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Biomedical subjects

H Hayashi

Publications and source records attributed to H Hayashi.

At least 487 records · Page 27Linked to original sources

Effects of adrenergic and nitrergic blockade on theophylline-induced increase in peripheral blood flow in rat ear.

A bolus injection of theophylline produced a significant increase in peripheral blood flow in anesthetized rat ear, monitored by laser-Doppler flowmetry, with increases in arterial blood pressure and heart rate. These effects were attenuated by previous treatment with reserpine, but reserpine had no effect on the blood flow increase produced by acetylcholine. A dose of propranolol, which caused attenuation of the theophylline-induced increase in heart rate, did not change the peripheral blood flow. The higher dose of propranolol, which nearly canceled the increases in blood pressure and heart rate, caused attenuation of the blood flow increase but did not cancel it. However, the theophylline-induced flow increase was completely reversed by a nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester, which alone had no effect, without any change in arterial blood pressure and heart rate. Treatment of the rats with the dose of inhibitor slightly and significantly reduced the response of peripheral blood flow to acetylcholine. The other isomer, NG-nitro-D-arginine methyl ester, and the other inhibitor, NG-monomethyl-L-arginine, did not have such an effect. These results suggest that the flow increase is due to an independent effect on the heart with modification by autonomic reflexes and involves the adrenergic and nitrergic pathways.

Acetylcholine↗

Tuberculous pericarditis: MRI features with contrast enhancement.

Tuberculous pericarditis has decreased in incidence, but early diagnosis and treatment are critical because constrictive pericarditis is a serious complication of this condition. The appearances of tuberculous pericarditis on gadolinium enhanced magnetic resonance imaging are described and the value of this modality in achieving an early diagnosis is emphasized.

Adolescent↗

Molecular identification of the active ninja retrotransposon and the inactive aurora element in Drosophila simulans and D. melanogaster.

How transposable elements evolve is a key facet in understanding of spontaneous mutation and genomic rearrangements in various organisms. One of the best ways to approach this question is to study a newly evolved transposable element whose presence is restricted to a specific population or strain. The retrotransposons ninja and aurora may provide insights into the process of their evolution, because of their contrasting characteristics, even though they show high sequence identity. The ninja retrotransposon was found in a Drosophila simulans strain in high copy number and is potent in transposition. On the other hand, aurora elements are distributed widely among the species belonging to the Drosophila melanogaster species complex, but are immobile at least in D. melanogaster. In order to distinguish the two closely resembled retrotransposons by molecular means, we determined and compared DNA sequence of the elements, and identified characteristic internal deletions and nucleotide substitutions in 5'-long terminal repeats (LTR). Analyses of the structure of ninja homologs and LTR sequences amplified from both genomic and cloned DNA revealed that the actively transposable ninja elements were present only in D. simulans strains, but inactive aurora elements exist in both D. melanogaster and D. simulans.

Animals↗

Synthesis and biological activities of (-)-6-n-octyl-indolactam-V, a new potent analogue of the tumor promoter (-)-indolactam-V.

(-)-Indolactam-V (1) without a hydrophobic chain at positions 6 and 7 of the indole ring is a weak tumor promoter compared with teleocidin Bs. To investigate the effects of the hydrophobic substituent at position 6 of teleocidin Bs, we synthesized (-)-6-n-octyl-indolactam-V (2) by a palladium-catalyzed coupling reaction from (-)-6-bromo-indolactam-V (7) which had been obtained by microbial conversion with Streptoverticillium blastmyceticum NA34-17 as the key step. (-)-7-n-Octyl-indolactam-V (3) with potent biological activities comparable to those of teleocidin Bs was similarly synthesized from (-)-7-bromo-indolactam-V as a positive control. Compound 2 showed similar biological activities to those of 3, indicating that the effect of the hydrophobic substituent at position 6 of 1 was identical to that at position 7.

Antigens, Viral↗

[A biomechanical study of anterior cruciate ligaments reconstructed with patella tendons augmented by absorbable artificial materials. A biomechanical study in rabbits].

