Search PubMed⌕ Search

Biomedical subjects

S Terada

Publications and source records attributed to S Terada.

At least 163 records · Page 9Linked to original sources

Hemostatic effect of a heat-treated factor VIII concentrate (Haemate P) in von Willebrand's disease.

A heat-treated factor VIII (F VIII) concentrate (Haemate P) has been administered to patients with various types of von Willebrand's disease (vWD). The 4 activities of F VIII/vWF as well as change in the multimeric structure of vWF were then studied. In 4 patients with type I vWF who were given a Ristocetin cofactor (Rcof) dose of 42-78 U/kg, there was a clear reduction of the bleeding time and an increase of F VIII: C, F VIII: Ag, Rcof and vWF: Ag for several hours. The recovery of Rcof. after 1 h was 50-75%. Although the multimeric composition of vWF in these patients was similar to that of normal plasma, the density of each multimer band was very low. After infusion, however, the density of all multimer bands increased for several hours, to decrease again after 24 h. In 4 patients with type II A vWD who received a dose of Rcof of 55-76 U/kg, the 4 activities of F VIII/vWF increased similarly as was the case in type I. All patients had only 3-4 smaller multimer bands. New larger and intermediate multimers appeared for several hours after infusion of the preparation. Two patients with type III vWD who received doses of Rcof of 52 and 65 U/kg showed also a similar increase in the 4 activities of F VIII/vWF after infusion. All the multimers lacking in these patients appeared for several hours after infusion.

Adolescent↗

Monoclonal anti-Thy-1.2 antibody induced hematopoiesis in vivo.

The intravenous injection of a monoclonal anti-Thy-1.2 alloantibody (IgM class) induced a rapid increase in the number, and the ratio, of multipotent hematopoietic stem cells (CFU-S) in S-phase. The onset of hematopoiesis was thymus-independent. Reconstitution of lethally-irradiated mice with bone marrow cells from mice injected with antibody augmented the T-cell responsiveness to mitogens. No activation was observed in granulocyte/macrophage progenitors. The monoclonal antibody did not directly stimulate CFU-S in vitro, although hematopoietic activity could be found in the sera of antibody-injected mice. Immediately after injection, the antibody was found bound on Thy-1+ cells in spleen. No decrease in the number of peripheral T cells was seen. These results seem to indicate that Thy-1.2-positive cells bound with anti-Thy-1.2 alloantibody may secrete a factor which induces the proliferation of hematopoietic stem cells.

Animals↗

Factor VIII polypeptide specificity of monoclonal anti-factor VIII antibodies.

Four monoclonal antibodies against factor VIII, NMC-VIII/1, NMC-VIII/2, NMC-VIII/3 and NMC-VIII/4, were produced. The first three antibodies were of the IgG1 immunoglobulin subclass, while the fourth was IgM. The affinity of each antibody for factor VIII was high and anti-factor VIII clotting activity was detected in NMC-VIII/2, NMC-VIII/3 and NMC-VIII/4. NMC-VIII/1 had no inhibitory effect on factor VIII clotting activity. Immunoblotting using purified intact and thrombin-treated factor VIII identified the antibodies' factor VIII polypeptide specificities. With thrombin-treated factor VIII the factor VIII fragments for NMC-VIII/1 and NMC-VIII/2 were 80 kDa and 54 kDa, respectively, while both NMC-VIII/3 and NMC-VIII/4 recognised a 44 kDa fragment. With intact factor VIII, antibodies NMC-VIII/2-4 bound to polypeptides larger than 90 kDa, especially NMC-VIII/2, which reacted with a chain of 330 kDa thought to be a mature form of factor VIII protein. We also detected a mature form of factor VIII in hepatic sinusoidal endothelial cells by immunoperoxidase staining. Identification of the factor VIII polypeptides bearing these fragments enabled us to clarify the localization of the factor VIII thrombin cleavage site, and suggested the existence of factor VIII in hepatic sinusoidal endothelial cells.

