Search PubMed⌕ Search

Biomedical subjects

H Wada

Publications and source records attributed to H Wada.

At least 307 records · Page 17Linked to original sources
PubMed1998

Simultaneous humoral and cellular immune response against cancer-testis antigen NY-ESO-1: definition of human histocompatibility leukocyte antigen (HLA)-A2-binding peptide epitopes.

A growing number of human tumor antigens have been described that can be recognized by cytotoxic T lymphocytes (CTLs) in a major histocompatibility complex (MHC) class I-restricted fashion. Serological screening of cDNA expression libraries, SEREX, has recently been shown to provide another route for defining immunogenic human tumor antigens. The detection of antibody responses against known CTL-defined tumor antigens, e.g., MAGE-1 and tyrosinase, raised the question whether antibody and CTL responses against a defined tumor antigen can occur simultaneously in a single patient. In this paper, we report on a melanoma patient with a high-titer antibody response against the "cancer-testis" antigen NY-ESO-1. Concurrently, a strong MHC class I-restricted CTL reactivity against the autologous NY-ESO-1-positive tumor cell line was found. A stable CTL line (NW38-IVS-1) was established from this patient that reacted with autologous melanoma cells and with allogeneic human histocompatibility leukocyte antigen (HLA)-A2(-), NY-ESO-1-positive, but not NY-ESO-1-negative, melanoma cells. Screening of NY-ESO-1 transfectants with NW38-IVS-1 revealed NY-ESO-1 as the relevant CTL target presented by HLA-A2. Computer calculation identified 26 peptides with HLA-A2-binding motifs encoded by NY-ESO-1. Of these, three peptides were efficiently recognized by NW38-IVS-1. Thus, we show that antigen-specific humoral and cellular immune responses against human tumor antigens may occur simultaneously. In addition, our analysis provides a general strategy for identifying the CTL-recognizing peptides of tumor antigens initially defined by autologous antibody.

Aged↗
PubMed1998

Granulocyte colony-stimulating factor and its receptor in acute promyelocytic leukemia.

Expression of granulocyte colony-stimulating factor (G-CSF) receptor (G-CSFR) and in vitro proliferative response to G-CSF were investigated by quantitative immunofluorescence and [3H] thymidine uptake, respectively, in a series of acute myeloid leukemias (AML). The results indicated that G-CSFR was detected at high levels in acute promyelocytic leukemia (APL) cells, in comparison with other types of AML. Moreover, APL cells were also seen to predominantly proliferate in response to G-CSF. Based on these observations, we administered recombinant human G-CSF to a patient with APL in the third relapse that was resistant to both cytotoxic agents and all trans retinoic acid, in an attempt to sensitize the leukemic cells to cell-cycle-dependent agents. Complete remission was achieved. The finding that APL cells are exquisitely responsive to G-CSF supports the view that G-CSF is useful for augmentation of their vulnerability to cell-cycle specific agents.

Adult↗
PubMed1998

Poor outcome in disseminated intravascular coagulation or thrombotic thrombocytopenic purpura patients with severe vascular endothelial cell injuries.

Various hemostatic and vascular endothelial cell markers were measured in patients with disseminated intravascular coagulation (DIC), non-DIC, or thrombotic thrombocytopenic purpura (TTP) and in healthy volunteers to examine the relationships between the hemostatic abnormalities or vascular endothelial cell injuries and the patients' outcomes. Although the plasma levels of soluble fibrin monomer, thrombin-antithrombin complex, plasmin-plasmin inhibitor complex, and D-dimer were significantly increased in the DIC patients, there were no significant differences in these markers between the DIC patients who survived and those who died, suggesting that these markers might not be directly related to the patient outcome. The plasma thrombomodulin (TM) levels in the DIC and TTP patients were significantly higher than those in the healthy volunteers, and the plasma TM levels in the patients who died were significantly higher than those in the patients who survived. These findings showed that the TM level reflected the outcome, and that the outcome of the diseases underlying DIC and TTP might depend on vascular endothelial cell injuries. The plasma protein C and antithrombin activities were markedly reduced in the DIC, non-DIC, and TTP patients who died compared to those who survived. These findings suggest that reduced plasma antithrombin and protein C activities are useful markers of systemic vascular endothelial injuries. Although the plasma tissue factor (TF) levels were significantly increased in the DIC patients, there was no significant difference in the plasma TF levels between the DIC patients who died and those who survived. In conclusion, we found that the outcome of the diseases underlying DIC and TTP is related to vascular endothelial cells, and that plasma TM, antithrombin, and protein C are useful markers for systemic vascular endothelial cell injury.

