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Biomedical subjects

Y Kodera

Publications and source records attributed to Y Kodera.

At least 109 records · Page 6Linked to original sources

Asian Pacific cooperative study of allogeneic bone marrow transplantation.

The first cooperative study of the Asian Pacific bone marrow transplantation group included 75 patients with early leukemia who received human leukocyte antigen-matched sibling bone marrow transplants and were randomized into granulocyte colony-stimulating factor and control groups. The selected patients were registered from 10 centers in six countries and areas within Asia (Beijing, Taipei, Hong Kong, Japan, Korea, and Malaysia). The incidence of grades II-IV acute graft-vs.-host disease was 22.2%, and the 2-year survival rate was 62.7%. The period of protective isolation (27.1-66.7 days), period of hospitalization (38.6-130.5 days), and medical costs for 4 months (US $10,300-US $80,803) varied considerably. Good cooperation, i.e., low rate of protocol violation or rapid and precise presentation of case reports, was obtained.

Bone Marrow Transplantation↗

[Nationwide survey of allogeneic peripheral blood stem cell transplantation from related donors in Japan: current trends and issues].

In December 1997, we conducted a nationwide survey of cases of primary allogeneic peripheral blood stem cell transplantation (allo-PBSCT) performed in Japan between December 1994 and November 1997 Data was collected on 103 patients with hematologic malignancies, aplastic anemia, or solid tumors. Eighty-seven patients received transplants from HLA-identical siblings, and 16 from HLA-mismatched related donors. Granulocyte-colony stimulating factor (G-CSF) mobilized peripheral blood stem cells (PBSC) were collected from donors by 1 to 3 aphereses. Apheresis products contained a median 5.4 (1.0-30.4) x 10(6) CD34 + cells/kg. Most patients were given cyclosporine and methotrexate for graft-versus-host disease (GVHD) prophylaxis. Median days to ANC > 500/microliter and platelets > 50,000/microliter were 13 (7-49) and 16 (10-94), respectively. Grade II-IV acute GVHD developed in 37/99 (37.4%) and chronic GVHD in 59/86 (68.6%) patients. The incidence of treatment-related mortality within 100 days after transplant was 16.1%. Fifty-five patients (59.6%) were alive after a median follow-up of 794 days. More patients and longer follow-up periods will be required to assess the efficacy of allo-PBSCT and evaluate graft-versus-leukemia effect along with the incidence of acute and chronic GVHD.

Adolescent↗

High-resolution solution NMR structure of the minimal active domain of the human immunodeficiency virus type-2 nucleocapsid protein.

The retroviral nucleocapsid (NC) protein is a multifunctional protein essential for RNA genome packaging and viral infectivity. The NC protein, NCp8, of the human immunodeficiency virus type-II (HIV-2) is a 49 amino acid peptide containing two zinc fingers, of the type C-X2-C-X4-H-X4-C, connected by seven amino acid residues, called the "basic amino acid cluster." It has been shown that the N-terminal zinc finger flanked by the basic amino acid cluster is the minimal active domain for the specific binding to viral RNA and other functions. However, the structure-activity relationships of NCp8 have not been investigated in detail. In the present study, the three-dimensional structure of a 29 amino acid peptide, including the minimal active domain (NCp8-fl), was determined by two-dimensional 1H NMR spectroscopy with simulated annealing calculations. A total of 15 converged structures of NCp8-fl were obtained on the basis of 355 experimental constraints, including 343 distance constraints obtained from nuclear Overhauser effect connectivities, 12 torsion angle (phi, chi1) constraints, and four constraints for zinc binding. The root-mean-square deviation of the 15 converged structures was 0.29 +/- 0.04 A for the backbone atoms (N, C(alpha), C) and 1.27 +/- 0.13 A for all heavy atoms. Interestingly, the basic amino acid cluster itself was defined well, with a loop-like conformation in which three arginine residues in the cluster and one arginine residue in the zinc finger are located approximately in the same plane of the molecule and are exposed to the solvent. The structure-activity relationships are discussed on the basis of the comparison of this well-defined structure with those of other NC proteins.

