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Biomedical subjects

A Takada

Publications and source records attributed to A Takada.

At least 181 records · Page 10Linked to original sources

Spinocerebellar ataxia 1 (SCA1) in the Japanese in Hokkaido may derive from a single common ancestry.

Spinocerebellar ataxia 1 (SCA1) is caused by expansion of an unstable CAG triplet repeat located on the short arm of chromosome 6. Precise mapping has shown a positional relationship to closely linked markers in the order of D6S109-D6S274-D6S288-SCA1-AM10GA-D6S89+ ++-EDN1 from centromere to telomere. The haplotype which cosegregated with the disease was determined in 12 Japanese pedigrees with SCA1. Although the alleles of the SCA1 haplotype varied from pedigree to pedigree, depending on the distance from the SCA1 locus, the affected and presymptomatic subjects carried the same alleles at D6S288 and D6S274. All the families with SCA1 had migrated from either Miyagi or Yamagata Prefectures, neighbouring areas in the Tohoku District, the northern part of Honshu which is the main island of Japan. It seems highly likely that SCA1 in the Japanese, at least those residing in Hokkaido, derives from a single common ancestry.

Chromosome Mapping↗

Studies on Taiwan folk medicine, thang-kau-tin (II): Measurement of active oxygen scavenging activity using an ESR technique.

Using an electron spin resonance (ESR) technique, we measured the superoxide radical (O2) and hydroxyl radical (OH) scavenging activity from Mallotus repandus (Willd.) Muell.-Arg., Bauhinia championii Benth., Uncaria hirsuta Haviland and Uncaria rhynchophylla Miquel. O2- and OH were detected as spin adducts of spin traps 5,5-dimethylpyrroline-N-oxide (DMPO). The scavenging potencies of water extracts of crude drugs were evaluated in terms of their ability to reduce the peaks of spin adducts. The extract of B. championii showed the greatest superoxide radical and hydroxyl radical scavenger activity.

Ascorbic Acid↗

Hemifacial spasm: three-dimensional MR images in the evaluation of neurovascular compression.

PURPOSE: To assess the diagnostic accuracy of three-dimensional (3D) magnetic resonance (MR) images in the preoperative evaluation of hemifacial spasm. MATERIALS AND METHODS: In 27 patients with surgically confirmed hemifacial spasm, the axial source images from 3D time-of-flight MR angiography were evaluated for 27 symptomatic sides and 26 asymptomatic sides by three observers in a blinded manner for neurovascular compression and identification of compressive vessels. RESULTS: Sensitivity was 95% and specificity was 77%. Vascular compression on the symptomatic sides could be identified retrospectively in all 27 patients. On the asymptomatic sides, vascular compression could be excluded retrospectively in all but one patient. In the blinded study, as the mean value of three observers, the vertebral artery and posterior inferior cerebellar artery could be identified correctly in seven and 7.7 of seven and nine patients, respectively, whereas the compressive anterior inferior cerebellar artery was identified correctly in 7.7 of 16 patients. CONCLUSION: Three-dimensional MR images have a high diagnostic accuracy and are useful in the preoperative evaluation of hemifacial spasm.

Adult↗

Thrombosed growing giant aneurysms of the vertebral artery: growth mechanism and management.

Results in three patients with thrombosed giant aneurysms of the vertebral artery are reported. Each of the aneurysms presented as a mass lesion. On postcontrast computerized tomography and magnetic resonance imaging, each aneurysm demonstrated a patent lumen and intrathrombotic vascular channels. Two patients died and were autopsied, and the other patient was successfully treated. Pathological examination revealed that the aneurysms had staged clots, an open lumen, intrathrombotic channels with endothelial lining, and aneurysmal walls with intimal thickening. The authors suggest that the development of the intrathrombotic capillary channels may be an important factor in the growth of thrombosed giant aneurysm of the vertebral artery. Trapping of the aneurysm followed by aneurysmectomy appears to be the best treatment for this type of aneurysm.

Adult↗

Mapping of the gene for Machado-Joseph disease within a 3.6-cM interval flanked by D14S291/D14S280 and D14S81, on the basis of studies of linkage and linkage disequilibrium in 24 Japanese families.

