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Biomedical subjects

H Hayashi

Publications and source records attributed to H Hayashi.

At least 1,081 records · Page 60Linked to original sources

[Linac based radiosurgery; a technical report].

A method for highly dose-localized irradiation using a linear accelerator (linac) for a brain tumor has been developed. The method requires a linac, a computed tomography (CT) system, a CT simulator, and a treatment planning system for radiotherapy, with which most major radiotherapy centers are equipped. To immobilize a patient during irradiation, a custom-made device made of synthetic material which became flexible with heating was used. With the CT system and the CT simulator the target was identified and geometrical data for positioning the tumor at a point to which x-ray beams were directed (an isocenter of the linac) were obtained. By rotating a treatment couch it was made possible for the x-ray source to rotate around the isocenter on multiple planes. Dose distribution obtained with this method was compared to that of the gamma unit and found comparable. Since the method requires no invasive procedure, it appears suitable for treatment, with fractionated irradiation, of malignant tumors.

Brain Neoplasms↗

Phosphorylation in vitro of the 85 kDa subunit of phosphatidylinositol 3-kinase and its possible activation by insulin receptor tyrosine kinase.

Insulin causes a dramatic and rapid increase in phosphatidylinositol 3-kinase activity in the anti-phosphotyrosine immunoprecipitates of cells overexpressing the human insulin receptor. This enzyme may therefore be a mediator of insulin signal transduction [Endemann, Yonezawa & Roth (1990) J. Biol. Chem. 265, 396-400; Ruderman, Kapeller, White & Cantley (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 1411-1415]. At least two questions remain to be elucidated. Firstly, does the insulin receptor tyrosine kinase phosphorylate phosphatidylinositol 3-kinase directly, or does it phosphorylate a protein associated with the 3-kinase? Second, if the enzyme is a direct substrate for the insulin receptor tyrosine kinase, does tyrosine phosphorylation of phosphatidylinositol 3-kinase by the kinase alter the specific enzyme activity, or does the amount of the tyrosine-phosphorylated form of the phosphatidylinositol 3-kinase increase, with no change in the specific activity? We report here evidence that the 85 kDa subunit of highly purified phosphatidylinositol 3-kinase is phosphorylated on the tyrosine residue by the activated normal insulin receptor in vitro, but not by a mutant insulin receptor which lacks tyrosine kinase activity. We found that an increase in enzyme activity was detected in response to insulin not only in the anti-phosphotyrosine immunoprecipitates of the cytosol, but also in the cytosolic fraction before immunoprecipitation. In addition, we partially separated the tyrosine-phosphorylated form from the unphosphorylated form of the enzyme, by using a f.p.l.c. Mono Q column. The insulin-stimulated phosphatidylinositol 3-kinase activity was mainly detected in the fraction containing almost all of the tyrosine-phosphorylated form. This result suggests that tyrosine phosphorylation of phosphatidylinositol 3-kinase by the insulin receptor kinase may increase the specific activity of the former enzyme in vivo.

Animals↗

Glycinebetaine enhances and stabilizes the evolution of oxygen and the synthesis of ATP by cyanobacterial thylakoid membranes.

Glycinebetaine (betaine), an osmoregulant in halophilic plants, stabilized the evolution of oxygen and the synthesis of ATP by thylakoid membranes from the cyanobacterium Synechocystis PCC6803 when it was present during the preparation and incubation of the thylakoid membranes. Moreover, betaine enhanced the evolution of oxygen and the synthesis of ATP when present during assays. When betaine at 1.0 M was present during the preparation of thylakoid membranes and during the measurement of activity, the rate of evolution of oxygen was equivalent to that of intact cells.

2,6-Dichloroindophenol↗

Usefulness of QRST time-integral values of 12-lead electrocardiograms in diagnosing healed myocardial infarction complicated by left bundle branch block.

