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Biomedical subjects

T Shibata

Publications and source records attributed to T Shibata.

At least 1,225 records · Page 68Linked to original sources

Prolonged repolarization during hypoxemia in epicardial electrogram: difference from ischemia and a competitive action of cyclic AMP.

The effects of regional hypoxemia and ischemia on epicardial electrogram were studied in anesthetized, open-chest dogs. The left circumflex artery (LCx) was cannulated and perfused with either arterial blood or hypoxic solution. A contact electrode for recording monophasic action potential (MAP) was applied to the epicardial site of the LCx area. Epicardial electrograms and MAP in the LCx perfusion territory were recorded 1) just before and at the end of a 2-min coronary occlusion (ischemia) and 2) just before and at the end of a 2-min perfusion of hypoxic solution (hypoxemia). The activation-recovery interval (ARI), defined as an interval from the minimum derivative of the QRS complex to the maximum derivative of the T-wave in the unipolar electrogram, changed linearly with MAP duration during above interventions. The ARI decreased by 29% from 189 +/- 14 to 134 +/- 30 ms during ischemia (p < .001), and it increased by 39% from 183 +/- 11 to 254 +/- 31 ms during hypoxemia (p < .001). Hypoxemia produced a giant negative T-wave whose pattern was not modified by pretreatments with autonomic nerve blockers (propranolol and atropine), a Ca2+ channel blocker (verapamil), an ATP-sensitive K+ channel (KATP blocker (5-hydroxydecanoate or transient outward K+ current (I(to) blocker (4-aminopyridine). Isoproterenol, forskolin or aminophylline inhibited both the appearances of giant negative T and the ARI prolongation. Accordingly, unlike ischemia, hypoxemia prolongs repolarization process and this prolongation is inhibited by the augmentation of intracellular cyclic AMP.

Action Potentials↗

Elevation of serum phospholipase A2 in patients at an intensive care unit.

To evaluate the organ specificity of pancreatic phospholipase A2 (PLA2) and the diagnostic value of the elevation of serum PLA2 levels in patients with serious diseases not involving the pancreas, we studied the organ distribution of PLA2 in autopsy specimens and serum level of PLA2 in patients who required admission to an intensive care unit (ICU). PLA2 was measured by a specific radioimmunoassay (RIA), using monoclonal antibody against human pancreatic PLA2. Organ distribution of PLA2 revealed that the pancreas showed a much higher content of pancreatic PLA2 immunoreactivity than any other organ. An abnormally high value of serum PLA2 was observed in 18 of 30 patients (60%) at ICU. Both serum PLA2 and pancreatic isoamylase were elevated in 11 patients (37%). Of 11 patients with hyperphospholipasemia and hyperamylasemia, serum creatinine was elevated in five patients and blood urea nitrogen in nine patients. Serum PLA2 levels did not always rise comparably to serum creatinine and blood urea nitrogen levels. Serum PLA2 values showed the best correlation with serum lactate dehydrogenase levels among routine blood-chemistry tests. The elevation of serum PLA2 was ascribable to renal dysfunction or ischemic pancreatic damage secondary to circulatory collapse with multiple organ failure.

Adult↗

Heterotopic gastric mucosa in the gallbladder: sonographic and CT findings.

We present computed tomographic (CT) and sonographic findings of heterotopic gastric mucosa incidentally found in a 63-year-old male. CT showed a slightly high density area in the gallbladder, which was intermediately enhanced early after bolus injection of contrast medium. Ultrasonography showed an echogenic sessile polyp. Histologically, the tumor consisted of gastric fundic glands containing parietal cells and chief cells.

Choristoma↗

Induction of sister-chromatid exchanges in human lymphocytes by indirect carcinogens with and without metabolic activation.

Sister-chromatid exchanges (SCEs) were examined in cultured human lymphocytes after exposure for 1 h to aflatoxin B1 (AFB1), Trp-P-1, Trp-P-2, dimethyl-nitrosamine (DMN), diethylnitrosamine (DEN) and benzo[a]pyrene (BP) with and without a metabolic activation system (S9 mix). With metabolic activation, all the carcinogens produced significant and dose-dependent increases in SCE frequency. However, the molar concentrations that induced a 2-fold increase in SCEs per cell over the control level were distributed over a range of more than 10(4). Without metabolic activation, AFB1, at 10(-4) M, caused a significant increase in SCE induction, whereas the other compounds caused little or no increase in SCE frequency above the control levels.

Aflatoxin B1↗

Induction of sister-chromatid exchanges by N-nitrosocimetidine in cultured human lymphocytes and its inhibition by chemical compounds.

