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Biomedical subjects

T Matsuda

Publications and source records attributed to T Matsuda.

At least 1,171 records · Page 65Linked to original sources
PubMed1989

Effects of tumor necrosis factor and epidermal growth factor on cell morphology, cell surface receptors, and the production of tissue inhibitor of metalloproteinases and IL-6 in human microvascular endothelial cells.

The effect of human TNF on cultured human microvascular endothelial (HME) cells was examined. Incubation with TNF alone transformed the morphology of HME cells from a cobblestone-like appearance into a disordered array of criss-crossed, elongated, spindle-shaped cells. Coadministration of epidermal growth factor (EGF) and TNF caused even more dramatic morphologic changes than TNF alone. Addition of basic fibroblast growth factor or insulin-like growth factor-I showed rather weak effects on cell morphology than EGF. Cell growth of HME cells was stimulated up to two-fold by TNF whereas addition of EGF additively enhanced the growth rate. Treatment of HME cells with 10 ng/ml EGF increased the binding of 125I-TNF, and Scatchard analysis showed increased TNF-R number by EGF treatment. Cellular response to TNF in the absence or presence of EGF was assessed by analyzing SDS-PAGE patterns of secreted proteins from HME cells. TNF enhanced the secretion of a protein of molecular weight 25,000 Da (25 kDa) which was found to be IL-6. In contrast, secretion of a polypeptide of 29 kDa was significantly increased when HME cells were treated with EGF, but not with TNF. Coadministration of TNF and EGF synergistically increased the secretion of the 29-kDa protein. This 29-kDa protein was found to be tissue inhibitor of metalloproteinases when assayed with antitissue inhibitor of metalloproteinases antibody. TNF and EGF also enhanced secretion of collagenase with Mr of approximately 55 kDa. Increased steady state levels of the inhibitor mRNA were observed when HME cells were treated with EGF, and coadministration of TNF further increased the levels. The morphologic transformation of HME cells by TNF and/or EGF is discussed in relation to their expression of the secreted proteins.

Cell Division↗
PubMed1989

Interleukin-6 triggers the association of its receptor with a possible signal transducer, gp130.

Interleukin-6 mediates pleiotropic functions in various types of cells through its specific receptor (IL-6-R), the cDNA of which has already been cloned. We report here that an 80 kd single polypeptide chain (IL-6-R) is involved in IL-6 binding and that IL-6 triggers the association of this receptor with a non-ligand-binding membrane glycoprotein, gp130. The association takes place at 37 degrees C within 5 min and is stable for at least 40 min in the presence of IL-6, but does not occur at 0 degree C. Human IL-6-R can associate with a murine gp130 homolog and is functional in murine cells. Mutant IL-6-R lacking the intracytoplasmic portion is functional, suggesting that the two polypeptide chains interact to involve their extracellular portion. In fact, a soluble IL-6-R lacking the transmembrane and intracytoplasmic domains can associate with gp130 in the presence of IL-6 and mediate its function. These findings indicate that the complex of IL-6 and IL-6-R can interact with a non-ligand-binding membrane glycoprotein, gp130, extracellularly and can provide the IL-6 signal.

Animals↗
PubMed1989

[Studies on treatment results and prognostic factors of intraoperative radiotherapy in pancreatic carcinoma].

Results of intraoperative radiotherapy (IORT) in 70 patients who were treated for pancreatic carcinoma during the recent eleven years are presented. For analysis of treatment results, patients were divided into three groups depending on the treatment period: the initial period ('76.4-'79.12), the mid period ('80.1-'83.3) and the latest period ('83.4-'87.6). Median survival in each period was 4 months, 6 months and 11.5 months, respectively. As for the clinical stage, the median survival of patients with Stage I or II, Stage III and Stage IV were 10.5 months, 8 months and 3 months, respectively. The patient's survival with a combination of tumor resection and postoperative external radiotherapy (ExRT) seemed superior to that of other treatment modalities. As a result of statistical comparison of prognostic factors among each group, it was shown that the treatment period was most significant (p less than 0.01). Besides this, clinical stage, tumor resection and ExRT were significant factors in obtaining long survival. The patient's characteristics, however, were different in each group, so Stage IV was excluded from each group and survival was re-analyzed. As a result, the treatment modality consisting of IORT plus ExRT was found to be the most important prognostic factor. In conclusion, IORT should be applied to patients with pancreatic carcinoma except for Stage IV cases. The dose in IORT ranging from 20Gy to 25Gy combined with the dose in ExRT ranging from 40Gy to 50Gy was considered to contribute to the improvement of prognosis without causing serious side effects.