The usefulness of QRST time-integral (IQRST) values of 12-lead electrocardiograms for diagnosing a prior myocardial infarction complicated by left bundle branch block (LBBB) was determined. The study consisted of 25 patients with LBBB (11 with and 14 without myocardial infarction). The IQRST values in each lead point of 12-lead electrocardiograms were calculated. Data from 607 normal subjects were used as controls and mean +/- 2 standard deviations was regarded as the normal range. The following parameters were derived: number of leads less than the normal range of IQRST values (nQRST) and sum of the differences between the normal mean IQRST value and IQRST value of a given patient in leads where this value was less than the normal range (sigma QRST). The criteria of nQRST (12-lead) greater than or equal to 5 and sigma QRST (12-lead) greater than or equal to 500 microV in 12-lead electrocardiograms were selected on a relative cumulative frequency distribution and demonstrated the presence of a myocardial infarction in LBBB with a sensitivity of 82% and a specificity of 100% for each. With regard to the localization of the myocardial infarction, the criterion of sigma QRST (V1-6) greater than or equal to 300 microV in leads V1-6 of 12-lead electrocardiograms demonstrated the presence of an anterior myocardial infarction in the LBBB with a sensitivity of 88% and a specificity of 77%. It was difficult to localize an inferior myocardial infarction in patients with LBBB by using IQRST values of inferior leads.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Tyrosine-130 in bullfrog thyroglobulin is a thyroid hormone generating site.

Bullfrog thyroglobulin was digested with lysyl endopeptidase, known to be highly specific to cut the C-terminal side of lysine residue in protein, after reduction and carboxymethylation. We isolated one peptide which lacked the C-terminal lysine, and which corresponds to 103-129 of bovine thyroglobulin sequence. Tyrosine 130 in the mammalian thyroglobulin molecule is known to be an iodination site. These findings suggest that tyrosine 130 in frog thyroglobulin is a thyroid hormone generating site.

Amino Acid Sequence↗

The crucial role of cyclic GMP in the eclosion hormone mediated signal transduction in the silkworm metamorphoses.

The signal transduction of the peptide, eclosion hormone, in the silkworm Bombyx mori appears to be mediated via the second messenger cyclic GMP throughout their life cycle. Injection of 8-bromo-cGMP induced the ecdysis behavior in pharate adults with similar latency to eclosion hormone-induced ecdysis; the moulting occurred 50-70 min after the injection. The potency of 8Br-cGMP was 10(2) fold higher than that of cGMP and the efficacy was increased by the co-injection of the phosphodiesterase inhibitor IBMX. On the other hand, in the silkworm pupal ecdysis the eclosion hormone and also 8Br-cGMP induced the moulting behavior in a dose-dependent manner. The adult development of the ability to respond to 8Br-cGMP took place concomitantly with the response to the eclosion hormone. Both the developmental time courses were shifted by a shift of light and dark cycles. Accordingly, the sensitivities to the peptide and cyclic nucleotide developed correspondently under the light and dark circadian rhythm. Thus throughout the silkworm life cycle, eclosion hormone is effective to trigger the ecdysis behavior and cGMP plays a crucial role as the second messenger in the eclosion hormone-mediated signal transduction.

1-Methyl-3-isobutylxanthine↗

Identification of intermediates after inhibition of cholesterol synthesis by aminotriazole treatment in vivo.

Cholesterol synthesis from mevalonate is inhibited by aminotriazole treatment in vivo. We tried to identify intermediates accumulated in liver of aminotriazole-treated rats. At 6 h after the aminotriazole treatment, the liver was excised. Sterols were extracted from it, and subjected to capillary gas-liquid chromatography, high-performance liquid chromatography, gas-liquid chromatography linked to mass spectrometry and gas-liquid chromatography linked to Fourier-transform infrared spectrometry. It was found that 4 alpha-methyl-5 alpha-cholest-7-en-3 beta-ol and 4,4-dimethyl-5 alpha-cholest- 8-en-3 beta-ol were accumulated in the liver, mainly as the free forms. The contents of the former and the latter were increased to 25- and 64-times the control values, respectively. In another experiment, [2-13C]mevalonate was injected at 2 h after aminotriazole treatment, and 4 h later the liver was excised. The sterols extracted from the liver were subjected to gas-liquid chromatography linked to mass spectrometry. Specific fragment ions reflecting the incorporation of [13C] mevalonate were detected in the mass spectra of the intermediate sterols. Accumulation of 4 alpha-methyl-5 alpha-cholest-7-en-3 beta-ol and 4,4-dimethyl-5 alpha-cholest-8-en-3 beta-ol after aminotriazole treatment suggests that elimination of the 4 alpha-methyl group from 4-methyl intermediate sterols is inhibited by aminotriazole.

