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Biomedical subjects

H Ohtomo

Publications and source records attributed to H Ohtomo.

At least 73 records · Page 4Linked to original sources
PubMed1987

Inhibitory immunization using complete Freund's adjuvant on ongoing eosinophilia induced by repeated antigen-stimulations in guinea pigs.

Ongoing eosinophilia, in guinea pigs repeatedly sensitized with dinitrophenylated (DNP)-Ascaris antigen (DNP-Asc) into the peritoneal cavity, was suppressed significantly by complementary immunizations with a heterologous antigen, e.g., ovalbumin (OA) or bovine gamma-globulin (BGG) emulsified in complete Freund's adjuvant (CFA). Challenge injections of DNP-OA or DNP-BGG elicited peritoneal eosinophilia in animals that were sensitized repeatedly with DNP-Asc. Under these conditions, antigen specificity in suppressive immunization was studied. Eosinophilia, induced by DNP-OA challenge, was suppressed by immunization with either OA in CFA or BGG in CFA. However, Asc (homologous carrier of sensitizing antigen) elicited no suppression. Additionally, CFA, used as an adjuvant, played an important role in suppressive immunization, but CFA alone had no effect in suppressing peritoneal eosinophilia. Anti-DNP antibody, detected by hemagglutination test or passive cutaneous anaphylaxis, was not affected by complementary immunization. These results suggested that peritoneal eosinophilia was suppressed concomitantly by a supplemental immunization in an antigen-nonspecific manner. Eosinophilia in the bone marrow also was suppressed significantly by complementary immunization, but the pattern was quite different from that shown in the peritoneal cavity. The first nuclear cell response peak after challenging, including eosinophils, was stanched completely by CFA itself. The second nuclear cell peak, on day 5, recovered, but eosinophil response continued to be suppressed.

Animals↗
PubMed1987

Protective effects of indeloxazine hydrochloride on cerebral ischemia in animals.

Effects of indeloxazine hydrochloride [(+/-)-2-[(inden-7-yloxy)methyl]morpholine hydrochloride, YM-08054] on cerebral ischemia were investigated in animals. Indeloxazine prolonged the gasping duration dose-dependently in decapitated mice. Bilateral occlusion of the carotid artery for 5 min shortened the latency of step-through in passive avoidance task 4 days following ischemia in mongolian gerbils. The i.p. administration of indeloxazine was started just after the surgical operation and repeated twice a day for 4 days. Indeloxazine (2 mg/kg) significantly prolonged the latency of step-through in this amnesic model, indicating a reversal effect on the ischemia-induced amnesia. In biochemical studies, decreases in brain ATP and total adenine nucleotide levels were inhibited by indeloxazine (2 mg/kg i.p., once a day for 7 days) in four-vessel occluded rats. These findings indicate that indeloxazine possesses protective effects on cerebral ischemia presumably due, in part, to improvement of the cerebral energy metabolism.

Animals↗
PubMed1987

[Effects of S-adenosyl-L-methionine on the cerebral energy metabolism and microcirculation in the rats subjected to transient forebrain ischemia].

Effects of S-adenosyl-L-methionine (SAM) on the improvement of cerebral energy metabolism and microcirculation were examined in postischemic rat brain. Male Wistar rats, whose vertebral arteries were electrically cauterized last day, were subjected to forebrain ischemia by temporary clipping of both common carotid arteries. After 60 min of ischemic insult, they were intravenously administered with SAM at doses of 30 or 100 mg/kg; this was followed by recirculation for 60 min. To determine cerebral concentrations of energy metabolites, the brain was frozen in situ. Adenine nucleotides (ATP, ADP, AMP) were assayed by anion-exchange HPLC system, and other metabolites (PCr, glucose, lactate, pyruvate) were analyzed by enzymatic fluorometry. In order to estimate regional cerebral blood flow (rCBF) and glucose utilization, double-tracer autoradiography was undertaken using 14C-iodoantipyrine (14C-IAP) and 18F-fluorodeoxyglucose (18F-FDG). In animals without SAM treatment (60-60 group), energy metabolites did not recover and neither CBF nor glucose uptake restored during 60 min of recirculation. In contrast, in SAM-treated animals (60-60 SAM group), values of the energy metabolites improved significantly and both CBF and glucose uptake recovered, though incompletely. These results indicate that SAM is able to improve postischemic cerebral microcirculation and energy metabolism. For mechanisms of the effects, it is suggested to the enhancement of erythrocyte deformability by phospholipid methylation, the stabilization of mitochondria, and the normalization of injured metabolic reactions. Therefore, we conclude that SAM is able to be effective clinically as a drug treated for the acute phase of cerebrovascular diseases.

