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Biomedical subjects

T Shimazaki

Publications and source records attributed to T Shimazaki.

At least 37 records · Page 2Linked to original sources

[On the validity of applying associative learning model to the acquisition process of human contingency judgment].

The assessment process of contingency between two binary events was examined in the present experiments using university students. Some researchers have obtained a learning curve in judging contingency and have thereby applied an associative model to an explanation of human contingency judgment. Other researchers, however, claimed that the task structure did not adequately reflect the structure of 2 x 2 contingency tables and failed to obtain learning curves. After having resolved methodological problems of task structure and procedure (Experiments 1 & 2), we demonstrated little evidence of learning curve in judging contingency (Experiment 3). These results were discussed in terms of associative viewpoints and rule-based models.

Adolescent↗

New platelet fibrinogen receptor glycoprotein IIb-IIIa antagonists: orally active series of N-alkylated amidines with a 6,6-bicyclic template.

The design, synthesis, and pharmacological evaluation of (S)-(-)-ethyl [6-[4-(morpholinoformimidoyl)benzamido]-3, 4-dihydro-2H-1-benzopyran-3-yl]acetate hydrochloride ((S)-4.HCl, MS-180), an orally active glycoprotein IIb-IIIa (GPIIb-IIIa) antagonist, are reported. Pharmacophore mapping of amidino and carboxyl groups of already known GPIIb-IIIa antagonists led to the synthesis of nine amidino acids containing 6,6-bicyclic ring skeletons (10a-i). Among them, the compounds 10a,c,e having an amide bond and 1,2,3,4-tetrahydronaphthalene or 3, 4-dihydro-2H-1-benzopyran skeleton showed marked inhibitions with IC50 values of 46-57 nM in human platelet aggregation assay in vitro, but low oral activities. N-Alkylation of the amidino group coupled with the ester prodrug approach afforded MS-180 ((S)-4.HCl), which generates in vivo the corresponding carboxylic acid (S)-3 as an active species. In vitro, (S)-3 inhibited ADP-induced aggregation of guinea pig, dog, and human platelets (IC50 = 110, 253, and 35 nM, respectively) and inhibited the binding of fibrinogen to immobilized GPIIb-IIIa of human platelets (IC50 = 0.12 nM). After oral administration of MS-180 ((S)-4.HCl) to fasted beagle dog, ex vivo inhibition of platelet aggregation was observed. The maximal inhibitions were observed 2-4 h after dosing with dose dependency (60% inhibition at a dose of 1 mg/kg, 85% at 3 mg/kg, and 100% at 10 mg/kg, respectively) and the extent of the inhibitions paralleled the plasma concentration of the active species (S)-3. On the basis of these studies, we selected MS-180 ((S)-4.HCl) as a candidate for clinical evaluation as a drug for the treatment and prevention of thrombosis in patients.

Acetates↗

[Clinical results of acute closing aortic dissection].

The therapeutic outcomes of 43 patients with acute closing aortic dissection treated during the past 10 years were evaluated. The patients consisted of 30 men and 13 women with a mean age of 65 +/- 9 years. Ten were classified as Stanford type A, and the remaining 33 as type B. During follow-up (6 to 120 months; average 55 months), recanalization and an enlarged ulcer-like projection (ULP) were observed in 5 and 2 type a patients. Although recanalization was not observed in type B patients, enlarged ULP was observed in 10 of them, in 6 of whom developed aneurysm. During the follow-up period, ULP was observed at 30 sites in 26 patients. Monitoring the change in ULP over time showed that the ascending and the proximal descending aorta frequently tended to be enlarged and progressed to aorta frequently tended to be enlarged and progressed to aneurysm. Surgery was performed in 3 patients with recanalization, 5 with enlarged ULP, and 3 with atheroscloerotic aortic aneurysm. Although one patient died of cerebral complications, the other 10 patients showed favorable postsurgical courses. Among 8 patients who died, the actuarial survival rate was favorable, being 96, 91 and 83% at 1, 3 and 5 years. However, the survival rate free from complications related to aortic dissection, defined as rupture, ercanalization, enlarged ULP and aneurysmal change, was 78, 58 and 54% at 1, 3 and 5 years, indicating that aortic dissection-related complications are likely to develop within 3 years. This being the case, conservative therapy may be selected for closing aortic dissection when there are no serious complications in the acute phase. However, closely following patients with diagnostic imaging techniques is essential as there may be complications such as recanalization or enlarged ULP. Such complications should be surgically treated because they may affect long-term prognosis.

