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Biomedical subjects

H Onodera

Publications and source records attributed to H Onodera.

At least 109 records · Page 6Linked to original sources
PubMed1997

Liver tumour-promoting effects of oxfendazole in rats.

To examine whether oxfendazole has tumour-promoting activity, a total of 100 male Fisher 344 rats were initiated with a single ip injection of 100 mg/kg of diethylnitrosamine (DEN) or given saline vehicle alone and starting 1 wk later given diet containing 500, 250, 100, 10 or 0 ppm of oxfendazole for 8 wk. Sub-groups of five rats each from the DEN plus 250 and 0 ppm groups were killed after wk 1 of oxfendazole treatment and the remaining animals at wk 8. At the termination relative liver weights were significantly increased in the DEN-initiated and non-initiated groups treated with 250 ppm and 100 ppm or more, respectively, compared with the corresponding controls values. Light microscopical examination showed centrilobular hepatocellular hypertrophy in all animals receiving 100 ppm or more. Electron microscopy also revealed marked increases in smooth endoplasmic reticulum in hepatocytes of the DEN plus 500 ppm group. Furthermore, induction of cytochrome P-450 (CYP) 1A1/2, 2B1/2 or 4A1 was observed in the DEN plus 100 ppm group, that of CYP 1A1/2 being most marked. A similar change in CYP 1A1/2 was seen in the DEN plus 10 ppm group. The numbers and areas of connexin 32 (Cx32)-positive spots per hepatocyte were also significantly decreased in a dose-dependent manner. Similar changes in liver weights, P-450 isozymes and Cx32 immunohistochemistry were already evident in the DEN plus 250 ppm group at wk 1. The number of placental form glutathione S-transferase positive single cells was significantly increased in the DEN-initiated groups treated with 250 ppm or more. The results therefore strongly suggest that oxfendazole exerts liver tumour promotion potential.

Administration, Oral↗
PubMed1997

Presence of ERK2 in rat retinal cells.

PURPOSE: Extracellular signal-regulated kinase 2 (ERK2) participates in the phosphorylation cascade that is activated in the an early intracellular response to various hormones and growth factors. We examined the expression and distribution of the ERK2 protein and mRNA in the rat retina before and after light exposure. METHODS: Rats were held on a 12 hr light/dark cycle and their retinas were removed and examined either just before or 2 or 30 min after light exposure. The tissue was processed for Western blotting to evaluate the presence of the protein for ERK2, and for in situ hybridization to evaluate the mRNA of ERK2. RESULTS: The Western blotting method showed a strong specific staining of a 42 kDa protein band in the retinal samples. This band corresponded to the expected size of p42 MAP kinase (ERK2). In situ hybridization histochemistry showed an intense localization of ERK2 mRNA in the outer nuclear layer (ONL), the inner nuclear layer (INL), and the ganglion cell layer (GCL) of the retina. The intensity and distribution of these signals did not differ among the animals, regardless of exposure to light. CONCLUSIONS: While ERK2 may be involved in the signal transduction system activated in retinal cells by light exposure, its precise role remains to be defined.

Animals↗
PubMed1997

Cutaneous mixed tumor containing ossification, hair matrix, and sebaceous ductal differentiation.

A 58-year-old Japanese male presented with a cutaneous mixed tumor containing ossification and hair matrix differentiation on the left side of the chin. Histologically, the tumor consisted almost exclusively of apocrine-type epithelial ductal structures and chondroid stroma. Strands and aggregation of basaloid cells which contained keratinous cystic structures with a column of shadow cells arising from basophilic basaloid cells, sebaceous duct-like structures, and ossification in the stroma were also evident. These findings suggest that cutaneous mixed tumors with ossification and hair matrix differentiation are related to both the whole hair follicle and the sweat apparatus.

Adenoma, Pleomorphic↗
PubMed1997

Anti-murine antibody response to mouse monoclonal antibodies in cancer patients.