Animals↗
PubMed1986

Simplified enzymatic synthesis and biodistribution of 11C-S-adenosyl-L-methionine.

11C-S-Adenosyl-L-methionine (11C-SAM) was synthesized enzymatically from 11C-L-methionine using rat-liver extract [40%-50% saturated (NH4)2SO4 fraction] as the enzyme source. In biodistribution studies in rats, the highest uptake of 11C-SAM was found in the kidneys. 11C-SAM was also accumulated in the small intestine, pancreas, adrenal gland, liver, and spleen. The uptake of 11C-SAM in the brain increased with time, but remained low. At 30 min after injection, about 50%-60% of the 11C radioactivity was present in the acid-insoluble fraction of the kidneys and liver. When a high loading dose of 11C-SAM was administered, the kidney uptake was enhanced, but the proportion of the radioactivity present in the acid-insoluble fraction was lower. In a study of one rabbit, the kidney uptake was of 11-SAM clearly visualized using positron-emission tomography.

Animals↗
PubMed1986

Characterization of experimental ischemic brain edema utilizing proton nuclear magnetic resonance imaging.

Correlations between T1 and T2 relaxation times and water and electrolyte content in the normal and ischemic rat and gerbil brains were studied by means of both nuclear magnetic resonance (NMR) spectroscopic and imaging methods. In the spectroscopic experiment on excised rat brains, T1 was linearly dependent on tissue water content and T2 was prolonged in edematous tissue to a greater extent than expected by an increase in water content, showing that T2 possesses a greater sensitivity for edema identification and localization. Changes in Na+ and K+ content of the tissue mattered little in the prolongation of relaxation times. Serial NMR imaging of gerbil brains insulted with permanent hemispheric ischemia offered early lesion detection in T1- and especially T2-weighted images (detection as soon as 30 min after insult). The progressive nature of lesions was also imaged. Calculated T1 and T2 relaxation times in regions of interest correlated excellently with tissue water content (r = 0.892 and 0.744 for T1 and T2, respectively). As a result, detection of cerebral ischemia utilizing NMR imaging was strongly dependent on a change in tissue water content. The different nature of T1 and T2 relaxation times was also observed.

Animals↗
PubMed1986

[Magnetic resonance imaging of experimental cerebral ischemia: correlations between NMR parameters and water content].

Recent studies on proton NMR imaging revealed its remarkable sensitivity for detecting cerebral ischemia. Since proton NMR reflects the distribution and state of water in the brain, an NMR imager becomes a sensitive in vivo detector of brain edema developing soon after the energy state is compromized by ischemia. To further clarify the usefulness of NMR imaging to characterize the ischemia-induced changes, correlations between T1 and T2 relaxation times and water content of the normal and ischemic rat and gerbil brain were studied by means of both spectroscopic and in vivo imaging methods. In the spectroscopic experiment on excised rat brain (cortex, white matter, hippocampus and thalamus for normal and ischemia-laden brain), T1 and T2 relaxation times and water content were determined. The ischemic insult was induced for 60 min by the method of Pulsinelli followed by 60 min of reperfusion. All of the T1, T2 and water content significantly increased in the ischemic tissue. Gray-white difference was evident in T1 and T1 was linearly correlated with the water content of the tissue. T2 was by far prolonged in the ischemic tissue compared with the increase in the water content, showing greater sensitivity of T2 for detection of ischemia. In the imaging experiment, coronal NMR imaging at 0.5 tesla was performed employing proton density-weighted saturation recovery (TR = 1.6 s, TE = 14 ms), T1-weighted inversion recovery (TR = 1.6 s, TI = 300 ms, TE = 14 ms) and T2-weighted spin echo (TR = 1.6 s, TE = 106 ms) pulse sequences.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

[Effects of indeloxazine hydrochloride on brain energy and glucose metabolism in the four-vessel occlusion rat model].

