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Biomedical subjects

H Ariyoshi

Publications and source records attributed to H Ariyoshi.

At least 55 records · Page 3Linked to original sources
PubMed1992

Purification and characterization of a calpain activator from human platelets.

A calpain (Ca(2+)-activated neutral protease) activator was purified from human platelets by ammonium sulfate fractionation, gel-filtration, ion-exchange chromatography, followed by heat-treatment. The purified calpain activator with a Mr of 47.5 kDa was a heat-stable protein as demonstrated in other cells. The calpain activator did not change the Ca2+ sensitivity of calpain but activated calpain activity about 2-fold. This calpain activator may play an important role in the activation of the protease system leading to the Ca(2+)-mediated physiological process of platelets.

Biological Factors↗
PubMed1992

The effects of okadaic acid and calyculin A on thrombin induced platelet reaction.

Okadaic acid and calyculin A, specific and cell permeable inhibitors of protein phosphatase 1 and 2A, inhibited aggregation, secretion and delta [Ca++]i in thrombin stimulated platelets. The inhibitory effect of calyculin A (IC50: 3.6-4.8nM) was about two hundred times more potent than that of okadaic acid (IC50: 0.8-1.3 microM), which is consistent with the difference of the reported Ki values for protein phosphatase 1. These phosphatase inhibitors and PGI2 synergistically enhanced the phosphorylation of 50kDa protein (P50), which is solely related to the inhibition of platelet reaction. These results indicate that serine/threonine protein phosphatase 1 might play a role in platelet activation.

Adenosine Triphosphate↗
PubMed1992

Membrane binding and autolytic activation of calpain-I in human platelets.

The binding of calpain-I (Ca2+ activated neutral protease with high Ca2+ sensitivity) to the membranes of human platelets and the subsequent autolytic activation of calpain-I were analyzed by an immunoblot technique. In A23187 stimulated platelets, cytosolic calpain-I translocated to the membranes with autolysis in a Ca2+ dependent manner and simultaneously underwent autolysis. Although calpeptin, a cell permeable calpain inhibitor, inhibited autolysis of calpain-I, it was unable to prevent the translocation of calpain-I. In a cell re-constituted system, the membrane binding of calpain-I was also Ca2+ dependent and was significantly inhibited by a substrate of calpain. It was suggested that the binding of calpain-I to the membranes required the substrate binding site of this enzyme.

Biological Transport↗
PubMed1991

Proteasome and its novel endogeneous activator in human platelets.

Proteasome, a high molecular weight multicatalytic protease, was purified from the cytosolic fraction of human platelets for the first time. The biochemical properties of the enzyme including substrate specificity, optimal pH and effects of various inhibitors were almost identical with those of other cells. During the purification with a Heparin-Sepharose chromatography, a novel endogenous activator of the protease was identified and was partially purified. The activator enhanced both chymotrypsin or trypsin like activities of the proteasome in a dose related manner and was inactivated by heating at 56 degrees C for 30 min. This newly identified activator may serve as an important regulator or cofactor of intracellular activities of the proteasome.

Amino Acid Sequence↗
PubMed1991

[Phase I study of CI-898. CI-898 Study Group].

We conducted a phase I study of CI-898 (trimetrexate), a new diaminoquinazoline antifolate in 22 patients with solid cancer in a multicenter collaborative study. The dosage schedule was single-dose intravenous administration (single treatment), followed by one or two courses of 5-day intravenous administration (5-day treatment) at 3-week intervals. Starting at 2 mg/m2 (1 n), the dose was increased up to 15 mg/m2 (7.5 n) for single treatment and 12 mg/m2 (6 n) for 5-day treatment. Evaluable cases numbered 18 for single treatment and 17 for 5-day treatment. In single treatment, the highest dose of 15 mg/m2 caused no serious side effect and did not reach the maximum tolerated dose (MTD). In 5-day treatment, leukocytopenia and thrombocytopenia were found dose dependently, the dose-limiting factor was bone marrow depression, and MTD was 10 mg/m2/day. The leukocyte and platelet counts reached the nadir in 1-3 weeks after initiation of 5-day treatment. The recovery from the nadir required about one week. Subjective side effects included mucitis (mouth, anus), malaise and gastro-intestinal symptoms (nausea, anorexia, diarrhea). None of alopecia, cardiotoxicity and nephrotoxicity were found. In the present phase I study, a tendency of tumor reduction was found in one case each of breast cancer (adenoma) and lung cancer (squamous cell carcinoma). The plasma concentration of the unchanged compound after single treatment showed a biphasic elimination pattern (t1/2 alpha 0.8-1.4 hr, t1/2 beta 9.4-13.0hr). The urinary excretion of the unchanged compound was 14.7-23.5% of the administered dose. In 5-day treatment, no accumulation was found. From the results of the present study, the recommended dosage of CI-898 in the early phase II study was considered to be 8 mg/m2/day intravenously for 5 days (every 3-4 weeks).

