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Biomedical subjects

H Onodera

Publications and source records attributed to H Onodera.

At least 163 records · Page 9Linked to original sources
PubMed1994

Role of cell adhesion molecules in brain injury after transient middle cerebral artery occlusion in the rat.

Activated neutrophils appear to be directly involved in tissue injury after focal cerebral ischemia and reperfusion. Intercellular adhesion molecules-1 (ICAM-1) and CD11/CD18 integrins have been implicated in ischemia-reperfusion induced neutrophil endothelial adhesion and transmigration. We therefore investigated the roles of CD11a/CD18 (LFA-1) and ICAM-1 in cerebral ischemia-reperfusion injury by using monoclonal antibodies, WT1 (anti-CD11a), WT3 (anti-CD18), and 1A29 (anti-ICAM-1). Rats were subjected to 1 h of middle cerebral artery occlusion (MCAO). Individual antibodies were administered at a dose of 5 mg/kg intraperitoneally at 15 min before ischemia and immediately after reperfusion. Rats were killed at 24 h after reperfusion, and brain edema, neutrophil infiltration and infarct size were measured. Sustained enhancement of ICAM-1 expression on capillaries was observed up to 24 h (beginning between 1 and 3 h after reperfusion). While, leukocytes began to infiltrate into the ischemic hemisphere between 6 and 12 h after reperfusion. Treatment with individual antibodies against cell adhesion molecules reduced edema formation and infarct size in addition to neutrophil accumulation 24 h after reperfusion. These results strongly implicate the invasion of neutrophils in the development of post-ischemic brain injury, and suggest that interactions between CD11a/CD18 and ICAM-1 contribute to neutrophil infiltration into the ischemic brain.

Animals↗
PubMed1994

[Posterior proctomucosectomy and ileal pull-through reconstruction: a new restorative procedure after total proctocolectomy].

We reported a new method of restorative proctocolectomy using posterior approach and pull-through reconstruction. This method obviated transanal manipulation, a major factor causing damage to the internal sphincter, thus preventing fecal incontinence due to sphincter dysfunction. Also, temporary ileostomy was not necessary because the spout of an S-pouch was pulled down below the anal verge and its distal free end acted as a diverting stoma while the more proximal, healing zone (future anastomotic line) was kept from fecal contamination. This method was applied to a 32-year-old woman with familial polyposis coli and a 50-year-old woman with ulcerative colitis. Their bowel movements steadily decreased to three times and five times a day, respectively. There was no fecal leakage or perianal excoriation. The advantages as well as disadvantages of this method compared with the conventional techniques were discussed.

Adenomatous Polyposis Coli↗
PubMed1994

Synergistic effects of phenobarbital and thiourea on proliferative lesions in the rat liver.

To evaluate the effects of phenobarbital (PB) and thiourea (TU), alone or in combination, on proliferative lesions of the liver, thyroid and lung, male F344 rats initiated with 2000 mg/kg body weight N-bis(2-hydroxypropyl) nitrosamine (DHPN) were given diet and/or drinking water containing 0% PB/TU (group 1), 1000 ppm PB (group 2), 0.1% TU (group 3) and 500 ppm PB and 0.05% TU (group 4), from weeks 2 to 20 for 19 weeks. Group 4 showed remarkable increases in the number of hepatocellular altered foci per animal, the values being superior to the averages of groups 2 and 3. The number of thyroid proliferative lesions per animal was highest in group 3 and lowest in group 2. Lung proliferative lesions were induced in all groups, but no modifying influence on their development was evident in the combined group. The present results indicate that combined administration of PB and TU exerts synergistic enhancing effects on hepatocarcinogenesis.

Animals↗
PubMed1994

NMDA receptor (NMDAR1) expression in the rat hippocampus after forebrain ischemia.

