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Biomedical subjects

H Onodera

Publications and source records attributed to H Onodera.

At least 235 records · Page 13Linked to original sources
PubMed1990

Post-ischemic synaptic plasticity in the rat hippocampus after long-term survival: histochemical and autoradiographic study.

The hippocampus provides a suitable area in the brain for the analysis of neuronal plasticity after application of a selective lesioning technique. Using histochemistry and autoradiography, we studied synaptic reorganization in the rat hippocampus with selective CA1 pyramidal cell lesioning caused by transient forebrain ischemia after long-term survival. An autoradiographic study was performed on second messenger systems ([3H]inositol 1,4,5-trisphosphate, [3H]forskolin and [3H]phorbol 12,13-dibutyrate binding). One-hundred days after ischemia, depletion of CA1 pyramidal cells and marked shrinkage of the CA1 subfield was noted in spite of unaltered thickness of the CA3 band and of the dentate molecular layers. Although neuronal density in the CA3 region of animals killed seven days after ischemia was not different from the normal group, 78% of animals showed neuronal loss of 30-50% in the stratum pyramidale of the CA3b 100 days after recirculation. Sixty-seven per cent of animals exhibited supragranular mossy fiber sprouting in the dentate gyrus. However, CA3 neuronal loss did not correlate with mossy fiber sprouting. Succinic dehydrogenase was depleted in the CA1 100 days after ischemia, and animals with CA3 damage showed a reduction of succinic dehydrogenase activity in the CA3. In contrast to the unaltered acetylcholinesterase in the animals killed seven days after ischemia, high density bands of acetylcholinesterase activity in the stratum pyramidale of the CA1 were found to be broadened 100 days after ischemia. In the CA1 subfield, subnormal activity of [3H]phorbol 12,13-dibutyrate and [3H]forskolin binding were observed in spite of the depleted [3H]inositol 1,4,5-triphosphate binding. [3H]Forskolin binding in the hilus had increased by 62% 100 days after ischemia, although binding in the stratum lucidum of the CA3 and in the stratum moleculare of the dentate gyrus was unaltered. However, no visible supragranular increase in [3H]forskolin binding was observed. These results indicate that long-term survival after CA1 pyramidal cell depletion caused by transient forebrain ischemia induced the modulation of neuronal activity and synaptic rearrangements in the whole hippocampal formation.

Acetylcholinesterase↗
PubMed1990

Paradoxical effects of 5-FU/folinic acid on lymphokine-activated killer (LAK) cell induction in patients with colorectal cancer.

The effects of treatment with 5-FU/folinic acid on interleukin-2 related lymphocyte responses was investigated in 21 patients with advanced colorectal cancer. The treatment was not suppressive of IL-2 related lymphocyte responses. Furthermore, at certain time points in the treatment cycles the capacity to generate lymphokine-activated killer (LAK) cells from the peripheral blood mononuclear cells of these patients was significantly augmented above that observed prior to treatment. These results provide a logical basis for the design of regimens which combine two approaches, each of low individual therapeutic efficacy, to treat patients with advanced colorectal cancer in the hope of increasing clinical response rates.

Aged↗
PubMed1990

Staurosporine, a novel protein kinase C inhibitor, prevents postischemic neuronal damage in the gerbil and rat.

The protective effects of protein kinase inhibitors and a calmodulin kinase inhibitor (W-7) against ischemic neuronal damage were examined in the CA1 subfield of the hippocampus. Staurosporine, KT5720, and KT5822 were used as inhibitors of protein kinase C (PKC), cyclic AMP-dependent protein kinase, and cyclic GMP-dependent protein kinase, respectively. All test compounds were injected topically into the CA1 subfield of the hippocampus. In the gerbil ischemia model, staurosporine (0.1-10 ng) administered 30 min before ischemia prevented neuronal damage in a dose-dependent manner. However, KT5720, KT5822, and W-7 were ineffective, even at a dose of 10 ng. In the rat ischemia model, staurosporine (10 ng) also prevented neuronal damage when administered before ischemic insult, although staurosporine administered 10 or 180 min after recirculation was ineffective. These results suggest the involvement of PKC in CA1 pyramidal cell death after ischemia and that the fate of vulnerable CA1 pyramidal cells through PKC-mediated processes could be determined during the early recirculation period.