Adult↗
PubMed1989

Subacute brain atrophy after radiation therapy for malignant brain tumor.

Brain atrophy with mental and neurologic deterioration developing a few months after radiation therapy in patients without residual or recurrent brain tumors has been recognized. Two illustrative case reports of this pathologic entity are presented. Six autopsy cases with this entity including the two cases were reviewed neurologically, radiographically, and histopathologically. All patients presented progressive disturbances of mental status and consciousness, akinesia, and tremor-like involuntary movement. Computerized tomography (CT) demonstrated marked enlargement of the ventricles, moderate widening of the cortical sulci, and a moderately attenuated CT number for the white matter in all six patients. Four of the six patients had CSF drainage (ventriculoperitoneal shunt or continuous lumbar drainage), however, none of them improved. Histologic examination demonstrated swelling and loss of the myelin sheath in the white matter in all patients, and reactive astrocytosis in three of the six patients. Neither prominent neuronal loss in the cerebral cortex or basal ganglia, nor axonal loss in the white matter was generally identified. The blood vessels of the cerebral cortex and white matter were normal. Ependymal layer and the surrounding brain tissue were normal in all patients. These findings suggested that this pathologic condition results from demyelination secondary to direct neurotoxic effect of irradiation. The authors' previous report was reviewed and the differential diagnoses, the risk factors for this pathologic entity, and the indication for radiation therapy in aged patients with a malignant brain tumor are discussed.

Aged↗
PubMed1989

[Clinical significance of bone scintigraphy for early detection of bone metastasis from breast cancer].

Forty four patients, presenting metastasis only to bone from a primary breast cancer previously undergone mastectomy from 1975 to 1985 at Kinki University Hospital, were investigated for the purpose of early detection of bone metastasis. Clinical follow up and bone scintigraphy at regular interval were the most important to detect the early phase of bone metastasis. The patients with early phase of bone metastasis, detected by regular scintigraphy in every 6 months, had the frequent metastatic lesions in rib and sternum as well as lumbar. These metastatic lesions could not be found by X-ray examination but were confirmed by aspiration cytology. Among the tumor markers, Al-p and LDH, rather than CEA and Ca, were more useful for the diagnosis of early phase of bone metastasis.

Biomarkers, Tumor↗
PubMed1989

Production of interleukin 6 and its relation to the macrophage differentiation of mouse myeloid leukemia cells (M1) treated with differentiation-inducing factor and 1 alpha,25-dihydroxyvitamin D3.

We have studied the production of interleukin 6 (IL-6) and its relation to the macrophage differentiation in murine myeloid leukemia cells (M1). As has been reported, differentiation-inducing factor (D-factor), 1 alpha, 25-dihydroxyvitamin D3 [1 alpha, 25(OH)2D3], and recombinant IL-6 similarly induced differentiation of M1 cells into macrophages. The three compounds also induced mRNA expression of IL-6 in M1 cells. M1 cells treated with D-factor or 1 alpha, 25(OH)2D3 produced biologically active IL-6, but the amounts of IL-6 secreted into culture media did not appear to be enough to induce differentiation of M1 cells. Furthermore, simultaneous addition of anti-IL-6 antibody did not suppress the differentiation of M1 cells induced by D-factor or 1 alpha, 25(OH)2D3. These results show that IL-6 production is an essential property associated with the macrophage differentiation of M1 cells, but it may not be responsible for the D-factor- and 1 alpha, 25(OH)2D3-induced differentiation.