The purpose of this study was to investigate the biomechanical properties of anterior cruciate ligament (ACL) reconstruction using an absorbable artificial material in rabbits. Experimental studies were carried out on 58 New Zealand white rabbits. After total resection of ACL, 22 knees were reconstructed with patella tendons alone (non-augmented group) and 27 knees with patella tendons augmented by polyglactin 910 mesh (augmented group). The animals were sacrificed for biomechanical testing at 0, 2, 4, 6, 8, 12 and 24 weeks, respectively, after the operation. The stiffness of reconstructed ACL in the augmented group showed a mean of 26.58 +/- 5.78 N/mm at 8 weeks, and that of the non-augmented group 16.47 +/- 11.34 N/mm. There were significant differences between the augmented and non-augmented groups (p < 0.05). The ultimate load and energy of the reconstructed ACL were also significantly higher in the augmented group than in the non-augmented group at 8 weeks. The mean elastic module was higher in the augmented than in the non-augmented group, but the differences were not significant. The mean tan delta of both groups was significantly higher than that of the normal ACL at 24 weeks. These results suggests that polyglactin 910 mesh induces earlier maturation of transplanted patella tendons biomechanically, and may be a useful material for ACL reconstruction.

Animals↗

New radiographic projections for avulsion fractures of the lateral malleolus.

We report two new radiographic projections for evaluating avulsion fractures at the lateral malleolus. We used seven freshly amputated legs with simulated avulsion fractures and radiopaque markers to assess their value. The projections allow accurate assessment of the displacement of fragments without superimposition, and also show whether they affect the anterior talofibular or the calcaneofibular ligament or both.

Adult↗

Contribution of a missense mutation (Trp64Arg) in beta3-adrenergic receptor gene to multiple risk factors in Japanese men with hyperuricemia.

Epidemiological data reveal that hyperuricemia is a risk factor of atherosclerosis. The risk is possibly caused by a link between hyperuricemia and insulin resistance-related metabolic syndrome. Recently it has been proposed that a missense mutation (Trp64Arg) in the beta3-adrenergic receptor (beta3-AR) gene may contribute to the accumulation of multiple risk factors related to insulin resistance. The present study was undertaken to further clarify an association between the Trp64Arg mutation and the metabolic syndrome in 47 Japanese men with hyperuricemia, who are substantially at high risk of atherosclerosis. One patient (2%) had the homozygous mutation, 12 (26%) were heterozygous for the mutation, and 31 (72%) had no mutation found by the PCR-RFLP analysis. The Trp64Arg mutation was not related to past maximal body mass index (BMI), BMI and waist/hip ratio. The subjects with the heterozygous mutation showed a slightly higher incidence of impaired glucose tolerance and diabetes mellitus in the 75 g oral glucose challenge (67%), as compared with those without the mutation (39%). Serum insulin response at 60 min and the sum of serum insulin in the glucose challenge were greater in the former subjects than those in the latter subjects (P=0.041 and 0.076, respectively). An increase in serum lipoprotein(a) was also observed in the subjects with the heterozygous mutation, but the Trp64Arg mutation was not associated with other dyslipidemia, blood pressure or ischemic changes on the electrocardiogram. These results indicate that the heterozygous mutation of Trp64Arg in the beta3-AR gene partly contributes to the accumulation of multiple risk factors in male subjects with hyperuricemia. A larger prospective study is necessary to elucidate a possible role of the Trp64Arg mutation in atherosclerotic diseases in future.

Adult↗

Bradykinin directly triggers GLUT4 translocation via an insulin-independent pathway.

Physical exercise induces translocation of GLUT4 from an intracellular pool to the cell surface in skeletal muscles and increases glucose uptake via an insulin-independent pathway. However, the molecular mechanism remains to be identified. Some studies have suggested that bradykinin is locally released from contracting muscles and may be responsible for GLUT4 translocation and the increase of glucose transport in skeletal muscles. To determine whether bradykinin directly triggers GLUT4 translocation, we established L6 myotubes, 3T3-L1 adipocytes, and Chinese hamster ovary cells stably expressing c-myc epitope-tagged GLUT4 (GLUT4myc) and bradykinin B2 receptors. We found that bradykinin directly triggered GLUT4myc translocation and increased the rate of glucose uptake in a dose-dependent manner in these cells. The translocation with bradykinin occurred even after pretreatment with an islet-activating protein, wortmannin, and phorbol 12,13-dibutyrate. The signaling pathway does not seem to be mediated by Gi, phosphatidylinositol 3-kinase, or protein kinase C. It is insulin-independent and via trimeric G-protein Gq. Bradykinin is probably one of the factors responsible for exercise-stimulated glucose uptake in skeletal muscles.