Indeloxazine hydrochloride (Indeloxazine) has been known as a new type drug with enhancing effects on memory and learning processes in various experimental models. In the present studies, effects of Indeloxazine on brain energy and glucose metabolisms were determined in four-vessel occlusion rat model. Since a critical point of ischemic time for the recovery of brain energy levels existed between 30 min and 60 min in this model, effects of Indeloxazine were determined in the rat model of 60 min recirculation following 60 min ischemia. One-week dosing of Indeloxazine at 2 mg/kg showed slight increases in ATP and total adenine nucleotides levels. To elucidate the mechanism of improving action of Indeloxazine on brain energy levels, effects on glucose metabolism were determined. Non-treated group of 60 min ischemia-60 min recirculation showed severe reduction of 14C-2-deoxyglucose metabolism in comparison to normal control group. Indeloxazine-treated group showed a slight improvement of 14C-2-deoxyglucose metabolism in comparison to non-treated group. Furthermore, high 14C-2-deoxyglucose metabolism was observed in parts of hippocampus, cortex and thalamus. From these results, it seems possible that Indeloxazine has some protective effects on brain damage in four-vessel occlusion rat model.

Animals↗
PubMed1985

Correlations between proton nuclear magnetic resonance imaging and retrospective histochemical images in experimental cerebral infarction.

Evaluation of ischemic brain injury in experimental cerebral infarction in gerbils and rats was performed by means of both proton nuclear magnetic resonance imaging ([1H]NMR-CT) and various histochemical analyses. In vivo nuclear magnetic resonance (NMR) imaging was carried out employing saturation recovery, inversion recovery, and spin echo pulse sequences. Spatial resolution of the images was excellent. The ischemic lesions were detected with a remarkable contrast in inversion recovery and spin echo images within a few hours after insult. Those changes in NMR images consistently corresponded with the various retrospective histochemical observations, especially with methods related to brain edema (K+ staining) rather than structural (enzymatic) studies. Calculated T1 and T2 relaxation times indicated the evolution of the edema state in the brain in situ. They correlated excellently with the retrospective water content measurement. As a result, detailed characterization of the edema state induced by cerebral ischemia was possible in vivo using [1H]NMR imaging.

Adenosine Triphosphatases↗
PubMed1985

HLA antigens in patients with unexplained hepatitis following halothane anesthesia.

We examined HLA-A,B,C and DR locus antigens in 38 Japanese patients who had recovered from halothane hepatitis. The patients were divided into two subgroups, i.e. jaundice and non-jaundice groups, because the clinical features were quite different in each. DR2 was positive in 14 (58.3%) of 24 patients with jaundice, compared with 281 (33.6%) of the 837 Japanese healthy controls (chi-square with Yates' correction = 5.30, relative risk = 2.77, P less than 0.025). Conversely, Bw44 was increased in non-jaundice patients (50.0%), compared with 157 (12.7%) of the 1234 Japanese healthy controls (chi-square with Yates' correction = 13.75, relative risk = 6.86, P less than 0.001). The haplotype frequency (Hf) of Aw24-Bw52-DR2 was high in the patients with jaundice (Hf = 0.2362), while it was zero in the patients without jaundice (P less than 0.0042). These data suggest that the two groups of halothane hepatitis have different genetic backgrounds.

Adolescent↗
PubMed1985

Evaluation of sequential glucose metabolism in cerebral ischemia using a chrono-autoradiographic method.

A chrono-autoradiographic technique (sequential double label 2-deoxyglucose method) was performed to evaluate postischemic regional glucose metabolism. Using this method, two sequential autoradiograms, one immediately after the stroke and one 7-8 hr after the stroke, were obtained from the same brain slice. Comparison of the two images strongly suggested that the ischemic core and the regions adjacent to the core died, while the periphery recovered from the metabolic injury, and that postischemic metabolic abnormality itself didn't necessarily determine the fate of the ischemic tissue.

Animals↗