Animals↗
PubMed1989

Angiotensinogen production by rat hepatoma cells is stimulated by B cell stimulatory factor 2/interleukin-6.

Angiotensinogen has been identified as one of the acute-phase reactants. In vitro studies were carried out using the Reuber H35 hepatoma cell line to identify the species of cytokines contributing to the increased synthesis of angiotensinogen in the liver. Angiotensinogen secretion by H35 cells was maximally increased 4-fold by the addition of 10(-7) M dexamethasone. Under this condition, angiotensinogen secretion was further stimulated by B cell stimulatory factor 2/interleukin-6 (IL-6, 50 U/ml), but not by interleukin-1 or interferon-alpha. In the absence of glucocorticoid, IL-6 did not affect angiotensinogen secretion by H35 cells, indicating that the presence of glucocorticoid is required for the stimulatory activity of IL-6. These results suggest that IL-6 is a mediator responsible for the increased synthesis of angiotensinogen in the liver during acute inflammation.

Angiotensinogen↗
PubMed1989

Rat pyruvate kinase M gene. Its complete structure and characterization of the 5'-flanking region.

Genomic clones containing the rat pyruvate kinase M gene, which encodes the M1- and M2-type isozymes, were isolated and their exon sequences were determined. This gene contains 12 exons and 11 introns and is 20 kilobases (kb) long. The sequences specific to the M1- and M2-types exist in exons 9 and 10, respectively (Noguchi, T., Inoue, H., and Tanaka, T. (1986) J. Biol. Chem. 261, 13807-13812). The seventh intron begins with the GC dinucleotide instead of the consensus GT dinucleotide, but other exon-intron boundaries are consistent with the "GT-AG" rule. S1 mapping analysis showed that M1- and M2-type mRNAs had multiple, but the same transcription initiation sites. Thus, the M1- and M2-type isozyme mRNAs are concluded to be produced from the same M gene transcript by alternative RNA splicing. RNA blot hybridization analysis indicated that developmental changes of the isozymes in brain and skeletal muscle were regulated at the level of RNA splicing. The 5'-flanking region of the gene has no "TATA box" or "CAAT box," but contains potential Sp1 binding sites. Bacterial chloramphenicol acetyltransferase assay revealed that a fragment of about 0.5 kb of the 5'-flanking region of the gene was sufficient for promotor activity in the rat hepatoma cell line, dRLh-84. This activity was not present in adult rat hepatocytes, indicating that the 0.5-kb fragment has tissue-specific promoter activity. A processed-type pseudogene that resembles the M2-type pyruvate kinase cDNA was also characterized.

Animals↗
PubMed1989

Variable region cDNA sequences and antigen binding specificity of mouse monoclonal antibodies to isomaltosyl oligosaccharides coupled to proteins. T-dependent analogues of alpha(1----6)dextran.

Four mouse hybridomas specific for alpha(1----6)dextran, 16.4.12E (IgA kappa, C57BL/6), 28.4.10A (IgM kappa, BALB/c), 35.8.2H (IgG1 kappa, BALB/c), and 36.1.2D (IgM kappa, BALB/c) were obtained by immunization with the T-dependent Ag isomaltohexaose or isomaltotriose coupled to keyhole limpet hemocyanin or to BSA. Immunochemical characterization of the hybridoma antibodies showed that 16.4.12E and 36.1.2D had cavity-type combining sites, recognizing the terminal non-reducing end of alpha(1----6)dextran, whereas 28.4.10A and 35.8.2H had groove-type sites, recognizing internal linear segments of the dextran. The V region cDNA of the H and L chains of the antibodies were cloned and sequenced. VH of 16.4.12E and VH of 36.1.2D belonged to the X24 and Q52 germ-line gene families, respectively. The VH and V kappa sequences of 16.4.12E and V kappa sequence of 36.1.2D were highly homologous to those of W3129, the only anti-alpha(1----6)dextran mAb with a cavity-type site thus far sequenced; 16.4.12E differed from W3129 in the D, JH, and J kappa. VH genes of 28.4.10A and 35.8.2H were homologous to those of several anti-alpha(1----6)dextrans with groove-type sites, but belonged to the J558 germ-line gene family, differed from the other J558 anti-alpha(1----6)dextrans, probably representing a different germ-line subfamily. The L chain sequence of 28.4.10A encoded by V kappa-Ars and J kappa 2 was almost identical to other groove-type anti-alpha(1----6)dextrans obtained by immunizing with the T-independent glycolipid Ag, stearyl-isomaltotetraose. Use of T-dependent Ag such as isomaltosyl oligosaccharide-protein conjugates provides an additional parameter for probing the fine structure of antibody combining sites and evaluating the V-gene repertoire of anti-alpha(1----6)dextrans.