Although development of human anti-murine immunoglobulin antibody (HAMA) is often seen in patients receiving murine antibodies, the variety of methods used for detecting HAMA makes it difficult to compare directly the HAMA responses measured by different assays. In the present study, several parameters of the HAMA response to two murine monoclonal antibodies were evaluated. The anti-sialosyl Tn antibody MLS102 and anti-CA125 antibody 145-9, which were labeled with 111In, were injected intravenously into 17 colorectal cancer patients and 11 ovarian cancer patients for immunoscintigraphy, respectively. HAMA was measured by enzyme-linked immunosorbent assay. There was no difference in baseline HAMA levels before antibody injection between the two groups. HAMA developed more frequently in ovarian cancer patients receiving the 145-9 antibody than in colorectal cancer patients receiving the MLS102 antibody (9/11 vs. 6/17, P < 0.05). No significant difference was observed in maximal HAMA levels between the two groups of patients. However, time to reach the maximal levels was delayed and the duration of the response seemed longer in ovarian cancer patients. Among 11 patients receiving the 145-9 antibody three patients became positive for HAMA more than 2 months after antibody injection and the other two had HAMA activity in their sera for more than 17 months. HAMA response was different between the two antibodies, and late onset or long duration of HAMA response against the 145-9 antibody suggests the importance of HAMA measurement in patients who receive a second injection of murine antibodies even after a long interval.

Adult↗
PubMed1997

Treatment of experimental allergic encephalomyelitis by selective removal of CD4+ T cells.

Experimental allergic encephalomyelitis (EAE) is a major animal model of human multiple sclerosis (MS). The pathogenesis of both MS and EAE directly involves CD4+ helper T cells. To remove CD4+ T cells selectively from the circulation, we designed a new column in which anti-CD4 monoclonal antibody was immobilized on the activated substance. Most of the CD4+ T cells, including pathogenic T cells, were selectively adsorbed from whole blood with a direct perfusion through the column in vitro, resulting in depletion of the antigen-specific T cell responses. A preliminary trial of ex vivo treatment with the column in EAE rats lowered the percentages of CD4+ populations but failed to alter the course of the disease, suggesting repeated treatment would be necessary to suppress the development of the disease. We conclude that this new column is potentially useful, and repeated treatment would be beneficial in MS and other CD4+ T cell dependent autoimmune diseases.

Animals↗
PubMed1997

Incidence of hepatocellular carcinoma after interferon therapy in patients with chronic hepatitis C.

We examined the effect of interferon (IFN) therapy for chronic active hepatitis (CAH) C in 207 patients by estimating the incidence of hepatocellular carcinoma (HCC) after IFN therapy using the person-years method. Statistical analysis was performed using the Mantel-Haenszel chi-square test. No HCC was detected in patients with normal serum alanine aminotransferase (ALT) levels after IFN therapy (response-effect group), and in patients with both normal serum ALT levels and hepatitis C virus (HCV)-RNA clearance after IFN therapy (complete-responder group). The incidence per 100,000 person-years in the patients with elevated serum ALT level after IFN therapy (other-effects group) were 1968 and 1624, respectively. The incidence in control patients who did not achieve IFN therapy was 901. No statistically significant differences were observed between the other-effects group, non-responder group, and the control group. Our results so far suggest that normalization of the serum ALT levels and/or HCV clearance might reduce the incidence of HCC.

Adult↗
PubMed1997

A case of Marchiafava-Bignami disease with complete recovery: sequential imaging documenting improvement of callosal lesions.

Serial CT and MR imaging findings in a 44-year-old woman with Marchiafava-Bignami disease (MBD) are reported. In the acute stage, CT studies disclosed subtle hypodensity in the splenium, and T2-weighted MR images revealed apparent high signal intensity of the splenium and the central portion of the corpus callosum. Treatment with vitamin B complex resulted in complete recovery. T2-weighted MR images obtained three weeks after admission revealed dramatic resolution of imaging abnormalities, with only faint high signal intensity remaining in the splenium. The sequential changes observed on CT and MR images provided early diagnosis of MBD and the resolution of the lesion considered as brain edema, which suggested that edema might, in addition to demyelination or necrosis, be involved in the acute progression of MBD.

Adult↗
PubMed1997

The protein tyrosine kinases of the sea urchin Anthocidaris crassispina.

