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Biomedical subjects

M Okuma

Publications and source records attributed to M Okuma.

At least 253 records · Page 14Linked to original sources
PubMed1986

A lower molecular weight gamma-chain variant in a congenital abnormal fibrinogen (Kyoto).

A gamma-chain variant with a lower molecular weight than the normal gamma chain was detected in a new congenital abnormal fibrinogen with impaired polymerization of the fibrin monomer and with normal release of fibrinopeptides A and B in a 45-year-old male. Purified fibrinogen analyzed on SDS-polyacrylamide gel electrophoresis under the reduced condition contained an abnormal protein band with an apparent molecular weight of 48,000 compared with the gamma chain with a molecular weight of 50,000. This abnormal protein band was found to be a gamma-chain variant from the molar ratio of A alpha chain:B beta chain:gamma chain:abnormal protein (about 2:2:1:1), with positive staining for carbohydrate and crosslinking ability. Crosslinked fibrin contained three types of gamma-gamma dimers with apparent molecular weights of 94,000 (the same as normal major gamma-gamma dimer), 92,000 and 90,000, and the plasmic digests of crosslinked fibrin in the presence of calcium retained three types of gamma-gamma dimer remnants. This suggests that the abnormal gamma-chain variant has a shorter polypeptide chain not in the NH2-terminal but in the COOH-terminal portion, probably at or near the polymerization site. This patient's two daughters had the same abnormal fibrinogen. This unique inherited abnormal fibrinogen was designated as fibrinogen Kyoto, and the gamma-chain variant as gamma Kyoto.

Blood Coagulation Disorders↗
PubMed1985

Decreased plasma prostacyclin-regenerating activities in diabetics.

We assessed prostacyclin-regenerating activities (PGI2-RA) in 27 each of diabetic patients and of normal subjects by incubating plasma with "exhausted" rat aortic tissues, and compared these activities with platelet aggregability, vascular complications and the levels of fasting blood sugar (FBS) as an indicator of diabetic control. Patients' plasma showed a significantly decreased PGI2-RA when compared with normal (p less than 0.001). The activities in the patients with enhanced ADP-induced platelet aggregation in plasma or in whole blood were significantly decreased as compared with those with normal platelet functions (p less than 0.01). The patients with diabetic retinopathy showed significantly decreased PGI2-RA compared with those without this complication (p less than 0.02). A significant negative correlation was found between PGI2-RA and FBS levels before or during treatment. This abnormality found in patients' plasma appeared to be reversible and related to the degree of diabetic control. These results suggest that the decreased PGI2-RA could play a pathogenetic role together with platelet hyperaggregability in the development of microvascular and thrombotic complications in some diabetic patients.

Adult↗
PubMed1983

Altered arachidonate metabolism by leukocytes and platelets in myeloproliferative disorders.

The arachidonate metabolism by leukocytes and platelets was studied in 14 patients with myeloproliferative disorders including 7 patients with chronic myeloid leukemia (CML), 5 with polycythemia vera (PV) and 2 with essential thrombocythemia (ET). When the leukocytes were incubated with arachidonate and A23187, leukotriene B4 and hydroxyeicosatetraenoic acids (HETEs) were constantly detected using reversed-phase high-performance liquid chromatography in normal subjects, while selective deficiency of 5-lipoxygenase products (leukotriene B4 and 5-HETE) was found in 4 patients with CML. this novel abnormality of the leukocytes seemed to be derived from the possible deficiency of 5-lipoxygenase in these patients' polymorphonuclear neutrophils (PMNNs). The formation of 15-HETE appeared to be almost normal in all the patients. Platelet 12-lipoxygenase deficiency was detected in 2 patients with PV and 2 with CML in whom one was associated with the deficiency of 5-lipoxygenase products. These bicellular abnormalities of the arachidonate metabolism might contribute to understand dysfunctions of PMNNs and platelets in some patients with myeloproliferative disorders.

Arachidonate Lipoxygenases↗
PubMed1982

Effects of etamsylate on platelet functions and arachidonic acid metabolism.

The effects of etamsylate on human platelet aggregation and ATP release as well as on the arachidonate metabolism by the platelet have been studied. Etamsylate enhanced these platelet functions induced by arachidonic acid (AA), thromboxane A2, collagen and calcium ionophore A23187 but not those induced by ADP and epinephrine. In experiments with cyclooxygenase-inhibited platelets, AA-induced platelet aggregation was completely inhibited and it was not enhanced by etamsylate, while A23187-induced aggregation was partially inhibited and this aggregation was enhanced by etamsylate. Platelet AA metabolism including thrombin-induced AA liberation from phospholipids as well as the lipoxygenase and cyclo-oxygenase pathways was not significantly affected by etamsylate. These results suggested that etamsylate enhanced platelet response to thromboxane A2 and calcium ionophore and that this could be included as a mechanism for its potentiating effect on platelet functions.

Arachidonic Acid↗
PubMed1982

The recovery of platelet malondialdehyde production after a single intake of aspirin--the effect of dosage.

We studied the recovery pattern of platelet malondialdehyde (MDA) formation after a single intake of various doses of aspirin (ASA). In normal subjects, there were striking differences in the recovery pattern between large doses (1,000 or 500 mg) and small doses (100 or 50 mg) of oral ASA. The 2 day lag phase was present in the large dose group which showed the complete inhibition of the circulating platelets 2 hr after oral ASA but not in the small dose group which showed the incomplete inhibition. The difference of recovery time between these two groups was about 2 days. These data suggest that ASA's effect on megakaryocytes might affect the recovery pattern of MDA formation by the circulating platelets. In 2 patients with chronic idiopathic thrombocytopenic purpura, the 2 day lag phase was not observed in the recovery even after a large ASA dose.