The effect of nitrosocimetidine (NC) on the frequency of sister-chromatid exchanges (SCEs) in human lymphocytes has been studied. The frequency of SCEs induced by a 1-h exposure to 2.6 X 10(-4) M NC was 4-fold greater than that in the solvent control. A 72-h exposure to NC had a similar dose-related effect. We also examined the effect of the sulfhydryl compounds cysteine, cysteamine, cystamine and glutathione, the reducing agent dithionite, and vitamins C and E on the NC-induced SCEs. None of these compounds induced SCEs. Cysteine, cysteamine, and cystamine significantly reduced the number of NC-induced SCEs, and the others did not.

Ascorbic Acid↗

Monoclonal antibodies and mechanistic studies on recA protein.

A protein has various epitopes, and a monoclonal antibody specifically binds to the protein by recognizing 1 of the epitopes. This characteristic of the monoclonal antibody has opened various new approaches in a wide variety of research works. In studies about recA protein and its promoted various reactions relating to genetic recombination, anti-recA protein-monoclonal antibodies are very useful to analyse reaction mechanisms and to detect transition in the higher order-structure of the protein, as well as to measure the amounts of recA protein in vitro or in vivo and to identify the related proteins. In this article, we will review studies on recA protein in which monoclonal antibodies were used as major tools. By using anti-recA protein-monoclonal IgGs as specific inhibitors, the partial reactions of the homologous pairing and strand exchange promoted by recA protein were separated, and by use of a set of anti-recA protein IgGs the stages of activation of recA protein in the above reactions were discriminated.

Antibodies, Monoclonal↗

Binocular interactions in visual evoked cortical potentials with two light-emitting-diodes.

Binocular interaction for a central field was studied with transient scalp visual evoked cortical potentials (VECPs) using two light-emitting-diodes. VECPs were obtained for binocular and monocular visions with dominant and non-dominant eyes, and arithmetical sums of monocular VECPs with dominant and non-dominant eyes were calculated. Amplitude and latency of remarkable initial three peaks were tested with the multivariate analysis of variance. Significant differences were noted among the four VECPs. Pairwise comparisons showed that (1) the amplitude of the first peak for the binocular VECPs was larger than that for the monocular VECPs but smaller than that for the sum-VECPs; the latency of the first peaks for the binocular VECPs were earlier than that for the monocular VECPs with the non-dominant eye; (2) the amplitude of the first negative peak for the sum-VECPs was larger than that for the binocular VECPs, and the peak latency for the sum-VECPs showed later than that for the binocular VECPs; (3) the amplitude of the second positive peak for the binocular VECPs and monocular VECPs with the dominant eye was larger than that with the non-dominant eye, but smaller for the binocular VECPS than that for the sum-VECPs; the latency for the binocular VECPs showed earlier than that for the monocular VECPs with the dominant eye and for the sum-VECPs. Binocular suppression was noted in amplitude for the three peaks and binocular facilitation was noted in latency for the latter two peaks.

Adult↗

Green fluorescent protein is a suitable reporter of tumor hypoxia despite an oxygen requirement for chromophore formation.

The oxygen requirement for chromophore formation potentially limits the use of green fluorescent protein as a reporter under hypoxic conditions. In the light of this, the applicability of a hypoxia-responsive enhanced green fluorescent protein (EGFP)-based system to the measurement of tumor hypoxia was tested in human HT 1080 fibrosarcoma cells stably transfected with a destabilized EGFP vector containing the hypoxia-responsive 5HRE-hCMVmp promoter or, as a positive control, the strong constitutive CMV promoter. After various schedules of hypoxia and reoxygenation, EGFP fluorescence of live cells was assessed by flow cytometry, and protein levels were analyzed by Western blot. Fluorescence of CMV promoter positive control cells dropped to 38+/-5% of aerobic levels after 12 hours at <0.02% oxygen, but was unaffected by higher oxygen concentrations. Following 12 hours at <0.02% oxygen, cells transfected with the hypoxia-responsive vector exhibited maximum fluorescence after 4 hours of subsequent reoxygenation, reaching 68+/-2% of the levels in CMV promoter controls under aerobic conditions. With such reoxygenation, these cells exhibited a constant increase in fluorescence between 2% and <0.02% oxygen. EGFP chromophore formation is only affected by near-anoxic oxygen concentrations. The correlation of fluorescence and oxygen concentration is restored by a 4-hour reoxygenation period due to oxidation of pre-synthesized EGFP and a delayed increase in EGFP protein synthesis.