Amino Acid Sequence↗
PubMed1989

Quantitative estimation of elastase-alpha 1-proteinase inhibitor (E-alpha 1 PI) complex in leukemia: marked elevation in cases of acute promyelocytic leukemia.

The concentrations of elastase-alpha 1-proteinase inhibitor (E-alpha 1 PI) complex were assayed in 43 patients with various types of leukemia. Marked to moderate elevation of E-alpha 1 PI complex levels was observed in patients with acute myelocytic leukemia (AML), acute promyelocytic leukemia (APL), acute myelomonocytic leukemia (AMMoL), or chronic myelocytic leukemia (CML) at diagnosis. The ratio of E-alpha 1 PI complex concentrations in plasma to leukocyte counts markedly elevated in the patients with APL, especially. During the course of remission induction therapy, levels of E-alpha 1 PI complex decreased in parallel with decline of leukocyte counts in the patients with leukemia other than APL, however the E-alpha 1 PI complex was persistently elevated regardless of leukopenia in some patients with APL. In APL, concentrations of fibrin/fibrinogen degradation products (FDP) markedly increased even when levels of plasmin-alpha 2-antiplasmin complex were within normal limits. However, levels of E-alpha 1 PI complex usually increased in these cases. From these results, it is strongly suggested that promyelocytes contain markedly elevated amounts of elastase which participates in degradation of fibrin or fibrinogen in some cases of APL.

Blood Proteins↗
PubMed1989

Identification of alpha 2-macroglobulin as a carrier protein for IL-6.

In this report we demonstrate that alpha 2-macroglobulin (alpha 2M) is a carrier protein for IL-6. IL-6 was found to bind plasma proteins and an immunoblot analysis revealed that the complex between IL-6 and plasma proteins contains alpha 2M. Furthermore, purified alpha 2M bound IL-6. alpha 2M did not inhibit IL-6 activity or its binding to homologous receptor. IL-6 bound to alpha 2M retained its biologic activity and became resistant to treatment with proteases, although free IL-6 was easily degraded. These findings indicate that alpha 2M plays an important role as a carrier protein for IL-6 in serum and makes IL-6 produced at the local inflammatory site available to lymphocytes, hepatocytes, and hematopoietic stem cells, resulting in the induction of the coordinate systemic host defense reactions, such as immune response, acute phase reaction, and hematopoiesis.

Carrier Proteins↗
PubMed1989

Changes in hemostatic and fibrinolytic proteins in patients receiving L-asparaginase therapy.

