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H Toda

Publications and source records attributed to H Toda.

At least 37 records · Page 2Linked to original sources

Thiopental enhances human platelet aggregation by increasing arachidonic acid release.

Conflicting results have been reported regarding the effect of thiopental on aggregation and cytosolic calcium levels in platelets. The present study attempted to clarify these phenomena. Using platelet-rich plasma or washed suspensions, platelet aggregation, thromboxane (TX) B2 formation, arachidonic acid (AA) release, and cytosolic free calcium concentrations ([Ca2+]i) were measured in the presence or absence of thiopental (30-300 microM). Platelet activation was induced by adenosine diphosphate (ADP, 0.5-15 microM), epinephrine (0.1-20 microM) arachidonic acid (0.5-1.5 mM), or (+)-9,11-epithia-11,12-methano-TXA2 (STA2, 30-500 nM). Measurements of primary aggregation were performed in the presence of indomethacin (10 microM). Low concentrations of ADP and epinephrine, which did not induce secondary aggregation in a control study, induced strong secondary aggregation in the presence of thiopental (> or = 100 microM). Thiopental (> or = 100 microM) also increased the TXB2 formation induced by ADP and epinephrine. Thiopental (300 microM) increased ADP- and epinephrine-induced 3H-AA release. Thiopental (300 microM) also augmented the ADP- and epinephrine-induced increases in [Ca2+]i in the presence of indomethacin. Thiopental appears to enhance ADP- and epinephrine-induced secondary platelet aggregation by increasing AA release during primary aggregation, possibly by the activation of phospholipase A2.

Arachidonic Acid↗

Plasma level of triglyceride-rich lipoprotein remnants is closely associated with the activation of coagulation factor VII in patients with myocardial infarction.

Remnant-like particles, which have been recognized to be atherogenic derivatives of chylomicrons and very low density lipoproteins, can be measured using a new assay kit. The purpose of the present study was to investigate the association of remnant-like particles with the coagulation system that has an important role in the pathogenesis of myocardial infarction. We assayed blood levels of total cholesterol, triglyceride, HDL-cholesterol, apolipoproteins, remnant-like particles-cholesterol, remnant-like particles-triglyceride, fibrinogen, factor VII antigen, activated factor VII, and tissue factor in 111 patients with a history of myocardial infarction and 128 control subjects. In simple regression analysis, plasma levels of remnant-like particles-cholesterol and remnant-like particles-triglyceride showed a significant positive correlation with the levels of activated factor VII (r=0.319, p<0. 001, and r=0.286, p=0.002, respectively) and the activated factor VII/factor VII antigen ratio (r=0.241, p=0.011, and r=0.249, p=0.008, respectively) in patients with myocardial infarction. In contrast, there were no significant differences between remnant-like particles and activated factor VII in control subjects. In stepwise multivariate regression analysis, the significant determinants of activated factor VII were remnant-like particles-cholesterol (10.2%), apolipoproteins A-I (5.1%), and E (7.1%); for the activated factor VII/factor VII antigen ratio, remnant-like particles-triglyceride (6. 2%), age at blood sampling (5.1%), and apolipoprotein A-I (4.0%) in patients with myocardial infarction. However, the significant determinants of activated factor VII and the activated factor VII/factor VII antigen ratio were HDL-cholesterol (9.9% and 9.2%, respectively) in control subjects. It is concluded that remnant-like particles may be a risk factor for myocardial infarction by activating the extrinsic coagulation pathway.

Adult↗

Neurons generated from adult rat hippocampal stem cells form functional glutamatergic and GABAergic synapses in vitro.

Basic fibroblast growth factor-responsive neural stem cells (NSCs) derived from adult rat hippocampus were earlier demonstrated to generate neurons and glia. These stem-cell-derived neurons express GABA, acetylcholinesterase, tyrosine hydroxylase, or calbindin. It has not been clear, however, whether or not these stem-cell-derived neurons are able to form functional synapses. In the present study, we investigated the development of synapse formation by adult hippocampus-derived neural stem cells. NSCs from adult rat hippocampi and primary embryonic rat hippocampal neurons were cocultured on a glial feeder layer. Immunofluorescence studies revealed that some of the NSCs became immunoreactive for microtubule-associated protein 2ab, neurofilament 200, synaptobrevin, or synaptophysin. These cells possessed properties of functional neurons such as action potentials and miniature postsynaptic currents (mPSCs). The elicited mPSCs with rapid kinetics were blocked by 6,7-dinitroquinoxaline-2,3-dione (DNQX), but not by bicuculline (excitatory mPSCs). The remaining mPSCs had slower kinetics and were blocked by bicuculline, but not by DNQX (inhibitory mPSCs). We considered that the neurons derived from the adult NSCs expressed both non-NMDA glutamate receptors and the GABA(A) receptors and formed functional synapses. Our results demonstrate that adult NSCs can differentiate into neurons with functional glutamatergic and GABAergic synaptic transmission in vitro and support the concept that such neurons could integrate into the neuronal circuitry.