Aerobiosis↗

Lack of oncogenicity of wood creosote, the principal active ingredient of Seirogan, an herbal antidiarrheal medication, in Sprague-Dawley rats.

Seirogan, an herbal medicine containing wood creosote (tablets, 10.0% w/w), has been developed and marketed for almost a century in various countries for the control of acute diarrhea and treatment of associated symptoms, such as abdominal cramping. Wood creosote (CAS no. 8021-39-4) is a mixture of simple phenolic compounds, including guaiacol and creosol and related compounds, and is chemically distinct from, and should not be confused with, coal tar creosote, a known carcinogen. In the current study, the oncogenic potential of wood creosote was assessed in a 96/103-week oral gavage study in Sprague-Dawley rats. Groups of 60 rats/sex received wood creosote at dose levels of 20, 50, or 200 mg/kg body weight [bw]/day. An additional group of rats received the vehicle, 0.5% carboxymethylcellulose in deionized, distilled water, at the same dose volume as the treatment groups (10 ml/kg) and served as the controls. Treatment-related decreases in survival, body weight, and food consumption, as well as increased incidences of clinical signs that included rales, decreased activity, and salivation, were noted at 200 mg/kg bw/day when compared with the control group. There was an increased incidence of reddened and edematous lungs in rats from the 200 mg/kg bw/day group that died during the study. The lung findings were suggestive of test article aspiration during dose administration or agonal aspiration preceding and possibly resulting in death, especially because these observations were not seen in animals that survived to scheduled sacrifice. Additionally, phenols are generally recognized as having corrosive properties. There were no changes in clinical pathology and no increases in neoplastic or non-neoplastic lesions, excluding the lung findings, related to treatment with wood creosote at any dose level. Although the results of this study indicate that the maximum tolerated dose of wood creosote was met or exceeded at 200 mg/kg bw/day, there was no evidence of oncogenicity at any dose level. The lack of any evidence of oncogenicity supports the safety profile of the active ingredient in Seirogan, wood creosote.

Animals↗

Novel class of DNA binding motifs based on bistetrahydrofuran and bisfuran skeleton with long alkyl chains.

Small molecules with DNA-binding affinity within the minor groove have become of great interest. In this paper, new DNA binding molecules; diamino-bistetrahydrofuran (bisTHF) and diamino-bisfuran are reported. The bisTHF ligand with RR configuration at the amino groups and C8 alkyl chains (RR8) stabilized GC-rich duplex. In contrast, bisfuran compounds stabilized AT-rich duplex. The binding affinity of RR8 with 12 mer duplex DNA was determined by isothermal titration calorimetry to be 3.3 x 10(8) M-1.

Binding Sites↗

Primary thyroid lymphoma: MR appearance.

Magnetic resonance imaging was evaluated in six patients with primary thyroid lymphoma. Five patients had a solitary localized tumor and one had multiple tumors. These masses showed homogeneous iso- or high intensity compared with the uninvolved thyroid tissue on T1-weighted images and homogeneous high intensity on T2-weighted images. Diffuse lobulated goiter with homogeneous intensity was seen in the sixth case, where the differentiation between lymphoma and Hashimoto thyroiditis was impossible. Extrathyroidal tumor extension occurred in two cases and cervical lymphadenopathy in one case. In five of six cases, identification and staging of primary thyroid lymphoma were possible with MR imaging. Magnetic resonance imaging was comparable to CT in the detection of tumors (five cases), extrathyroidal extension (two cases), and cervical lymphadenopathy (one case). In three cases, the pseudocapsule (a low-intensity band forming the border between tumor and thyroid tissue) was detected only by MR imaging. In one case, the discrimination between tumor and uninvolved thyroid gland was clearer on MR imaging than on CT.

Adult↗

Ibudilast protects against neuronal damage induced by glutamate in cultured hippocampal neurons.

1. The effect of ibudilast, a drug that has been clinically used for asthma and the improvement of cerebrovascular disorders, was examined on glutamate neurotoxicity in cultured neurons from rat hippocampus. 2. The extent of neuronal damage induced by exposure of the neurons to glutamate for 5 min was estimated by the activity of lactate dehydrogenase (LDH) released from degenerated neurons into the medium during a 24 h postexposure period. When ibudilast was added into all pre-incubation, exposure and postexposure media, the extent of neuronal damage decreased to approximately half that of control at an ibudilast concentration of 43 mumol/L. 3. The neuroprotective effects of ibudilast were dose-dependent. Sufficient protection was detected even when ibudilast was added only into the postexposure medium. 4. The extent of 45Ca2+ influx during glutamate exposure was slightly reduced by the addition of ibudilast. Intracellular cAMP, as measured by radioimmunoassay, was increased by neuronal exposure to glutamate and then decreased after the removal of glutamate; however in the presence of ibudilast, AMP was maintained at the high level. 5. These results suggest that protection against glutamate neurotoxicity by ibudilast is not only attributable to the inhibition of phenomena that occur during glutamate exposure, such as Ca2+ influx, but also to some beneficial metabolic changes that are induced by a sustained high level of intracellular cAMP.