3T3 Cells↗

Carboxyflavins, novel inhibitors of Taq DNA polymerase.

Carboxyflavins were found to be potent selective inhibitors of Taq DNA polymerase in a polymerase chain reaction. The inhibitions were dose-dependent, and complete inhibitions were observed at the concentration of 3.0 microM. Carboxyflavins were much less, or not sensitive to the DNA polymerases tested such as calf thymus DNA polymerase alpha, rat DNA polymerase beta, human immunodeficiency virus type 1 reverse transcriptase, the Klenow Fragment of E. coli DNA polymerase I and T4 DNA polymerase. To our knowledge, there is no other report of an agent that selectively inhibits only a thermophilic polymerase. Interestingly, the carboxyflavins were able to prevent DNA synthesis in the murine lymphoid leukemia cell line L1210 in vitro; almost complete inhibitory levels were achieved in the range of less than 10 microM.

Animals↗

A new nonamyloid transthyretin variant, G101S, detected by electrospray ionization/mass spectrometry. Mutations in brief no. 201. Online.

Familial amyloidotic polyneuropathy is caused by transthyretin (TTR) variants. The identification of new variants with and without amyloidosis may help to clarify the mechanism of amyloid fibril formation. We detected several variant TTRs from patients with and without symptoms of amyloidosis using mass spectrometry (MS). TTR was isolated by mixing test serum with anti-transthyretin antiserum, and the generated immunoprecipitate was analyzed by high performanced liquid chromatography/electrospray ionization (HPLC/ESI) MS. Variant TTRs showed extra peaks in addition to normal TTR peaks. A variant found in nonamyloid group was sequenced by HPLC/ESI tandem MS using peptides obtained by protelytic digestion of TTR and by DNA analysis. The structure was new, [G101S], and was found in a 74 years old Japanese male. This mutation results from substitution in a CpG hot spot. The substitution in the surface loop, 98-102, between F and G b-strands may not cause amyloid formation.

Aged↗

Anti-thrombotic effects of CX-397, a recombinant hirudin analog, in a canine model of coronary artery thrombosis.

CX-397, a recombinant hirudin analog, is a potent and specific inhibitor of human alpha-thrombin. We conducted a comparative study of CX-397 and heparin in a canine model of left circumflex (LCX) coronary artery thrombosis to evaluate the anti-thrombotic efficacy of CX-397. Administration of drugs (i.v.; bolus + infusion) was commenced 10 min prior to the initiation of LCX coronary artery electrolytic injury (100 microA for 300 min). All saline-treated control animals (7/7) developed thrombotic occlusion during the experimental period, leaving a residual thrombus mass of 15.4 +/- 3.8 mg. Treatment with CX-397 at three incremental dose levels reduced the incidence of occlusion (4/7, 2/5 and 0/7) and decreased thrombus weight (12.6 +/- 2.5 mg, 6.3 +/- 3.0 mg and 2.1 +/- 1.3 mg, respectively) in a dose-dependent manner. At the intermediate dose (15,000 ATU/kg + 15,000 ATU/kg/h) or higher, CX-397 showed significant anti-thrombotic effects (p <0.05 and p <0.01) and suppressed increases in thrombin-antithrombin III complex (TAT) levels (p <0.01 and p <0.001). In the heparin (80 U/kg + 60 U/kg/h)-treated group, the incidence of occlusion (5/7) and thrombus weight (14.1 +/- 6.2 mg) did not differ significantly from the control group. Plasma TAT levels in the heparin group decreased compared with the control group (p <0.01), but was less potent than the intermediate dose CX-397 (p <0.01). The anti-coagulation (activated partial thromboplastin time and activated clotting time) and template bleeding time prolongation effects of heparin were more potent than those of the intermediate dose CX-397 which showed significant anti-thrombotic effects. In conclusion, CX-397 dose-dependently suppressed thrombus formation by inhibition of thrombin activity in a canine coronary artery injury model. The anti-thrombotic efficacy of CX-397 was more potent than that of heparin at equivalent anti-coagulation dosage.

Animals↗

Multiple inhibition of platelet activation by aurintricarboxylic acid prevents vascular stenosis after endothelial injury in hamster carotid artery.

