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Biomedical subjects

M Sugimoto

Publications and source records attributed to M Sugimoto.

At least 361 records · Page 20Linked to original sources

Chemical synthesis and expression of copper metallothionein gene of Neurospora crassa.

The gene coding for the Neurospora crassa copper metallothionein (MT) was synthesized and inserted in the lacZ' gene of pUC18 plasmid to give the same translational reading frame as the latter gene. The MT-beta-galactosidase fused gene was expressed in Escherichia coli to produce a fused protein in which the amino and carboxy termini of MT are linked to the beta-galactosidase through methionine residues. An MT derivative containing an extra homoserine residue at the carboxy terminus was prepared by cyanogen bromide cleavage of the fused protein followed by a reverse-phase HPLC separation. The spectral features of the MT derivative and its copper complex were similar to those of the corresponding native MTs.

Amino Acid Sequence↗

Disappearance of inhibitor to factor IX in a patient with severe haemophilia B and immunological characterization of the inhibitor.

Disappearance of an inhibitor to factor IX in an 11-year-old boy with haemophilia B is described. He had been given a total of 14,200 units of a prothrombin complex concentrate (PCC) before an inhibitor to factor IX developed. He subsequently received four separate infusions of PCC and his inhibitor titre rose in response to the treatment for the following 4 years. No inhibitor is presently detected despite repeated administration of PCC. Immunological characterization of the inhibitor by inhibitor neutralization assays, modified crossed-immunoelectrophoresis and enzyme-linked immunosorbent assay demonstrated that it contained IgG2 and IgG4 heavy chains and kappa and lambda light chains. No large deletion of the factor IX gene in the patient was observed using cDNA (cVII).

Child↗

Effects and virulences of recombinant vaccinia viruses derived from attenuated strains that express the human T-cell leukemia virus type I envelope gene.

We constructed recombinant vaccinia viruses (RVVs) that expressed human T-cell leukemia virus type I (HTLV-I) envelope glycoproteins by using attenuated vaccinia viruses (VVs) which have much lower neurovirulence than the WR strain that is extensively used as a vector. The RVV produced from the LC16mO strain, one of the attenuated VVs, elicited a high titer of anti-HTLV-I antibody in rabbits and protected them against HTLV-I infection. The env gene was inserted into the VV hemagglutinin gene. The resultant inactivation of the hemagglutinin gene led to the attenuation of VVs, but the extent of their attenuation depended on the VV strain. The propagation of LC16mO and its RVV in rabbit brain was poorer than that of LO-1, a cloned derivative of Lister strain, and its RVV, although LC16mO replicated in other organs better than did LO-1. Taken together, these results suggest that LC16mO is a good candidate as a vector for vaccination of humans.

Animals↗

Mouse peritoneal macrophages produce CFU-gm and CFU-meg growth-promoting factors.

The effect of peritoneal macrophage-conditioned medium (macrophage CM) from lipopolysaccharide-injected mice on granulocyte-macrophage colony (CFU-gm) and megakaryocyte colony (CFU-meg) formation was examined using a plasma clot culture system. Macrophage CM stimulated mouse bone marrow cells to form CFU-gm and CFU-meg in the presence of pokeweed mitogen-stimulated spleen cell-conditioned medium, but it had no effect on colony formation in the absence of exogenous colony-stimulating factors (CSF). CFU-gm and CFU-meg colony formation was enhanced by low concentrations of exogenous GM-CSF or Meg-CSF alone. These data demonstrate that macrophage CM contains an activity that sensitized CFU-gm and CFU-meg to exogenous CSF.

Animals↗

Megakaryocyte colony-stimulating factor and burst-promoting activity in LPS-treated mouse spleen cell-conditioned medium.

In order to clarify the mechanism(s) of increased splenic hematopoiesis noted in lipopolysaccharide (LPS)-injected mice, the effects of spleen cell-conditioned medium (SPCM) on megakaryocyte colony (CFU-meg) formation and early erythroid (BFU-e) differentiation were investigated. After spleen cells from LPS-injected mice were incubated for 3 days, the SPCM was assayed for megakaryocyte colony-stimulating factor (Meg-CSF) in CFU-meg assay and for burst-promoting activity (BPA) and erythropoietin (Epo) in erythroid colony assays (i.e., CFU-e, BFU-e). Colony formation of CFU-meg and BFU-e peaked with the addition of 30 and 10-15% SPCM, respectively. Spleen cells from LPS-injected mice produced Meg-CSF and BPA when compared with controls. However, conditioned medium from spleen cells depleted of phagocytic cells had low Meg-CSF and BPA. SPCM did not contain detectable quantities of Epo. It appears likely that local splenic production of Meg-CSF and BPA may affect proliferation of CFU-meg and erythroid progenitor cells in the spleen.

Animals↗

C1q and C3 in bronchoalveolar lavage fluid from patients with summer-type hypersensitivity pneumonitis.

