transplant.

Selective neutropenia lasting over five months occurred in a 17-year-old adolescent male who received an allogeneic bone marrow transplantation (BMT) from an HLA-identical sibling for severe aplastic anemia. Bone marrow specimens showed maturation arrest of myeloid precursor cells despite sustained engraftment. Cytogenetic analyses revealed complete donor-type chimerism in hematopoietic cells and mixed lymphoid chimerism. The patient received a second BMT from the same donor following more intensive conditioning, including total body irradiation. Neutrophil recovery was rapid and complete donor-type hematopoietic and lymphoid chimerism was observed within three weeks of the second transplant. The present case suggests that prolonged selective neutropenia following BMT is due to residual host-derived immunity which is resistant to the standard immunosuppressive conditioning used prior to BMT for aplastic anemia.

Adolescent↗

PubMed1997

Metastatic gastric lymph node rate is a significant prognostic factor for resectable stage IV stomach cancer.

BACKGROUND: Stage IV gastric carcinoma is rarely curatively resected and almost invariably carries a poor prognosis. Several clinicopathologic factors are involved, but lymphatic spread of the cancer may significantly affect survival. STUDY DESIGN: A retrospective study was designed to evaluate whether the nodal metastatic rate (number of lymph node metastases/number of resected lymph nodes) is a parameter of lymphatic spread and could provide a significant prognostic factor. Several prognostic factors were assessed by multivariate analysis in 153 stage IV gastric carcinoma patients with histopathologic data on nodal metastasis. RESULTS: A significant difference in survival was observed in the stage IV cancer patients with total nodal or gastric nodal metastatic rates < 50% versus those with rates > 50%. Multivariate analysis revealed that a total nodal or gastric nodal metastatic rate > 50% was a highly significant prognostic factor. The gastric nodal metastatic rate can be used in patients who do not undergo an extended lymphadenectomy. CONCLUSIONS: Lymphatic spread of gastric carcinoma expressed in terms of the total nodal or gastric nodal metastatic rate is a significant prognostic factor. The latter can be calculated without pathologic data derived from extended lymphadenectomy, and so it is universally applicable.

Humans↗

PubMed1997

Anti-inflammatory activity of superoxide dismutase conjugated with sodium hyaluronate.

Superoxide dismutase (SOD) from bovine erythrocytes was conjugated with sodium hyaluronate (HA) with a mean molecular weight of 10(6) to have greater anti-inflammatory activity in vivo. Amino groups of SOD were coupled with carboxyl groups in the hyaluronate molecule using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide. The HA-SOD conjugate was composed of 1.5 mol of SOD molecule per 1 mol of hyaluronate on the average, and retained 70% of the activity of unmodified SOD. The conjugate was essentially non-immunogenic in mice, and exhibited much higher anti-inflammatory activities than HA or SOD in models of inflammatory diseases such as ischemic oedema of the foot-pad in mice, carrageenin-induced pleurisy and adjuvant arthritis in rats.

Animals↗

PubMed1997

Neurotrophic activity of organosulfur compounds having a thioallyl group on cultured rat hippocampal neurons.

Several organosulfur compounds found in garlic extract promoted the survival of rat hippocampal neurons in vitro. From the analysis of structure-activity relationship, thioallyl group in these compounds is essential for the manifestation of neurotrophic activity. S-Allyl-L-cysteine (SAC), one of the organosulfur compounds having thioallyl group in garlic extract, also promoted the axonal branching of cultured neurons. These results suggest that thioallyl compounds make a unique group of neurotrophic factors.

Animals↗

PubMed1997

Hepatic injury localized to the field of total lymphoid irradiation.

A 37-year-old woman with severe aplastic anemia underwent allogeneic bone marrow transplantation following cyclophosphamide (CY) and total lymphoid irradiation (TLI). On day +30, a CT scan was carried out because of a mild elevation in liver enzymes, and it revealed a low density area with a sharp border in the left lobe corresponding to the irradiated area. MRI showed a hypersignal intensity on both T1 and T2-weighted images and suggested that hepatic damage was mainly severe fatty change. These abnormalities resolved with no treatment. CY with TLI for adult patients with severe aplastic anemia may induce hepatic injury.

Adult↗

PubMed1997

Cell cycle arrest and apoptosis of leukemia cells induced by L-asparaginase.

Apoptotic cell death of murine leukemia cells induced by E. coli L-asparaginase was studied. Deprivation of L-asparagine from the culture of L5178Y cells by L-asparaginase caused the fragmentation of chromosomal DNA of the leukemia cells within 24 h. Prior to the degradation of DNA, cell cycles of L5178Y cells were found to be arrested in G1 phase, and evidence of the DNA strand breaks was initially observed in G1 phase cells as early as 8 h after the asparaginase treatment. Therefore, apoptosis of leukemia cells induced by L-asparaginase is an event that is associated with the cell cycle arrest in G1 phase.

Animals↗

PubMed1997

Plasma levels and production of soluble stem cell factor by marrow stromal cells in patients with aplastic anaemia.

