Magnetization and neutron-diffraction studies of magnetic properties of single-crystal DyMn2Ge2.
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Journal Article↗
Biomedical subjects
H Onodera
Publications and source records attributed to H Onodera.
Effects of nerve growth factor and cAMP on expression of acetylcholine receptor in PC12 cells.
The developmental change in acetylcholine-induced current (IACh) was investigated in PC12 cells cultured in the presence or absence of either nerve growth factor (NGF) or 8-Br-cAMP for 10 days. Currents were recorded in the whole-cell mode of the conventional patch-clamp technique. Morphological observations revealed that control cells do not undergo a change in morphology during culture. NGF-treated cells developed long neurites and had dense connections with other cells. 8-Br-cAMP-treated cells developed short neurites, and did not have dense connections. Control cells did not show a change in the mean density of IACh (VH = -80 mV) during the culture period. NGF-treated cells had a maximal increase in the current density of IACh at 5 days after the beginning of treatment, and did not show any further increase until 10 days. 8-Br-cAMP-treated cells had a decrease in current density during the first 6 days, but recovered to the control level after 7 days of treatment. It is concluded that maximal expression of ACh receptors occurs in the relatively early days of development, and that intracellular cAMP does not contribute greatly to their expression.
8-Bromo Cyclic Adenosine Monophosphate↗
Long-term toxicity/carcinogenicity study of calcium lactate in F344 rats.
The long-term toxicity/carcinogenicity of calcium lactate, a food additive, was examined in F344 rats. Calcium lactate was given ad lib. in the drinking-water at levels of 0, 2.5 or 5% to groups of 50 male and 50 female rats for two years. No clear toxic lesion was specifically caused by long-term administration of calcium lactate. No significant dose-related increase was found in the incidences of tumours in any organ or tissue. The results indicated that calcium lactate had neither toxic nor carcinogenic activity in F344 rats.
Animals↗
Involvement of lipid peroxidation and inhibitory mechanisms on ischemic neuronal damage in gerbil hippocampus: quantitative autoradiographic studies on second messenger and neurotransmitter systems.
We investigated, to examine the involvement of lipid peroxidation and inhibitory mechanisms, a novel lipid peroxidation inhibitor (KB-5666) and a GABAA receptor-effector (pentobarbital) on ischemic neuronal damage and the alterations in the second messenger and neurotransmitter systems in Mongolian gerbils by means of morphology and in vitro receptor autoradiography. Quantitative receptor autoradiography visualized binding sites for [3H]inositol 1,4,5-trisphosphate, [3H]forskolin, [3H]phorbol 12,13-dibutyrate, [3H]isradipine (PN200-110), [3H]N6-cyclohexyl-adenosine, and [3H]quinuclidinyl benzilate indicating binding sites for inositol 1,4,5-trisphosphate, forskolin, protein kinase C, L-type calcium channels (or dihydropyridine binding sites), adenosine A1, and muscarinic cholinergic receptors, respectively. In the morphological study, KB-5666, 10 and 50 mg/kg, i.v., 5 min before ischemia, protected against ischemic neuronal damage to the hippocampal CA1 subfield following 5 min of bilateral carotid artery occlusion in a dose-dependent manner. Pentobarbital, 30 mg/kg, i.v., 5 min before ischemia, also had a protective effect. In receptor autoradiographic studies, all receptor bindings decreased significantly in the CA1 subfield seven days after ischemia. In particular, [3H]inositol 1,4,5-trisphosphate binding in the CA1 subfield was completely lost after ischemia. [3H]Inositol 1,4,5-trisphosphate and [3H]forskolin binding decreased as early as 6 h after ischemia. In the CA3 subfield, [3H]inositol 1,4,5-trisphosphate, [3H]PN200-110, and [3H]N6-cyclohexyladenosine bindings decreased seven days after ischemia. In the dentate gyrus, [3H]inositol 1,4,5-trisphosphate binding decreased seven days after ischemia. KB-5666 and pentobarbital prevented reductions in these receptor bindings in the CA1 subfield at 6 h and seven days after ischemia. These results indicate that KB-5666 and pentobarbital protect the brain from both structural and functional damage after ischemia, and that lipid peroxidation and inhibitory mechanisms may play a pivotal role in the neuronal damage of the hippocampal CA1 subfield after ischemia.