Animals↗

"Deep-forehead" temperature correlates well with blood temperature.

PURPOSE: To evaluate the accuracy and precision of "deep-forehead" temperature with rectal, esophageal, and tympanic membrane temperatures, compared with blood temperature. METHODS: We studied 41 ASA physical status 1 or 2 patients undergoing abdominal and thoracic surgery scheduled to require at least three hours. "Deep-forehead" temperature was measured using a Coretemp thermometer (Terumo, Tokyo, Japan). Blood temperature was measured with a thermistor of a pulmonary artery. Rectal, tympanic membrane, and distal esophageal temperatures were measured with thermocouples. All temperatures were recorded at 20 min intervals after the induction of anesthesia. We considered blood temperature as the reference value. Temperatures at the other four sites were compared with blood temperature using correlation, regression, and Bland and Altman analyses. We determined accuracy (mean difference between reference and test temperatures) and precision (standard deviation of the difference) of 0.5 degrees C to be clinically acceptable. RESULTS: "Deep-forehead" temperature correlated well with blood temperature as well as other temperatures, the determination coefficients (r2) being 0.85 in each case. The bias for the "deep-forehead" temperature was 0.0 degrees C, which was the same as tympanic membrane temperature and was smaller than rectal and esophageal temperatures. The standard deviation of the differences for the "deep-forehead" temperature was 0.3 degrees C, which was the same as rectal temperature. CONCLUSIONS: We have demonstrated that the "deep-forehead" temperature has excellent accuracy and clinically sufficient precision as well as other three core temperatures, compared with blood temperature.

Aged↗

Effects of localized lesions in the lateral suprasylvian cortex on convergence eye movement in cats.

We evaluated the effects of electrolytic lesions in the extrastriate cortical area on the amplitudes and velocities of vergence eye movements in six alert cats that were trained to track a target moving in depth. Bilateral or unilateral lesions in the lateral suprasylvian (LS) cortex reduced the amplitudes and velocities of vergence eye movements, but the positive correlation between them was maintained. Furthermore, unilateral lesions changed the symmetry of eye movements. Movements of the left eye were decreased by lesions in the right LS cortex, resulting in asymmetric vergence eye movement with right eye predominance, and vice versa. These results support the hypothesis that the LS cortex plays an essential role in controlling vergence eye movement.

Animals↗

Suppression of BCR-ABL mRNA by various ribozymes in HeLa cells.

Ribozymes are RNA molecules with enzymatic activity that can cleave target RNA molecules in a sequence specific manner. To date, various types of ribozyme have been constructed to cleave other RNAs and such trans-acting ribozymes include hammerhead, hairpin and HDV ribozymes. External guide sequence (EGS) can also induce the suppression of a gene-expression by taking advantage of cellular RNase P. Here we compared the activities of various functional RNA cleavers both in vitro and in vivo. The first purpose of this comparison was intended to determine the best ribozyme motif with the highest activity in cells. The second purpose is to know the correlation between the activities of ribozymes in vitro and in vivo. Our results indicated that the intrinsic cleavage activity of ribozymes is not the sole determinant that is responsible for the activity of a ribozyme in cultured cells.

Endoribonucleases↗

Comparative contractile effects of halothane and sevoflurane in rat aorta.