Aged↗

[Postoperative changes in the coagulation and fibrinolytic systems in endoluminal stent-graft treatment of thoracic aortic aneurysms].

We studied changes in blood coagulation and fibrinolytic system in 18 cases of thoracic aortic aneurysm and 5 cases of aortic dissection treated with stent grafts. The mean operation time was 259 +/- 67 minutes and the amount of blood loss during operation was 472 +/- 456 ml. Although blood transfusion of 220 +/- 360 ml was performed in 7 cases, 16 of 23 cases (70%) received no homologous blood transfusion. Consequently, the endoluminal stent graft treatment was minimally invasive compared with the conventional surgical procedure. On the 1st postoperative day, platelet counts and AT-III decreased and TAT increased. The promotion of blood coagulability was found in these patients on the 1st day after the operation. Changes in the fibrinolytic system were less marked than that in coagulation. These results suggest that the thrombosed aneurysm was excluded from systemic blood flow by the stent graft. There was no consumption coagulopathy in any case with aneurysm excluded by stent graft deployment. Stent-graft treatment for thoracic aortic aneurysm can be successfully performed without consumption coagulopathy when the aneurysm is completely excluded.

Aged↗

[Clinical results of endovascular stent graft repair for fifty cases of thoracic aortic aneurysms].

Between February 1995 and December 1997, 50 cases (55 lesions) of thoracic aortic aneurysms including 20 cases of aortic dissections were treated with an endovascular technique using the stent grafts. All patients were treated in the operating room under general anesthesia and the stent grafts were implanted through 18 Fr. or 20 Fr. sheaths via femoral arteries under fluoroscopic guidance. The stent graft was composed of several units of self-expanding stainless-steel Z stents covered with an ultra-thin polyester fabric. Stent graft deployment was technically successful in 53 of 55 lesions (delivery success rate: 96.4%). Exclusion of the aneurysms and entry closing without endoleak were achieved within two weeks after the operation in 43 of 53 lesions (initial success rate: 81.1%). Endoleak was found in 10 lesions (minor endoleak: 8 and major endoleak: 2 lesions). Two patients died in the periopertive period of delivery failures as injury to external iliac artery and damage to the delivery sheath caused by tortuous and narrow access routes. Endovascular stent graft repair of thoracic aortic aneurysms is minimally invasive operation in comparison with conventional surgical graft replacement with extracorporeal circulation. These early results suggest that the stent graft repair is possibly safe and useful treatment for the patients of thoracic aortic aneurysms especially in high risk patients. However, careful long-term follow-up is necessary to prove the value and the effects of this endovascular treatment and improvement of the stent graft system and technical training of endovascular surgery for operators are required to reduce the delivery failure and to determine the stent graft repair is reliable treatment.

Adult↗

[Prediction of spinal cord ischemia with a retrievable stent graft on endovascular treatment for a case of thoracic aortic aneurysm].

Multiple aortic aneurysms in Behçet's disease were repaired with transluminaly placed endovascular stent grafts. Before deploying the stent graft device for permanent implantation for the saccular aneurysm located in the descending thoracic aorta, from which feeding arteries for the spinal cord possibly branched, a retrievable stent graft was inserted and evoked spinal cord potential (ESP) were monitored in order to predict spinal cord ischemia. The original retrievable stent graft, constructed of a self-expandable Z-shaped stainless steel stent covered with e-PTFE, can be easily withdrawn into a 18 Fr. sheath after deployment. Blood flow into intercostal arteries branching from that part of the descending aorta where the permanent stent graft is planned to be implanted, is intercepted by the retrievable stent graft. A change of ESP during the temporary implantation of the device indicates that spinal cord ischemia would be caused by permanent implantation of the stent graft. In this case, no change of ESP was observed and the patient showed no postoperative paraplegia. The retrievable stent graft was useful for prediction of spinal cord ischemia before endoluminal stent graft repair of the descending aortic aneurysm. However, the device is not flexible enough to fit a severely tortuous aorta, therefore we are obliged to select patients to some extent. Further improvement of the device is required to make prediction of spinal cord ischemia with the retrievable stent graft possible in all cases.

Aortic Aneurysm, Thoracic↗

Absorption-enhancing effects of sodium caprate and palmitoyl carnitine in rat and human colons.

