Biomedical subjects

H Onodera

Publications and source records attributed to H Onodera.

At least 127 records · Page 7Linked to original sources

PubMed1996

Inflammation of the brain after ischemia.

Cytokines which promote emigration of leukocytes from the vascular lumen into the injured brain tissue are produced at the site of incipient cerebral infarction. The blood-borne invaders then accelerate the decomposition of brain cells by their toxic by-products, phagocytic action, and by the immune reaction. Recently accumulated data in our laboratories and other research facilities show that depleting the amount of circulating leukocytes or administering anti-inflammatory chemicals such as cytokine blocking agents, anti-adhesion molecule antibodies, and immunosuppressants effectively minimize the size of ischemia induced cerebral infarction. Based on the fact the leukocyte invasion of the affected brain tissue occurs 6 to 24 hours after onset of ischemia, administration of an anti-inflammatory therapy may widen the therapeutic window against stroke.

Acute-Phase Reaction↗

PubMed1996

Morphometric and immunohistochemical studies on atrophic changes in lympho-hematopoietic organs of rats treated with piperonyl butoxide or subjected to dietary restriction.

Changes observed in lympho-hematopoietic organs in rats given piperonyl butoxide may be attributable either to direct toxic effects or to undernutrition. Male F344 rats were therefore fed diet containing 2.5% piperonyl butoxide or subjected to a 64% restriction of food intake for 2 weeks. Marked inhibition of body weight gain, decreased white blood cell count, depletion of T/B lymphocytes in lymphoid tissues, hypoplasia of the bone marrow, and decreased proliferating cell nuclear antigen (PCNA) labeling indices in these tissues were seen in both dietary restriction and 2.5% piperonyl butoxide groups. The depletion of T lymphocytes in the thymus and spleen was stronger in the 2.5% piperonyl butoxide group, as indicated by PCNA labeling indices and image analysis of T lymphocyte areas of the spleen, however, the toxicological profile observed for the chemically treated group was essentially the same as for animals on the restricted diet. These results suggest that the lympho-hematopoietic findings in rats receiving 2.5% piperonyl butoxide are probably due to undernutrition resulting from a reduced food intake.

Animals↗

PubMed1996

Corticotropin-releasing factor up-regulates its own receptor mRNA in the paraventricular nucleus of the hypothalamus.

We investigated the role of CRF in regulating receptor expression in the paraventricular nucleus (PVN). First, to clarify the effect of exogenously administered CRF, 1 microgram of ovine CRF was injected into rat lateral ventricle and changes in concentration of the CRF type 1 receptor (CRF1-R) and CRF mRNA in the PVN were semiquantified after in situ hybridization. Second, we determined the effect of stress, as a stimulant of endogenous CRF secretion, on mRNA accumulation. While CRF1-R mRNA expression was low to be undetectable in the PVN of controls, both intracerebroventricular administration of CRF and restraint significantly increased CRF1-R and CRF signals in the parvocellular PVN. Thus CRF may modulate CRF production and release from the PVN, by regulating CRF1-R expression.

Animals↗

PubMed1996

Determination of interferon-alpha-producing capacity in whole blood cultures from patients with various diseases and from healthy persons.

To assess the clinical value of determination of the interferon (IFN)-producing capacity of patients, IFN production induced by Sendai virus (HVJ) in vitro was measured in cell cultures of whole blood from patients with various diseases. IFN production in patients with lung cancer, myelodysplastic syndromes, noninsulin-dependent diabetes mellitus, pulmonary tuberculosis, and asymptomatic HIV-1 infection was lower than that in healthy persons. Furthermore, periodic measurements of IFN production revealed decreasing IFN producing capacities in patients with lung cancer with progression of the tumor stage. However, increased IFN-producing capacities were observed in patients with tuberculosis after standard therapy. Further experiments showed that the main type of IFN induced in whole blood cultures was IFN-alpha, and decreased IFN production in patients did not result from a decreased number of leukocytes but rather from an impairment of cellular IFN production. The evaluation of IFN production in whole blood cell cultures may be a feasible method of assessing the impaired immune status.

Adult↗

PubMed1996

Cell proliferation and p53 protein expressions in cutaneous epithelial neoplasms.