Antifibrinolytic Agents↗
PubMed1998

Clonal analysis of hematopoietic cells using a novel polymorphic site of the X chromosome.

Clonality of hematopoietic cells on a smale scale (nanogram amounts of DNA) can be detected by X-chromosome inactivation using the polymerase chain reaction (PCR). The human androgen-receptor gene (HUMARA) has a polymorphic short tandem repeat (STR), and has generally been used for clonality analysis since heterozygosity for the gene occurs in 90% of caucasian females. We examined heterozygosity of the STR on HUMARA in 110 Japanese females and found heterozygosity in 74 of 110 (67%). To examine for hematologic clonality in females with HUMARA homozygosity, we used a primer specific for a novel polymorphic STR site between DXS15 and DXS134 (DXS15-134) on Xq28. Heterozygosity for this site was found in 50 of 110 females (46%). Clonality of the hematopoietic cells was detected in 91 of 110 females (83%) using PCR of either the STR sites on HUMARA or DXS15-134. The X-inactivation patterns using PCR of DXS15-134 corresponded exactly with those obtained using PCR of HUMARA in 18 females who were heterozygous for both DXS15-134 and HUMARA. Using PCR of DXS15-134, we examined the clonality of bone marrow cells separated by flow cytometry in a patient with erythroleukemia (M6). Clonality was found not only in myeloid lineage cells but also in B lymphocytes. The clonality assay for DXS15-134 may be useful to assess for clonality of hematopoietic cells in the Japanese population, when combined with the HUMARA assay.

Base Sequence↗
PubMed1998

Regulation of IFN-gamma production in granulocyte-macrophage colony-stimulating factor-deficient mice.

Granulocyte-macrophage colony-stimulating factor-deficient (GM-CSF-/-) mice produce far lower serum levels of IFN-gamma in response to LPS than GM-CSF+/+ mice. CD4+ and CD8+ T cells from LPS-injected GM-CSF-/- mice showed a deficiency in IFN-gamma production and proliferative activity in response to IL-2 and IL-12, whereas IFN-gamma production by NK cells was not compromised. These defects of T cells were reversed by administration of GM-CSF in vivo, but not by supplementation with GM-CSF in vitro. GM-CSF-/- mice do not have an intrinsic defect in IFN-gamma production, because IL-12 injection induces the same high levels of IFN-gamma in GM-CSF-/- and GM-CSF+/+ mice. To investigate the inhibitory effect of LPS on GM-CSF-/- T cells and the indirect restorative activity of GM-CSF, we tested the action of supernatants from cultured dendritic cells (DC). A factor or factors in the DC supernatant normalized serum IFN-gamma levels and T cell responses in LPS-injected GM-CSF-/- mice. IL-18 reproduced some but not all of these in vivo and in vitro effects of DC supernatants. Our results indicate that GM-CSF is important in protecting T cells from inhibitory signals generated during immunization or exposure to LPS, and that this effect of GM-CSF is indirect and mediated by factors produced by DC.

Animals↗
PubMed1998

Lewis Y antigen expression and postoperative survival in non-small cell lung cancer.

BACKGROUND: In contrast to other Lewis blood group-related antigens, Lewis Y antigen (LeY) has not been fully investigated in non-small cell lung cancer. METHODS: To assess the significance of LeY expression, 236 patients with completely resected pathologic stage 1-3a were reviewed with immunohistochemical analysis. RESULTS: LeY expression was positive in 179 patients (75.8%). In poorly differentiated cancer, percentage of LeY-positive patients was lower than in moderately to well-differentiated cancer (67.2% versus 81.2%, p = 0.028). Five-year survival rate of LeY-positive patients was 78.2%, significantly higher than that of LeY-negative patients (59.7%, p = 0.001). Combined with p53 status, differences in survival proved to be marked; 5-year survival rate of patients with positive LeY expression and without aberrant p53 expression, was as high as 83.3%, whereas that of patients with negative LeY expression and with aberrant p53 expression was only 38.4% (p < 0.001). Multivariate analysis confirmed that LeY expression was a significant independent factor to predict better survival. CONCLUSIONS: LeY expression is a significant prognostic factor related to grade of cancer differentiation.