The influence of transient forebrain ischemia on the temporal alteration of NMDA receptor (NMDAR1) mRNAs in the hippocampal formation was analysed by in situ hybridization, RNA blot and in vitro receptor autoradiography ([3H]3-((+)2-carboxypiperazin-4-yl)-propyl-1- phosphonic acid). In the CA1 subfield of the hippocampus, decrease of NMDAR1 mRNA levels was not observed until death of the CA1 pyramidal cells. Reactive astrocytes, which appear after CA1 pyramidal cell death, expressed few NMDAR1. The CA3 and dentate gyrus also showed a reduction of NMDAR1 mRNA levels 7 days after ischemia. Temporal profiles of NMDAR1 mRNA levels correlated well with those of NMDA receptor-binding in the CA1 and CA3/dentate gyrus. These results indicate that NMDA receptors in the CA1 are predominantly located on the CA1 pyramidal cells and that these receptors are preserved during early recirculation period. Histologically intact neurons in the CA3 and dentate gyrus also had marked modulation in glutamatergic neurotransmission after ischemia.

Animals↗
PubMed1994

Evaluation of melanin-related metabolites as markers of melanoma progression.

BACKGROUND: Urinary excretion of 5-S-cysteinyldopa (5-S-CD) has been used as a biochemical marker of melanoma progression. Melanomas produce not only 5-S-CD but also 5,6-dihydroxyindole-2-carboxylic acid (5,6DHI2C) as major intermediates in melanin formation. 5,6DHI2C is then metabolized to the two O-methyl derivatives, 5H6MI2C and 6H5MI2C. The aim of this study was to determine which marker in serum and urine most sensitively reflected the progression of melanoma. METHODS: Serum and 24-hour urine samples were collected and assayed serially by high-performance liquid chromatography every 1 to 4 months in 28 patients with primary or recurrent melanomas, for up to 48 months. RESULTS: Serum concentration and urinary excretion of 5-S-CD and 6H5MI2C in patients with melanoma without metastases were close to those obtained from normal subjects. Metastases developed in 9 of the 28 patients. In seven of these nine patients, serum or urinary 5-S-CD values were elevated before or at the time of clinical detection of visceral metastases. However, serum 5-S-CD was elevated significantly earlier and reflected melanoma progression better than the physical examination and/or laboratory tests, such as scintigraphy and echography. Serum 6H5MI2C values exceeded the normal range shortly before death in three patients, and urinary 6H5MI2C did not increase at any stage in most patients, therefore these metabolites did not reflect progression of disease. CONCLUSIONS: Among the four markers, serum 5-S-CD appears to be the best biochemical marker for the detection of progression of melanotic melanoma, a value of more than 10 nmol/l suggesting the presence of metastasis.

Adult↗
PubMed1994

Blocking of interleukin-1 activity is a beneficial approach to ischemia brain edema formation.

We examined the therapeutic value of an interleukin-1 inhibitor on brain edema formation using a transient focal ischemia model in rats. Rats were given an interleukin-1 blocker, or interleukin-1 release inhibitor immediately after reperfusion. In rats treated with interleukin-1 inhibitor, ischemic brain edema 1 day after reperfusion was significantly decreased compared to that of saline-treated control rats. The simultaneous application of an IL-1 release inhibitor and a lipoxygenase inhibitor showed an additive beneficial effect on brain edema formation. These findings suggest that blocking IL-1 activity ameliorates brain edema and attenuates the neuronal damage induced by focal transient ischemia in rats.

Animals↗
PubMed1994

Reduced bone marrow uptake of indium-111 labelled monoclonal antibody after radiotherapy.

Uptake of indium-111 in bone marrow is seen in patients who have received 111In-labelled antibody. We report a case in which 111In uptake was not seen in the area of previous irradiation whereas fairly high uptake was noted in other bone marrow areas. 111In-labelled monoclonal antibody, which reacts with mucin, was injected into a patient with cancer of the sigmoid colon who had received radiotherapy for uterine cervical cancer 5 years previously. Marked accumulation of the antibody was observed in the tumour. Uptake of 111In in bone marrow was also seen except in the previously irradiated pelvic region. This phenomenon supports the idea that bone marrow uptake of 111In is the result of transchelation of 111In from antibody to transferrin.

Aged↗
PubMed1994

Outcomes of 116 patients with hepatocellular carcinoma.