Adrenal Cortex Hormones↗
PubMed1982

Subnormal platelet response to thromboxane A2 in a patient with chronic myeloid leukaemia.

A new type of acquired platelet dysfunction was found in a chronic myeloid leukaemia patient with petechiae and thrombocytosis. Platelet aggregation induced by arachidonic acid (AA), collagen and A23187 was decreased, secondary aggregation by ADP and epinephrine was defective and ristocetin-induced aggregation was completely reversible. No platelet ATP was released by AA and collagen. Only high concentrations of AA (greater than or equal to 2 mM) induced minimal reversible aggregation. 14C-serotonin uptake by the platelet and platelet adenine nucleotide contents were normal. Normal AA metabolism was demonstrated by thin-layer radiochromatographic analysis of the metabolites of 14C-AA and the determination of thiobarbituric acid reactive substances produced by the incubation of AA or thrombin with the platelets. Minimal reversible aggregation was observed when patient's platelet-rich plasma was added to a reaction mixture in which thromboxane A2 (TXA2) had been generated. TXA2 produced by patient's platelets showed normal platelet-aggregating activity. These results suggest that a subnormal platelet response to TXA2 is included as a mechanism for this acquired hypofunction of the platelet.

Adenosine Triphosphate↗
PubMed1980

A simple method for estimation of lipoxygenase and cyclo-oxygenase pathways in human platelets--the use of thiobarbituric acid reaction.

To develop a simple method for estimation of platelet lipoxygenase (PLO) and cyclo-oxygenase (PCO) pathways, the arachidonic acid (AA) metabolism of human platelet was investigated under various experimental conditions by the use of the thiobarbituric acid (TBA) reaction and a radioisotope technique. A TBA-reactive substance different from malondialdehyde (MDA) via PCO pathway was detected and shown to be derived from the PLO pathway. Since the optimal pH and time course of its formation were different from those of MDA formation via PCO pathway, PLO and PCO pathways were estimated by quantitating the TBA-reactive substances produced by the incubation of AA either with aspirin-treated platelets or with untreated ones, respectively, each under optimal conditions. Normal values expressed in terms of nmol MDA/10(8) platelets were 1.17 +/- 0.34 (M +/- SD, n = 31) and 0.79 +/- 0.15 (n = 31) for PLO and PCO pathways respectively.

Adult↗
PubMed1980

Generation of prostacyclin-like substance and lipid peroxidation in vitamin E-deficient rats.

Endogenous generation of prostacyclin (PGI2)-like substance and lipid peroxidation were studied in the aorta of rats fed on vitamin E-deficient diet and/or vitamin E-supplemented one for 4 to 10 months after they were weaned at 4 weeks. PGI2-like substance was produced by the incubation of the aortic ring in pH 9.0 borate-buffered saline and was estimated by comparison of its antiaggregatory activity with that produced by known amounts of synthetic PGI2. Thiobarbituric acid-reacting substance (TBARS) was determined as an indicator of lipid peroxidation. The generation of PGI2-like substance was significantly reduced in rats fed on vitamin E-deficient diet for 8 and 10 months as compared with that in the animals fed on vitamin E-supplemented one for the same period (p less than 0.001). Mean concentration of TBARS in the aortae of rats fed on vitamin E-deficient diet for 10 months was significantly higher than that of the animals fed on vitamin E-supplemented diet for the same feeding period (p less than 0.001). These alterations in the aortae of rats fed on vitamin E-deficient diet were corrected by feeding them on vitamin E-supplemented diet for subsequent 2 months.

Animals↗
PubMed1979

Production of prostacyclin-like substance in stroke-prone and stroke-resistant spontaneously hypertensive rats.

Activities of aortae to produce prostaglandin (PG) I2-like substance in stroke-prone spontaneously hypertensive rats (SHRSP), stroke-resistant SHR (SHRSR) and normotensive control rats from the Wistar-Kyoto (WK) colony were compared. PGI2-like substance was produced by the incubation of the aortic ring in pH 9.0 borate-buffered saline and the amount produced was estimated by comparison of its anti-aggregatory activity with that produced by known amounts of the sodium salt of synthetic PGI2. Before the development of stroke, amounts of this substance generated in SHRSP and SHRSR were significantly higher than those in WK rats (p less than 0.01 and p less than 0.02, respectively). Remarkably reduced capacity to generate PGI2-like substance was observed in some SHRSP after the development of stroke.

Animals↗
PubMed1979

Altered arachidonate metabolism by platelets in patients with myeloproliferative disorders.

Platelet lipoxygenase and cyclo-oxygenase pathways were investigated by the incubation of 1(-14) C-arachidonic acid with washed platelets in 33 patients with myeloproliferative disorders, including 14 patients with chronic myeloid leukemia (CML), 12 with polycythemia vera (PV), 4 with essential thrombocythemia (ET), and 3 with myelofibrosis (MF). In patients with MF and CML, mean activities of the lipoxygenase pathway were significantly lower when compared with normal controls (p less than 0.001 and p less than 0.01, respectively). When a normal range of the activity was defined as mean +/- 2 SD, all patients with MF, 8 with CML, 6 with PV, and 1 with ET showed decreased lipoxygenase activities, while activities of the cyclo-oxygenase pathway were decreased in one of each patient with CML, PV, and ET. In 4 of 10 patients with a selective lipoxygenase deficiency, platelets were aggregated by lower concentrations of arachidonic acid than those necessary to induce normal platelet aggregation. It is suggested that the lipoxygenase activity could modulate platelet functions through its effect on arachidonate metabolism by the cyclo-oxygenase pathway and that a selective lipoxygenase deficiency could offer a mechanism for hyperfunction of the platelet, which may lead to a thrombotic tendency, one of the common features of myeloproliferative disorders.

Adult↗