Adolescent↗
PubMed1998

Thirty-day operative mortality for thoracotomy in lung cancer.

OBJECTIVE: The 30-day operative mortality for thoracotomy in lung cancer is described herein. METHODS: From January 1994 through December 1994, the Japanese Association for Chest Surgery surveyed the number of thoracotomies for lung cancer by operative procedure, age, and operative mortality. The operative mortality was defined as death within 30 days of operation. RESULTS: The total number of operations was 7099. The overall 30-day operative mortality was 1.3%. By operative procedure, the mortalities were 3.2% for pneumonectomy, 1.2% for lobectomy, and 0.8% for a lesser operation, which showed a significant difference between pneumonectomy and lobectomy (p < 0.01). The mortality by age was 0.4% for patients younger than 60 years, 1.3% for those aged 60 to 69, 2.0% for those aged 70 to 79, and 2.2% for those aged 80 or older, which showed significant differences between the less than 60-year and 60- to 69-year-old groups, and between the 60- and 69-year-old and 70- and 79-year-old groups (p < 0.01 and p = 0.047, respectively). Pneumonia and respiratory failure caused most deaths (51.6%). CONCLUSIONS: The operative mortality in Japan for thoracotomy in lung cancer was satisfactorily low. The results of this study on a large population could serve as a standard when discussing the operative outcome of lung cancer.

Age Factors↗
PubMed1998

Carcinosarcoma of the breast: molecular-biological study for analysis of histogenesis.

The histogenesis of carcinosarcoma of the breast is controversial. In the current case, the demarcation between the carcinomatous and sarcomatous components was distinct in all microscopic fields. Immunohistochemical analysis was negative for epithelial membrane antigen (EMA) and keratin in the sarcomatous component and was negative for desmin in the carcinomatous component, suggesting that this tumor could be derived from the two different stem cells. To determine the histogenesis of this tumor, both carcinomatous and sarcomatous lesions were microdissected from formalin-fixed tissues and DNAs were prepared by proteinase K digestion. PCR amplification of the human androgen receptor (HUMARA) short tandem repeat (STR), after Hpa II digestion of the genomic DNA, indicated that the patterns of X-chromosome inactivation were identical in both components. Moreover, both components contained the identical TGT --> TTT transversion in codon 275 of the p53 gene. These observations strongly support the hypothesis that this tumor is derived from a single totipotent stem cell.

Breast Neoplasms↗
PubMed1998

Measurement of guinea pig basilar membrane using computer-aided three-dimensional reconstruction system.

Cochleas are known to have the ability to analyze a frequency widely, and this ability seems to be owed mostly to the basilar membrane (BM) configuration. However, the relationship between the cochlear frequency-position map and the BM configuration is not clear. Therefore, in this paper, the internal structures of a guinea pig cochlea, especially the BM configuration, were reconstructed and measured using a computer-aided three-dimensional (3-D) reconstruction system. Then, an attempt was made to examine the influence of the BM configuration on the cochlear frequency-position map. The measurement results indicate that the width of the BM increased and its thickness decreased with an increase in the distance from the basal turn towards the apical turn. Theoretical consideration reveals that the wide frequency-position of the cochlea is achieved by not only the BM configuration change along the length of the cochlea but also the change of the Young's modulus of the BM along the length of the cochlea.

Animals↗
PubMed1998

Recombinant human erythropoietin for late-onset anemia after allogeneic bone marrow transplantation.

Recombinant human erythropoietin (rHu EPO) has been reported to accelerate early erythroid reconstitution after bone marrow transplantation (BMT). We conducted a pilot study on rHu EPO for late-onset anemia in 9 patients after allogeneic BMT. The patients achieved initial erythropoietic recovery (hemoglobin (Hb) range 9.1-13.4, mean 10.8 g/dl), but then developed transplant-related anemia (Hb range 6.3-9.7, mean 8.2 g/dl) more than 50 days after BMT. This type of anemia was related to graft-versus-host disease (GVHD), cytomegalovirus infection, and/or impaired EPO secretion. The patients received 3,000 or 12,000 U of rHu EPO subcutaneously three or seven times weekly. Hb levels increased by more than 2 g/dl in 6 of the 9 patients, but were unchanged in the 3 patients with severe GVHD. These findings suggest that in some cases rHu EPO is effective for the treatment of late-onset anemia after BMT.