Alkaloids↗
PubMed1990

High yields of granulosa cell tumors/luteomas in F344 rat ovaries after transplacental administration of N-nitrosobis(2-oxopropyl)amine.

Ovarian tumors were induced at very high incidence in the offspring of F344 rats receiving 3 subcutaneous injections of 10 mg/kg of N-nitrosobis(2-oxopropyl)amine on the 14th, 18th and 20 days of gestation. Histologically, all ovarian tumors were of the granulosa cell tumor and/or luteoma type. Many of them consisted of large, polygonal cells with abundant eosinophilic or vacuolated cytoplasm, arranged in sheets or in a pseudo-palisaded pattern separated by thin fibrovascular stroma, and they exhibited typical luteoma morphological character. The high yields, and the similarities in morphology as well as putative hormonal influence suggest that this experimental system may serve as a good animal model for granulosa cell tumor and/or luteoma development in women.

Animals↗
PubMed1990

Calcium antagonist, adenosine A1, and muscarinic bindings in rat hippocampus after transient ischemia.

The protective roles of Ca2+ channel blockers against ischemic hippocampal damage are still debated. We used autoradiography to study postischemic L-type Ca2+ channels (1,4-dihydropyridine Ca2+ channel blocker binding), adenosine A1 receptors, and muscarinic cholinergic receptors in the rat hippocampus using [3H]PN200-110 (PN), [3H]cyclohexyladenosine (CHA), and [3H]quinuclidinyl benzilate (QNB), respectively, in 49 rats subjected to 20 minutes of forebrain ischemia. The rats were decapitated after 1 (n = 7), 3 (n = 7), 6 (n = 8), 12 (n = 7), 24 (n = 6), 48 (n = 6), or 168 (n = 8) hours of recirculation; eight control rats were sham-operated but experienced no cerebral ischemia. Reduced receptor binding preceding the delayed death of CA1 pyramidal cells was first observed in the stratum oriens of the CA1 subfield. Significant reductions in [3H]PN, [3H]CHA, and [3H]QNB bindings of this stratum compared with control were noticed after 3 (35%, p less than 0.01), 12 (31%, p less than 0.01), and 1 (10%, p less than 0.05) hours of recirculation, respectively. By 168 hours after ischemia (when the populations of CA1 pyramidal cells were depleted) all strata in the CA1 subfield had lost most of their receptor sites, and [3H]PN, [3H]CHA, and [3H]QNB bindings in the stratum oriens were decreased to 23%, 30%, and 63% of control (p less than 0.01). Although [3H]PN binding in the CA3 subfield did not change significantly during 168 hours after ischemia, the histologically intact dentate gyrus exhibited a 31% loss of binding sites compared with control (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1990

Tumor promoting effect of goitrogens on the rat thyroid.

To evaluate the mechanism of the promoting effect of goitrogens on thyroid tumorigenesis, well-known goitrogens having different pharmacologic action, i.e., thiourea, phenobarbital sodium (PB), potassium thiocyanate (KSCN), and 3,4,5,6-tetrachloro-2',4',5',7'-tetraiodo-fluorescein sodium salt (Rose Bengal B, FD&C Red No. 105) (FR105) were administered to the DHPN-initiated and non-initiated F344 male rats in the drinking water for 25 weeks. Remington's iodine deficient diet (I-def) was fed as a positive control. These goitrogens showed significant tumor promoting effect or promoting tendency on the rat thyroids. According to the changes in thyroid morphology and thyroid-related hormone titers observed in the present study, we proposed to classify goitrogens at least into 2 groups, i.e., iodine deficiency-type promoters and the iodine excess-type promoters. The former contains goitrogens inducing TSH-stimulated diffuse goiter composed of uniform follicles with activated tall follicular epithelial cells, such as thiourea, KSCN and PB, and the latter contains goitrogens inducing colloid goiter composed of a mixture of colloid-rich follicles with flat follicular cells and normal-looking follicles with cuboidal follicular cells, such as FR105. This classification may be useful for the risk assessment of goitrogens.

