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Biomedical subjects

K Fukutake

Publications and source records attributed to K Fukutake.

At least 19 recordsLinked to original sources
PubMed1992

Fluctuations in plasma levels of thrombomodulin in patients with DIC.

Plasma thrombomodulin (TM) has attracted considerable attention as a marker of endothelial cell membrane injury. We examined fluctuations in plasma TM levels in patients receiving therapy for the disseminated intravascular coagulation syndrome (DIC) using an enzyme immunoassay. Sixty healthy controls and 18 patients with DIC were studied. The mean +/- SD of the TM values initially measured immediately after the onset of DIC was 42.00 +/- 20.85 ng/ml, which was markedly increased as compared with the control value of 15.36 +/- 4.85 ng/ml (p < 0.001). Fluctuations in the TM levels over time were studied after dividing the patients according to the presence or absence of improvement in the underlying disease and improvement or lack thereof in the coagulation findings. Group I showed improvement in both categories, Group II showed improvement only in the latter, and Group III showed no improvement in either category. In Group I, the mean +/- SD of initial measured TM levels was 37.02 +/- 10.12 ng/ml and the mean of final values decreased to 58.9% of the initial value. This decrease was significant by paired Student's t-test (p < 0.01). The initial value in Group II was 45.86 +/- 18.86 ng/ml and the final values increased to 117.0% of the initial values, this difference was not significant. The initial value in Group III was 44.48 +/- 21.53 ng/ml and the final values increased to 143.4% of the former. This increase was significant by paired Student's t-test (p < 0.05). The difference in % fluctuations between Group I and Group III was significant by Wilcoxon's test (p < 0.01). These results suggest that the measurement of plasma TM can be useful in the management of DIC.

Adolescent↗
PubMed1992

5-Hydroxydecanoate inhibits ATP-sensitive K+ channel currents in guinea-pig single ventricular myocytes.

We investigated the effect of 5-hydroxydecanoate, a novel antiarrhythmic agent, on the electrical activity of guinea-pig ventricular myocytes. The outward K+ current increased by lowering the intracellular ATP concentration (0.5 mM) was efficiently blocked by 5-hydroxydecanoate when recording in the whole cell configuration with the application of voltage ramps. The increase in the time-independent outward K+ current induced by reducing intracellular ATP to 0 mM was also blocked by 5-hydroxydecanoate (10 or 100 microM) and by tolbutamide (1 mM). Using the single channel recording technique, we found that 5-hydroxydecanoate blocked ATP-sensitive K+ channels when its channel open probability was increased by 1 mM ATP together with 1 mM ADP or by an intracellular pH of 6.6. These conditions are well documented to reflect metabolic changes in the early stages of myocardial ischemic attack. These results suggest that 5-hydroxydecanoate could inhibit ATP-sensitive K+ channels, resulting in an antiarrhythmic effect specifically on ischemic hearts.

Adenosine Triphosphate↗
PubMed1992

A cAMP-dependent protein kinase inhibitor modulates the blocking action of ATP and 5-hydroxydecanoate on the ATP-sensitive K+ channel.

We studied the blocking mechanism of 5-hydroxydecanoate, a novel antiarrhythmic agent, on the ATP-sensitive K+ channel in the single ventricular myocytes using the inside-out patch clamp technique. The channel activity in response to 5-hydroxydecanoate varied with each membrane patch corresponding to the sensitivity to ATP. In this condition the exogenous application of cAMP or cAMP-dependent protein kinase (PKA) obviously recovered the ATP-sensitive K+ channel activity after channel deactivation. By contrast, in membrane patches exhibited low sensitivity to ATP, endogenous cAMP-dependent protein kinase inhibitor (PKI) depressed the channel activity and restored the inhibitory action of 5-hydroxydecanoate and ATP on the channel. These results suggest that PKA-PKI system is involved in the regulatory mechanism of gating activity of the ATP-sensitive K+ channel and the blocking action of 5-hydroxydecanoate and ATP appears to be exerted by potentiating the inhibitory action of PKI on the channel.

Adenosine Triphosphate↗
PubMed1992

Hypolipidemic effect of ethyl all-cis-5,8,11,14,17-eicosapentaenoate (EPA-E) in rats.

