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H Onodera

Publications and source records attributed to H Onodera.

At least 181 records · Page 10Linked to original sources
PubMed1994

[A 28-day repeated dose toxicity study of nitrobenzene in F344 rats].

To examine toxicities of nitrobenzene as part of the re-evaluation of toxicities of existing chemicals, a 28-day repeat dose toxicity study was performed in male and female F344 rats at dosages of 0, 5, 25 and 125 mg/kg/day of nitrobenzene. All rats in each group consisting of 6 males and 6 females received a daily intragastric administration of this chemical for 28 days. Additional two groups of animals exposed to 0 and 125 mg/kg/day were used for examinations of subsequent recovery for 2 weeks. One female in the 125 mg/kg group died on day 27. Decreased movement, pale skin, gait abnormality and decreases of body weights or their gains were seen in the 125 mg/kg group. Hematology revealed decreases of RBC, Hb and Ht in the 25 and/or 125 mg/kg groups. Blood biochemistry revealed increases of total cholesterol and albumin and decreases of BUN in the 25 and 125 mg/kg groups, and increases of A/G ratio in both sexes and ALT, ALP and total protein in females in the 125 mg/kg group. In the organ weight, increases of the liver, spleen, kidney weight and decreases of the testis and thymus were seen in the 125 mg/kg group. In addition, the increased liver weight was also seen in males receiving 5 mg/kg, and the increased spleen weight in both sexes receiving 25 mg/kg. Histopathology revealed spongiotic changes and brown pigmentation in perivascular region of the cerebellum, increased extramedullary hematopoiesis of the liver, brown pigmentation of renal tubular epithelium and degeneration of seminiferous tubular epithelium and atrophy of seminiferous tubule in the 125 mg/kg group, and congestion, increased brown pigmentation in red pulp and increased extramedullary hematopoiesis of the spleen and increased hematopoiesis of the bone marrow in treated groups. Findings mentioned above disappeared or tended to be decreased during or at the end of the recovery period. Although no effect-dose level was detected in this study, severe anemia and disorder of spermatogenesis and central nervous system which have been reported in the long-term toxicity study could be reconfirmed.

Administration, Oral↗
PubMed1994

[13-week subchronic oral toxicity study of isopropyl p-hydroxybenzoate in F344 rats].

A 13-week subchronic oral toxicity study of isopropyl p-hydroxybenzoate was performed in both sexes of F344 rats. CRF-1 diet containing 0, 0.25, 1.25, 2.5 or 5% isopropyl p-hydroxybenzoate was fed to 5 randomly constituted groups of animals, each consisting of 10 males and 10 females, to determine appropriate dose levels for a subsequent 2-year carcinogenicity study. No animals died during the administration period. Significant suppression of body weight gain was observed in males of the 2.5% and 5% isopropyl p-hydroxybenzoate groups, and in females of the groups treated with 1.25% or above as compared with the control group. Serum biochemistry evaluations revealed increases in gamma-GTP and total cholesterol in male groups treated with 2.5% or more and increases in gamma-GTP, ALP and BUN in female groups treated with 1.25% or more, as compared to the controls. Histopathologically, centrilobular hepatocellular swelling was observed in males treated with 2.5% or more and in females of the 5% group. In the affected populations, hepatocytes filled with small vacuoles, possibly of lipid native, were sometimes found. An increased severity of intracytoplasmic eosinophilic globule formation in the renal proximal tubular epithelia of males of the 5% group was noted. Based on these results, a dietary concentration of 1% in males or 0.5% in females was concluded to be a suitable maximum tolerable dose (MTD) of this chemical for a 2-year carcinogenicity study in rats.

Administration, Oral↗
PubMed1993

Exposure to sub-lethal ischemia failed to prevent subsequent ischemic death of dentate hilar neurons, as estimated by laminin immunohistochemistry.

The CA1 pyramidal cells and dentate hilar neurons are selectively vulnerable to forebrain ischemia. Although brief ischemia induces tolerance to subsequent ischemia in the CA1 pyramidal neurons, a protective effect of preceding brief ischemia on the dentate hilar neurons has not been established. We observed that vulnerable dentate hilar neurons were strongly laminin-immunopositive and used laminin immunohistochemistry to estimate the fate of dentate hilar neurons after ischemia. Pretreatment of brief sublethal ischemia, which effectively protects the CA1 neurons, failed to prevent the death of dentate hilar neurons. These results indicate that brief ischemia failed to induce tolerance to subsequent longer ischemia in the dentate hilar neurons.