Animals↗
PubMed1990

Effect of nimodipine on ischemia-induced brain edema and mortality in a novel transient middle cerebral artery occlusion model.

A novel transient middle cerebral artery (MCA) occlusion model in the rat was used to evaluate the effect of nimodipine on brain edema and mortality. Nimodipine (30 micrograms/kg) administered immediately after 3 hr of transient unilateral MCA occlusion attenuated significantly the post-ischemic increase of tissue water content and partly attenuated 45Ca accumulation in the parieto-temporal cortex ipsilateral to the left MCA occlusion 3 hr after reperfusion. Nimodipine decreased the mortality rate at 6 and 9 hr after recirculation, although the survival rate at 24 hr after recirculation was not different from the control group. These results suggest that nimodipine has beneficial effects in the early phase of the reperfusion period.

Animals↗
PubMed1990

Potassium iodide inhibits neutrophil chemotaxis.

We studied the effect of potassium iodide on the chemotaxis of neutrophil in 15 healthy subjects with a modified Boyden chamber method. Orally administered potassium iodide (15 mg/kg/day for 3 days) significantly inhibited the neutrophil chemotaxis in peripheral blood. It is postulated that the therapeutic effect of potassium iodide on erythema nodosum, nodular vasculitis, and Sweet's syndrome might be mediated through the inhibition of neutrophil chemotaxis by this agent.

Adult↗
PubMed1990

[Subchronic oral toxicity study of tannic acid in F344 rats].

A 13-week subchronic oral toxicity study of tannic acid (TA) was carried out in F344 rats at dose levels of 0, 0.025, 0.05, 0.1, 0.2 and 0.4% in the drinking water, to determine appropriate dose levels for a subsequent 2-year carcinogenicity study. The rats were randomly allocated to 6 groups, each consisting of 12 males and 12 females. No animals died during the administration period. There were no significant difference in body weight gain, food consumption and organ weights between the treated and control groups, although a slight decrease in water intake was seen in the 0.4% TA treated group. No specific changes were observed in any parameters in the hematological and biochemical investigations. Histopathological examination, revealed toxic changes in the TA treated male groups, in the form of necrosis in the liver, but toxicologically it was of minor importance. From these results, it was concluded that the provable maximum tolerable dose of TA in the drinking water would be more than 0.4%. In consideration of the avoidance of drinking water, the maximum tolerable dose of tannic acid was determined to be 0.5%, when given in the drinking water.

Administration, Oral↗
PubMed1990

[Toxicity and carcinogenicity studies of musk xylol in B6C3F1 mouse].

Toxicity and carcinogenicity studies of musk xylol were examined in B6C3F1 mice. The LD50 of the chemical was considered to be more than 4000 mg/kg. In the acute toxicity and 14-day repeated-dose oral toxicity studies, tremor was observed in some animals given high doses of the chemical. In the 17-week repeated-dose oral toxicity study, musk xylol was given at dietary dose levels of 0.0375, 0.6%. During the experimental period, almost all mice given 0.3% or more died. There was no difference in the body-weight gain between the treated groups given 0.15% or less and the control group. Histologically, enlargement and irregularity of hepatocyte were found in both sexes given 0.15% or more. Based on the results, the chemical was given at dietary levels of 0 (control), 0.075 or 0.15% for 80 weeks in the carcinogenicity study. Overall tumor incidences in all treated groups of both sexes were significantly higher than those in the respective controls. Combined malignant and benign liver cell tumors increased clearly in both sexes and a significant positive trend for the occurrence of hepatocellular carcinomas was noted in males. Incidences of lung and Harderian gland tumors and lymphomas in treated groups were also slightly higher than those in controls. In addition, incidences and total numbers of malignant tumors increased significantly in treated groups of both sexes, although no dose-relation was evident. The results demonstrated that musk xylol is carcinogenic in B6C3F1 mice of both sexes when given at dose-levels of 0.075 or 0.15% in the diet for 80 weeks.

Administration, Oral↗
PubMed1990

[A simplified method for the assessment of C1 esterase inhibitor function].