We examined the enhancing action of sodium caprate and palmitoylcarnitine on the permeability of fluorescein isothiocyanate dextran 4000 as a paracellular permeant compound in isolated rat and human colon samples using the Ussing-type chamber method. In the absence of an enhancer, the permeation clearance of fluorescein isothiocyanate dextran 4000 was not significantly different in the rat and human colons, but the electric membrane resistance was smaller in the rat colon than in the human colon. Sodium caprate and palmitoylcarnitine increased permeation clearance and decreased electric membrane resistance in both types of colonic membrane, showing that the rat colon can be used as a model of the human colon for studies of enhancer effects. A calmodulin antagonist significantly inhibited the action of sodium caprate in both colonic membranes. However, it tended to promote the effects of palmitoylcarnitine on permeation clearance and electric membrane resistance. These results suggest that sodium caprate induces the contraction of the perijunctional actomyosin ring to widen the tight junction and that the mechanism of palmitoylcarnitine is different from that of sodium caprate in the human colon, as reported previously for Caco-2 cell monolayers.

Aged↗

Morphological study of the intrapharyngeal ganglia and ganglionic neurons in cats.

The distribution, number and nature of intrapharyngeal ganglia and their neurons in cats were examined by means of serial sections, histochemical and immunohistochemical methods. Six to eight large ganglia around the palatine tonsils and five to eight small ganglia in the laterodorsal wall of pharyngeal mucous membrane were observed. The intrapharyngeal ganglionic neuron (25-30 microns in diameter) totalled 600-800 and more than 80% of them were located around the palatine tonsils. The ganglionic neurons were acetylcholinesterase reaction positive. On immunohistochemistry, many choline acetyltransferase-immunoreactive and vasoactive intestinal polypeptide-immunoreactive neurons and a few tyrosine hydroxylase-immunoreactive nerve cells were found, but no calcitonin gene-related peptide-immunoreactive or substance P-immunoreactive neurons were recognized in the ganglion. The present findings indicate that intrapharyngeal ganglionic neurons are mainly parasympathetic and partially sympathetic in nature.

Acetylcholinesterase↗

Segregation of bovine viral diarrhea virus isolated in Japan into genotypes.

It was suggested that 3 strains of bovine viral diarrhea virus (BVDV) isolated from persistently infected calves in Tochigi prefecture in Japan belonged to BVDV type II. It was recognized lack of PstI site on the 5'-untranslated region of genome of them as well as BVDV type II reported previously. Inoculated with the 3 strains, the calves showed the mild decrease of platelet counts which was specific clinical sign of BVDV type II. We should report that the 3 strains were the first BVDV type II isolated in Japan. Neutralizing antibody titers of the antisera against the 3 strains using laboratory strains as neutralizing virus were lower than those of them using homologous strains. Therefore, it was indicated that the difference between BVDV type I and BVDV type II in the antigenicity.

Animals↗

Variation from cytopathogenic biotype to non-cytopathogenic biotype is correlated with the deletion of cellular sequence from bovine viral diarrhea viruses.

Non-cytopathogenic (NCP) viruses of bovine viral diarrhea (BVD) virus were detected at a low ratio by the reverse plaque formation method from virus samples after several plaque clonings of cytopathogenic (CP) BVD viruses; NADL and Osloss strains. This phenomenon suggests that the NCP BVD viruses are produced at a low ratio during the propagation of CP BVD viruses in vitro. To investigate the differences between the parent CP BVD virus and the NCP BVD virus as a real progeny, the regions flanking the insertion of cellular mRNA in the p125 domain of NADL and Osloss strains were amplified by RT-PCR and cloned into pGEM 3Z plasmid vector, and then sequenced. Consequently, it was confirmed that sequences of cellular mRNA insertion of CP BVD viruses, NADL and Osloss strains, were completely and exactly deleted from the NCP BVD viruses which were real progeny of CP BVD viruses, NADL and Osloss strains. These results suggest that NCP BVD viruses may revert from CP biotype to NCP biotype by the deletion of cellular mRNA insertion in the viral genome of CP BVD viruses (NADL and Osloss strains).

Amino Acid Sequence↗

Inhibitory effects of TA-993, a new 1,5-benzothiazepine derivative, on platelet aggregation.