Amino Acid Sequence↗

Effect of matching of class I HLA alleles on clinical outcome after transplantation of hematopoietic stem cells from an unrelated donor. Japan Marrow Donor Program.

BACKGROUND: The requirements with respect to HLA compatibility and the relative importance of matching for individual class I and class II HLA alleles in the transplantation of hematopoietic stem cells from unrelated donors have not yet been established. METHODS: We performed retrospective DNA typing of alleles at 11 polymorphic loci of HLA genes in 440 recipients of hematopoietic stem cells from unrelated donors who were serologically identical with their respective recipients for HLA-A, B, and DR antigens. Of these recipients, 80 percent had leukemia; the rest had lymphoma, marrow failure, or a congenital disorder. RESULTS: Multivariate analysis showed that incompatibility for HLA-A alleles and incompatibility for HLA-C alleles were independent risk factors for severe acute graft-versus-host disease (GVHD) (HLA-A, P=0.006; HLA-C, P=0.001). Mismatching of HLA-A, but not of HLA-C, alleles was an independent risk factor for death (P<0.001). Matching [corrected] of HLA-C alleles was a significant risk factor for relapse of leukemia (P=0.035). HLA-B disparity was a significant risk factor for both GVHD and death in the univariate analysis, but not in multivariate analysis. Disparities in class II HLA alleles of the DRB1, DQA1, DQB1, DPA1, and DPB1 loci were not identified as significant risk factors for acute GVHD or death in the multivariate analysis. CONCLUSIONS: Genomic typing of class I HLA alleles adds substantially to the success of transplantation of hematopoietic stem cells from unrelated donors, even if the donors are serologically identical to their recipients with respect to HLA-A, B, and DR antigens.

Adolescent↗

Prognostic value and clinical implications of disseminated cancer cells in the peritoneal cavity detected by reverse transcriptase-polymerase chain reaction and cytology.

Free cancer cells exfoliated from the cancer-invaded serosa contribute to peritoneal dissemination, the most frequent pattern of recurrence in gastric carcinoma patients. This study was designed to evaluate the prognostic relevance of such free cells in peritoneal washes detected by reverse transcriptase-polymerase chain reaction (RT-PCR) and cytology. RT-PCR analysis with primers specific for carcinoembryonic antigen and conventional cytologic examination by Papanicolaou staining were performed on peritoneal washes, collected at laparotomy from 148 gastric carcinoma patients. Prognostic analyses were performed with 1) death due to cancer recurrence and 2) peritoneal dissemination as endpoints. RT-PCR was found to be more sensitive than cytologic examination for detection of free cancer cells in the peritoneal washes, with a higher detection rate for each of the T categories in the tumor-node-metastasis (TNM) classification. Five patients with synchronous or recurrent peritoneal dissemination were found among 17 patients with positive RT-PCR and negative cytologic results. Both positive cytologic results and positive RT-PCR results had significant influences over the survival of patients with advanced gastric carcinomas (n = 75, p < .002). Detection of free cancer cells in peritoneal washes, most reliably by RT-PCR, is promising as a predictor of peritoneal dissemination in patients with gastric carcinoma.

Carcinoembryonic Antigen↗

The promoter of the human 25-hydroxyvitamin D3 1 alpha-hydroxylase gene confers positive and negative responsiveness to PTH, calcitonin, and 1 alpha,25(OH)2D3.