BACKGROUND: Volatile anesthetic agents have been shown to have contractile effects in vascular tissues during specific conditions. This study compared contractile effects of halothane and sevoflurane in rat aorta treated with verapamil. This study also tried to elucidate the mechanism of the contraction. METHODS: Endothelium-denuded rat thoracic aorta was used for recording of isometric tension and measurement of influx of 45Ca2+. All experiments were performed in the presence of verapamil. In recording of tension, rings were precontracted with a submaximum dose of phenylephrine, followed by exposure to halothane or sevoflurane. For measurement of influx of 45Ca2+, rat aortic strips were exposed to phenylephrine and then to additional halothane or sevoflurane. Influx of Ca2+ was estimated by incubating the strips in 45Ca2+-labeled solution for 2 min. RESULTS: Halothane (0.5-4.0%) induced contraction in a dose-dependent manner, whereas sevoflurane (1-4%) had no effect on tension. Influx of 45Ca2+ was strongly enhanced by halothane at 1% and 2%, but only slightly at 4%, and was not affected by 1-4% sevoflurane. SK&F 96365, a blocker of voltage-independent Ca2+ channels, abolished contraction and influx of 45Ca2+ by 1% halothane. Depletion of Ca2+ from the sarcoplasmic reticulum with ryanodine or thapsigargin reduced the contraction induced by halothane at 4% but not that at 1% and 2%. CONCLUSION: Halothane is suggested to cause contraction by enhancing influx of Ca2+ via voltage-independent Ca2+ channels at concentrations up to 2% and by inducing release of Ca2+ at 4%. Sevoflurane (1-4%) is devoid of these contractile effects.

Anesthetics, Inhalation↗

Selenium and glutathione peroxidase mRNA in rat glioma.

The purpose of current study was to determine the step at which dietary selenium (Se) regulates the transcriptional expression of the gene for Se-glutathione peroxidase (Se-GPx) in rat brain and transplanted glioma tissue. Wistar rats were fed a Se-free diet or the same diet supplemented with 0.5, 2.0, and 4.0 mg Se/kg as sodium selenite for at least 3 wk. Then, the rats were transplanted with C6 rat glioma cells into the right frontal lobe parenchyma. All rats were observed for 30 d, then tumor and contralateral brain tissue were excised and divided into three portions for purification of selenium content, for the assay of Se concentration, Se-GPx activity, and for Se-GPx mRNA. Se concentration and Se-GPx activity are increased with Se supplementation both in tumor tissue and contralateral brain tissue, and Se concentration in tumor is higher than that in contralateral brain tissue at each dietary Se content. Se-GPx mRNA of brain and tumor were probed with fragments from a rat Se-GPx cDNA in Northern blot analysis. There was significant differences of Se-GPx mRNA transcription in brain tumor tissue among each dietary group of the Se content, and the steady-state level of Se-GPx mRNA was markedly reduced by Se deficiency. These results suggest that dietary Se exerts its augmenting effect on Se-GPx gene transcription.

Animals↗

[Usefulness of rapid bedside cardiac troponin T assay for the diagnosis of acute myocardial infarction].

Cardiac troponin T(cTnT) is one of the most myocardial-specific markers for the diagnosis of acute myocardial infarction(AMI). Recently, the rapid bedside cTnT assay(Trop T rapid assay sensitive version), which can provide qualitative determinations within 15 min, has been developed for the emergency clinical setting. To evaluate the usefulness of rapid bedside cTnT assay, we performed the Trop T test and measured serum levels of myoglobin(Mb), creatine kinase MB isoenzyme(CK-MB) and cTnT in 256 consecutive emergency patients with suspected AMI(65 found to have AMI and 191 without AMI). The diagnostic sensitivities for AMI of Trop T, Mb and CK-MB measurements were 66%, 92% and 52%, respectively, whereas the specificities were 80%, 18% and 74%, respectively. The diagnostic accuracy for AMI of Trop T(77%) was significantly higher than that of Mb(37%, p < 0.001) and CK-MB(69%, p < 0.05). The sensitivity for AMI of Mb(86%) was significantly(p < 0.001) higher than that of Trop T (31%) and CK-MB(31%) in patients admitted < or = 3 hr after the onset of AMI. In contrast, the sensitivities of Trop T(80% and 100%) in patients admitted at 3-6 hr and > 6 hr showed no significant differences from those of Mb(100% and 96%). Furthermore, Trop T in patients admitted > 6 hr had significantly(p < 0.01) higher sensitivity compared with CK-MB(69%). The mortality rate in the non-AMI group during hospitalization in patients with positive Trop T test(39%) was significantly(p < 0.001) higher than that in patients with negative test(9%). When the positive Trop T test was regarded as > or = 0.10 ng/ml of serum cTnT, Trop T test had the best concordance of 92% with a quantitative of cTnT assay.