We investigated correlations between cell proliferation, p53 overexpression, and degree of malignancy in cutaneous epithelial neoplasms. One hundred and fourteen cases of epithelial neoplasms, including seborrheic keratosis (SEB), basal cell carcinomas (BCCs), solar keratosis (SK), Bowen's disease (BD), and squamous cell carcinomas (SCCs) were examined using argyrophilic nucleolar organizer region (AgNOR) staining. In addition, immunohistochemical analysis using the Ki-67 (MIB-1) and anti-p53 (DO-7) monoclonal antibodies was performed. The ratio of tumorous to normal cells according to AgNOR staining was defined as the AgNOR rate, and the ratio of tumorous to normal cells according to Ki-67 recognition was defined as the Ki-67 rate. SCC lesions showed the highest AgNOR rate among the investigated epithelial neoplasms, followed in order by BD, BCC, SK, and SEB lesions. The Ki-67 rate was highest in BD lesions, followed in order by SK, SCC, BCC, and SEB lesions. Expression of p53 protein was highest in SK lesions. SCC is generally considered to be the most malignant neoplasm, followed in order by BCC, BD, and SK. Thus, our results suggest that the Ki-67 rate and overexpression of p53 protein do not always reflect the degree of malignancy in neoplasms.

Adult↗

PubMed1996

Sclerosing peritonitis associated with luteinized thecoma of the ovary.

A unique case of bilateral luteinized thecomas of the ovary associated with sclerosing peritonitis is reported and the clinical and pathological features of this and previously reported cases are reviewed. The patient, 52 years of age, presented with abdominal distension and diarrhea. Pelvic imaging studies revealed bilateral ovarian tumors with ascites. Total abdominal hysterectomy and bilateral salpingo-oophorectomy with adhesiotomy of the small bowel were performed. Histologically, the ovarian tumor was composed of closely packed spindle to round-shaped cells, and within the spindle cell population, lutein-like cells were scattered singly or in clusters. Mitotic counts of spindle cells revealed 12 mitotic figures (MF) per 10 high-power fields (HPF) in one part of the left ovarian tumor, but other areas of the tumor showed less than 3 MF/10 HPF on average. The lesion from the resected small bowel showed prominent fibrosis, confined to the serosa with no evidence of metastasis from the ovarian tumor. The patient has undergone adhesiotomy with partial resection of the small bowel seven times since the first laparotomy because of the recurrent small bowel obstruction. The patient has survived with complications due to short bowel syndrome for 7 years after the initial surgery and so far no recurrence or metastasis of the ovarian tumor has been identified. The case reported here also supports the idea that luteinized thecoma of the ovary associated with sclerosing peritonitis may be a distinct clinicopathologic entity, in terms of the unique association and of the unique features of thecoma; that is, bilateral, hormonally inactive and apparently benign in spite of its highly mitotic activity. Additional attention should be paid to the patient's quality of life, which is often degraded by peritoneal fibrosis and small bowel obstruction.

Female↗

PubMed1996

Ultrastructure and cell proliferative activities of karyomegalic alveolar epithelial cells in early pulmonary inflammatory lesions of Syrian golden hamsters induced by N-methyl-N-nitrosourethane.

To clarify the biological behavior of karyomegalic alveolar epithelial cells induced by N-methyl-N-nitrosourethane (MNUR) and whether these cells progress to lung tumors, female Syrian golden hamsters, 6 weeks old, were given five subcutaneous injections of 0.6 mg/animal of MNUR at two week intervals and their lungs were examined at weeks 1, 4, 8 and 12 after the termination of treatment. At week 1, in severely affected areas where marked multifocal thickening of alveolar walls due to interstitial edema and cellular infiltration was observed, some regenerative alveolar epithelial cells had abundant eosinophilic cytoplasm and gigantic bizarre nuclei. The cells were confirmed ultrastructurally to be derived from alveolar type II cells. The number of these karyomegalic epithelial cells became significantly decreased thereafter, together with the reduction of inflammatory changes. On AgNOR staining, normal alveolar epithelial cells had 1.8 +/- 0.03 black dots within their nuclei while the karyomegalic epithelial cells had 4 black dots or more, from 1 week. The PCNA labeling index of the karyomegalic epithelial cells at week 1 was 14.6 +/- 2.4, and was significantly decreased from 4 week. This epithelial cell population also displayed a wider range of DNA contents (2.1-5.5C) than normal epithelial cells (1.6-2.3C). These results suggest that karyomegalic alveolar epithelial cells may be mutant cells which occur after initiation with MNUR, but the possibility that they can act as progenitors of alveolar epithelial cell tumors was considered to be extremely low.