We studied the outcomes of 116 patients with hepatocellular carcinoma (HCC) diagnosed in our hospital between January 1980 and August 1992. The patients were divided into groups according to the principal treatment procedure. The 3-year survival rates in the patients treated by percutaneous ultrasonically guided ethanol injection (PEI), operation (hepatic resection), and transcatheter hepatic arterial embolization (TAE) were 90.9%, 53.6%, and 29.0%, respectively. None of the patients treated by one-shot injection of an anticancer agent into the hepatic artery and chemotherapy survived for more than 2 years. The outcomes of the patients treated by PEI and hepatic resection were significantly better than those of the patients treated by the other procedures. There was no significant difference when the patients were stratified according to the year of detection. The 3-year survival rate was 57.3% for 19 patients in whom HCCs were detected during clinical follow-up for chronic liver disease and 17.3% for the other 97 patients. We concluded that hepatic resection in patients with good liver function and PEI for early HCC yielded significantly better survival rates than the other procedures. Moreover, for early detection and treatment of HCC, we recommend clinical follow-up of patients with chronic liver disease.

Adult↗
PubMed1994

The prognostic role of the DNA ploidy pattern in colorectal cancer analysis using paraffin-embedded tissue by an improved method.

To assess the prognostic value of DNA ploidy in colorectal cancer, compared with the histopathological findings, paraffin-embedded surgical specimens from 330 patients who underwent resection for primary adenocarcinoma were studied using a new modified method of flow cytometry. Of these specimens, 141 were DNA diploid and 189, DNA aneuploid, among which there were 3 DNA hypodiploid lesions. Of the ten variables studied in curative resection, DNA ploidy ranked fourth in prognostic significance according to the linear trend by the chi 2 test, after nodal status, grade of cellular differentiation, and degree of invasive growth, if the DNA ploidy pattern was classified into three categories. Conversely, DNA ploidy was the sixth most significant factor if DNA hypodiploidy was included in the DNA aneuploidy. The Cox multivariate analysis showed that DNA ploidy was one of the five significant factors independently determining prognosis; however, if adjustment for the modified Dukes' stage was made by the Mantel-Haenszel test, the survival difference between the diploid and aneuploid groups did not reach a statistically significant level. Thus, we conclude that from a practical point of view, DNA ploidy is not an essential factor which must be combined with histopathological variables for a better prediction of patient outcome.

Colorectal Neoplasms↗
PubMed1994

Study on the carcinogenicity of tannic acid in F344 rats.

The carcinogenicity of tannic acid, a compound that is used as a food additive, a clarifying agent and a refining agent, was examined in F344 rats of both sexes. Tannic acid was dissolved in distilled water at concentrations of 0.25 and 0.5%. The doses were selected on the basis of results from a 13-wk subchronic study. Groups of 50 male and 50 female rats were given one of these solutions ad lib. as their drinking water for up to 2 yr. The mean body weights of the treated males were essentially comparable with those of the controls, whereas treated females had lower mean body weights than the control group. A variety of tumours developed in all groups, including the control group, but all the neoplasms were histologically similar to those known to occur spontaneously in this strain of rats, and no statistically significant increase in the incidence of any tumour was found in the treated groups of either sex. Thus, it is concluded that, under the conditions of the experiment, tannic acid has neither carcinogenic potential in F344 rats nor modifying effects on spontaneous tumour development.

Administration, Oral↗
PubMed1994

Experimental induction of pulmonary fibrosis in Syrian golden hamsters by N-methyl-N-nitrosourethane.

A range finding study for experimental induction of pulmonary fibrosis in which female Syrian golden hamsters received five subcutaneous injections of 0.8, 0.6, 0.4, 0.2 or 0 mg of N-methyl-N-nitrosourethane (MNUR) once a week or once per two weeks revealed most of the animals of the 0.8 mg group to die of acute pulmonary injury due to MNUR while typical interstitial pneumonia was induced in the 0.6 mg group. Based on these results hamsters were given five subcutaneous injections of 0.6 mg/animal of MNUR once per two weeks and then reared without any treatment for 12 weeks. Marked interstitial edema and intraalveolar infiltration of macrophages due to alveolar capillary damage were seen in treated animals at week 1, and secondary diffuse fibrotic thickening of the alveolar septa, as evidenced by increased type III collagen demonstrated immunohistochemically, was marked thereafter. The content of hydroxyproline in the lung was significantly increased from week 4. The present study indicates that lung injuries attributable to primary damage of alveolar capillaries progress to diffuse alveolar fibrosis in hamsters treated with MNUR, suggesting that this animal model might be of advantage for pathogenetic analysis of the relationship between pulmonary fibrosis and lung cancer development.