Amitrole↗

HLA DR2 in narcolepsy with sleep-onset REM periods but not cataplexy.

To determine the association of HLA DR2 in patients with narcolepsy without cataplexy, a case-control study was performed. Patients receiving the diagnosis of narcolepsy without cataplexy had excessive daytime sleepiness (EDS) and polysomnographic findings consistent with narcolepsy but no clinical evidence of cataplexy. Of 28 patients identified, 12 agreed to return for HLA typing. Respondents did not differ from nonrespondents in demographic, clinical, or sleep laboratory data. The comparison group was 503 individuals, those 30 years and older, on the Michigan Kidney Transplant Registry. The odds ratio obtained from logistic regression indicated a strong association between narcolepsy without cataplexy and HLA DR2. To control for potential confounding variables, multivariate models were constructed to explore the joint effects of HLA DR2 and each one of the covariates (age, sex, and race), their possible combinations, and the effect of all three covariates. The odds ratios decreased minimally and the association between the disease and HLA DR2 remained significant.

Adult↗

Quantification of intracellular free sodium ions by using a new fluorescent indicator, sodium-binding benzofuran isophthalate in guinea pig myocytes.

Isolated guinea pig myocytes were loaded with the Na(+)-sensitive fluorescent probe, sodium-binding benzofuran isophthalate (SBFI). The 340/380 nm fluorescence ratios were measured with fluorescence microscopy. The distribution of intracellular Na+ concentration ([Na+]i) was homogenous, and the mean resting [Na+]i was 8.4 +/- 0.5 mM. There was a significant relationship (r = 0.66, p less than 0.001) between elevation of [Na+]i and shortening of longitudinal length of the cells, during the perfusion of 100 microM strophanthidin. It is concluded that this method is suitable for measuring [Na+]i in isolated myocytes.

Animals↗

Role of peroxisomal fatty acyl-CoA beta-oxidation in phospholipid biosynthesis.

We have already reported that peroxisomal beta-oxidation has an anabolic function, supplying acetyl-CoA for bile acid biosynthesis [H. Hayashi and A. Miwa, 1989, Arch. Biochem. Biophys. 274, 582-589]. The anabolic significance of peroxisomal beta-oxidation was further investigated in the present study by using clofibrate, a peroxisome proliferator, as an experimental tool. Clofibrate suppressed 3-hydroxymethylglutaryl-CoA reductase activity (the key enzyme of cholesterol synthesis) and enhanced fatty acyl-CoA oxidase activity (the rate-limiting enzyme of beta-oxidation). Rats were fed a chow containing 0.25% clofibrate for 2 weeks, and then a bile duct fistula was implanted. [1-14C]lignoceric acid, which is degraded exclusively by peroxisomal FAOS, was injected into the rats 24 h after the operation. By this time, the secondary bile acids and pooled cholesterol which would normally be secreted into the bile are considered to have been exhausted from the liver. Clofibrate significantly decreased the incorporations of radioactivity into biliary bile acid (40% of the control) and cholesterol (50%), but did not affect biliary lipid contents. [14C]Acetyl-CoA formed by peroxisomal beta-oxidation of [1-14C]lignoceric acid was preferentially utilized for syntheses of long-chain fatty acids and phospholipids rather than synthesis of cholesterol or triglyceride. The radioactivities incorporated into the former two lipids were increased 2-fold over the control by administration of clofibrate, while the incorporation into triglyceride was decreased to approximately half. In particular, the incorporation into phosphatidylethanolamine was increased as much as 3.5-fold over the control. The contents of these lipids in the liver were not affected by clofibrate. The results suggest that peroxisomal beta-oxidation plays an important role in the biosynthesis of functional lipids such as phospholipids (this work), in addition to bile acids and cholesterol (previous report) by supplying acetyl-CoA.

Acyl Coenzyme A↗

Distribution of trigeminal sensory nucleus neurons projecting to the mesencephalic parabrachial area of the cat.