Activated platelets are instrumental in restenosis due to their role in thrombus formation. Aurintricarboxylic acid (ATA) has been reported to prevent platelet activation by inhibiting von Willebrand factor binding to platelet glycoprotein (GP)Ib. We investigated the effects of ATA in vitro and in vivo in hamsters. ATA inhibited the in vitro platelet aggregation induced by ADP, botrocetin and thrombin, but not by collagen. The IC50 values during the ex vivo platelet aggregation by ADP, botrocetin and thrombin were 8.2 +/- 1.8 microM, 0.9 +/- 0.4 microg/ml and 2.4 +/- 0.8 unit/ml, respectively. The platelet retention time to collagen-coated beads of hamster blood samples was inhibited by ATA (0.1, 0.3 and 1.0 mg/kg per hour) in a dose-dependent manner. Continuous administration of ATA (0, 0.1, 0.3, 1.0, 3.0 and 10.0 mg/kg per h) via an infusion pump produced dose-dependent antithrombotic effects: the time to occlude the carotid artery after vascular injury with a modified catheter was prolonged. Only when infused at doses of 3.0 and 10.0 mg/kg per hour, bleeding times were significantly prolonged. The continuous treatment with ATA (1.0 mg/kg per h) using a 2ML1 Alzet infusion pump for 2 weeks, resulted in a decrease in neointimal area by 22.2 +/- 6.8% when measured 2 weeks after injury induction. DNA synthesis using DDT1MF2 hamster SMCs was decreased by ATA in a dose-dependent manner. ATA reduced the number of platelets adhering on the injured area, as detected by electron microscopy. These results indicated that treatment with ATA inhibited platelet adhesion but also SMC proliferation. These observations may explain the effect of ATA on neointima formation.

Animals↗

[Three-dimensional CT angiography for cerebral aneurysm using a multi-angle reconstruction plan method].

The purpose of this study was to evaluate the clinical usefulness of three-dimensional CT angiography (3D-CTA) for the diagnosis of cerebral aneurysm using a new reconstruction method called Multi-Angle Reconstruction Plan (MARP). The threshold values, region of interest and six angles of view were preset for the MARP method on the basis of our experience with cerebral 3D-CTA. Spiral CT angiography was performed in 27 patients with 29 aneurysms. The six images reconstructed with the MARP method were generated from the volumetric CT data. Two radiologists independently reviewed the six 3D-CT images for the presence of aneurysm. It took about five minutes to semiautomatically reconstruct the six 3D-CT images with the MARP method. There were no discrepancies in the evaluation of the 3D-CT images. Twenty-six aneurysms of 24 patients were demonstrated on the six 3D-CT images. Three aneurysms in 3 patients were not depicted on the 3D-CT images by the MARP method. In them, the additional 3D-CT images which were generated after evaluating the 2D-CT images clearly showed the aneurysms. The MARP method is considered to be a useful three-dimensional reconstruction technique for the diagnosis of cerebral aneurysm.

Adult↗

Expression of facilitative glucose transporter isoforms in lung carcinomas: its relation to histologic type, differentiation grade, and tumor stage.

Expression of facilitative glucose transporter (Glut) isoforms was studied immunohistochemically in lung carcinomas. Glut-1 was expressed in 45 (74%) of 61 lung carcinomas, including 19 (100%) of 19 squamous cell carcinomas. No Glut-1 staining was seen in normal lung epithelium surrounding the tumors. In squamous cell carcinomas and small cell carcinomas, Glut-1 immunostaining was stronger in the central area of tumor cell nests corresponding to the hypoperfused region. Focal staining was seen in 14 (58%) of 24 adenocarcinomas, and positive staining was correlated to lesser differentiation, larger tumor size, and positive lymph node metastasis. Glut-2 was detected in normal airway epithelium, but no positive staining was seen in lung carcinomas. Glut-3 and Glut-4 were not positively stained in normal lung epithelia, but a few lung carcinoma samples showed positive reaction (9 of 61 in Glut-3; 4 of 61 in Glut-4). Glut-4 immunoexpression was seen in regenerating alveolar and bronchiolar epithelia around and in cancer tissues. Glut-5 expression was not detected in normal and tumor tissues. Reverse transcriptase-polymerase chain reaction for Glut-1, Glut-3, and Glut-4 confirmed the expression revealed by immunohistochemical analysis. Overexpression of Glut could enhance uptake of glucose into lung carcinoma cells, and the increased glucose influx could be involved in cell biologic activities.

Adenocarcinoma↗