Adenosine↗
Systematic computer-aided search of optimal staging system for colorectal cancer.
Two hundred and ninety-eight patients with curatively resected colorectal cancer were classified into 12 categories according to the depth of tumour penetration (T1-T4), and lymph node status (N0-N2). Using a computer, these categories were grouped into 2-12 stages in every possible combination, so a total of 146,975 logical classifications were generated. The optimal model was selected for each group of classifications with equal stage number, thus giving the greatest prognostic information on 5-year survival according to the Akaike criterion. The results showed that (1) 13% of the total classifications, including 85% of the 3-stage classifications, were better than the Dukes system in predicting our patients' outcomes; (2) the T-level was a stage-determinant even more important than the N-level; and (3) major changes in prognosis occurred at more advanced stages than the classical "turning points". We conclude that in order to find an optimal staging of cancer, systematic computer-aided search through all the possible classifications is necessary, using the appropriate database.
Colorectal Neoplasms↗
[Dose-response relationship of promotion by phenobarbital in rat two-stage hepatocarcinogenesis].
Investigation of the effect of various doses of phenobarbital (PB) in Experiment I (PB dose levels: 0, 38, 75, 150, 300 or 600 ppm) and Experiment II (PB dose levels: 0, 1, 4 or 16 ppm) given to male F344 rats (20 animals/group) in drinking water for 39 weeks after a single intraperitoneal injection of diethylnitrosamine (DEN) was performed using incidence of hepatic tumors and number or area of enzyme-altered foci as end-point lesions. There were no significant differences in the final body weight changes between DEN-initiated PB treatment (DEN+PB) and DEN-initiated (DEN) groups. Dose-dependent increases in the absolute and relative liver weights and in the incidence of hepatic carcinoma were found in the DEN+PB groups treated with 38 ppm PB or above 75 ppm PB or above, respectively. The numbers or areas of gamma-GTP or GST-P positive foci of the liver were increased in the DEN+PB groups treated with 38 ppm PB or above. Additional investigation of 7-ethoxycoumarin o-deethylase (7-ECDE) induction in Experiment III, 7 groups consisting of 3 animals/group being fed water containing PB (0, 1, 4, 16, 75, 300 or 1200 ppm) for 1 week after the initiation of DEN and a further 7 groups (5 rats/group) receiving the same drinking water without DEN treatment, revealed dose-dependent increases of 7-ECDE in the DEN+PB groups and PB groups treated with 16 ppm PB or above. The present studies indicate that the threshold for promotion by PB is 38 ppm.
Administration, Oral↗
[Subchronic oral toxicity study of cyanoguanidine in F344 rats].
A 13-week subchronic oral toxicity study of cyanoguanidine was performed in male and female F344 rats by feeding of CRF1 powder diets containing 0, 1.25, 2.5, 5 and 10% cyanoguanidine to determine appropriate dose levels for a subsequent 2-year carcinogenicity study. The rats were randomly allocated to 5 groups, each consisting of 10 males and 10 females. No animals died during the administration period. Inhibition of body weight gain was more marked in both sexes of the 10% group and in females of the 5% group as compared with the control group. Mean food intake in males of the groups treated with 5% or 10% and in females of the 10% group was significantly higher than that in the control group. Serum biochemical investigation revealed a higher level of serum BUN in both sexes of the 10% group. On histopathological examination, toxic changes characterized by the occurrence of intranuclear eosinophilic inclusion bodies in the proximal tubular epithelium of the kidney were observed in both sexes of the 10% group. Similar inclusion bodies were also seen in 2 out of 10 males of the 5% group. From these results, it was concluded that a level of 10% of cyanoguanidine in the diet is unequivocally toxic. A dose level, 5% cyanoguanidine, in the diet might be appropriate as a high dose for a carcinogenicity study.
Administration, Oral↗
[Twenty-eight day repeated dose toxicity test of m-nitroaniline in F344 rats].