Aged↗

Edrophonium-induced macrosaccadic oscillations in myasthenia gravis.

In a myasthenia gravis patient with profound ophthalmoplegia who was given edrophonium during forward fixation or horizontal/vertical saccades, horizontal macrosaccadic oscillations occurred that were conjugate, 2 to 3 Hz, and of peak-to-peak amplitude up to 50 degrees. The intersaccadic interval averaged 129.5 msec as measured by electro-oculography. Eye closure or the use of Frenzel goggles markedly reduced the amplitude and frequency of the macrosaccadic oscillations. This short latency is similar to that of a corrective saccade, and suggests that edrophonium induces macrosaccadic oscillations through a non-visually guided reflex saccade by temporarily unmasking the adaptively increased saccadic gain to overcome myasthenic ocular paresis.

Edrophonium↗

Delayed thrombus propagation after parent artery clipping for giant fusiform aneurysms of the circle of Willis.

BACKGROUND: Obliteration of a giant fusiform aneurysm without significant therapeutic morbidity is extremely difficult. Ischemic complications have been often reported. METHODS: Two patients with giant fusiform aneurysms of the circle of Willis are presented. Both patients underwent proximal parent artery clipping after a bypass procedure. Balloon occlusion tests confirmed both patients' ability to tolerate flow reduction after proximal clipping. RESULTS: Although both patients awoke from anesthesia without neurologic deficit, they developed contralateral hemiparesis several hours after the operation as a result of a small infarct in the basal ganglia. These ischemic events might be attributed to the delayed thrombosis involving the orifice of the distal perforating arteries. CONCLUSIONS: In the treatment for giant fusiform aneurysms of the circle of Willis, special attention should be paid not only to flow reduction, but also to delayed thrombus propagation that may not be predicted by preoperative balloon occlusion testing.

Adult↗

Hepatoma-specific antitumor activity of an albumin enhancer/promoter regulated herpes simplex virus in vivo.

Targeting viral vectors to appropriate cell types so that normal cells are not adversely affected is an important goal for gene therapy. Previously, we described a novel approach to viral gene therapy using a conditional, replication-competent herpes simplex virus (HSV), where replication and associated cytotoxicity are limited to a specific cell-type by the regulated expression of an essential immediate-early viral gene product. In this report we analyze the hepatoma-specific replication, cytotoxicity and anti-tumor effect of recombinant HSV G92A, regulated by the albumin enhancer/promoter. G92A efficiently replicated in vitro in two human hepatoma cell lines expressing albumin, but not in four human non-hepatoma, albumin-non-expressing tumor cell lines, while all cell lines were equally susceptible to a tissue nonspecific HSV recombinant, hrR3. In vivo, G92A replicated well in subcutaneous xenografts of human hepatoma cells (Hep3B) in athymic mice, but not in non-hepatoma subcutaneous tumors (PC3 and HeLa), whereas, hrR3 replicated well in both tumor types. Intratumoral inoculation of G92A inhibited the growth of established subcutaneous hepatoma tumors in nude mice, but not prostate tumors. Replication-competent viral vectors controlled by cell-specific transcriptional regulatory sequences provide a new therapeutic strategy for tumor therapy.

Albumins↗

Propofol has both enhancing and suppressing effects on human platelet aggregation in vitro.