In order to know the function of protein tyrosine kinases (PTKs) in the development of sea urchin embryos, we performed reverse transcription-polymerase chain reaction (RT-PCR) to obtain partial cDNA fragments for PTK genes using primers to highly conserved regions of the PTK family. A total of seven PTK sequences were identified, two of which represented receptor PTK (RTK1 and RTK2), and five of which were non-receptor PTKs (NRTK1-5). RTK1 was highly similar to FGF receptor and Ret kinase, while RTK2 showed features of the insulin receptor family. NRTK1 and 2 belonged to the Src family and could be involved in egg activation at fertilization. NRTK3 showed the features of the Btk family kinases, while NRTK4 seemed to be a member of the Syk/ZAP70 family. NRTK5 is the Csk-type kinase of the sea urchin, which is known to negatively regulate the Src family kinases. RTK1 was not detected in unfertilized eggs and was activated after blastula stage. All the other PTK genes were expressed both maternally in unfertilized eggs and zygotically after fertilization, though each gene showed distinct temporal patterns.

Amino Acid Sequence↗
PubMed1997

[Small increase of CR1 and CR3 by C5a-receptors on polymorphonuclear leukocytes in systemic lupus erythematosus].

One of the anaphylatoxins, C5a, is known to increase the expression of the complement receptors, CR1 and CR3, on PMNs which play important roles in the phagocytosis. We measured the expression of these receptors before and after the stimulation with C5a and C5a-receptors (C5aR) on PMNs in patients with systemic lupus erythematosus (SLE). PMNs from 16 patients and 11 normal controls were tested. All the patients with SLE were administered with prednisolone orally and were in the inactive stage. The CR1 expression in SLE was significantly weak (p < 0.01) before and after stimulation with 4.55 nM (50 micrograms/ml) of C5a. There was no significant difference of CR3 expression before stimulation. However, after the stimulation with C5a, the increase of CR3 on PMNs from SLE was significantly small (p < 0.01). C5aR on PMNs showed no difference between the two groups. However, the expression of C5aR was significantly suppressed in patients treated with a high dosage of prednisolone (> = 10 mg/day) compared to those with a low dosage of prednisolone (< 10 mg/day). There was no significant difference of CR1 and CR3 expression between these groups. It is concluded that the increase of CR1 and CR3 on PMNs by C5a in small in SLE, of which impaired increase is not due to C5aR on PMNs, and that the expression of C5aR is suppressed by prednisolone.

Antigens, CD↗
PubMed1997

[13-week subchronic oral toxicity study of phaffia colour in F344 rats].

A 13-week subchronic oral toxicity study of phaffia colour was performed in both sexes of F344 rats by feeding of CRF-1 powder diet containing 0, 0.2, 0.6, 1.7 and 5%. Rats were randomly divided into 5 groups, each consisting of 10 males and 10 females. No animals died during the administration period. There were no treatment-related changes in body weight gain, hematological and blood biochemical examination. No treatment-related histopathological changes were also observed in any dosed groups. These findings indicate that the treatment of 5% phaffia colour in diet for 13 weeks does not cause any toxicological changes in rats.

Administration, Oral↗
PubMed1997

[A 13-week subacute oral toxicity study of pectin digests in rats].

A 13-week subacute oral toxicity study of pectin digests was performed in both sexes of F344 rats. Water containing 0, 0.15, 0.5, 1.5 or 5% pectin digests was fed to 10 males and 10 females per group to detect its toxicity. No animals died during the administration period. Body weight gain was suppressed in male of the 5% group compared with the 0% group. Serum biochemistry analysis revealed a significant increase in BUN in male group treated with 5% and increases in CRN in male group treated with 1.5% or more. The weight of liver was significantly increased in female groups treated with 1.5% or more. Histopathologically, no treatment-related damage was observed in any dosed groups. Based on these results, the NOEL of pectin digests for both sexes in F344 rats was considered to be 0.5% in drinking water (male 545, female 657 mg/kg/day).

Administration, Oral↗
PubMed1996

Okadaic acid suppresses neural differentiation-dependent expression of the neurofilament-L gene in P19 embryonal carcinoma cells by post-transcriptional modification.