A twenty-eight day repeated oral dose toxicity test of m-nitroaniline (m-NA) was carried out in male and female F344 rats at dose levels of 0, 15, 50 or 170 mg/kg/day. Animals of both sexes were divided into 6 groups, each consisting of 30 animals, 4 groups being used for the 28 days dosing study and the remainder for investigation of subsequent recovery. Inhibition of body weight gain, and induction of cyanosis and methemoglobinemia were observed in the highest dose groups of both sexes, but there were no animal mortalities. Testicular atrophy was evident but there was no effect on the ovaries in the same group. In addition to these findings, hemolytic anemia and increases of liver, spleen and kidney weights were also observed in both sexes in a dose-related fashion. Histologically, the highest dose group showed reduction of spermatogenesis with multinucleated giant cell formation, lipofuscin deposition mainly in the proximal renal tubules, and increases in hemosiderin deposition and extramedullary hematopoiesis in the liver. Dose-related increases in the incidence of hemosiderin deposition in the spleen, erythroid hyperplasia in the bone marrow and swelling of hepatocytes were observed in treated groups. After a 14 day recovery period, these findings were attenuated or had disappeared. Based on these results obtained under the present experimental conditions, it was concluded that m-NA induces hemolytic anemia and exerts testicular toxicity in rats and that the non-observed-effect level of m-NA is less than 15 mg/kg/day.
Administration, Oral↗
[Kinetics of immune complex deposition and influence of decomplementation on their clearance in cationized antigen induced acute serum sickness].
Using a murine acute serum sickness model caused by cationized bovine gamma-globulin (CBGG), the histological findings, accumulation of CBGG in the organs and the effect of decomplementation for the clearance of immune complex (IC) were investigated. The accumulation of CBGG increased in the lungs in the presence of anti-CBGG antibody 1 hour after injection of CBGG, but did not change in the kidneys. This suggests that CBGG forms IC in situ in the kidneys, and that circulating IC accumulates in the lungs. Decomplementation did not influence the uptake of CBGG immediately after challenge but delayed the clearance of CBGG in the kidneys, lungs, liver and spleen. A beneficial role of the complement system in the clearance of IC even for those formed in situ was recognized. Histological changes, cellular infiltration and microvascular destruction, evoked in the lungs in this experimental model immediately after challenge, were not seen in the kidney, suggesting the different modes of complement activation in these organs.
Animals↗
[The relationship between complement C3 receptors (CR1, CR3) on polymorphonuclear leukocytes and complement fragments during hemodialysis].
The expression of complement receptor type 1 (CR1) and type 3 (CR3) on polymorphonuclear leukocytes (PMNs) and generation of complement fragments, C3a, C5a, C4d, iC3b and Bb, were studied in patients during hemodialysis using cuprammonium rayon (Cu) membranes. Furthermore, the relation between the expression of CR1 and CR3 on PMNs from healthy donors and complement fragments was investigated. The expression of CR1 and CR3 on PMNs increased during hemodialysis. Plasma C3a, C5a and iC3b levels increased in the first 15 minutes and then decreased at 120 minutes of dialysis. But plasma Bb level remained high until the end of hemodialysis. Purified Bb had no effect on the expression of CR1 and CR3 on PMNs, but C5a augmented those expression in vitro. Nafamostat mesilate, an artificial proteinase inhibitor, inhibited augmentation of complement receptors on PMNs in concentration dependent fashion. C5a generated through the activation of complement was thought to take an important role in the increased expression of CR1 and CR3 on PMNs.
Aged↗
[Complement fragments in patients with bronchial asthma].
In this study, we investigated the pharmacological reactions induced by ibudilast to the complement system with the aim of clarifying the functional relation of the complement system to allergic reactions and pathology in patients with bronchial asthma. Complement hemolytic activities (CH50 and ACH50), complement profile, anaphylatoxins (C3a and C5a) and complement fragments (Bb, iC3b and C4d) were measured in 20 patients with bronchial asthma. One of antiasthmatic activities induced by ibudilast was concluded to be brought about though inactivation of the alternative complement pathway working on type III allergic reaction. Ibudilast increased the complement fragment Bb in the patients' plasma with the fairly controlled bronchial asthma. This increase in circulating Bb was suspected to be a result of inactivation of intermediate complement complexes, for example C3b.Bb.P, because the amounts in plasma of C3 and C5 showed no changes, while those of factor, B, P, H and I were decreased by ibudilast administration in patients with fairly controlled bronchial asthma. This antiasthmatic ability of ibudilast was restrained in those patients whose peripheral leukocytopenia was advanced before ibudilast administration, and in those whom ibudilast did not provoke an increase in the plasma level of iC3b, or did not prevent the serum level of C5 from increasing. In those unfairly controlled cases, enough anaphylatoxins, especially C5a might be produced to make the margination of peripheral neutrophils to the lung and increase CR3 on neutrophils binding with iC3b.