The gene locus of Machado-Joseph disease (MJD) has recently been mapped within a 29-cM subregion of 14q chromosome. We did a linkage study of 24 multigenerational MJD Japanese pedigrees, in an attempt to narrow the candidate region of this gene. Pairwise and multipoint linkage analysis, together with haplotype segregation analysis, led to the conclusion that the MJD gene is located at the 6.8-cM interval between D14S256 and D14S81 (Zmax = 24.78, multipoint linkage analysis). D14S291 and D14S280, located at the center of this interval, showed no obligate recombination with the MJD gene (Zmax = 5.93 for D14S291 and 9.99 for D14S280). A weak, but significant, linkage disequilibrium of MJD gene was noted with D14S81 (P < .05) but not with D14S291 or D14S280. These results suggest that a 3.6-cM interval flanked by D14S291/D14S280 and D14S81 is the most likely location of the MJD gene and that it is closest to D14S81.

Adult↗

N,N,N-trimethylsphingosine modifies aggregatory response and ATP release from platelets in whole blood.

We investigated the influence of N,N,N-trimethylsphingosine (TMS), a potent inhibitor of protein kinase C (PKC), on whole blood aggregation and ATP release from platelets. The preincubation with TMS at 1 microM for 2 min enhanced ATP release during arachidonic acid-induced aggregation. The ristocetin-induced agglutination was inhibited in a TMS concentration-dependent manner, which suggests that TMS may interact with the vWF receptor on platelets. TMS suppressed aggregatory response and ATP release from platelets after the addition of collagen. In contrast, the platelet aggregation induced by ADP and 12-O-tetradecanoylphorbol-13-acetate (TPA) was only slightly inhibited and the ATP release was not influenced after preincubation with TMS. Our results are in contrast to previous reported data, which were obtained using PRP and washed platelets.

Adenosine Diphosphate↗

Heparin and heparan sulfate enhancement of the inhibitory activity of plasminogen activator inhibitor type 1 toward urokinase type plasminogen activator.

To study effects of glycosaminoglycan on the interaction between two chain urokinase type plasminogen activator (tcu-PA) (EC 3.4.21.31) and plasminogen activator inhibitor type 1 (PAI-1) the second order rate constant (k1) between high molecular weight tcu-PA and active recombinant prokaryotic PAI-1 (rpPAI-1) was determined employing a continuous method using chromogenic substrate S-2444 either in the presence or absence of various kinds of glycosaminoglycans. k1 was (5.9 +/- 1.6).10(6)/mol per s in the absence of effector molecule, and following addition of heparin (1.0 U/ml) k1 was enhanced to (3.22 +/- 0.73).10(7). A significant enhancement of k1 was also obtained by heparan sulfate (1.87 +/- 0.25).10(7). Dermatan sulfate or chondroitin sulfate did not show a significant effect on k1 although a slight decrease was obtained by mono-dextran sulfate (4.2 +/- 1.2).10(6). The intrinsic fluorescence of rpPAI-1 was shown to be slightly increased following addition of heparin (1.49 +/- 0.22%, n = 6), suggesting that heparin may enhance the inhibitory activity of PAI-1 toward tcu-PA both by a template mechanism and by a modification of PAI-1 structure.

Buffers↗

Serotonergic measures in cyclosporine A treated rats.

Whole blood and plasma serotonin (5-HT), its major metabolite--5-hydroxyindoleacetic acid (5-HIAA), renal cortical blood flow, serum creatinine and whole blood cyclosporine A (CyA) levels were investigated in rats administered with CyA at a dose of 5 mg/kg b.w. or 10 mg/kg b.w. for 14 consecutive days. Serum creatinine remained unaltered during CyA treatment and no apparent changes in excised kidneys were found. Dose-dependent increases in whole blood and plasma 5-HT as well as whole blood 5-HIAA levels were observed. Renal cortical blood flow declined significantly and correlated inversely with whole blood 5-HT and 5-HIAA as well as with plasma 5-HT. Whole blood 5-HT was positively related to whole blood CyA levels. Taking all these data into account and considering the fact that 5-HT is a potent vasoconstrictor, a possible role of this amine in the pathogenesis of renal ischemia during CyA administration is suggested.

Animals↗

Fibrinolysis and serotonin under cyclosporine A treatment in renal transplant recipients.