25-Hydroxyvitamin D3 1 alpha-hydroxylase (1 alpha-hydroxylase) catalyzes hydroxylation, mainly in the kidney, of 25-hydroxyvitamin D3 [25(OH)D3] into 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25(OH)2D3], a hormonal form of vitamin D, acting as a key enzyme of vitamin D biosynthesis. Reflecting its biological significance, this enzymatic activity is differentially regulated by several factors involving calcium homeostasis, though the molecular mechanism is poorly understood. In our recent study (K. Takeyama, et al., 1997), we cloned the cDNA of mouse 1 alpha-hydroxylase, and this led us to investigate the regulation of gene expression and the function of the promoter of this gene. Here we report the isolation of the 5' flanking region of the human 1 alpha-hydroxylase gene and the identification of the human 1 alpha-hydroxylase promoter by a primer extension assay. We found that in the identified promoter, a positively regulatory region to parathyroid hormone (PTH) and calcitonin and a negatively regulatory region to 1 alpha,25(OH)2D3 are located around -4 and -0.5 kb, respectively. Thus, we provide direct evidence that the positive and negative regulation of 1 alpha-hydroxylase gene expression by hormones takes place at transcriptional levels through two distinct promoter regions.

Animals↗

A small deletion in the 3'-untranslated region of the cyclin D1/PRAD1/bcl-1 oncogene in a patient with chronic lymphocytic leukemia.

The cyclin DI/PRAD1 oncogene, a key regulator of the G1 phase of the cell cycle, has been incriminated in the pathogenesis of human neoplasia. Cyclin D1 was also demonstrated to be identical to the long-sought bcl-1 oncogene in B-cell malignancies with the t(11;14)(q13;q32) translocation. We report here a small deletion in the 3'-untranslated portion of the cyclin D1 gene in leukemia cells of a patient diagnosed with B-chronic lymphocytic leukemia (CLL), associated with overexpression of the corresponding cyclin D1 mRNA. During a Northern blot survey of B-cell malignancies, we identified a patient whose CLL cells showed a marked increase in 1.5-1.6 kb cyclin D1 mRNA species. Subsequent Southern blot analysis showed that genomic DNA from the patient's cells contained an extra band in the EcoRI digest, suggesting that one allele of the cyclin D1 gene may be altered. Polymerase chain reaction (PCR) analysis of the genomic DNA and direct DNA sequencing clearly disclosed that one allele of the cyclin D1 gene was deleted in the 3'-untranslated region, which would contribute to an increased stability of its mRNA. Reverse transcription-polymerase chain reaction (RT-PCR) analysis and direct DNA sequencing revealed that the cyclin D1 mRNA was deleted at the corresponding region. This finding provides further evidence for a critical role of cyclin D1 in the pathogenesis of B-cell malignancies and highlights a novel mechanism, a small deletion in the 3'-untranslated region, responsible for deregulation of the cyclin D1 gene in oncogenesis.

Base Sequence↗

Family history and subsite of gastric cancer: data from a case-referent study in Japan.

A comparative case-referent study was conducted using data from the Hospital-Based Epidemiologic Research Program at Aichi Cancer Center (HERPACC) (Nagoya, Japan), with the aim of clarifying the effect of family history on gastric cancer by subsite. Our study comprised 995 histologically confirmed gastric cancer cases (180 cardia, 430 middle, 365 antrum and 20 unclassified) and a total of 43,846 non-cancer outpatients at Aichi Cancer Center Hospital between 1988 and 1995. Logistic regression was used to calculate odds ratios (ORs) for family history of gastric cancer and other cancers, adjusted for age, year and season at first hospital visit, habitual smoking, habitual alcohol drinking, regular physical exercise, preference for salty food and raw vegetable intake. In both genders, a positive family history of gastric cancer was associated with a moderate, but statistically significant increase in risk of gastric cancer [OR = 1.51, 95% confidence interval (95% CI) = 1.29-1.76], while no association was observed between the risk of gastric cancer and a family history of other cancers [OR = 0.97, 95% CI = 0.84-1.13]. OR increased for the middle and antrum parts of gastric cancer, but an increment for the cardiac part was observed only in those with a maternal history of gastric cancer. Our results suggest that the risk of gastric cancer in relation to family history varies by subsite and, furthermore, that the subsite-specific risk of gastric cancer is linked to a maternal history of gastric cancer.