Adult↗
PubMed1991

Characteristics of various synthetic peptide calpain inhibitors and their application for the analysis of platelet reaction.

Calpeptin (a cell permeable synthetic peptide calpain inhibitor) inhibited the generation of thromboxane B2 (TxB2) by the direct inhibition on Tx synthetase in platelets at the concentrations more than 30 microM. Calpeptin, its analogues and E-64d (EST) were further examined with regard to cell permiability and inhibitory spectra. Among all compounds, only calpeptin inhibited the degradation of substrate proteins of calpain with negligible effect on TxB2 generation in intact platelets at the concentrations less than 30 microM. These concentrations of calpeptin did not inhibit the platelet aggregation, the elevation of [Ca2+], nor the formation of inositol 1,4,5-trisphosphate (IP3) in thrombin or collagen activated platelets. These results indicate that calpain dose not participate in the process of platelet activation induced by thrombin or collagen.

Arachidonic Acids↗
PubMed1990

Potential participation of calpain in platelet activation studied by use of a cell penetrating calpain inhibitor (calpeptin).

Employing a cell penetrating calpain inhibitor (calpeptin), the role of calpain in platelet activation was examined. In washed platelets (WPs) both thrombin and collagen-induced platelet aggregation were dose-dependently inhibited by calpeptin. The addition of plasma to WPs interfered with the action of calpeptin, however more than 3 min preincubation of calpeptin with WPs completely abolished the influence of plasma. In thrombin-activated WPs with calcium, the increase of intracellular calcium concentration, [Ca2+]i, and the production of inositol triphosphate (IP3) were dose-dependently inhibited by calpeptin. The generation of thromboxane B2 (TxB2) was inhibited by calpeptin in collagen and thrombin-activated WPs. In [3H]-arachidonic acid (AA)-labelled platelets, calpeptin increased the amount of [3H]-AA liberated by inhibiting [3H]-AA degradation after collagen or thrombin stimulation. When [14C]-AA degradation by the platelet suspension was observed, calpeptin inhibited TxB2 and hydroxyheptadecatrienoic acid (HHT) generation but increased prostaglandin (PG) E1, E2, 12-hydroxyeicosatetraenoic acid (12HETE) and AA. Based on these findings, calpain may be involved in the activation phospholipase C and thromboxane synthetase.

Arachidonic Acid↗
PubMed1990

An early phase II study of CPT-11: a new derivative of camptothecin, for the treatment of leukemia and lymphoma.

An early phase II study of a new camptothecin analog and an inhibitor of topoisomerase I, CPT-11, was conducted in 62 patients with refractory leukemia and lymphoma by four different treatment schedules in a multiinstitutional cooperative study. CPT-11 therapy resulted in four complete remissions (CRs) and three partial remissions (PRs) in 29 assessable non-Hodgkin's lymphoma (NHL) patients, one PR in three Hodgkin's disease (HD), one CR and one PR in 11 acute lymphoblastic leukemia (ALL), and one PR in 15 acute myelogenous leukemia (AML) patients. Single infusion of 200 mg/m2 every 3 to 4 weeks produced no response in both leukemia and lymphoma patients. Sixty-minute infusions of 40 mg/m2/d for 5 days every 3 to 4 weeks or for 3 days weekly produced four CRs (17%) and four PRs (17%) in 24 patients with malignant lymphoma. Sixty-minute infusions of 20 mg/m2 twice a day for 7 days every 3 to 4 weeks resulted in one CR and two PRs in 12 patients with acute leukemia. No response was seen in an acute leukemia patient by another treatment schedule. CPT-11 was effective in two (15%) of 13 primarily refractory leukemia and lymphoma cases, in two of four relapsed cases, and in seven (17%) of 41 relapsed and refractory cases. Major side effects were leukopenia (91%) and gastrointestinal (GI) (76%). CPT-11 was shown to be effective against refractory leukemia and lymphoma, and thus deserves further clinical study; the novel antitumor activity mode of this drug predicts no cross-resistance to presently available antitumor drugs.