Animals↗
PubMed1994

The disposition of the tolcapone 3-O-methylated metabolite is affected by the route of administration in rats.

Catechol-O-methyltransferase (COMT) catalyses the transfer of the methyl group from S-adenyl-L-methionine (SAM) to one of the hydroxy groups of a catechol, usually the hydroxy group in position 3. COMT is present mainly in a soluble form (S-COMT) in the cytosol, but a small fraction is bound to cell membranes (MB-COMT). MB-COMT has higher affinity for the catechol substrate than does S-COMT by a factor of > 10, and high MB-COMT activity is observed in the intestinal muscle layer. The present study investigates the effect of the administration route on the disposition of the tolcapone 3-O-methylated metabolite following intravenous and oral tolcapone administration in rats. Tolcapone is a substrate for COMT although the 3-O-methylated metabolite produced has no pharmacological actions. The 3-O-methylated metabolite was eliminated very slowly following oral administration of tolcapone, and its concentration approached a plateau level, which was in contrast to the situation following intravenous administration of tolcapone. It is thought that the oral dose of tolcapone receives a high exposure to MB-COMT in the intestinal muscle layer during its absorption, and tolcapone seems to form a complex with MB-COMT having a high affinity constant (i.e. a very low Ki). The fraction of the intravenous dose of tolcapone metabolized to the 3-O-methylated metabolite at 10 mg kg-1 was 2.6%, whereas those of the oral doses, which were corrected by the bioavailability, were 5.4% for 20 mg kg-1 and 2.7% for 40 mg kg-1.

Administration, Oral↗
PubMed1994

Correlation between myeloperoxidase-quantified neutrophil accumulation and ischemic brain injury in the rat. Effects of neutrophil depletion.

BACKGROUND AND PURPOSE: Neutrophils have been implicated in the pathogenesis of ischemia-reperfusion injury. The aim of the present study was to evaluate the correlation between neutrophil infiltration into ischemic tissues and brain injury after transient focal ischemia. METHODS: We evaluated the effects of depletion of circulating neutrophils by administration of an antineutrophil monoclonal antibody (RP3) on brain edema formation, infarct size, and neutrophil infiltration (myeloperoxidase [MPO]-quantified) in rats with 1 hour of middle cerebral artery (MCA) occlusion. RESULTS: In the cerebral cortex perfused by the anterior cerebral artery (ACA area), there was a significant increase in MPO activity only 24 hours (P < .05) after reperfusion. In the cerebral cortex perfused by the middle cerebral artery (MCA area) and caudate putamen, MPO activity was significantly increased at 12 (MCA area, P < .01; caudate putamen, P < .05), 24 (MCA area, P < .05; caudate putamen, P < .01), and 72 hours (MCA area, P < .01; caudate putamen, P < .05) and returned to near-normal level by 168 hours after reperfusion. Brain MPO activity after transient MCA occlusion correlated well with the appearance of neutrophils. Depletion of neutrophils by RP3 treatment completely inhibited the increase in MPO activity in the ischemic brain after 24 hours of reperfusion. In addition, treatment with RP3 significantly attenuated the postischemic increase in brain water content at 24 hours after reperfusion. RP3 also significantly reduced the size of infarct area. CONCLUSIONS: These results indicate that the increase in brain MPO activity after transient focal ischemia virtually reflects the neutrophil infiltration and that neutrophil infiltration into the ischemic brain is implicated in postischemic brain injury.

Animals↗
PubMed1994

Thyroid proliferative lesions induced by anti-thyroid drugs in rats are not always accompanied by sustained increases in serum TSH.