Animals↗
PubMed1993

Alterations of Ca2+ currents and their sensitivities to Ca2+ antagonists during application and after deprivation of nerve growth factor.

The alterations in morphology and Ca2+ currents (ICa) were assessed in PC12 cells, which were (1) control (untreated), (2) treated with nerve growth factor (NGF), and (3) deprived of NGF. NGF treatment induced neuronal differentiation morphologically and increased the current density of ICa, and especially that of the omega-conotoxin (omega-CgTX)-sensitive component. NGF-deprived cells manifested morphological deterioration and did not exhibit remarkable changes in the current density of the total ICa and dihydropyridine components, whereas the omega-CgTX-sensitive ICa component was decreased significantly compared with that in NGF-treated cells. The results suggest that the total function of Ca2+ channels, including the dihydropyridine component, does not seem to be lost at the initial stage of neuronal deterioration, whereas omega-CgTX-sensitive Ca2+ channels lost their function early.

Animals↗
PubMed1993

Fetal hippocampal transplants reduce aberrant mossy fiber sprouting after CA3 pyramidal cell damage.

The CA3 pyramidal cells receive mossy fibers from the dentate granule cells, and the damage to CA3 pyramidal cells induces aberrant mossy fiber sprouting near the site of normal targets. Fetal CA1 and CA3 subregions were separately transplanted into the host CA3 subfield, where CA3 pyramidal neurons were previously damaged with kainic acid. In vitro [3H]inositol 1,4,5-trisphosphate (IP3) receptor autoradiography was used to analyze the purity of CA1 neurons. CA1 transplants had high IP3 receptor density compatible with adult CA1 subfield, while CA3 transplants had trace IP3 receptors. Animals with successful graft-host connections exhibited no aberrant mossy fiber sprouting, and mossy fibers invaded into the fetal CA3 grafts. However, animals without direct host mossy fibers-grafts connection showed aberrant mossy fiber sprouting in the CA3 subfield. These observations demonstrate that aberrant mossy fiber sprouting was suppressed by molecular cues presented on the grafted neurons and that [3H]IP3 receptor autoradiography provides an excellent marker for the identification of the CA1 pyramidal cells in grafts.

Animals↗
PubMed1993

Time-dependent expression of Na and Ca channels in PC12 cells by nerve growth factor and cAMP.

Changes in voltage-dependent Na+ (INa) and Ca2+ currents (ICa) were investigated in PC12 cells cultured without or with either nerve growth factor (NGF) or 8-Br-cAMP for 10 days. Current recordings were made in the whole-cell mode by using the conventional patch-clamp technique under voltage-clamp conditions. Membrane capacitance, an indicator of the total cell surface area, was increased 3- and 1.5-fold by 10-day treatment with NGF and 8-Br-cAMP, respectively. At the same time, NGF increased the current density of both INa and ICa approximately 25 and 2.5 times greater than in their respective controls. 8-Br-cAMP also increased both current densities; the effect on the INa was one-third less than that of NGF, while the effect on the ICa was similar to that of NGF. It was concluded that NGF has strong and moderate effects, respectively, on the expression of voltage-dependent Na+ and Ca2+ channels. 8-Br-cAMP mimicked the effect of NGF especially in Ca2+ channel expression.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1993

Neural grafting to ischemic CA1 lesions in the rat hippocampus: an autoradiographic study.

Fetal hippocampal neurons were stereotaxically transplanted to five-day-old ischemic CA1 lesions in adult rat hippocampi. The recipient brains were examined 14 or 100 days later. The grafts survived well, and transplanted cells usually formed clusters in the host CA1 subfield. In vitro receptor autoradiography was employed to map the following receptors, the ligands indicated in parentheses being used for labeling: muscarinic cholinergic ([3H]quinuclidinyl benzilate), adenosine A1 ([3H]cyclohexyladenosine), kainate ([3H]kainic acid), spirodecanone ([3H]spiperone), opioid ([3H]naloxone), and GABAA ([3H]muscimol). The receptor autoradiographic technique showed significant binding of the six ligands in all hippocampal grafts two weeks after transplantation. One hundred days following transplantation, almost all receptors, especially muscarinic cholinergic, adenosine A1 and opioid receptor bindings in grafts, had significantly increased compared to bindings two weeks after transplantation. At this time, kainate and muscarinic cholinergic receptors in grafts had increased up to the near normal level of the CA1 in the hippocampus. Interestingly, adenosine A1 receptors in the grafted side had significantly increased not only in the CA1 but also in the stratum oriens of the CA3 compared with that in the non-grafted side. The increase of [3H]quinuclidinyl benzilate binding corresponded well with the innervation of acetylcholinesterase-positive fibers at 100 days after grafting. These results demonstrate that the transplanted neurons, which showed both pre- and post-synaptic autoradiographic markers in the ischemic CA1 lesions, are able to develop their properties and express the nature of normal hippocampal neurons.