TA-993, an l-cis 4',8-dimethyl derivative of the Ca2+ antagonist diltiazem, and some of its metabolites inhibited platelet aggregation induced by collagen, ADP, epinephrine, platelet activating factor, arachidonic acid, and U-46619 in human platelets in vitro. Among the metabolites, MB3 was the most potent (IC50, <1 micromol/L; several hundred times more potent than the parent compound). The d isomer of MB3 was >100 times less potent than the l isomer. Unlike acetylsalicylic acid (ASA), TA-993 inhibited both primary and secondary phases of ADP-induced platelet aggregation and also exhibited a disaggregating effect on human platelet aggregates. The inhibitory effect of TA-993 was enhanced when used in combination with ASA. In ex vivo studies involving rats, TA-993 (approximately 0.3 to 100 mg/kg PO) dose-dependently inhibited collagen-induced platelet aggregation (ED50, 3 mg/kg PO). In the whole-blood platelet aggregation system in rats, orally administered TA-993 was also inhibitory in single (3 to 30 mg/kg) or repeated daily (10 mg/kg per day for 10 days) dosage. Orally administered TA-993 dose-dependently inhibited ADP-induced platelet aggregation ex vivo in dogs (0.3 to 10 mg/kg), significantly protected mice against collagen + epinephrine-induced thromboembolic death (10 mg/kg), and inhibited thrombus formation in an arteriovenous shunt in rats (30 mg/kg). The Ca2+-antagonistic action of TA-993 was very weak in depolarized canine basilar arteries: the potency was approximately 1/10 that of diltiazem (d-cis) and d-TA-993. These results suggest that antiplatelet action is more characteristic of the l-cis than the d-cis 1,5-benzothiazepine structure and that TA-993 may become a clinically useful antiplatelet agent of this structure series.

Animals↗

[Morphological study of laryngeal ganglions and associated nerve cells in humans and five mammals].

The arrangement and numbers of intralaryngeal ganglia and associated neurons in humans and four mammals (dogs, rabbits, guinea pigs and rats) were investigated morphologically and compared with the results obtained in the cat which have been reported previously. Intralaryngeal ganglia were mostly distributed in branches of the internal branch of superior laryngeal nerve in all species, dorsal and/or dorsolateral to the posterior cricoarytenoid muscle in humans, dogs and cats and around the inferior laryngeal nerve in humans, dogs, cats, guinea pigs and rats. The total number of laryngeal ganglionic neurons was 2,000 to 2,400 in humans, 300-450 in dogs, 600-800 in cats, 250-320 in rats, and 100-150 in rabbits and guinea pigs. More than 80 percent of ganglionic neurons were present in the supraglottis in all species, except the rat, in which about 60 percent were in the subglottis. Each ganglion in all species existed within the nerve bundle, and was chiefly encapsulated with fibrous tissue, many ganglionic cells, glial cells, Schwann cells, vessels and connective tissue. The present morphological study of intralaryngeal ganglia in humans and four mammals suggests that the laryngeal ganglionic neurons have the same arrangement as in cats.

Adult↗

A novel non-xanthine adenosine A1 receptor antagonist.

FK453, (+)-(R)-[(E)-3-(2-phenylpyrazolo[1,5-alpha]pyridin-3-yl) acryloyl]-2-piperidine ethanol, was examined for adenosine receptor antagonistic activity using isolated guinea-pig atria and aorta and for affinity for adenosine receptors in the rat cerebral cortex and striatum in comparison with FR113452 (S enantiomer of FK453), PD116948 (1,3-dipropyl-8-cyclopentylxanthine), theophylline (1,3-dimethylxanthine) and CGS15943 ([1,2,4]triazolo[1,5-c]quinazolone). FK453 showed potent inhibition of the negative inotropic activity elicited by 10 microM adenosine with an IC50 of 560 pM in guinea-pig atria. However, FK453 was less potent in inhibiting the relaxation induced by 3.2 microM adenosine and had an IC50 of 1.18 microM in guinea-pig aorta. The IC50 values for FR113452, PD116948, theophylline and CGS15943 were 1.18 microM, 1.31 nM, 20.2 microM and 74.2 nM in atria and > 100 microM, 656 nM, 239 microM, 127 nM in aorta respectively. In the binding study, FK453 antagonized [3H]N6-cyclohexyladenosine binding to the rat cortical adenosine A1 receptor with an IC50 of 17.2 nM. The IC50 values for FR113452, PD116948, theophylline and CGS15943 were 10.1 microM, 4.7 nM, 67.7 microM and 241 nM respectively. FK453 inhibited [3H]5'-N-ethylcarboxamideadenosine binding to rat striatum adenosine A2 receptor with an IC50 of 11.3 microM. FK453 had no adenosine A1 receptor agonistic activity, since it had no negative inotropic activity up to 100 microM in isolated guinea-pig atria. These results demonstrate that FK453 is a novel non-xanthine adenosine receptor antagonist and is potent and selective for the adenosine A1 receptor subtype.