Horseradish peroxidase (HRP) retrograde tracing experiments in the cat demonstrated projections from the trigeminal sensory nuclei to the mesencephalic parabrachial area (PBA), which is located ventral to the inferior colliculus and dorsal to the brachium conjunctivum and includes the nucleus cuneiformis and the most lateral part of the periaqueductal gray. After HRP injection into the mesencephalic PBA, HRP-labeled neuronal cell bodies in the trigeminal sensory nuclei were mainly distributed in the interpolar and caudal spinal trigeminal nuclei (Vi and Vc) bilaterally with a clear-cut contralateral dominance. In Vi, HRP-labeled neurons were mainly distributed in the lateral and medial border regions. In Vc, labeled neurons were located mainly in laminae I and V.

Animals↗

Guinea pig bone marrow cells treated with platelet-activating factor generate factor(s) which affects their DNA synthesis and microbicidal activity.

We have previously reported that platelet-activating factor (PAF) induces proliferation and microbicidal activity of guinea pig bone marrow cells. In the present study, we have found that the conditioned medium of PAF- or nonmetabolizable PAF agonist-treated guinea pig bone marrow cells augmented DNA synthesis and induced microbicial activity of bone marrow cells. A PAF specific antagonist, CV-6209, inhibited generation of the active conditioned medium by PAF. Addition of the PAF antagonist only partially suppressed the augmentative effect of the active conditioned medium on DNA synthesis; this is consistent with the fact that, because of the rapid breakdown, no appreciable amount of PAF remained in the conditioned medium of PAF-treated cells. Although mouse bone marrow cells did not respond to PAF unlike guinea pig cells, their DNA synthesis was significantly enhanced by the conditioned medium of PAF-treated guinea pig bone marrow cells. Thus, some newly generated factor(s) distinct from the originally inoculated PAF seemed to modulate the bioactions of PAF on bone marrow cells. An appreciable amount of PAF was produced by calcium ionophore-treated guinea pig bone marrow cells. These findings indicate that PAF synthesized in guinea pig bone marrow cells induces generation in the cells of some factor(s) which affects proliferation or microbicidal activity.

Animals↗

Biological response of guinea pig peritoneal macrophages to platelet-activating factor.

We investigated the effects of platelet-activating factor (PAF) on guinea pig peritoneal macrophages. Specific and high-affinity binding sites for PAF were detected on guinea pig peritoneal macrophages. Scatchard analysis of PAF binding revealed high affinity binding sites (7.9 x 10(4)/cell) with a dissociation constant of 2.3 x 10(-10) M. When treated with 10(-9)-10(-5) M PAF, guinea pig peritoneal macrophages released hydrogen peroxide into the medium in a time-dependent manner. The release reaction upon stimulation with 10(-5) M PAF reached a plateau within 30 min and the extent of release was twice as high as that when stimulated by N-formyl-L-methionyl-leucyl-L-phenylalanine (fMLP; 2 microM)-treated cells. Neither lysoPAF nor the PAF enantiomer was effective. PAF-induced H2O2 release was inhibited specifically by PAF antagonists, suggesting that PAF activated macrophages through binding to specific sites. Lysosomal enzyme (N-acetyl-beta-D-glucosaminidase) was released from guinea pig peritoneal macrophages upon treatment with 10(-5) M PAF for 60 min. Guinea pig peritoneal macrophages were treated with PAF for 8 hr and the conditioned medium was examined for cytokines. The medium exhibited cytocidal activity against mouse fibroblast L929 cells [tumor necrosis factor (TNF) activity], and this activity was comparable to that detected after treatment of cells with the bacterial lipopolysaccharide (LPS). Furthermore, the same conditioned medium also showed colony-stimulating factor (CSF) activity. Generation of these cytokines was stereospecific. Our findings suggest that PAF is a unique macrophage activator that potentiates both respiratory burst/lysosomal enzyme release (early-phase response) and monokine production/glucose consumption (late-phase response).

Animals↗

Activity of antibodies to hepatitis C virus of patients with chronic non-A, non-B hepatitis decreases during interferon alpha therapy.

The activity of antibodies to hepatitis C virus (anti-HCV) was investigated in 80 patients with chronic non-A, non-B liver diseases. Anti-HCV antibodies were positive in 82.5% (66/80), and the titers were 1 for 18 patients, 2 for 40 and 3 for 8, respectively. The frequency of anti-HCV was significantly lower in patients with chronic persistent hepatitis (8/13, 61.5%) than in those with chronic active hepatitis (42/49, 85.7%) (P less than 0.05). There was no significant difference in the distribution of anti-HCV titers among the different stages of hepatitis. There was no correlation between anti-HCV titer and histology activity index score in chronic hepatitis. Activity of anti-HCV decreased more frequently in the patients who responded to interferon alpha (IFN alpha) therapy (8/22, 36.4%) than in those who did not (0/9, 0%) (P less than 0.05). These results indicate that anti-HCV activity does not correlate with the activity or disease stage of chronic hepatitis, but that anti-HCV activity decrease more frequently during IFN alpha treatment in patients who responded to IFN alpha therapy.