Adult↗
PubMed1998

Myelodysplastic syndrome with B cell clonality in a patient five years after renal transplantation.

A female patient received a renal transplantation from an unrelated cadaver donor, and five years later developed myelodysplastic syndrome (MDS) with immunological abnormalities. Chromosomal analysis showed trisomy 8 in bone marrow cells. FISH analysis indicated that trisomy 8 was present in 4% of CD19 + cells, suggesting that the MDS clone involved B lymphocytes. Polymerase chain reaction of the human androgen receptor gene indicated B cell clonality (54%) and granulocyte clonality (63%). There have been no previous reports of secondary MDS following renal transplantation in which the MDS clone involved the B cell lineage. The abnormal MDS B cell clone may have caused the immunological abnormalities.

B-Lymphocytes↗
PubMed1998

Advantage of post-operative oral administration of UFT (tegafur and uracil) for completely resected p-stage I-IIIa non-small cell lung cancer (NSCLC).

OBJECTIVE: Although adjuvant therapy after surgery for non-small cell lung cancer (NSCLC) has been reported to be ineffective, it has been recently reported in prospective randomised studies conducted by two different groups in Japan that oral administration of a 5-fluorouracil (5-FU) derivative drug, UFT (a combination drug of tegafur and uracil) can improve the post-operative survival [The Study Group of Adjuvant Chemotherapy for Lung Cancer (Chubu, Japan). A randomized trial of postoperative adjuvant chemotherapy in non-small cell lung cancer (the second cooperative study). Eu J Surg Oncol 1995;21:69-77; Wada, H., Hitomi, S., Teramatsu, T, West Japan Study Group for Lung Cancer Surgery. Adjuvant chemotherapy after complete resection in non-small-cell lung cancer. J Clin Oncol 1996;14:1048-1054]. To examine the efficacy of UFT as post-operative adjuvant therapy, a retrospective study was performed. METHODS: A total of 655 consecutive patients who underwent complete tumor resection for pathologic stage I-IIIa, NSCLC at the Department of Thoracic Surgery, Chest Disease Research Institute, Kyoto University between 1976 and 1992 were retrospectively reviewed. As post-operative adjuvant therapy, UFT was administrated to 98 patients (UFT group), and was not administered to the other 557 patients (Control group). RESULTS: The 5-year survival rate of the UFT group was 76.5%, which was significantly better than that of the Control group (5-year survival rate: 58.6%, P = 0.005). Stratified with pathologic stage, the efficacy of UFT was seen in the p-stage I disease (5-year survival rate: 88.6% for the UFT group, 72.0% for the Control group, P = 0.013) and in the p-stage IIIa, pN2 disease (5-year survival rate: 54.3% for the UFT group, 37.5% for the Control group, P = 0.037). Multivariate analysis of the prognostic factors also revealed the efficacy of UFT (P = 0.004, 95% confidence interval of relative risk: 0.325-0.840). Post-operative intravenous chemotherapy or radiation therapy did not prove to be significant factors affecting the prognosis. CONCLUSIONS: Efficacy of oral administration of UFT as post-operative adjuvant therapy for completely resected NSCLC was proposed. To confirm the efficacy, a prospective randomized study for a more homogenous patient group is needed.

Administration, Oral↗
PubMed1998

In vitro excess ammonia production in human myeloma cell lines.