3',5'-Cyclic-AMP Phosphodiesterases↗

Arrangement and number of intralaryngeal ganglia and ganglionic neurons: comparative study of five species of mammals.

The arrangement and number of intralaryngeal ganglia and their neurons in five mammals (dog, rat, guinea pig, rabbit and cat) were examined morphologically. Intralaryngeal ganglions were situated mainly in branches of the internal branch of superior laryngeal nerve (Int-SLN), dorsal and/or dorsolateral to the posterior cricoarytenoid muscle, and around the inferior laryngeal nerve in dogs, rats, guinea pigs and cats, but they were identified at the branching out point of the Int-SLN exclusively in rabbits. The ganglion of each animal was spindle-shaped, with a surrounding fibrous capsule, and it contained many ganglionic neurons, vessels and connective tissue cells. The ganglionic neuron was oval-shaped and had a round nucleus: the diameter was smaller (20-25 microns) in the rat than in the other mammals (25-30 microns). More than 80 per cent of ganglionic neurons occurred in the supraglottis of all the animals except the rat. In the rat, this value was approximately 40 per cent.

Animals↗

Enhanced replication of orbiviruses in bovine testicle cells infected with bovine viral diarrhoea virus.

Bovine testicle (BT) cells infected with non-cytopathogenic (NCP) bovine viral diarrhoea virus (BVDV) developed cytopathogenic effect (CPE) after superinfection with 7 Orbiviruses, whereas no CPE was induced by them in the absence of NCP BVDV infection. The CPE was accompanied by the enhanced replication of Orbiviruses. Seven of 10 strains of NCP BVDV induced the enhanced replication of Ibaraki virus, a member of Orbivirus. These 7 strains of NCP BVDV were END phenomenon positive. In contrast, the absence of CPE and the suppression of growth of Ibaraki virus were seen in BT cells infected with the other 3 strains which were END phenomenon negative. The END phenomenon negative viruses were different markedly from the END phenomenon positive viruses with respect to interactions with Orbivirus. The mechanism of the enhanced replication of Orbivirus seems to be explained with the suppression by the END phenomenon positive NCP BVDV to the interferon production of Orbivirus in BT cells.

Animals↗

Important contribution of the methylene part of LTB4 toward binding affinity to the LTB4 receptors and rise in intracellular-free calcium concentration.

In order to examine a role of the C(16)-C(20) methylene part of leukotriene B4 (LTB4) toward the activation of leukocytes, we synthesized the LTB4-analogues in which the length of the C(16)-C(20) part of LTB4 is varied systematically while the two hydroxyl groups at C(5) and C(12) positions and the 6(Z), 8(E), 10(E) conjugated triene unit remained untouched. We examined their binding affinity to the LTB4 receptors present in the rat polymorphonuclear leukocytes (PMNLs) and their ability to raise intracellular-free calcium concentration ([Ca2+]i) in the rat PMNLs loaded with fura-2. As the length of the chain of LTB4 was increased or decreased one by one, the binding affinity to the LTB4 receptors diminished, and the analogues of more than three carbon atoms shorter chain were of about three log order less activity than LTB4. The biological potency as assessed in [Ca2+]i rises pararelled that of the binding affinity to the PMNL membrane. These results indicate that the C(16)-C(20) part of LTB4 plays important role for the activity. In a similar way we prepared the LTB4-analogues of a different chain length between C(2)-C(4) of LTB4 and tested their biological activity. We found that the C(2)-C(4) part of LTB4 also affects the activity.

Animals↗

Nucleotide sequence of a rice cDNA similar to a maize NADP-dependent malic enzyme.

We have isolated a rice cDNA clone that is homologous to the gene for the maize NADP-dependent malic enzyme (EC 1.1.1.40; NADP-ME). The deduced amino acid sequence coded for by the cDNA indicates a high level of homology to chloroplast type NADP-ME, including a transit peptide with pronounced hydrophobic properties at the amino terminus. Northern blot analysis indicates that the expression of this gene is regulated by external stress such as submergence.

Amino Acid Sequence↗