Adult↗

Lymph node status assessment for gastric carcinoma: is the number of metastatic lymph nodes really practical as a parameter for N categories in the TNM Classification? Tumor Node Metastasis.

BACKGROUND AND OBJECTIVES: The anatomical extent of nodal metastasis has been replaced by the number of metastatic nodes as a key indicator of prognosis (pN categories) in the fifth edition of Tumor Node Metastasis Classification for gastric carcinoma by the International Union Against Cancer. The rate of metastatic nodes among all the nodes harvested is also a good prognostic factor. The object of this study is to evaluate which of the three parameters for the assessment of nodal status is the most appropriate for use in the stage classification. METHODS: Retrospective survival analyses were performed in 656 consecutive patients with advanced gastric carcinoma who underwent D2 lymphadenectomy and for whom histopathologic data of more than 20 lymph nodes were available. RESULTS: Although all three systems served well to classify the patients into distinct groups in terms of survival curves, stratification by the number of metastatic nodes was vulnerable to stage migration because of differences in the number of lymph nodes harvested. Such stage migration was not evident for the other two parameters. CONCLUSIONS: Lymph node metastatic rate can be recommended as an internationally applicable parameter for lymph node involvement of gastric carcinoma.

Adult↗

Preoperative embolization therapy for esophageal operation.

BACKGROUND AND OBJECTIVES: Since 1993, we have performed preoperative embolization therapy (PET) in an attempt to augment the blood flow of the gastric tube and prevent anastomotic leakage after esophageal resection. The clinical effects and complications associated with PET are reported. METHODS: The femoral artery was punctured and the left gastric artery, right gastric artery, and splenic artery underwent embolization, leaving the right gastroepiploic artery as the only patent feeding artery for the stomach. PET was performed in 54 patients, and data concerning blood flow of the stomach before and after the construction of the gastric tube were available in 51 patients. Of the 25 patients who were operated in the same period without undergoing PET, similar data were available in 20 patients. RESULTS: In the group of patients who underwent PET, the blood flow of the gastric tube after its construction was 67% of the value measured at the upper part of the stomach just after opening the abdominal cavity. For those who were not pretreated by PET, it declined to 33%. CONCLUSIONS: PET for esophageal cancer is a safe procedure that contributes to the decrease in the frequency of anastomotic dehiscence after esophageal operation, owing to the augmented tissue blood flow of the upper portion of the stomach following the construction of gastric tubes.

Anastomosis, Surgical↗

The number of metastatic lymph nodes: a promising prognostic determinant for gastric carcinoma in the latest edition of the TNM classification.

BACKGROUND: The number of metastatic regional lymph nodes determines the new pN categories in the 5th edition of the TNM classification. STUDY DESIGN: Our retrospective study was conducted to compare the new method of defining lymph node status with the conventional classification, consisting of the anatomic extent of lymph node metastases, a well-established prognostic factor. The study was based on clinical data for 493 patients with gastric carcinomas who underwent potentially curative operations and had histologically confirmed nodal metastases. These patients were stratified into 1) n categories according to the Japanese Classification of Gastric Carcinoma, 2) the new pN categories, and 3) the pN categories determined by the number of metastatic perigastric nodes resected by standard D1 gastrectomy. Survival data were analyzed for each group. RESULTS: The number of metastatic nodes after D2 lymphadenectomy reflected prognosis well and was shown by multivariate analysis to be a strong independent prognostic factor. When the classification was performed limited to the metastatic perigastric nodes, stage migration was evident, but the variable remained competent as a prognostic indicator. CONCLUSIONS: The number of metastatic nodes is a promising determinant in the new international stage classification.

Adult↗

Characterization of peripheral blood progenitor cells mobilized by nartograstim (N-terminal replaced granulocyte colony-stimulating factor) in normal volunteers.