Immune complexes have been thought to participate in the pathogenesis of hypersensitivity pneumonitis, but the role of complement components is not defined. In our study of nine patients with summer-type hypersensitivity pneumonitis (summer-type HP), C1q in bronchoalveolar lavage fluid (BALF) was strikingly increased (mean 3.7, range 0.4 to 10 micrograms/ml). The value of C1q/albumin was several to 20 times greater in BALF than in serum samples from individual patients. In contrast, BALF samples from control subjects (ten patients with sarcoidosis and nine normal subjects) contained an undetectable amount (less than 0.02 micrograms/ml) of C1q. C3 in BALF also increased in the summer-type HP patients. Furthermore, C1q (as well as specific IgG and IgA antibody activities to Trichosporon cutaneum antigen) in BALF correlated with clinical symptoms and diffusing capacity (DCO), while the BAL lymphocytosis or the change of OKT4/OKT8 ratio did not. These findings are indicative of local secretion or concentration mechanism of C1q and C3, supporting the involvement of immune complexes in the respiratory tract of the patients.

Alveolitis, Extrinsic Allergic↗

[Clinical study of the effect of cisplatin therapy in unresectable hepatocellular carcinoma].

Twenty-one cases of unresectable hepatocellular carcinoma (HCC), including 15 cases receiving intravenous infusion of CDDP in addition to transcatheter arterial embolization (TAE), and 6 cases receiving intraarterial infusion of CDDP in combination with sodium thiosulfate rescue (STS rescue) were studied. In the 15 cases given intravenous infusion therapy with TAE, favorable effects were observed in 33.3% of patients, and the 50% survival period was 22.5 months. In the 6 cases given intraarterial infusion, favorable effects were obtained in 66.6% of patients, but the 50% survival period was 2 months. The side effects observed most frequently were nausea and vomiting. All the other side effects observed were not so severe. These results suggest that intravenous CDDP infusion in addition to TAE is favorable, producing a life-prolongation effect.

Aged↗

[Five-year trend in new patients with prostatic carcinoma].

Seventy-four new cases of prostatic carcinoma treated between 1981 and 1985 were analyzed. The patients were between 40 and 86 years old with a mean age of 72.2 +/- 7.7 years. More than 70% of the patients had clinical stage C and D carcinoma. All cases proved histologically to be adenocarcinoma of the prostate. Eighteen patients had well differentiated, 21 moderately differentiated and 35 poorly differentiated adenocarcinoma. Various hormonal treatments were performed as the initial treatment in 88.9% (64/72) of the cases. Among them, 37 cases were treated by estrogen and 22 cases by luteinizing hormone releasing hormone analogues. Fourteen of 64 patients (21.9%) who received hormonal treatment discontinued the therapy within 10.1 +/- 9.1 months because of relapse of the disease or no therapeutic response. Salvage therapy following hormonal treatment were chemotherapy (9/14) and radiation therapy (4/14). During the 5-year follow up 12.1% (9/74) of the patients died due to prostatic carcinoma.

Adult↗

Tumoricidal activity of lymphotoxin (tumor necrosis factor beta) in vivo: its effects on macrophages.

We investigated the cytotoxic activity of recombinant human lymphotoxin (rHuLT) against Meth A sarcoma in vitro and in vivo. In direct cytotoxic assay, Meth A cells showed very low, if any, sensitivity to rHuLT. However, rHuLT was found to be strongly cytotoxic for subcutaneously implanted Meth A cells. In order to explain this discrepancy, we examined the indirect effects of rHuLT on Meth A cells particularly through macrophages. rHuLT showed macrophage chemotactic activity in vitro and also in vivo. Thus, injection of rHuLT into the mouse peritoneal cavity caused migration of macrophages to the peritoneal cavity. In addition, histologic analysis revealed that 6 h after intratumor injection of rHuLT, nonspecific esterase-positive cells started to migrate into Meth A tumor tissues, and after a further 24 h, a larger number of nonspecific esterase-positive cells had migrated into the Meth A tumor tissues. Moreover, peritoneal exudate cells induced by rHuLT showed considerably higher cytotoxic activity against Meth A cells than proteose peptone- or phosphate-buffered saline-induced peritoneal exudate cells. Furthermore, the cytotoxic activity of peritoneal exudate cells was found to reside in macrophages. Investigation of the mechanism of macrophage activation by rHuLT revealed that rHuLT can activate macrophages for cytotoxicity synergistically with mouse interferon-gamma. These results strongly suggest that rHuLT, when injected into the tumor, can induce the migration of macrophages into the tumor and activate macrophages in situ to kill tumor cells.

Animals↗

In vitro characterization of various heat-treated prothrombin complex concentrates (PCC).

All of 6 heat-treated prothrombin complex concentrates (PCC) tested contained adequate levels of factor IX but factor VII content was low. Levels of factors II, X, protein C and protein S were variable and antigen levels were always greater than those of functional activities. On crossed-immunoelectrophoresis factor IX showed variable anodal shift in all concentrates tested and in some activated factor IX was demonstrated by immunoblotting technique. These findings suggested some activation and/or denaturation during production and/or heating. Modest amount of factor VIII clotting activity by solid-phase amidolytic method and of factor VIII antigen was demonstrated in some concentrates but none contained more than a trace factor VIII inhibitor bypassing activity. The results suggested that heat-treated PCC should provide safe therapeutic products for hemophilia B.

Blood Coagulation Factors↗