From the result that the activated form of C1-s(C1-s) prolonged the kinetics of hemolysis via complement, this assay was applied to assess C1 esterase inhibitor (C1INH) function. In the kinetic assay, the complement hemolytic activity was evaluated by the time which required to cause 50% reduction of the initial turbidity of sensitized sheep erythrocytes, and was expressed as T1/2. (1) T1/2 of pooled normal human sera (p-NHS) showed dose-dependent prolongation by the addition of various amounts of C1-s. (2) Preincubation of various amounts of functionally pure C1INH with the constant amounts of C1-s inhibited dose-dependently the prolongation of T1/2 by C1-s. (3) The C1INH activity of NHS was 840 +/- 80 units/ml (n = 6) and that of the C1INH deficient serum was 80 units/ml, which were calculated from the standard curve established by the addition of various amounts of purified C1INH. This test requiring only C1-s and sensitized sheep erythrocytes is simple technically and high in sensitivity, and seems to be useful for the routine assay for C1INH function of human sera.

Animals↗
PubMed1990

[Plasma levels of complement fragments during hemodialysis in patients with chronic renal failure].

The kinetics of hemodialysis-induced leukopenia and generation of complement fragments including C3a, C5a, C4d, iC3b and Bb were investigated in 14 patients during hemodialysis using cellulose acetate (CA), cuprophan (Cu) and ethylenevinyl alcohol (EVA) membranes. A marked leukopenia in the first 15 minutes was observed in CA and Cu. Plasma C3a levels were higher in CA than in Cu and EVA. Plasma C5a levels were higher in CA and Cu than in EVA. There was a negative correlation between the white blood cell counts and plasma C5a levels at 15 minutes (gamma = -0.85, p less than 0.001). Plasma C4d levels showed no increase in all membranes. Plasma iC3b levels were higher significantly in Cu than in CA and EVA. Plasma Bb levels in the first 15 minutes increased significantly in all membranes, and furthermore continued to increase till the end of hemodialysis in CA and Cu. This study revealed that all the membranes tested activated the complement via the alternative pathway to produce Bb, iC3b, C3a and C5a. C5a was thought to take an important role in transient leukopenia. Furthermore, Bb was accumulated during hemodialysis in CA and Cu, and its biological effects on patients undergoing hemodialysis should be studied.

Adult↗
PubMed1989

Mapping second messenger systems in the rat hippocampus after transient forebrain ischemia: in vitro [3H]forskolin and [3H]inositol 1,4,5-trisphosphate binding.

Autoradiographic imaging demonstrated predominant and reciprocal localization of forskolin and inositol 1,4,5-trisphosphate (IP3) binding sites in synaptic areas in the hippocampus. We produced selective damage to the CA1 pyramidal cells in the rat hippocampus by means of transient forebrain ischemia and analyzed the alteration of the intracellular signal transduction using quantitative autoradiography of these second messenger systems. The dendritic fields (stratum oriens, radiatum and lacunosummoleculare) in the CA1 showed 20% decrease in [3H]IP3 binding activity 3 h after ischemia, when no morphological abnormalities were obvious. Thereafter, grain density in these layers decreased and half of the binding sites were lost 2 days after ischemia. By contrast, the stratum pyramidale of the CA1 showed no significant change until 2 days after recirculation. Seven days after ischemia, when CA1 pyramidal cells were depleted, all layers in the CA1 subfield lost 85% of [3H]IP3 binding sites. In the CA3 subfield, only a small and transient alteration in the [3H]IP3 binding was noticed during recirculation. Postischemic reduction of [3H]forskolin binding sites was obvious in the CA1 only 1 h after ischemia followed by loss of 50% of binding activity 7 days after recirculation. These results suggest that forskolin and IP3 binding sites are predominantly distributed on the pyramidal cells in the CA1 subfield and that marked alteration of intracellular signal transduction precedes the delayed CA1 pyramidal cell death.

Animals↗
PubMed1989

Proto-oncogene c-fos is transiently induced in the rat cerebral cortex after forebrain ischemia.

The amounts of mRNAs for proto-oncogene c-fos and structural protein beta-actin were measured in the rat cerebral cortex after transient forebrain ischemia. A transient and specific induction of c-fos mRNA was noticed in the cerebral cortex 30-90 min after ischemia followed by decline to control value. In contrast, the level of mRNA for beta-actin was not altered throughout the recirculation period examined. These results suggest specific role of c-fos gene after brain damage.