It is well known that cases with multiple myeloma reveal various clinical manifestations such as pancytopenia, hyperproteinemia, renal dysfunction, bone lesions, hypercalcemia and immunodeficiency. Recently, a few more clinical features associated with myeloma, such as salivary type hyperamylasemia and elevated serum C-reactive protein (CRP) concentration, have been reported. The elevation of CRP is thought to be related to interleukin-6 (IL-6) production by myeloma cells, because of identification of IL-6 as an autocrine and/or paracrine growth factor for myeloma cells. More recently, there have been several reports of cases with myeloma associated with hyperammonemia. This hyperammonemia is not considered to be due to liver dysfunction, because in most of these cases tests revealed normal hepatic function, and some cases showed different patterns of serum amino acid distribution than that associated with hepatic failure. However, there have been no apparent observations of ammonia production by myeloma cells. In this study, we used six human myeloma cell lines including KMS-18, which was recently established from a myeloma case associated with hyperammonemia. These lines were treated with MRA (mycoplasma removal agent) to observe ammonia production in vitro. They produced and released significantly higher levels of ammonia into culture medium than non-myeloma hematological cell lines or the HepG2 human hepatic carcinoma cell line. Although attempts to analyze the relative expression levels of the enzymes related to ammonia biosynthesis using the reverse transcriptase-polymerase chain reaction assay failed to detect any differences between these myeloma lines and other cell lines, in vitro excess ammonia production by the myeloma cells was confirmed and the relevance to clinical manifestations is discussed.

Ammonia↗
PubMed1998

Significance of trilineage myelodysplasia in de novo acute myeloid leukaemia during remission rather than at diagnosis.

Patients with trilineage myelodysplasia (TMDS) in de novo acute myeloid leukaemia (AML) at diagnosis and remission were clinically evaluated between 1983 and 1996. AML with TMDS (AML/TMDS) was observed in 20 (12%) of 162 patients with de novo AML at diagnosis. Complete remission (CR) was achieved with combination chemotherapy in 12 (67%) of 18 AML/TMDS cases. This CR rate was relatively worse than the rate of 78% (106/136 cases) of AML without TMDS, but this difference was not significant. Disease-free survival curves also showed no difference between AML/TMDS and AML without TMDS. During remission, eight (67%) of 12 AML/TMDS cases had myelodysplastic remission marrow (AML/MRM). AML/MRM was also seen in seven (7%) of 106 AML cases without TMDS. The actuarial disease-free survival was significantly lower in AML/MRM than in AML without MRM (P = 0.0003). All of the AML/MRM cases exhibited early leukaemic relapse; median remission duration was only 9 months. Clonal changes occurred in two cases of AML/TMDS and five cases of AML/MRM at the time of relapse. These findings suggest that TMDS during remission predicts a poorer prognosis and early leukaemic relapse when compared with the absence of TMDS.

Acute Disease↗
PubMed1998

Homozygous missense mutation (band 3 Fukuoka: G130R): a mild form of hereditary spherocytosis with near-normal band 3 content and minimal changes of membrane ultrastructure despite moderate protein 4.2 deficiency.

The characteristics of phenotypic expression were studied in a Japanese family with hereditary spherocytosis and an extremely rare homozygous missense mutation of the band 3 gene (band 3 Fukuoka: G130R). The homozygous unsplenectomized proband was a 29-year-old male with compensated haemolytic anaemia (red cell count 4.21 x 10(12)/l, reticulocytes 278 x 10(9)/l, and indirect bilirubin 44 micromol/l). His red cell band 3 (B3) protein demonstrated a 9.3% reduction and his protein 4.2 (P4.2) level was substantially reduced (45.0%), compared to normal subjects. P4.2 protein was composed mostly of a wild type (72 kD) with a trace of 68 kD peptide. The binding properties of the mutated B3 to normal P4.2 were significantly impaired, which probably resulted in the substantial reduction of P4.2 in this proband, since no abnormalities were detected on the P4.2 gene. Electron microscopy (EM) using the freeze-fracture method demonstrated a mild decrease in intramembrane particles (IMPs) of near-normal size (8 nm in diameter) with no substantial increases in their oligomerization. Their distribution on the membrane P face was almost normal, although most of the IMPs could represent the homozygously mutated B3 protein. EM (quick-freeze deep-etching method) disclosed a skeletal network of near-normal size and size distribution of the skeletal units, suggesting that the mutated B3 protein itself did not have much effect on the skeletal network in situ. Therefore the reduced P4.2 content (45% of that of normal subjects), which remained on the red cell membrane of this proband, appeared to be nearly sufficient for maintaining the normal structure of the skeletal network and IMPs in situ, contrary to the marked abnormalities in both IMPs and the skeletal network in complete P4.2 deficiencies.

Adult↗