Hemostatic changes were evaluated in ten patients with acute lymphoblastic leukemia and lymphoma who received chemotherapy with L-asparaginase, vincristine, and prednisolone for 1 week. Following treatment, prothrombin time and activated partial thromboplastin time were significantly prolonged, while a marked decrease in fibrinogen levels was observed. The values for cross-linked fibrin degradation products, however, remained within normal limits during treatment, which excluded the possibility of disseminated intravascular coagulation. The concentrations of coagulation inhibitors (antithrombin III, protein C, and protein S), plasminogen, and alpha 2 antiplasmin also significantly decreased; however, levels of both tissue-type plasminogen activator and plasminogen activator inhibitor, which are synthesized in endothelial cells, increased during the treatment. Although a decrease was observed in concentrations of many coagulation factors, including subunits A and B of factor XIII, the activity and antigenicity of factor VII significantly increased following the treatment. From this study, we concluded that these hemostatic abnormalities caused by the administration of L-asparaginase produced a labile condition that easily inclines to bleeding or thrombosis.

Anticoagulants↗
PubMed1989

Human interleukin 6 and tumor necrosis factor alpha production studied at a single-cell level.

Individual peripheral blood mononuclear cells, which produced interleukin 6 (IL 6) or tumor necrosis factor alpha, (TNF alpha), were studied by cytokine-specific polyclonal or monoclonal antibodies (mAb) and immunofluorescence technique with UV microscopy. Lipopolysaccharide (LPS) induced IL 6 as well as TNF alpha production in the majority of the monocytes, but not at all in lymphocytes. Approximately every second monocyte made TNF alpha in response to LPS within 0.5 h from start of the cultures, when no IL 6 or TNF alpha production occurred. The maximal number of TNF alpha-synthesizing monocytes was observed 1.5 h later and then rapidly declined. LPS stimulation led to optimal IL 6 production 3 h after initiation of the cultures, with 90% of the monocytes expressing intracellular IL 6. LPS-induced IL 6 synthesis started about 1 h after that of TNF alpha. Polyclonal T cell activation with staphylococcal enterotoxin A or anti-CD3 mAb induced a biphasic production pattern of IL 6 as well as TNF alpha. Early IL 6 synthesis, which peaked 6-8 h from start of the cultures, occurred exclusively in monocytes, while late IL 6 production at 48 h was restricted to a small fraction of lymphoid cells. T cell mitogen induced early TNF alpha production, which peaked at 6 h, took mainly place in monocytes and to a minor degree in CD4+ as well as CD8+ T cells. The majority of the TNF alpha-producing mononuclear cells at 24 h were of the CD4+ T cell lineage in the staphylococcal enterotoxin A- or anti-CD3 mAb-activated cultures. IL 6 as well as TNF alpha accumulated in the Golgi system, which resulted in a characteristic morphology of the staining, eliminating problems with evaluation of background signals.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1989

Phase II trial of carboplatin in patients with advanced germ-cell testicular tumors and transitional cell carcinomas of the urinary tract.

Carboplatin, an analog of cisplatin, was evaluated in a phase II study involving 25 patients with advanced testicular tumor and 45 with transitional cell carcinoma (TCC) of the urinary tract; 21 and 38 cases, respectively, were evaluable for response. Prior treatment with cisplatin-based chemotherapy had occurred in 7 of the testicular cancer patients and in 11 with TCC. The response rate (complete + partial response) in testicular tumors was 47.6%. The best response rate was observed in seminomas (70.0%), whereas the response rate in nonseminomas was 27.3%. The seminoma patients had mainly stage IIIA or less than IIIA disease, with metastatic lesions restricted to the lymph nodes. Three responses were seen in patients previously treated with cisplatin. In TCC, the response rate was 18.4%. Good-risk patients were treated with a dose of 400 mg/m2 every 4 weeks, whereas poor-risk patients received a lower dose of 300 mg/m2. The response rates for good-risk patients were 50.0% in testicular lesions and 26.1% in TCC. For poor-risk patients, the response rates were 40.0% and 6.7%, respectively. Carboplatin was well tolerated, with no significant renal impairment or ototoxicity detected. Nausea and vomiting were experienced by 51.7% of patients, but the severity was low; half of these patients demonstrated WHO grade I toxicity. However, myelosuppression was severe. In conclusion, carboplatin demonstrated activity in both testicular tumors and TCC and is worthy of further study, especially in combination with other active drugs.

Adult↗