We performed an optimal dose-finding study of nartograstim, N-terminal amino acids-replaced rhG-CSF, for mobilization of PBPC in normal volunteers. Nartograstim was injected subcutaneously for 5 days (days 1-5) at a dose of 1 (n = 3), 2 (n = 3), 4 (n = 6) or 8 microg/kg/day (n = 6), and blood samples were obtained by venipuncture on days 1 (pre-treatment), 4, 5 and 6. Nartograstim was well tolerated up to 8 microg/kg/day. Many kinds of PBPC, such as various hematopoietic progenitors in clonal culture, long-term culture-initiating cells (LTC-IC), and CD34+ cells and their primitive subsets (CD33-, HLA-DR-, CD38-) were mobilized in a dose-related manner. At 8 microg/kg/day, the peak number of CD34+ cells and granulocyte-macrophage colony-forming unit (CFU-GM) reached 82.8 x 10(3)/ml and 16.7 x 10(3)/ml, respectively; LTC-ICMiX, which have the capability to produce mixed colony-forming units (CFU-Mix) for over 5 weeks on stromal cells, were detected after the administration of nartograstim. There is a significant relationship between the number of mobilized CD34+ cells and the number of various progenitor cells including LTC-IC. These results indicate that a 5-day administration of nartograstim at 8 microg/kg/day could mobilize PBPC effectively for allografting.

ADP-ribosyl Cyclase↗

The role of radical gastrectomy with systematic lymphadenectomy for the diagnosis and treatment of primary gastric lymphoma.

OBJECTIVE: We evaluated the therapeutic efficacy of radical gastrectomy for primary B-cell lymphoma of the stomach and attempted to identify patients who could be adequately treated with surgery alone. SUMMARY BACKGROUND DATA: Several recent gastric lymphoma reports have discussed the therapeutic benefits of various treatment strategies for stage IE and IIE lymphoma. However, few studies have been based on patients accurately staged by systematic lymphadenectomy with subsequent pathologic examination. METHODS: A retrospective study was performed to evaluate the survival and biologic behavior of lesions in 60 patients with gastric lymphoma who were treated by radical gastrectomy alone. Tumors were classified according to the histopathologic concept of mucosa-associated lymphoid tissue (MALT)-derived lymphoma. RESULTS: A low histopathologic grade was associated with a significantly lower incidence of nodal metastasis (p = 0.07) and less extensive infiltration of the gastric wall (p < 0.005) despite larger tumor size. A 5-year survival rate of >95% was attained with surgery alone for MALT lymphoma and for true stage IE lymphoma diagnosed by pathologic examination of up to N2 lymph nodes routinely performed after radical gastrectomy. CONCLUSIONS: Surgery alone is adequate treatment for stage IE or pure MALT lymphoma, provided that the staging is performed after radical gastrectomy.

Adult↗

[Efficacy of granisetron, a 5-HT3 antagonist, in the prevention of nausea and vomiting induced by conditioning for hematopoietic stem cell transplantation].

One hundred and eleven patients receiving conditioning regimens for hematopoietic stem cell transplantation (HSCT) were administered a single intravenous dose (40 micrograms/kg) of granisetron before chemo-radio therapy. The efficacy of the drug was assessed every 24 hours, rating the control of nausea and vomiting as complete, major, minor or failure. On day 1, 23 of 48 patients (47.9%) who received cyclophosphamide (60 mg/kg/day), achieved control of emesis with complete or major response. On day 2, 17 of 47 patients (36.2%) achieved control emesis. During total body irradiation (TBI) (10 approximately 12 Gy/2 approximately 3 days), 21 of 33 patients (63.6%) achieved control of emesis on day 1 and 22 of 32 patients (68.6%) achieved control of emesis on day 2. During melphalan administration (60 approximately 100 mg/m2/day), 20 of 28 patients (71.4%) achieved control of emesis on day 1. Adverse effects were observed in seven patients but were not serious. We concluded that granisetron has a major role in preparation for HSCT.

Adolescent↗