Cyclosporine A (CyA), a potent immunosuppressive drug, has been used in renal transplant recipients with increasing frequency since 1982. Despite its efficacy, CyA therapy has been associated with an increased incidence of thromboembolic complications. This has been attributed to increased thromboxane production, reduced prostacyclin synthesis and increased platelet aggregability. The coagulation system is also altered in CyA-treated patients and some of these changes would favor thrombosis. Increased fibrinogen and FVII:C levels have also been associated with an enhanced risk of thrombosis. In contrast, CyA therapy was reported to increase the levels of antithrombin III and protein C, two proteins known to protect against venous thromboembolism. However, the possible effect of CyA on the fibrinolytic system has not been thoroughly investigated and rather confusing data have been reported concerning both enhancement and suppression of fibrinolysis. Serotonin (5-hydroxytryptamine, 5-HT) may play a role in hemostasis and platelet/vessel wall interactions. It may facilitate platelet thrombus formation by potentiating the aggregatory response to other agents such as ADP, collagen or epinephrine and by causing vasoconstriction. Taking all these data into consideration we have measured some fibrinolytic parameters, whole blood and plasma serotonin concentration in cyclosporine A- and non-cyclosporine A-treated kidney transplant recipients.

Creatinine↗

Correlations between platelet aggregation, fibrinolysis, peripheral and central serotonergic measures in subhuman primates.

We have studied the relationships between whole blood and plasma serotonin (5-hydroxytryptamine, 5-HT), its major metabolite 5-hydroxyindoleacetic acid (5-HIAA) and serum lipids, platelet aggregation in the whole blood and in the platelet-rich plasma (PRP), and some fibrinolytic parameters in monkeys. Plasma 5-HT was found to be positively related to 5-HT- and ADP-induced platelet aggregation, tissue plasminogen activator (tPA) activity, serum cholesterol and LDL-cholesterol, whereas 5-HT in cerebrospinal fluid correlated inversely with serum cholesterol. Plasminogen activator inhibitor (PAI) activity was positively related to LDL. Euglobulin clot lysis time was related to both tPA and PAI activities. The significance of these findings and the possible role of 5-HT in atherogenesis and hemostasis are discussed.

Animals↗

Daily variations of platelet aggregation in relation to blood and plasma serotonin in diabetes.

The circadian rhythms of platelet aggregation in the whole blood and platelet rich plasma-PRP and plasma serotonin were studied in healthy volunteers (n = 10) and diabetic patients (type II diabetes mellitus n = 12). Platelet aggregation in the whole blood induced by collagen (2 micrograms/ml), ADP (10 microM), arachidonic acid (0.5 mM) and epinephrine (10 microM), and in PRP induced by collagen (2 micrograms/ml), ADP (5 microM), arachidonic acid (250 microM), epinephrine (10 microM) and serotonin-5-HT (1 microM) was measured at 7:30, 11:30, 17:00, 23:00, 4:00 and 7:00. In healthy subjects collagen- and ADP-induced platelet aggregation in the whole blood was significantly lower at 23:00 and 4:00 when compared to values at 7:30. In PRP normal and diabetic platelet response was the lowest during the night. Diabetic platelets exhibited an enhanced response to 5-HT starting from 17:00 until 4:00 when compared to 7:30. 5-HT-induced platelet aggregation was found to be significantly higher throughout the study in DM patients over controls in parallel to plasma 5-HT. In healthy volunteers plasma 5-HT was higher at 17:00 when compared to baseline values, whereas in DM patients plasma 5-HT was elevated starting from 17:00 until 4:00. An enhanced response of diabetic platelets to 5-HT together with elevated plasma 5-HT levels may contribute, at least partly, to the pathogenesis of diabetic vasculopathy and 5HT2 receptor blockers may be of value in DM patients.

Adenosine Diphosphate↗

Electric-foot-shock induced the suppression of fibrinolytic activity in rats.

Electric-foot-shock was given to rats to initiate constant mental stress and its effect on fibrinolytic activity was analyzed. After the termination of electric-foot-shock which was given for an hour, euglobulin clot lysis time in the stressed group significantly prolonged than those in the control group. tissue plasminogen activator activity was also significantly lower in the stressed group. These effects lasted at least for an hour and returned to the control values 24 hours after the stress. Whole blood serotonin levels, which mainly show serotonin contents in platelets, were higher in the stressed group. A negative correlation between whole blood serotonin and tPA activity in the stressed group was obtained. These results suggest that prolonged mental stress impairs fibrinolysis by decreasing tPA activity with a concomitant increase of serotonin contents in platelets.