Animals↗

Myristoylation of neutrophil proteins and their biological characteristics.

We have studied protein acylation in neutrophils of guinea pigs using [3H]myristate. A large number of neutrophil proteins were acylated with exogenously added myristic acid. The myristoylation was detected on 110, 77, 56, 54, 52, 42, and 37 kDa proteins. These myristoylations were stronger in peripheral blood than in peritoneal cells. Myristic acid was found to be covalently linked by an amid bond to these proteins since the proteins were resistant to boiling, chloroform/methanol and hydroxylamine treatment. Most myristoylated proteins appeared to be associated with the membrane fraction, while some of the proteins such as 77 kDa one was distributed also in the cytoplasm and translocated from the cytoplasm to the plasma membrane by stimulation. Lysozyme was myristoylated in vitro by the N-hydroxysuccinimide ester of myristic acid. The myristoylated lysozyme had an ability to be associated with phospholipid liposomes, and the membrane-associated lysozyme became a substrate of the rat brain Ca2+- and phospholipid dependent protein kinase (protein kinase C). These results indicate that myristoylation in neutrophil proteins may have an important role in metabolic regulation through their membrane association.

Animals↗

[Intraperitoneal (Ip) administration of cisplatin in combination with systemic chemotherapy in patients with malignant ascites of gastrointestinal cancer: clinical evaluation and pharmacokinetics].

Ten patients with carcinomatous peritonitis of gastrointestinal cancer have been treated with administrations of CDDP-Ip (50-150 mg/body), in combination with systemic chemotherapy simultaneously combined with sodium thiosulfate (STS) iv in 4 patients. All patients received transfusions of specific hydration. The pharmacokinetics of CDDP was studied in 4 patients, and the following results were obtained. (1) As for its effect on malignant ascites, according to Koyama's and Saito's criteria, 2 patients showed a complete response, 3 showed a partial response, and 5 showed no change. (2) As for its effect on the primary site, only one patient showed a partial response, and the others no change. (2) As to its side effects, 6 patients manifested nausea and vomiting, and only one showed a mild kidney dysfunction, and no myelosuppression. No significant difference in the side effects between the STS-combined group and the non-STS-combined group was found. (3) Serum CDDP levels were reached maximum 1-2 hours after Ip, and gradually decreased during the beta-phase of iv administration. Significant levels of non-protein-bound CDDP were found in the serum within 4 hours after Ip. These results indicate that the CDDP Ip is safe and useful for carcinomatous peritonitis of gastrointestinal cancer, however the combination of STS might weaken the systemic anti-cancer effect of CDDP by neutralizing the non-protein-bound CDDP in the serum.

Aged↗

[A case of acute adult T-cell leukemia with long-term remission by cisplatin therapy].

A 37-year-old man was admitted because of general malaise, slight fever, pain in the knee joint and lower extremities, polydypsia, polyuria and skin lesion in September, 1985. The white blood cell count was 16,920/cmm with 41% of abnormal lymphoid cells with convoluted nuclei, which were compatible with adult T-cell leukemia (ATL). The serum calcium level was 15.1 mg/dl, serum LDH 307 IU/l, and the titer of anti-ATLA antibody in serum x 160. The cell surface phenotype of abnormal lymphocyte was OKT-3+, OKT-4+ and OKT-8-. Therefore the diagnosis of acute ATL was made. He was treated with cisplatin because VEPA therapy was not effective. About five months after the start of chemotherapy, he entered remission with almost complete disappearance of abnormal lymphocyte. The remission continued over twenty-nine months with maintenance therapy by cisplatin alone. The clinical course of this patient suggests that cisplatin could be applied to a case of ATL which is refractory to the conventional treatment.

Adult↗

Detection of Ca2+-dependent cyclic GMP binding protein in frog rod outer segments.