To examine changes in serum TSH and determine whether the sustained excess is necessary for the development and/or progression of thyroid tumors, male F344 rats were administered drinking water containing thiourea (TU), at 0.1 or 0.05%, or sulfadimethoxine (SM), at 0.025 or 0.0125%, for one week in Experiment I. All of the treated animals showed decreased serum levels of T3 and T4 and an increased TSH. In Experiment II, male rats were given a s.c. injection of N-bis(2-hydroxypropyl) nitrosamine (DHPN:1500 mg/kg BW) and, starting one week later, received drinking water containing the same doses of TU or SM as in Experiment I for the following 20 weeks. Thyroid follicular proliferative lesions were induced in most rats treated with TU and SM. However, these treated animals did not demonstrate any consistent alterations in serum T3, T4 and TSH levels, except for the high dose TU group. The present studies thus suggest that thyroid tumors can grow even under conditions of fluctuating serum TSH levels during the progression phase, although TSH stimulation might be an absolute requirement in the early phase of tumor development.

Animals↗
PubMed1994

The mouse VLA-2 homologue supports collagen and laminin adhesion but not virus binding.

Human VLA-2 (alpha 2 beta 1) mediates cellular adhesion to collagen and laminin and cell attachment by the human pathogen echovirus 1. We report here the cloning, sequencing and functional expression of the mouse VLA-2 alpha subunit homologue. This integrin subunit is closely related to its human counterpart, with 84% amino acid identity between the human and murine proteins. Conserved structural features include an identical number of amino acids, the presence of an I domain, and identity in the number and position of N-linked glycosylation sites and putative divalent cation binding regions. Murine and human alpha 2 show 30% amino acid divergence within the cytoplasmic tail, a difference that can be detected with antisera directed against the C-terminal peptides. Functionally, mouse alpha 2 was capable of mediating cell attachment to collagen and laminin, and responded to both intra- and extracellular signals with changes in its ligand affinity. In contrast, unlike its human homologue, mouse alpha 2 did not promote binding of echovirus 1. Comparison of the primary structure of the homologues leads us to predict that echovirus 1 may bind in the region of the first two thirds of the human alpha 2 I domain, where the sequences are most divergent, whereas more conserved flanking regions, and the conserved terminal one third of the I domain, may be involved in adhesion to collagen and laminin.

Amino Acid Sequence↗
PubMed1994

[Ischemia and neuroimmunology--ischemia/reperfusion injury].

Immunological events are implicated in the brain damages after ischemia. Neutrophils have been implicated in the pathogenesis of ischemia-reperfusion injury. We showed beneficial effect of antineutrophol monoclonal antibody RP3, which depletes circulationing neutrophils, on brain edema formation and infarct size. In addition, marked increase in IL-8 concentration was detected in brain and serum during early reperfusion. Time course of IL-8 production precedes brain edema formation and neutrophil infiltration. It is reported that IL-1 induces IL-8 production and anti-IL-1 antibody significantly reduced ischemic brain damages. Neutralizing antibodies against cell adhesion molecules (ICAM-1 and LFA-1) regulate neutrophil: endothel adhesion and monoclonal antibodies against these adhesion molecules reduced the size of infarction. These results indicate that neutrophil infiltration into the ischemic brain is implicated in postischemic brain injury.

Animals↗
PubMed1994

[A case of a huge malignant lymphoma in the lesser omentum showing a long-term survival after combined treatment of surgery and VEP-THP chemotherapy].

A 33-year-old house wife with malignant lymphoma in the lesser omentum was treated with a combination of surgery and VEP-THP chemotherapy (consisting of pirarubicin, cyclophosphamide, fildesin and predonine). Complete remission has been observed by reduction surgery and subsequent chemotherapy of VEP-THP. Although mild bone marrow suppression was seen during the chemotherapy, gastrointestinal toxicity and alopecia were minimal, which led to 10 complete courses of VEP-THP regimen. The patient has been in good health 5 years after the operation with no sign of recurrence. This case indicates that even advanced malignant lymphoma may be successfully treated with a combination of surgery and proper chemotherapy.

Adult↗