Animals↗

Plasminogen activators and their inhibitors in non-small cell lung cancer. Low content of type 2 plasminogen activator inhibitor associated with tumor dissemination.

BACKGROUND: Evidence suggests that plasminogen activators and their inhibitors play an important role in tumor spread. METHODS: In this study, we measured the antigen levels of urokinase (u-PA), tissue plasminogen activator (t-PA), type 1 plasminogen activator inhibitor (PAI-1), and type 2 plasminogen activator inhibitor (PAI-2), and cancer tissue (19 adenocarcinomas and 19 squamous cell carcinomas) and normal lung tissue. RESULTS: u-PA, PAI-1, and PAI-2 antigen levels in cancer tissue were significantly higher than those in normal tissue (P < 0.001 in u-PA and PAI-1; P < 0.005 in PAI-2), whereas t-PA antigen levels in cancer tissue were significantly lower than those in normal tissue (P < 0.005). In case with lymph node involvement (LN+ cases), PAI-2 antigen levels were significantly lower than those in cases without lymph node involvement (LN- cases) (P < 0.02), whereas there was no difference in either u-PA or PAI-1 antigen levels between these two groups. Furthermore, u-PA antigen levels showed a significant positive correlation with PAI-2 antigen levels in LN- cases (r = 0.696; P < 0.005), although there was no correlation between these two parameters in LN+ cases. CONCLUSIONS: The antigen levels of u-PA, PAI-1, and PAI-2 in cancer tissue were significantly higher than those in normal tissue, and lower content of PAI-2 was associated with lymph node metastasis.

Adenocarcinoma↗

Effects of heparan sulfate analogue or other sulfated polysaccharides on the activation of plasminogen by t-PA or u-PA.

Effects of heparan sulfate analogue (HHS-5) and other sulfated polysaccharides on the fibrinolytic system were investigated. Activation rate of native plasminogen (Glu-plg) by tissue plasminogen activator (t-PA), urinary plasminogen activator (u-PA) and single-chain u-PA (scu-PA) was enhanced in the presence of HHS-5 dose dependently up to 10 micrograms/ml. Activation rate of Glu-plg by sct-PA was more enhanced than that by tct-PA in its presence. HHS-5 enhanced the activation of Glu-plg by t-PA or u-PA compared to the activation of Lys-plg. SDS-PAGE confirmed that the enhancement of the hydrolysis of S-2251 by the mixture of Glu-plg, sct-PA and HHS-5 was due to the facilitation of the conversion of Glu-plg to plasmin. HHS-5 only slightly enhanced the amidolytic activity of sct-PA or tct-PA. The enhancement of the activation of plasminogen by t-PA or u-PA was more significant in the presence of HHS-5 than in the presence of chondroitin sulfate C, dextran sulfate or heparin. It is possible that the enhancement of the activation of Glu-plg by activators in the presence of HHS-5 was due to the conformational change of Glu-plg upon interaction with HHS-5.

Chondroitin Sulfates↗

Postoperative changes in plasma tissue-type plasminogen activator and type 1 plasminogen activator inhibitor.

To clarify the changes which occur postoperatively in intravascular fibrinolysis, plasma levels of tissue-type plasminogen activator (t-PA) antigen, the total plasminogen activator inhibitor type-1 (PAI-1) antigen, and the t-PA-PAI-1 complexes were assayed in this study. Blood samples were taken the morning before surgery, then at 0, 12, 24, 36, 60, 108, and 156 h postoperatively in ten patients who underwent radical surgery for thoracic esophageal cancer. The plasma levels of the t-PA and total PAI-1 antigens, and the t-PA-PAI-1 complexes were then measured by enzyme immunoassay. The plasma t-PA and total PAI-1 levels increased significantly in the immediate postoperative period, the percent increase of the latter being much greater than that of the former. Moreover, the calculated free t-PA antigen level was decreased throughout the postoperative period, suggesting postoperative hypofibrinolysis. The platelet count and neutrophil elastase level were significantly correlated with the free t-PA antigen level at r = 0.630, P < 0.001, and r = -0.447, P < 0.01, respectively. The results of this study indicated that post-operative hypofibrinolysis caused by the increased synthesis of PAI-1 may enhance postoperative hypercoagulability, and this may lead to the development of organ damage. Thus, the concentration of the PAI-1 antigen may be a potentially important index for the prediction of postoperative illness.

Aged↗