Adult↗

Suppressive effect of SUN1165 on supraventricular tachycardia.

The electrophysiologic properties of SUN1165 and its suppressive effect on supraventricular tachycardia were assessed in 14 patients, nine with atrioventricular reentrant tachycardia (AVRT) and five with atrioventricular nodal reentrant tachycardia (AVNRT). This new agent prolonged the PR interval and QRS duration but did not alter the QT interval or the corrected QT interval. It did not alter the sinus cycle length or sinus node recovery time. The drug prolonged the AH interval, HV interval, and intraatrial conduction time but did not change the effective refractory periods of the right atrium or right ventricle. SUN1165 prevented the induction of tachycardia in six of nine patients with AVRT by a complete retrograde block of the accessory pathway and prevented AVNRT in four of five patients by a complete retrograde block of the fast atrioventricular nodal pathway as well. We conclude that SUN1165 is very effective in preventing AVRT or AVNRT. Larger studies with more patients are warranted.

Administration, Oral↗

Detection of myocardial infarction in the presence of Wolff-Parkinson-White syndrome by QRST isoarea map in dogs.

The possibility of detecting myocardial infarction (MI) in the presence of Wolff-Parkinson-White (WPW) syndrome by means of body surface QRST isoarea maps was studied in eight dogs. Eighty-seven body surface ECGs were recorded simultaneously. Recordings were taken during right atrial (RA) and right atrial and right ventricular (RA + RV) sequential pacing, which simulated WPW syndrome, during control periods and at 1-hour intervals for up to 5 hours after occlusion of the left anterior descending coronary artery. In ECGs during the RA drive, diagnostic findings of MI such as abnormal Q waves were observed but became obscure during the RA + RV drive. On the contrary, the QRST values over the anterior chest during both drives were positive soon after coronary occlusion, decreased gradually as time passed, and became abnormally negative after 5 hours. The QRST isoarea maps during RA and RA + RV pacing showed quite similar patterns and were highly correlated with each other throughout this study (r greater than 0.95). These findings demonstrate that localized abnormalities resulting from MI are evident in QRST isoarea maps even in the presence of preexcitation and fusion.

Animals↗

Dependency of the pulsed Doppler-derived transmitral filling profile on the sampling site.

In previous reports that evaluated pulsed Doppler transmitral filling, the sampling site has varied; we examined the effect of the sample volume location on Doppler measurements. Studied were 97 patients: 58 with normal echocardiograms, 20 with mitral regurgitation, and 19 with miscellaneous cardiac diseases. Transmitral filling was recorded at the mitral anulus and at the left atrial and left ventricular (LV) sides of the mitral tips. As the sample volume was moved from the mitral anulus to the LV side, the peak velocity and time-velocity integral of early diastole increased (40.6 +/- 13.8 versus 59.0 +/- 19.0 cm/sec, 5.26 +/- 1.65 versus 8.35 +/- 2.37 cm; p less than 0.001) as did those of late diastole (48.7 +/- 11.5 versus 57.5 +/- 17.0 cm/sec, 3.48 +/- 0.97 versus 4.59 +/- 1.39 cm; p less than 0.001). The late-to-early diastolic peak velocity and time-velocity integral ratios and the late-to-total diastolic time-velocity integral ratio decreased (1.33 +/- 0.51 versus 1.06 +/- 0.41, 0.71 +/- 0.24 versus 0.58 +/- 0.19, 0.40 +/- 0.09 versus 0.36 +/- 0.08; p less than 0.001). The dependency of these indices on the sampling site was in the same degree in all three groups. However, the peak filling rate normalized to mitral stroke volume (4.71 +/- 1.43 versus 4.63 +/- 1.32 l/sec; p = NS) was not influenced by the sample volume location; thus this parameter may be more reliable for assessing LV filling.

Adolescent↗