Adolescent↗
PubMed1989

[Basic and clinical evaluation of an immunoradiometric competitive inhibition assay for sialyl TN antigen: (2). Evaluation of clinical significance. STN Study Group].

The clinical significance of serum sialyl Tn antigen as a tumor marker was evaluated using "STN Otsuka" kits. Results indicated that the antigen was frequently elevated in sera from patients with ovarian cancers (43.1%, 140/325), including serous cystadenocarcinoma (51.6%, 63/122), mucinous cystadenocarcinoma (55.6%, 30/54), endometrioid carcinoma (56.5%, 13/23), and mesonephroid carcinoma (40.0%, 6/15). The positive frequency of sialyl Tn antigen in patients with ovarian carcinoma was less than the frequency of CA 125 (75.5%, 194/257) or sialyl SSEA-1 (47.2% 83/176). However, the false positive rate of sialyl Tn antigen in patients with benign gynecological disorders (3.7%, 15/401) was much lower than the false positive rates of other antigens; such as CA 125 (48.4%, 155/320) and sialyl SSEA-1 (19.2%, 51/266). The serum level of sialyl Tn antigen reflected the clinical activity of the disease quite well in patients with ovarian cancers. The sialyl Tn antigen was concluded to be a useful serum tumor marker for ovarian cancers.

Antigens, Neoplasm↗
PubMed1989

[Basic and clinical evaluation of an immunoradiometric competitive inhibition assay for sialyl Tn antigen: (1). Evaluation of assay conditions and normal values. STN Study Group].

An immunoradiometric competitive inhibition assay of the serum levels of the sialyl Tn antigen using "STN Otsuka" kits is described. The assay required only duplicate 50-microliters samples, and the concentration of sialyl Tn antigen in serum was determined by reference to a standard curve ranging from 0 to 400 arbitrary units/ml. The intra-and inter-assay reproducibilities were largely satisfactory. The serum levels of the antigen in normal individuals were not affected by ABO and Lewis blood type status of the tested individuals. Normal values were 25.5 +/- 9.8 in male, and 21.3 +/- 8.0 in female, and the difference was statistically significant at p less than 0.001. The serum level of the antigen was not affected by menstrual cycle or pregnancy in female, whereas the level of other tumor markers such as CA 125 was highly variable depending upon these conditions.

Adult↗
PubMed1983

Serological studies on volunteers inoculated experimentally with a dengue virus strain in 1943.

In 1943, a large dengue epidemic occurred in the Osaka district and several samples of dengue virus were isolated from patients with dengue fever by workers in this Institute. These were inoculated into human volunteers to confirm that they were dengue virus. In the present study, serum samples were collected from the volunteers who had been inoculated with dengue virus and were examined serologically. In the neutralization test, all the sera showed a higher titer against dengue type 1 virus (DEN-1) than against the other three types of dengue virus, indicating that the virus strain isolated in 1943 was DEN-1.

Antibodies, Viral↗
PubMed1981

Radiation-induced acute necrosis of the pancreatic islet and the diabetic syndrome in th golden hamster (Mesocricetus auratus).

Exposure of golden hamsters to 35 000 rad of X-rays induced acute and specific necrosis of the cells of thd isles of Longerham of the pancreas within 4 hours whereas no other tissue revealed any drastic changes which would lead to a critical illness until 36 hours. Animals began to show the characteristic signs of diabetes, that is, hyperglycaemia, hyperkaliemia, ketonemia, and acidosis at 12 hours and these continued until death, 56+/- 8 hours later. These were accompanied by the disappearance of beta-cell granules and a decrease of plasma insulin. Treatment of irradiated animals with injections of insulin resulted in a reduction in high blood glucose and the prolongation of survival time up to 5 days, which is comparable to this radiation-induced diabetic syndrome resulted from acute necrosis of the cell of the islets of Langerhans, a previously unreported lethal effect of radiation in golden hamsters.

Animals↗