For the identification of the cGMP-sensitive ion channel protein of frog rod outer segments (ROS), we analyzed cGMP binding proteins in the ROS by photoaffinity labeling with [3H]cGMP. We found three cGMP binding polypeptides (66 kDa, 92 kDa and 100 kDa) in the membrane protein fraction of ROS. cGMP binding to the 66 kDa polypeptide required the addition of 2 mM CaCl2. We propose that this polypeptide corresponds to the cGMP-activated channel protein reported by Cook et al. [(1987) Proc. Natl. Acad. Sci. USA 84, 585-589]. The 100 kDa and 92 kDa polypeptides are subunits of the cGMP phosphodiesterase.

Animals↗

Detection of cyclic GMP binding protein and ion channel activity in frog rod outer segments.

In order to identify the cGMP-sensitive ion channel protein in frog rod outer segments (ROS), we analyzed cGMP binding proteins in the ROS by means of photoaffinity labeling with [3H]cGMP. We found four cGMP binding proteins with molecular weights (Mws) of 250K, 100K, 92K, and 53K. The 250K protein was an integral-membrane protein, which we named cG-Protein, (cG stands for cGMP). The cGMP-binding to cG-Protein was slightly increased by CaCl2. cG-Protein has a carbohydrate moiety. The amount of cG-Protein per single rod outer segment was estimated to be 9.0 x 10(6) molecules. Light-dependent phosphorylation of cG-Protein with [gamma-32P]ATP was observed. The 100K and 92K proteins were peripheral-membrane proteins, corresponding to cGMP phosphodiesterase. The 53K protein was a soluble protein. Incorporation of a membrane protein fraction of frog ROS into a planar lipid bilayer resulted in the appearance of at least three kinds of ion channel activities; two of them were related to cGMP. The possibility that cG-Protein is the cGMP-sensitive ion channel in vivo is discussed.

Animals↗

Inhibitory effect of cholesterol on interaction between cytoplasmic actin and liposomes, and restorative effect of high osmotic pressure.

Although cholesterol is one of the major components of plasma membranes in eukaryotic cells, very little is known about its role in biological membranes. We reported previously (Okimasu et al., Cell Struct. Funct. 11, 273-283, 1986) that introduction of cholesterol into the liposomal membrane caused a decrease in membrane permeability, especially by the binding of cytoplasmic proteins to the liposomal membrane. The present study was carried out to further clarify the biochemical function of cholesterol in the membrane-protein interactions, especially under high osmotic pressure. The association of membranes with cytoplasmic proteins and their permeability were decreased by the introduction of cholesterol, but its effects were diminished in a hypertonic medium. The protein species associated with cholesterol-containing liposomes vary depending on the sort of hypertonic condition. It was suggested that since the degree of lipid packing by the cholesterol was reduced by the locally increased curvature in the lipid bilayer under high osmotic pressure, some cytoplasmic proteins can penetrate into the liposomal membrane.

1,2-Dipalmitoylphosphatidylcholine↗

Mechanism of polymorphonuclear leukocyte activation by myristate. Involvement of calcium ion and protein kinase C.

The stimulative effects of myristate on the superoxide generation and depolarization of membrane potential of polymorphonuclear leukocytes (PMN) are particularly strong, yet myristate does not affect the intracellular free Ca2+ level ([Ca2+]i) in the presence of 1 microM free calcium in calcium-EGTA buffer. The half maximum concentration of myristate was 10 microM. Myristate inhibited the transitory changes in [Ca2+]i induced by formylmethionyl-leucyl-phenylalanine (FMLP), but stimulated further the FMLP-induced superoxide generation; these effects are similar to those of phorbol myristate acetate (PMA). The myristate-induced superoxide generation was partially inhibited by H-7, a specific inhibitor of protein kinase C. Myristate stimulated the activity of Ca2+- and phospholipid-dependent protein kinase (protein kinase C) in a concentration-dependent manner in the presence of 10(-6) M Ca2+. The Ka was 100 microM. These results suggested that there is no relation between the superoxide generation and the [Ca2+]i change in PMNs and that the effects of myristate are similar to those of PMA against PMN.

Animals↗