Mouse P19 embryonal carcinoma cells in aggregation culture in the presence of 10(-6) M retinoic acid followed by monolayer culture differentiate into nerve and glial cells. In this study, we demonstrated that the neurofilament-L (NF-L) mRNA and protein levels of these cells were enhanced in accordance with their retinoic acid-induced neural differentiation. Okadaic acid (OA) treatment of the cells markedly suppressed this differentiation-dependent NF-L gene expression increase and neurite outgrowth of the cells. Similar results were obtained when tautomycin was used instead of OA, suggesting that inhibition of protein phosphatase(s) is involved in the suppression of neural differentiation. OA treatment did not affect the NF-L gene transcription level, determined by the nuclear run-on transcription assay, but it did reduce the stability of both the 3.5- and 2.3-kilobase NF-L mRNAs. The expression and activity levels of protein phosphatase 2A (PP2A) and 2B (PP2B) but not protein phosphatase 1 (PP1) in P19 cells increased in accordance with the enhanced NF-L gene expression. The presence of OA in the culture medium during the course of the neural differentiation caused a reduced PP2A activity but not PP1 and PP2B activities of the cell extracts. On the other hand, both PP1 and PP2B activities but not PP2A activity of cell extracts were suppressed by the addition of cyclosporin A or FK506 in the culture medium. However, both cyclosporin A and FK506 treatments affected neither NF-L gene expression nor neurite outgrowth. These results demonstrate that the OA treatment inhibits the differentiation-dependent increase in NF-L gene expression by destabilizing its mRNAs and suggest that PP2A plays key roles in the differentiation-dependent enhanced expression of the NF-L gene and is the point of the action of OA.

Animals↗
PubMed1996

Differential regulation of activation-induced tyrosine phosphorylation and recruitment of SLP-76 to Vav by distinct isoforms of the CD45 protein-tyrosine phosphatase.

The CD45 family of transmembrane protein-tyrosine phosphatases plays a critical role in T cell activation signaling by regulating the tyrosine phosphorylation of protein-tyrosine kinases and their substrates. Multiple alternatively spliced CD45 isoforms, differing only in their extracellular domains, are differentially expressed by subsets of T cells with distinct functional repertoires. However, the physiological function of the various isoforms remains elusive. Using a novel panel of Jurkat T cell clones that uniquely express either the smallest (CD45(0)) or the largest (CD45(ABC)) isoform, we previously demonstrated CD45 isoform-specific differences in interleukin-2 secretion and tyrosine phosphorylation of Vav. We now demonstrate differential activation-induced tyrosine phosphorylation of a 76-kDa Vav-associated protein (pp76) by cells expressing distinct CD45 isoforms. The tyrosine phosphorylation of Vav and associated pp76 follow parallel kinetics. pp76 interacts with the SH2 and SH3 domains of Vav. We have identified pp76 as SLP-76, a recently cloned Grb2-binding protein. After activation with anti-CD3, CD45(ABC) transfectants demonstrate increased tyrosine phosphorylation and physical association of SLP-76 with Vav compared to transfectants expressing CD45(0). These results establish a novel physical link between Vav and SLP-76 that is differentially regulated by CD45 isoform expression.

Adaptor Proteins, Signal Transducing↗
PubMed1996

The effect of long-term post-ischemic bifemelane hydrochloride treatment on cholinergic systems in the gerbil hippocampus.

Bifemelane hydrochloride (BF) is a modulator of various neurotransmitter systems. The effect of BF on the cholinergic system was studied in the gerbil hippocampus at 100 days after ischemic damage. Marked enhancement of AChE staining was noticed in the CA1 of saline-treated animals at 100 days after ischemia, while the post-ischemic enhancement of AChE staining intensity was milder in BF-treated animals. Muscarinic receptor density was markedly decreased in the CA1 subfield after ischemia. Interestingly, BF-treated animals showed higher muscarinic receptor binding in many brain areas, particularly in the dentate gyrus. These results indicate that BF modulates cholinergic neuronal plasticity in the ischemic hippocampus after long-term survival.

Acetylcholinesterase↗
PubMed1996

Promoting effect of large amounts of vitamin A on cell proliferation of thyroid proliferative lesions induced by simultaneous treatment with thiourea.