Acetylcholinesterase↗
PubMed1993

Coordinated expression of messenger RNAs for nerve growth factor, brain-derived neurotrophic factor and neurotrophin-3 in the rat hippocampus following transient forebrain ischemia.

Changes in nerve growth factor, brain-derived neurotrophic factor and neurotrophin-3 messenger RNA expression in the rat hippocampus following 20 min of transient forebrain ischemia were evaluated using Northern blot analysis and in situ hybridization histochemistry. Twelve hours after the insult, the level of nerve growth factor messenger RNA increased markedly in the granular cell layer of the dentate gyrus and by day 2 returned to control levels. The level of brain-derived neurotrophic factor messenger RNA showed a persistent and moderate increase. The highest expression of brain-derived neurotrophic factor messenger RNA was seen in the dentate granule cells on day 2 after the insult, and then the expression returned to the control levels. At 2 days post-ischemia, contents of messenger RNAs for nerve growth factor and brain-derived neurotrophic factor were reduced in the CA1 region, which may represent delayed loss of vulnerable CA1 pyramidal neurons. In contrast to brain-derived neurotrophic factor and nerve growth factor messenger RNA expression, the level of neurotrophin-3 messenger RNA declined in the CA1, the CA2 and the dentate granular layer immediately after ischemic insult. In the CA1 region, the reduced expression persisted for at least seven days, but in the dentate gyrus, neurotrophin-3 messenger RNA expression returned to the control levels after two days of post-ischemic recovery. These results suggest that nerve growth factor, brain-derived neurotrophic factor and neurotrophin-3 genes are differentially regulated and that each of their gene products may play different roles in the central nervous system under pathophysiological conditions.

Animals↗
PubMed1993

An experimental model for anaplastic astrocytomas and glioblastoma using adult F344 rats and N-methyl-N-nitrosourea.

An experimental model for induction of gliomas corresponding to human anaplastic astrocytomas and glioblastomas is reported. Eleven week old F344 and ACI rats were given 100 or 200 p.p.m. N-methyl-N-nitrosourea (MNU) solution as their drinking water for 42 weeks. Gliomas were induced at very high incidences (82.5-92.5%) in each group. Induced gliomas showed apparent evidence of morphologic malignancy by an analysis based on diagnostic criteria of human astrocytomas. All of the gliomas from the killed animals were classified histologically into subtypes according to the classification scheme used in the diagnosis of human gliomas. The majority of macrotumors more than 1 mm in diameter in both strains were diagnosed as anaplastic astrocytomas and glioblastomas. Immunohistochemically, tumor cells in these tumors were almost negative for glial fibrillary acidic protein, while ultrastructurally neoplastic astrocytes contained glial filaments. A strain difference was observed in the ratio of histological subtypes of macrotumors. In F344 rats, astrocytic tumors diagnosed as anaplastic astrocytomas and glioblastomas of an astrocytic type formed the majority, whereas glioblastomas of mixed oligo-astrocytic type predominated in ACI rats. The results indicate that MNU-administration to adult F344 rats may provide a suitable experimental model for gliomas which occur in adult humans.

Animals↗
PubMed1993

Effect of a novel thromboxane A2 receptor antagonist, S-1452, on postischemic brain injury in rats.