BACKGROUND: Volatile anesthetics are known to suppress platelet aggregation. In contrast, there is conflicting information regarding the effect of propofol on platelet function. The present study was designed to clarify the effects of propofol on platelet function and the mechanisms underlying these effects. METHODS: Propofol or an equivalent volume of 10% Intralipos (as a control) was added to test tubes 5 min before the induction of each reaction. Platelet aggregation induced by epinephrine, arachidonic acid (AA), prostaglandin G2 (PGG2), or STA2 (a thromboxane A2 [TXA2] analog) was measured using an eight-channel aggregometer. To determine type 1 cyclooxygenase activity, AA (0.5 mM) was added to an assay mixture containing type 1 cyclooxygenase, and the concentration of the final product, malonaldehyde, was measured by spectrophotometry. Epinephrine-, adenosine diphosphate-, AA-, and PGG2-induced TXA2 formation was measured using a commercially available radioimmunoassay kit. To estimate TXA2 receptor-binding affinity, 3H-S145, a specific TXA2 receptor antagonist, was added, and the radioactivity of receptor-bound 3H-S145 was determined using a liquid scintillation analyzer. Inositol 1,4,5-triphosphate formation was measured in STA2-stimulated platelets using a commercially available inositol 1,4,5-triphosphate assay kit. RESULTS: Propofol (40 microM) enhanced, whereas 100 microM suppressed, adenosine diphosphate- and epinephrine-induced secondary aggregation without affecting primary aggregation. Propofol (40 microM) also enhanced, but 100 microM suppressed, AA-induced aggregation. Propofol (100 microM) enhanced PGG2- and STA2-induced aggregation. Propofol (100 microM) suppressed AA-induced TXA2 formation but did not alter that induced by PGG2. Propofol (30-100 microM) suppressed AA-induced malonaldehyde formation, indicating inhibition of type 1 cyclooxygenase activity. Propofol did not alter TXA2 receptor-binding affinity. Propofol (30 and 100 microM) augmented inositol 1,4,5-triphosphate formation in STA2-stimulated platelets. CONCLUSIONS: The present findings clearly indicate that high concentrations of propofol suppress the activity of type 1 cyclooxygenase, the enzyme that converts AA to PGG2. Furthermore, propofol also enhanced STA2-induced inositol 1,4,5-triphosphate formation. These results may explain the inconsistent findings of previous investigators.

Adult↗

[Evaluation of mycobacteria growth indicator tube (MGIT), an automated culture system for detection of mycobacteria from clinical specimens].

We compared the Mycobacteria Growth Indicator Tube 960 (MGIT 960) and Ogawa medium (OM) for the detection of mycobacteria (acid fast bacteria: AFB) using 882 sputum specimens. Overall, 120 strains of AFB were isolated by the MGIT 960 system and 99 strains of AFB were isolated by using OM. As far as Mycobacterium tuberculosis is concerned, 88 and 71 isolates were achieved by the MGIT 960 and OM respectively. A total of 28 isolates (18 isolates of M. tuberculosis and 10 isolates of nontuberculous mycobacteria: NTM) were detected by the MGIT 960 only whereas only 2 isolates (1 M. tuberculosis and 1 NTM) were detected by OM only. Of these sputum specimens, 72 were smear positive for AFB. The rates of smear negative but culture positive specimens were 8.0% (65 out of 809) for the MGIT 960 system and 6.2% (50 out of 809) for OM. The contamination rate for MGIT 960 was only 1.2%. The average time required for detection of M. tuberculosis was 14.1 days by the MGIT 960 system and 24.6 days by OM. For the NTM, the average detection time were 8.3 days for the MGIT 960 system and 22.8 days for OM. These results indicate that the MGIT 960 system allows detection of mycobacteria significantly faster than OM.

Automation↗

Inhibition of rat vascular smooth muscle cell proliferation in vitro and in vivo by recombinant replication-competent herpes simplex virus.

BACKGROUND AND PURPOSE: The proliferation of vascular smooth muscle cells (VSMCs) is a common feature associated with vascular proliferative disorders such as atherosclerosis and restenosis after balloon angioplasty. We examined the antiproliferative effects of recombinant replication-competent herpes simplex virus (HSV), hrR3, to proliferative VSMCs both in vitro and in vivo. METHODS: Early passages of Sprague-Dawley rat VSMCs were infected with hrR3 at a low multiplicity of infection (0.01 to 1.0) to examine the in vitro cytotoxic activity of this recombinant HSV to VSMCs in a proliferative state. Sprague-Dawley rats underwent balloon dilatation injury of the left carotid artery to induce neointimal formation. The injured carotid arteries were infected with hrR3 five days after balloon injury. Two weeks after injury, the left carotid arteries were fixed, and the areas of the neointimal and medial layers were analyzed microscopically. Because the reporter Escherichia coli lacZ gene in hrR3 is expressed only in infected cells in which the virus is actively replicating, virus replication was confirmed by X-gal staining. RESULTS: A morphometric analysis revealed that there were significant differences in the intima/media ratio between the HSV-treated group and mock-infected group (0. 354+/-0.068 and 1.08+/-0.055, respectively). In the histological study (X-gal staining), positive X-gal staining was observed chiefly in the VSMCs in the medial layer just beneath the internal elastic lamina, indicating active viral replication. CONCLUSIONS: Virus-mediated cytocidal therapy using recombinant HSV vector is a promising modality for the treatment of the restenosis after balloon angioplasty.

Angioplasty, Balloon↗