Animals↗

Peritoneal absorption of pancreatic enzymes in bile-induced acute pancreatitis in dogs.

To clarify the contribution of peritoneal absorption of enzyme-rich exudate to the persistent elevation of serum amylase in bile-induced pancreatitis in dogs, serum amylase, lipase and immunoreactive trypsin (IRT) levels were measured during 24 h after induction of pancreatitis with and without peritoneal lavage. The basal level of serum amylase activity (m +/- s.e. = 1291 +/- 111 U/L) reached a plateau at 30 min (2688 +/- 185) after induction of pancreatitis and continued to rise until 24 h (7201 +/- 424). This persistent amylase elevation could be reduced significantly by peritoneal lavage. Serum IRT rose to a peak (378 +/- 103 ng/mL) at 30 min from the basal (20 +/- 5), then decreased until 3 h (211 +/- 34) and maintained a consistent level thereafter. Serum lipase elevation took an intermediate course between the levels of serum amylase and IRT. Intraperitoneal injection of 5 mL pancreatic juice could reproduce similar elevations to those of the respective enzymes, except lipase, seen in pancreatitis. These results suggest that transperitoneal absorption of pancreatic enzymes contributes to the elevation in serum enzymes levels and that rates of peritoneal absorption and serum disappearance differ from enzyme to enzyme.

Acute Disease↗

Plasma disappearance of homologous and heterologous pancreatic enzymes in dogs.

Homologous and heterologous (human) pure pancreatic juice was infused into dogs to compare the behaviour of pancreatic enzymes in the circulation. This was achieved by estimating the magnitude of elevation and speed of disappearance of pancreatic enzymes in plasma. The half-lives of the plasma enzymes did not differ significantly between dogs and humans. However the half-lives of other enzymes (longest for amylase and shortest for trypsinogen) did differ. The magnitude of elevation expressed as a ratio of peak (5 min) to basal level was greatest for trypsinogen (28 times) and least for amylase (1.4 times). However, 289% and 410% of the initial lipase enzyme activity was recovered 5 min after infusion of dog and human pure pancreatic juice, respectively (44% when measured by immunoreactive human lipase activity). The excess recovery requires re-evaluation of diagnostic value of turbidimetric activity of plasma pancreatic lipase.

Amylases↗

Protective effects of a prostaglandin E1 oligomer on taurocholate-induced rat pancreatitis.

Effects of prostaglandin E (PGE) on acute pancreatitis have been controversial. This study shows the effects of PGE1 oligomer, MR-356, on trypsin-taurocholate-induced acute pancreatitis in rats. Divided intraperitoneal doses of 0.6 mg/rat were administered, which increased 24 h survival rates when the oligomer was given both at 1 h before and after (group A) and immediately and 3 h after (group B) induction of pancreatitis. In group A MR-356 significantly improved the survival rates at 18 h (94 vs 61%, P < 0.05) and 24 h (68 vs 33%, P < 0.05) when compared with controls. MR-356 improved the survival rates dose-dependently up to 0.6 mg/rat when given by the same protocol of group A. In group B MR-356 also improved the survival rate (72 vs 39%, P < 0.05) only at 24 h, while other parameters failed to improve. The present results suggest that the PGE1 oligomer may play a beneficial role in bile-induced pancreatitis, probably through its proposed effects of stabilization of lysosomal membranes, maintenance of microcirculation and inhibition of protease in the pancreas.

Alprostadil↗

Serum alpha 2-macroglobulin-trypsin complex and early recognition of severe acute pancreatitis after endoscopic retrograde pancreatography.

Serum alpha 2-macroglobulin-trypsin complex (alpha 2M-T) was measured to differentiate the elevation of serum pancreatic enzymes caused by severe acute pancreatitis from simple elevation after endoscopic retrograde pancreatography (ERP). A patient with severe acute pancreatitis demonstrated marked elevation of serum alpha 2M-T. In patients without severe acute pancreatitis, serum alpha 2M-T did not rise in spite of elevated serum pancreatic enzymes. In conclusion, abdominal pain with elevated serum alpha 2M-T can be an early diagnostic clue to severe acute pancreatitis after ERP.

Acute Disease↗