Adult↗
Protein kinase C activity in the gerbil hippocampus after transient forebrain ischemia: morphological and autoradiographic analysis using [3H]phorbol 12,13-dibutyrate.
The influence of transient forebrain ischemia on the temporal alteration of protein kinase C (PKC) activity in the gerbil hippocampus was analyzed by quantitative autoradiography using [3H]phorbol 12,13-dibutyrate (PDBu). The [3H]PDBu binding activity in the stratum oriens of the CA1 subfield increased at 6 h after ischemia, but the binding activity in this subfield decreased at 7 days after ischemia. In contrast, the [3H]PDBu binding activity increased in the molecular layer of the dentate gyrus at 7 days after ischemia. Pre-treatment of pentobarbital prevented an increase in the [3H]PDBu binding activity in the stratum oriens of the CA1 subfield at 7 days after ischemia. These results indicate the possibilities that PKC may play a pivotal role in the post-ischemic neuronal damage in the hippocampal CA1 subfield.
Animals↗
The regional difference of neuronal susceptibility in the dentate gyrus to hypoxia.
The effects of hypoxia on neuronal activity in dentate gyrus granule cells were studied in submerged guinea pig hippocampal slices. In all regions of the dentate gyrus granule, the amplitude of the population spike recorded from the dentate granule cell layers, in response to electrical stimulation of the perforant path, decreased during hypoxia and recovered during reoxygenation. However, the ventral dentate gyrus granule cells (upper blade) were more susceptible to hypoxia than the dorsal ones (lower blade), indicating regional differences of neuronal susceptibility to hypoxia in the dentate gyrus.
Action Potentials↗
Ca2+/calmodulin-dependent protein kinase II immunoreactivity in the rat hippocampus after forebrain ischemia.
The influence of transient forebrain ischemia on the temporal alteration of Ca2+/calmodulin-dependent kinase II (CaM kinase II) in the rat hippocampus was analysed by the immunohistochemical method using antigen-affinity purified polyclonal antibodies against CaM kinase II of rat brain. Six to twenty-four hours after ischemia, CA1 and CA3 pyramidal cells, and dentate granule cells lost CaM kinase II immunoreactivity in neuronal perikarya, although immunoreactivity in the dendritic fields was preserved. The recovery of immunoreactivity of the CA3 pyramidal cells and dentate granule cells was noted 3 days after recirculation. Seven days after ischemia, immunoreactivity in the CA1 subfield was greatly reduced. These results suggest that CaM kinase II molecules in the CA1 subfield are preferentially located on the CA1 pyramidal cells and that CaM kinase II plays a critical role in the reconstruction of neuronal cytoskeleton and neuronal networks damaged by ischemic insult.
Animals↗
Two-year carcinogenicity study of 6-mercaptopurine in F344 rats.
The carcinogenicity of 6-mercaptopurine (6-MP), an anticancer drug, was examined in F344 rats of both sexes, administered the chemical at dietary levels of 0 (control), 25 ppm or 50 ppm for 2 years. Many tumors developed in all groups including the control group, the organ distribution and histological types being similar to those reported for spontaneous lesions. In males, there was no significant increase in the incidence of any tumor in the treated groups over that in the control group. In females, however, positive trends were noted in the occurrence of C-cell tumors, pheochromocytomas, uterine adenocarcinomas and gliomas, and the incidences of C-cell tumors and pheochromocytomas in the 50 ppm group were significantly higher than the values in the respective control group. In addition, the total numbers of malignant tumors increased significantly in the female 50 ppm group. However, most of the tumors demonstrating increase are frequently observed spontaneous lesions in this strain of rats, and their incidences in the present female control group were lower than in our historical data. In addition, there were no significant differences in the incidences of preneoplastic changes and induction times for the above-listed tumors between the female control and the 50 ppm groups. These results thus indicated that while the carcinogenic potential of 6-MP can not be precluded, it can be only very weak or marginal, after continuous administration in the diet at the 50 ppm level for 2 years. The leukemogenic action of 6-MP was negative under the present experimental conditions.
Animals↗
Spontaneous uterine adenocarcinomas in aged rats and their relation to endocrine imbalance.