Animals↗
PubMed1989

Protein kinase C activity in the rat hippocampus after forebrain ischemia: autoradiographic analysis by [3H]phorbol 12,13-dibutyrate.

The influence of transient forebrain ischemia on the temporal alteration of protein kinase C (PKC) activity in the rat hippocampus was analyzed by quantitative autoradiography using [3H]phorbol 12,13-dibutyrate [( 3H]PDBu). As reported previously, the grain density was highest in the strata oriens and radiatum in the CA1 subfield. After transient forebrain ischemia (20 min), the [3H]PDBu binding in the CA1 subfield gradually increased during early recirculation, and became maximum 6-12 h after ischemia, when no microscopic damage of the CA1 pyramidal cells was obvious. Thereafter, grain density decreased and binding activity in the CA1 was lost by approximately 40% 7 days after ischemia, when CA1 pyramidal cells had become necrotic. This indicated a close association of phorbol ester binding sites with CA1 pyramidal cells. By contrast, [3H]PDBu binding sites were unchanged in the stratum radiatum in the CA3 throughout the recirculation, although the number of binding sites in the stratum oriens of the CA3 was decreased during early recirculation period. Seven days after recirculation, in the molecular layer of the dentate gyrus, where granule cells remained intact, [3H]PDBu binding activity increased by 33%, with a higher grain density in the inner region (supragranular layer). These results suggest that enhancement of PKC activity and/or translocation of the enzyme play an important role in the postischemic modulation of synaptic efficacy in the hippocampal formation and neuronal death of CA1 pyramidal cells.

Animals↗
PubMed1989

Merkel cell carcinoma. A successful treatment with tumor necrosis factor.

A Merkel cell carcinoma of the mandibular area in a 78-year-old woman was treated successfully by direct intratumoral administration of recombinant human tumor necrosis factor. The patient received 2.5 x 10(5) U/d of recombinant human tumor necrosis factor every other day. A total of six injections (total dose, 1.5 x 10(6) U, 0.52 mg of protein) were administered over a period of 12 days. Soon after the therapy ended, the lesion softened and decreased in size. After 1 month, only erythema was visible. The lesion had completely disappeared clinically and histologically 5 months after the local injection of recombinant human tumor necrosis factor. Neither recurrence nor metastasis has been observed for at least 12 months following the treatment. Recombinant human tumor necrosis factor is suggested to be effective for the treatment of Merkel cell carcinoma.

Aged↗
PubMed1989

The reappraisal of prognostic classifications for colorectal cancer.

The prognostic usefulness of four variables and four staging systems were evaluated by the Akaike Information Criterion (AIC) and conventional statistical tests for survival time analysis (log rank test, generalized Kruskal-Wallis test, and linear trend test), based on the data of 394 colorectal cancer patients who had been followed for more than 5 years after surgery. The four variables were the histopathologic findings of cancer penetration through the bowel wall (w), lymphnode metastasis (n), intraoperative observations of liver metastasis (H), and peritoneal dissemination (P). They were graded according to the general rules proposed by the Japanese Society for Cancer of the Colon and Rectum (JRSCCR). The staging systems were Turnbull's modification of Dukes' classification, UICC's TNM system, the Japanese classification proposed by JRSCCR, and the authors' modification of the latter. AIC calculated changing the cutoff points of survival time, as well as by reclassifying predictor variables into two categories by different levels. The results of the standard tests differed from those of AIC in the evaluation of the four variables. The former statistics showed that the intraoperative observations were of more prognostic importance than the histopathologic findings, whereas AIC revealed that the histopathologic variables have more prognostic information except for prediction of early outcome. Further analysis of the w-factor showed that survival is more drastically changed by serosal involvement or extensive extramuscular invasion than by penetration of the muscularis propria. Analysis of the n-factor indicated that a major change in survival time occurs twice, i.e., when lymphnode metastasis occurs and when it extends beyond the paracolic level. Compared with single variables, the staging system using multiple factors gives more information on both early and long-term outcomes. The authors conclude that AIC analysis provides prognostic information that cannot be obtained with conventional tests.

Colorectal Neoplasms↗