We examined the effect of ethyl all-cis-5,8,11,14,17-eicosapentaenoate (EPA-E) with high purity on circulating lipids in rats under several experimental conditions. In normolipidemic rats, EPA-E decreased the lipids in a dose-dependent manner. Clofibrate (100 mg/kg/day) was more potent in lowering the lipids than EPA-E (1000 mg/kg/day). In high cholesterol diet-fed rats, EPA-E (300 mg/kg/day) decreased the total cholesterol. However, clofibrate (300 mg/kg/day) had little effect on the total cholesterol. In hypertriglycemic rats induced by corn oil, EPA-E (300 mg/kg/day) or clofibrate (100 mg/kg/day) reduced the rise of triglycerides. EPA-E (300 mg/kg/day), clinofibrate (100 mg/kg/day) or clofibrate (300 mg/kg/day) caused a significant reduction in the lipids induced by the injection of Triton WR-1339. Furthermore, EPA-E (300 mg/kg/day) or clinofibrate (100 mg/kg/day) decreased the elevation of lipids produced by feeding the rats a casein-rich diet. These results show that EPA-E possesses potent inhibitory activity on experimental hyperlipidemia induced either exogenously or endogenously.

Animals↗
PubMed1992

[Evaluation of novel assays for the detection of crosslinked fibrin degradation products in whole blood by the agglutination of the red blood cells].

We evaluated the clinical significance of two novel assays for the detection of crosslinked fibrin degradation products (XDP) in whole blood using the agglutination of the red blood cells (SimpliRED D dimer and SimpliRED D dimer-500, AGEN, Australia). XDP made serially by plasmin in vitro, were detected by the SimpliRED D dimer assay, but fibrinogen degradation products showed weak reactivity. Ten of the fifty four clinical samples collected with EDTA-2K, changed to positive on these assays after overnight incubation at 4 degrees C. Anemia and hemolytic samples had no effect on the assay results. The results obtained by the SimpliRED D dimer were negative for the normal subjects (n = 50) without exception. In our study, 81% and 95% of the patients, who showed abnormal levels of XDP in plasma and E fragments in serum respectively, were positive on the SimpliRED D dimer assay. The assay was as sensitive as the Rapidia-D dimer assay. In conclusion, the SimpliRED D dimer assay was clinically useful as a screening assay for the diagnosis of hypercoagulable and fibrinolytic states, since it could be performed simply and quickly.

Adult↗
PubMed1992

Herpes simplex virus type 1 and human immunodeficiency virus type 1 antigens in platelets from a hemophilia B patient with human immunodeficiency virus type 1-related thrombocytopenia.

We analyzed platelet-associated antigens from a hemophilia B patient with human immunodeficiency virus type 1 (HIV-1)-related thrombocytopenia. Two bands appeared at 31,000 and 37,000 daltons in the platelet lysate after reaction with autologous serum in SDS-PAGE and Western blots. The band at 37,000 daltons was obtained using anti-herpes simplex type 1 (HSV-1) rabbit antiserum. Doublet bands at 36,000 and 37,000 daltons also appeared after reaction with HSV-1 seropositive human serum. The band at 31,000 daltons appeared after reaction with anti-HIV-1 rabbit serum. These results suggest that the platelet-associated antigens in this patient are components of both HSV-1 and HIV-1 antigens. In addition, acyclovir decreased his PAIgG level and increased his platelet count, and zidovudine increased his platelet count. Thus, we concluded that each of the platelet-associated antigens is partially responsible for the thrombocytopenia by causing deposition of immune complexes in this patient.

Acyclovir↗
PubMed1992

[Complex formation of ulinastatin with alpha-thrombin].

The inhibition mode of ulinastatin was indicated noncompetitive by the Lineweaver-Burk's double reciprocal plotting method using the production rate of fibrinopeptide A. Consequently Km of alpha-thrombin could be calculated 2.8 mM and its Vmax was reduced from 24 U/l to 15 U/l by the addition of ulinastatin and Ki of ulinastatin was 1.05 x 10(-2) M. The complex of ulinastatin and alpha-thrombin were found. Furthermore, the mixing of alpha-thrombin, AT-III and ulinastatin produced a larger complex on SDS-PAGE at pH 7.0, and it was evident by the use of Western blotting method, that the complex was consisted of alpha-thrombin, AT-III and ulinastatin. Although ulinastatin and thrombomodulin showed multiple similarities in inhibitory functions on alpha-thrombin, still there are some differences functioning on alpha-thrombin, because of the different binding sites of ulinastatin and thrombomodulin on alpha-thrombin, indicating no crossreaction for antithrombomodulin monoclonal antibody relating to alpha-thrombin binding site of thrombomodulin and it could be contributed to form noncompetitive or uncompetitive inhibitors.