BACKGROUND AND PURPOSE: Arachidonate metabolites have been implicated in the development of cerebral injury after ischemia. Particular importance has been placed on the balance of thromboxane A2 and prostaglandin I2 because of its regulative activity on platelet functions and arterial tone. The purpose of the present study was to shed light on the role of thromboxane A2 in postischemic brain injury. METHODS: We evaluated the effects of S-1452, a novel thromboxane A2 receptor antagonist, on brain edema, infarct areas, and survival rate in rats with middle cerebral artery occlusion. A transient middle cerebral artery occlusion model was produced by inserting a piece of silicon-coated nylon thread into the internal carotid artery. RESULTS: The ratio of plasma thromboxane B2 to 6-keto-prostaglandin F1 alpha significantly rose at 0 hour (P < .05), 1 hour (P < .01), 3 hours (P < .05), and 12 hours (P < .05) and then nearly returned to the normal level at 24 hours after reperfusion following 1-hour occlusion. Pretreatment with S-1452 (5, 10, or 50 mg/kg PO) significantly attenuated the increase in postischemic water content in the cerebral cortex perfused by the anterior cerebral artery and the cerebral cortex perfused by the middle cerebral artery in a dose-dependent manner but slightly attenuated it in the caudate putamen 24 hours after reperfusion following 1-hour occlusion. Pretreatment with S-1452 (10 mg/kg PO) also significantly decreased the areas of infarction in the front parts of the cerebrum. The survival rate of animals after 2 hours of occlusion tended to be improved by treatment with S-1452 (10 mg.kg-1.d-1 PO), although there was no statistical significance. CONCLUSIONS: Our results suggest that thromboxane A2 is closely related to postischemic brain injury in the early phase of recirculation and that S-1452 may have a protective effect on postischemic brain injury.

6-Ketoprostaglandin F1 alpha↗
PubMed1993

Spontaneous histiocytic sarcoma with possible origin from the bone marrow and lymph node in Donryu and F-344 rats.

Ninety-five male and 96 female Donryu rats reared up to 120 wk of age and 244 male and 243 female F-344 rats used as untreated controls in 5 carcinogenicity studies were examined histopathologically to clarify the primary site of histiocytic sarcoma. Histiocytic sarcoma in Donryu rats was observed in 5 of 95 (5.3%) males and 4 of 96 (4.2%) females. In F-344 rats, 4 of 244 (1.6%) males and 3 of 243 (1.2%) females had the neoplasms. Histologically, sarcomas consisting of large pleomorphic histiocytic cells were seen in the bone marrow, liver, lymph node, spleen, and lung. Among 16 sarcomas observed, 15 had neoplastic lesions in the bone marrow, and 1 F-344 rat had the lesions only in the lymph nodes. Eleven (6 F-344 rats and 5 Donryu rats) of the 15 cases had the lesions in the liver, and 4 Donryu rats had no lesions in the liver but lesions in the lymph node and/or spleen, except for 1 case where the sarcoma occurred only in the bone marrow. Among the 11 cases with the lesions both in the liver and bone marrow, neoplastic lesions were found also in the lymph node, spleen, and/or lung, but the severity of neoplastic proliferation of these organs was not so marked as that in the bone marrow except for 2 cases. Although histiocytic sarcomas in rats are considered to originate from the liver, peritoneum, or subcutis, the present results strongly suggest that some histiocytic sarcomas in Donryu and F-344 rats may also originate from the bone marrow and lymph nodes.

Animals↗
PubMed1993

[Experimental acute lung injury in guinea pigs after aerosol challenge with sonicated Pseudomonas aeruginosa whole cells].

Acute hemorrhagic alveolitis was elicited in the lungs of guinea pigs by aerosol challenge with sonicated P. aeruginosa whole cells. Histological findings showed the severe inflammatory changes, which were characterized by the inflammatory infiltration of alveolar macrophages (AM), polymorphonuclear leukocytes (PMN) and eosinophils in the peribronchial and the alveolar space at 8 hours after the challenge. A marked increase of PMN as well as AM was noted in the bronchial alveolar lavage fluid (BALF) at 8 hours after the challenge and the increase of the numbers of AM and PMN in the BALF remained until 24 hours after challenge. The complement titer (CH50) and C3 component in the serum decreased at the early stage, and CH50 maintained low level and C3 component increased gradually. Polyethyleneglycol precipitation-complement consumption test (PEG-CC) of the BALF showed the existence of immune complexes formed in the airway after aerosol inhalation. These data suggest that the immune complexes of P. aeruginosa activate the complement system in the lungs, which is followed by the infiltration of inflammatory cells. Guinea pigs which were pretreated with cobra venom factor significantly reduced the extent of the inflammatory changes in the lungs. The results suggests that the complement system might act as an important factor of the acute lung injury in this model.

Administration, Inhalation↗
PubMed1993

[Circulating immune complexes and anti-mite specific IgG antibody in status asthmatics--effects of methylprednisolone and analysis of an anti-complementary factor].