In addition to spontaneous uterine endometrial adenocarcinomas at a high incidence (35.1%), development of endometrial hyperplasia/adenoma was also frequently detected in rats of the Donryu strain. The total yield of all observed proliferative endometrial lesions was very high (60.6%). The tumors arose commonly in the uterine horn of aged rats. Histologically, most demonstrated glandular structures, consisting of cuboidal or columnar cells with weak eosinophilic or basophilic cytoplasm and large nuclei. In about half of the animals with adenocarcinomas, metastasis to remote organs such as the lung was observed. Histological examination of the ovary and vaginal epithelium revealed ovarian cysts, atrophy of the ovary and cornification of the vaginal epithelium more frequently in rats with endometrial carcinomas than in animals without tumors. These findings indicate that adenocarcinoma development in Donryu rats is associated with endocrine imbalance [increased serum estrogen: progesterone (E2:P)ratios]. By comparative investigation of strain differences, it was confirmed that irregular estrous cycles began earlier with higher incidence in Donryu rats than in F344 rats, a low-incidence strain. Histological findings of the ovary and vaginal epithelium also suggested relatively increased estrogen levels in Donryu rats compared to F344 rats. Estimated plasma values of gonad steroids showed that the E2:P ratio in Donryu rats at 12 months of age was about five times that in F344 rats. These results therefore indicate that hormone imbalance, particularly an increased E2:P ratio, may play an important role in the spontaneous occurrence of endometrial adenocarcinoma in Donryu rats.
Adenocarcinoma↗
Lack of toxicity/carcinogenicity of monosodium succinate in F344 rats.
The toxicity/carcinogenicity of monosodium succinate, a food additive, was examined in F344 rats. The oral LD50 was greater than 8 g/kg body weight. In a 13-wk subchronic oral toxicity study, the only toxicological finding was suppression of body-weight gain in groups given greater than or equal to 2.5% monosodium succinate in the drinking-water. Histological examination revealed no toxic lesions specifically caused by the compound in any organs of any of the treated rats. The maximum tolerated dose was determined to be 2-2.5% on the basis of body-weight depression. In a long-term (2-yr) toxicity/carcinogenicity study, monosodium succinate was given ad lib. in drinking-water (distilled water) at levels of 0, 1 or 2% to groups of 50 male and 50 female rats. No toxic lesion specifically caused by long-term administration of monosodium succinate was detected. No dose-related increase was found in the incidences of tumours in any organ or tissue except for C-cell tumours of the thyroid gland of females. The incidence of these tumours in females given the 2% dose was higher than that in controls but not significantly so, and a positive trend for this tumour was noted in females. C-Cell tumour is one of the most commonly observed spontaneous tumours in ageing female rats of this strain and occurs at a variable incidence. There was no difference between the female control and treated groups in the incidence of preneoplastic change of the thyroid gland. Furthermore, the incidence of C-cell tumours in the female control group was lower than that in our historical controls. It is concluded that the increase in C-cell tumours in the female high-dose group and the detection of a positive trend for this tumour in females were probably a function of experimental variability and were not related to treatment. The results indicate that monosodium succinate had neither toxic nor carcinogenic activity in F344 rats when it was given continuously at levels of 1 or 2% in the drinking-water for 2 yr.
Animals↗
Long-term toxicity/carcinogenicity of musk xylol in B6C3F1 mice.
The long-term toxicity/carcinogenicity of musk xylol, a synthetic nitro musk, was examined in B6C3F1 mice of both sexes. Musk xylol was administered at dietary levels of 0 (control), 0.075 or 0.15% for 80 wk. The overall tumour incidences in all treated groups of both sexes were significantly higher than those in the corresponding controls. Combined malignant and benign liver cell tumours were clearly increased in both sexes, and in males a positive significant trend was also noted for the occurrence of hepatocellular carcinomas. In males the incidence of Harderian gland tumours was also significantly greater in treated groups than in controls. Some other neoplasms, such as lung tumours in both sexes and Harderian gland tumours and lymphomas in females, occurred in greater numbers in the treated groups, although the differences were not statistically significant in comparison with the controls. In addition, the incidences and total numbers of malignant tumours were significantly increased in treated groups of both sexes, although the increases were not dose dependent. The results demonstrated that musk xylol is carcinogenic in B6C3F1 mice when given at dose levels of 0.075 or 0.15% in the diet for 80 wk.
Administration, Oral↗