Binding Sites↗
PubMed1992

[Inhibitory effect of ulinastatin on the alpha-thrombin activation of factors V and VIII].

Ulinastatin is a remedy of urine serinprotease inhibitors and also it inhibits enzymatic activities of several blood coagulation factors. The action of ulinastatin on alpha-thrombin shows noncompetitive inhibition with the formation of enzyme-inhibitor complex. In this study, the effects of ulinastatin on the alpha-thrombin activation of factors V and VIII are observed by 5-20% gradient gel SDS PAGE with or without Western blotting method. The addition of ulinastatin to the mixture of factor V and alpha-thrombin inhibits the production of active peptides proceeded in the alpha-thrombin activation process of factor V. Furthermore, using anti-factor VIII 43KDa peptide monoclonal antibody with Western blotting method, the addition of ulinastatin to the mixture of alpha-thrombin and factor VIII indicates to inhibit the release of 43KDa peptide from factor VIII in the process of factor VIII activation induced by alpha-thrombin.

Factor V↗
PubMed1991

[Evaluation of an enzyme immunoassay for plasma thrombomodulin].

Thrombomodulin (TM) is an endothelial cell membrane glycoprotein which neutralizes thrombin clotting activity and accelerates thrombin-catalyzed activation of plasma protein C. Its role is considered to be very important to prevent thrombosis. Recently, TM has been found in circulating blood and the roles and the functions have been investigated. In this study, we evaluated the reliance and the clinical usefulness of a TM-measuring-kit by enzyme immunoassay (MGC-01-001: Mitsubishi Gas chemical company). Intraassay reproducibility test, dilution linearity test and in vitro recovery test was obtained satisfactory results. A correlation between plasma and serum on TM levels of healthy individuals was very good and the difference between them was not significant. Normal value of plasma TM levels was instituted 15.73 +/- 6.98 ng/ml by measuring 52 healthy adults. The difference between male and female was not significant. Plasma TM levels did not change significantly after venous occlusion test and on circadian fluctuation. Plasma TM levels in patients with occlusion test and on circadian fluctuation. Plasma TM levels in patients with disseminated intravascular coagulation (DIC) was 40.15 +/- 22.68 ng/ml (mean +/- SD, n = 14). It is significantly higher than the levels in healthy adults. However, the levels in patients with angina pectoris, acute myocardial infarction and aortic aneurysm were not significantly different from those of healthy adults. These findings suggest that the precision of this TM-measuring-kit is satisfactory and the measurement of plasma TM can be useful to diagnose of DIC.

Adult↗
PubMed1991

Clinical evaluation of recombinant human factor VIII (BAY w 6240) in the treatment of hemophilia A.

A pilot clinical trial was conducted in five patients with severe hemophilia A to evaluate the safety and efficacy of a recombinant human factor VIII preparation, BAY w 6240 (rFVIII). In a comparative pharmacokinetic study of rFVIII and a plasma-derived factor VIII preparation (pdFVIII), the mean t1/2 values for rFVIII at week 1 and week 13 were 16.8 and 14.4 h, while this value for pdFVIII at week -2 was 16.9 h. There were no statistical differences between these values. The mean in vivo recovery rates of rFVIII were comparable to those of pdFVIII. When rFVIII was administered prophylactically three times a week for 4 weeks, no bleeding episodes were observed. Seventy-four bleeding episodes were assessed during the 6-month treatment period. The efficacy rate of the hemostatic effect was confirmed to be 95.9%. No adverse reactions attributable to rFVIII were observed in a total of 178 infusions. Neither FVIII-inhibitors nor antibodies to foreign proteins were detected. Vital signs and laboratory findings showed no significant changes attributable to rFVIII. These results suggest that rFVIII is safe and efficacious as replacement therapy for hemophilia A.

Adult↗
PubMed1991

[Elevated Clq-bearing immune complexes in hemophiliacs with viral infections].