Serial changes of circulating immune complexes and anti-mite specific IgG antibody in the peripheral blood were measured eight times in six status asthmatics treated with high doses of methylprednisolone (MPS). Circulating immune complexes decreased to normal levels three hours after MPS administration. By contrast, anti-mite specific IgG antibody increased to beyond the normal range 14 days after MPS administration. Serum levels of IgE and allergen specific IgG4 antibody did not show any significant changes. In vitro experiments, circulating immune complexes in the sampled sera were decreased by an absorption test with anti-mite specific IgG antibody, and increased by reaction with an adequate volume of mite allergen. These facts indicate that circulating immune complexes are an anti-complementary factor working on the complement system, as previously reported, and that mite allergen and anti-mite IgG antibody relate to their conformation in status asthmatics. Clinically, MPS might possess an inhibitory effects on the formation of immune complexes and/or accelerate complement-dependent solubilization of antigen-antibody complexes, so that anti-mite specific IgG antibody increased markedly in the peripheral blood.

Adult↗
PubMed1993

[A case of pulmonary tuberculosis complicated with drug toxicosis--value of shosaikoto and hochuekito as anti-allergic agents].

A clinical course of pulmonary tuberculosis was reported about adverse reaction of anti-tuberculous chemotherapy. A fifty-eight-year-old male patient was complicated with agranulocytosis induced by RFP, hepatic dysfunction and systemic eruption induced by INH, and high fever induced by SM. Adjuvant therapy with Shosaikoto and Hocheukito suppressed INH induced hepato-dermatological toxicosis moderately and suppressed SM induced high fever completely. By these anti-allergic therapy, combined chemotherapy with SM, EB, PAS and PZA became possible during more than six months, and chemotherapeutic effect was marked. This case report suggested possibility and significance of those Kampo agents against serious allergic reaction complicated with the chemotherapy for pulmonary tuberculosis.

Antibiotics, Antitubercular↗
PubMed1992

Cyclosporin A protects against ischemia-reperfusion injury in the brain.

We investigated the protective effect of Cyclosporin A (CsA) against ischemia-reperfusion injury in the brain using a transient focal ischemia model in rats. In CsA-treated rats, ischemic brain edema formation 1 day after reperfusion in the cerebral cortex perfused by the middle cerebral artery (MCA) and infarct size were decreased compared with those in olive oil treated control rats. These results suggest that CsA is beneficial in reducing ischemia-reperfusion injury, possibly by the suppression of immunological reactions.

Alanine Transaminase↗
PubMed1992

Promoting effects of 6-mercaptopurine on carcinogenesis in various organs of F344 rats.

Possible promoting effects of 6-mercaptopurine (6-MP) on carcinogenesis in various organs, including the hematopoietic system, were investigated in female F344 rats, using a 2-stage carcinogenesis model. 6-MP was given as a dietary supplement (50 ppm) for 35 weeks subsequent to wide-spectrum initiation with N-ethyl-N-nitrosourea (ENU). Various tumors were observed in the carcinogen-initiated groups. No significant influence of 6-MP on their development, including the occurrence of leukemia, was apparent. However, the incidences of some proliferative lesions in the lung, intestine and kidney were slightly higher in the ENU/6-MP group than the ENU group. Further studies may be needed on promoting effects of 6-MP, based on dose-effect relation using several 6-MP doses and/or other initiators.

Animals↗
PubMed1992

Possible involvement of interleukin-1 in ischemic brain edema formation.

To determine the contribution of interleukin 1 (IL-1) on ischemic brain edema formation, the effect of recombinant human interleukin 1 beta (rhIL-1 beta), or zinc protoporphyrin (ZnPP) as an IL-1 blocker, on brain edema was studied in rats. The animals were subjected to 60 min of ischemia in a middle cerebral artery occlusion model. Immediately after reperfusion, rhIL-1 beta at a dose of 10 ng/2 microliters, or ZnPP at doses of 1 and 10 micrograms/2 microliters were topically applied into lateral cerebroventricle. In rhIL-1 beta-treated rats, ischemic brain edema formation was significantly increased in the dorsal and ventral areas of the caudate putamen 24 h after reperfusion, compared to that of vehicle-treated control rats. Furthermore, in ZnPP-treated rats, brain edema was decreased in both caudate-putamen areas. This suggests that IL-1 plays an important role in pathogenesis for post-ischemic brain edema.

Animals↗