In order to examine modifying effects of simultaneous treatment with large amounts of vitamin A (VA) and thiourea (TU) on the thyroid tumorigenesis in rats, male F344 rats were initiated with N-bis(2-hydroxypropyl)nitrosamine (2800 mg/kg body weight, single s.c. injection), and starting 1 week later received diet containing 0.1% VA (VA group), drinking water containing 0.2% TU (TU group), 0.2% TU + 0.1% VA (TU + VA group) or tap water/basal diet (control group) for 19 weeks. Serum T3 and T4 in the TU and TU + VA groups were significantly decreased as compared to the control group, while serum TSH levels were remarkably increased. The ratios of T3 and T4 decrease and TSH increase in the TU + VA group were remarkably more pronounced than in the TU group. Thyroid neoplastic lesions were only induced in the TU and TU + VA groups. The multiplicity of intracapsular follicular cell proliferative foci in the TU + VA group was significantly increased as compared to the TU group value. Cell proliferation of hypertrophic and subcapsular follicular cells, as well as in hyperplasias, and neoplasias with adenomatous growth pattern was significantly higher in the combined treatment case than after TU alone. In the liver, centrilobular hypertrophy of hepatocytes was seen in the TU and TU + VA groups, this being especially marked in the latter group. In the combined group case the affected cells were strongly positive for GST-P antibody binding. The results of the present study suggest that cell proliferation of thyroid follicular cell proliferative lesions in rats is enhanced by strong TSH stimulation with simultaneous treatment of TU and large amounts of VA.

Adenoma↗
PubMed1996

Regional difference in induction of heme oxygenase-1 protein following rat transient forebrain ischemia.

Heme oxygenase (HO) is a rate-limiting enzyme in heme catabolism, the end products of which include iron, carbon monoxide and bilirubin. We investigated the changes in expression of an inducible form, heme oxygenase-1 (HO-1), and a constitutive form, HO-2, in rat brain following 20 min of forebrain ischemia, using specific antisera for HO-1 and HO-2. HO-1 protein was remarkably induced in brain following ischemia, while the level of HO-2 protein was not noticeably affected. The level of HO-1 protein expression was maximal at 12 h, which is in good agreement with the time course of the HO-1 mRNA induction. In the cortical mantle, most of the cells expressing increased HO-1 protein were identified as pyramidal neurons and astrocytes by their shapes and locations. In hippocampal CA-2 and CA-3 subfields, prominent induction was observed in astrocytes rather than in neuronal cells. By contrast, the HO-1 protein was not detected in the CA1 subfield following the insult, although the increased level of transcripts was evident in neurons and glial cells. These results suggest that not only in neuronal cells but also in astrocytes within the CA1 subfield, there may be an impairment of protein metabolism, preceding the delayed CA1 pyramidal cell losses.

Animals↗
PubMed1996

Role of platelet-activating factor and thromboxane A2 in radical production during ischemia and reperfusion of the rat brain.

Oxygen radicals produced by activated neutrophils have been involved in brain injury during ischemia-reperfusion. Platelet-activating factor (PAF) is a candidate as one of the mediators of neutrophil activation during cerebral ischemia-reperfusion. Recent evidence indicates that PAF-induced neutrophil activation is mediated by thromboxane A2 (TXA2). To study the role of PAF and TXA2 in radical production during cerebral ischemia-reperfusion, we evaluated the effects of a PAF antagonist, Y-24180, and a TXA2 antagonist, S-1452, on radical formation in rats with 1 h middle cerebral artery (MCA) occlusion. In the present study, we employed a new electron spin resonance (ESR) method coupled with brain microdialysis. The method uses the endogenous ascorbyl radical (AR) concentration as a marker of oxygen radicals and requires no spin-trapping agents. In the vehicle controls, extracellular AR from the ischemic brain cortex decreased during MCA occlusion. Following reperfusion, AR significantly increased at 30 mm and 1 h, returned to near the basal levels at 2 h, and increased again at 24 h after reperfusion. In the rats treated with S-1452 or Y-24180, AR decreased during MCA occlusion to the same extent as in the vehicle control. However, pretreatment with Y-24180 or S-1452 significantly attenuated the increase in extracellular AR after reperfusion, while it exerted no effect on the changes in extracellular ascorbate or tissue pO2 throughout the experimental period. In conclusion, PAF and TXA2 might contribute to cerebral ischemia-reperfusion injury by increasing the generation of oxygen radicals.

Animals↗