One hundred hemophilia A and 30 hemophilia B patients who had been treated with non-heated and heated factor VIII or prothrombin complex concentrates were examined by immunological tests including Clq-bearing immune complexes assay. Antibodies to human immunodeficiency virus type 1 (HIV-1), hepatitis B virus (HBV), hepatitis C virus (HCV) and human parvovirus B19 (B19) were analyzed by Western blotting, enzyme immunoassay, passive hemagglutination or radio-immunoassay. Clq-bearing immune complexes were assayed by a monoclonal anti-Clq ELISA system (Immunomedics). Seropositivity to HIV-1, HBV, HCV, and B19 was 56.9%, 87.7%, 79.2% and 100% respectively. Clq-bearing immune complexes were positive in 109 of the 130 patients (83.8%). The positivity and the levels were extremely higher than those in normal individuals. Clq-bearing immune complex levels in patient positive for HIV-1, HCV, or HBV were higher than those in the negative group (HIV: P less than 0.001, HCV: P less than 0.005, HBV: P less than 0.05). When the patients were divided into four groups according to seropositivity to HIV-1 and/or HCV, Clq-bearing immune complex levels were the highest in the group positive for both antibodies, and the lowest in the group negative for both antibodies. These results suggested that each viral infection influences the formation of immune complexes and repeated viral infection increased the level of Clq-bearing immune complexes in these patients.

Adolescent↗
PubMed1991

[Simultaneous detection of antibodies for 3 different retroviruses using retrovirus EIA (triple antigen kit)].

We evaluated Retrovirus EIA kit (Roche Co.), in which virus components of three different viruses, HIV-1, HIV-2, and HTLV-I were used antigens. All the specimens from the patients with ATL, HAM, HTLV-I carrier, AIDS and AC, and from HIV-2 infected individuals were found to be positive. Four out of 40 specimens from hemophiliacs not infected with HIV-1 were found out to be positive. These specimens were confirmed to contain antibody against HTLV-I. Pseudo-negative or -positive reactions were not found in this study. Therefore, Retrovirus EIA kit should be evaluated more extensively, for the possible applications for screening of blood donors, and for selecting the sources of blood products as well as for clinical diagnoses.

Acquired Immunodeficiency Syndrome↗
PubMed1991

[Evaluation of a new enzyme immunoassay method for determination of t-PA-PAI-1 complex].

We evaluated a new enzyme immunoassay for determination of t-PA-PAI-1 complex (PAI-C) and studied the clinical utility of measuring PAI-C. This assay was performed by the capture/tag antibody technique using polystylene beads, in which the beads were coated with monoclonal antibody against PAI-1 and anti-t-PA polyclonal antibody was tagged (TDC-88, TEIJIN-LIMITED, Japan). The assay gave an excellent sensitivity with a detection limit of 0.1 ng/ml, and we were able to detect a trace amount of PAI-C in normal plasma. PAI-C in 6 volunteers showed significant daytime fluctuations. The normal value of PAI-C in plasma was below 13.8 ng/ml (n = 40). PAI-C levels in patients with accelerated fibrinolysis (n = 31) ranged from 2.9 to 66.4 ng/ml and 15 of them were outside the normal range. However, all of patients with DIC (n = 10) showed abnormally high PAI-C levels. In patients with accelerated fibrinolysis, PAI-C values correlated with t-PA antigen (r = 0.838), PAI-1 antigen (r = 0.519), ATIII activity (r = -0.669) (p less than 0.01) and D dimer levels (r = 0.391, p less than 0.05). However, PAI-C values did not correlate with plasminogen and alpha 2PI activity, alpha 2PI-plasmin complex or the FDP-E level in these patients. Our data suggests that PAI-C may be a new molecular marker that reflects t-PA release from endothelial cells and a useful indicator to study hypercoagulable states.

Fibrinolysis↗
PubMed1991

[Differentiation between fibrin degradation products and fibrinogen degradation products by using newly developed ELISAs].

We should distinguish fibrin degradation products (FbDP) from fibrinogen degradation products (FgDP) in order to analyze fibrinolysis in vivo. We analyzed some disorders associated with hyperfibrinolytic states using ELISA for FbDP, FgDP and total fibrin (ogen) degradation products (TDP) (ORGANON TEKNIKA). Each ELISA was useful in terms of reproducibility and dilution linearity of plasma samples. There was no cross-reaction between FbDP and FgDP. The FgDP/FbDP ratio in normal individuals was 1.65. In patients with DIC, it was 0.43, with FgDP level being increased. These results suggest that fibrinolysis is enhanced in patients with DIC, but it is accompanied by fibrinogenolysis. On the other hand, the FgDP/FbDP ratio in patients given urokinase (UK) was 2.88. This suggests that fibrinogenolysis is enhanced in them. In our study, the FgDP/FbDP ratio increased as DIC improved. Thus, we can regard this as an index of therapeutic effects in patients with DIC. We conclude that these three ELISA are useful in analyzing disorders associated with hyperfibrinolytic states.

Disseminated Intravascular Coagulation↗