Defective marrow stroma or microenvironment have been proposed as one of several mechanisms to account for bone marrow failure in aplastic anaemia (AA). Stem cell factor (SCF), the ligand for the c-kit receptor, is produced mainly by marrow stromal cells and seems to reflect the haemopoietic function of bone marrow stroma. We measured the plasma levels of soluble SCF in 8 7 patients with AA and investigated the production of soluble SCF by the marrow stromal cells of 46 patients with acquired AA. The mean plasma SCF concentrations in the AA patients and normal controls were not significantly different (1098 +/- 398 pg/ml versus 1160 +/- 316 pg/ml, respectively), and there was no significant correlation between the peripheral blood counts and the SCF concentrations. However, the mean SCF concentration in patients who received prednisolone +/- anabolic steroids at the time of sampling was significantly lower than that in the patients who did not receive both agents. We did not find any correlation between the changes in SCF concentrations and the response to immunosuppressive therapy, although it did increase significantly after bone marrow transplantation. The ability of marrow stromal cells to release soluble SCF did not differ significantly between the patients with AA and normal controls. We conclude that soluble SCF production does not appear to be altered in patients with AA and that defective production of soluble SCF is unlikely to be the cause of AA in most patients.

Adolescent↗

PubMed1997

Measurement of endogenous plasma thrombopoietin in patients with acquired aplastic anaemia by a sensitive enzyme-linked immunosorbent assay.

We measured the endogenous plasma concentration of thrombopoietin (TPO) in 76 patients with acquired aplastic anaemia (AA) by a sensitive sandwich enzyme-linked immunosorbent assay (ELISA). The plasma TPO concentrations were significantly higher in AA patients when compared to healthy control subjects (P < 0.0001) and there was a significant negative correlation between plasma TPO concentrations and platelet counts in 54 AA patients who had not received any platelet transfusions prior to sampling. On the other hand, there was no statistically significant correlation between the TPO concentrations and platelet counts in 22 AA patients who had previously received platelet transfusions. We studied serial changes of plasma TPO concentration in 24 patients who showed an increase in their platelet counts following bone marrow transplantation or immunosuppressive (IS) therapy. Although a decrease in plasma TPO concentration was observed, levels remained above the range of normal healthy controls even in the patients who attained normal platelet counts following therapy. A decrease in TPO concentrations was observed in only half of the responders to IS therapy. Whether exogenous TPO will result in increased platelet counts in AA patients with high TPO levels remains to be determined.

Adolescent↗

PubMed1997

A new macroscopic classification predicts prognosis for patient with liver metastases from colorectal cancer.

OBJECTIVE: The authors defined a new macroscopic classification of liver metastases from colorectal cancer. SUMMARY BACKGROUND DATA: There were different prognostic results after the same operative procedure for liver metastases with similar background factors. METHODS: Eighty-one resected liver metastases were classified into simple nodular (SN) or confluent nodular (CN) types according to the characteristics of the cut surface of the tumor. RESULTS: The 5-year survival rates after hepatectomy were 41.7% for the SN lesions (n = 39) and 23.1% for the CN lesions (n = 42). The difference between the survival curves was statistically significant (p = 0.0307). Multivariate analysis using Cox's proportional hazards model revealed that the macroscopic type (p = 0.023), the tumor diameter (p = 0.0001), and the presence of lymph node metastases (p = 0.0016) were statistically significant independent prognostic factors. CONCLUSION: The new macroscopic classification may be valuable as a prognostic factor reflecting the biologic behavior of liver metastases.

Colorectal Neoplasms↗

PubMed1997

Detection of carcinoembryonic antigen-expressing free tumor cells in peritoneal washes from patients with gastric carcinoma by polymerase chain reaction.

Cytological examination of peritoneal washes is a useful predictor of peritoneal recurrence in gastric carcinoma patients. In the present study, even more sensitive detection of free cancer cells could be achieved through amplification of carcinoembryonic antigen (CEA) mRNA by means of the reverse transcriptase-polymerase chain reaction (RT-PCR). CEA was first confirmed to be present in all the gastric cancer cell lines examined, irrespective of the differentiation degree, and absent in blood and mesothelium, indicating the specificity of this approach for detection of carcinoma cells in peritoneal lavage fluid. In sensitivity tests, CEA RT-PCR proved to be capable of detecting 10 carcinoma cells per sample. Peritoneal washes of 15 of 48 gastric carcinoma patients, including all 10 patients with positive cytology results, proved positive for CEA mRNA. None of the 5 patients with benign disease was positive. Moreover, a close association with the depth of cancer invasion was established. The results indicate that the assay is more sensitive for detection of free carcinoma cells in the peritoneal cavity than conventional cytology. This is the first study to suggest the feasibility of the RT-PCR method for prediction of peritoneal recurrence in gastric cancer patients.

Adult↗

PubMed1997

Surgical treatment of early cancer of the proximal third of the stomach.

A retrospective study was conducted in search of an optimal surgical procedure for early cancer of the proximal stomach. The clinicopathological findings and survival data of 128 patients operated on during a recent period of 16 years were analyzed. Nodal metastasis was found in 12% of the patients and had a significant influence on the survival. It was more frequently observed in the undifferentiated type, regardless of the tumor size. Most metastases were found in the proximal paragastric nodes, and no metastasis was observed in the pyloric region or at the splenic hilum. These facts suggest that while the resection of paragastric nodes is advocated, neither total gastrectomy nor splenectomy is required simply for the purpose of lymphadenectomy.

Humans↗