Animals↗

PubMed1996

[Demonstration and characterization of CD 46, membrane cofactor protein, in gastric cancer tissue].

CD 46, membrane cofactor protein, is a membrane protein which shows different expression and phenotypes with the organ or cell in the same individual. Previously, we reported that gastric CD 46 was expressed strongly in the mucosal epithelium, mucosa and endothelial cells of vessels in the submucosal layer. Western blot analysis revealed that gastric CD 46 was expressed as one broad band with a molecular weight ranging from 60 kDa to 69 kDa, which was different from that of lymphocytes. In this study, we investigated the differences in expression and characterization of CD 46 in gastric cancer obtained by surgery as compared with non-cancerous mucosa. Expression of CD 46 was greater in gastric cancer than in non-cancerous mucosa. In some cases, the phenotypes of CD 46 in gastric cancer were different from those in the non-cancerous tissue.

Aged↗

PubMed1996

[Expression and characterization of CD46, membrane cofactor protein, in human colonic mucosa].

CD 46, membrane cofactor protein (MCP), is a membrane regulatory glycoprotein of the complement system, and acts as a cofactor of factor I, which inactivates C3b and C4b bound on autologous cell membrane. MCP is present on human peripheral blood cells except erythrocytes, fibroblasts, epithelial and endothelial cells, and has been proved to exist in other organs including gastrointestinal tract recently. In this study the expression and characterization of MCP on normal human colonic mucosa was investigated. Immunohistochemical study showed MCP in the colonic mucosal epithelium. Western blot analysis revealed that MCP protein was expressed as a broad band of 50-65 kDa in all cases and another faint band of 43-46 kDa in 3 out of 20 cases, though the latter band was highly suspected to be originated from contaminated mononuclear cells in the colon.

Antigens, CD↗

PubMed1996

[Demonstration and characterization of CD46, membrane cofactor protein in the stomach].

CD46, membrane cofactor protein, is a glycoprotein widely present on the cell membranes and is different in molecular weight among organs or cells in the same individual. It acts as a cofactor of I of the complement system, which inactivates C3b bound to the autologous cells, and protects them from the attack of the complement. In this study CD46 was demonstrated in the stomach immunochemically. Gastric CD46 was expressed strongly in the mucosal epithelium, mucosa and endothelial cells of the vessels in the submucosal layer, whereas expressed weakly in the submucosa and muscle. Western blot analyses revealed that gastric CD46 was expressed as one broad band with molecular weight ranging from 60 kDa to 69 kDa, which was distinct from that of lymphocytes in the peripheral blood.

Aged↗

PubMed1996

[A case of hepatocellular carcinoma responding to oral administration of UFT].

A 77-year-old male with liver cirrhosis was admitted to our hospital for further examination and treatment of liver tumor. A tumor, which was in the S5 of liver and 7.2 cm in diameter, was revealed by ultrasonography, CT scan and MRI. The titers of serum AFP and PIVKA-II were 600 ng/ml and 3.5 AU/ml, respectively. According to the findings of imaging diagnosis and laboratory data, the patient was diagnosed as having hepatocellular carcinoma. He was treated by the oral administration of UFT (300 mg/day). Ultrasonically guided aspiration biopsy of the tumor and CT scan, which were performed ten and fourteen months after the beginning of administration of UFT, respectively, revealed the necrosis of the tumor. Twelve months later, the tumor size reduced to 1.4 cm in diameter, and the titer of PIVKA-II was reduced to the normal range. This case shows the clinical effectiveness of oral administration of UFT.

Administration, Oral↗

PubMed1996

A patient with plaque-stage mycosis fungoides has successfully been treated with long-term administration of IFN-gamma and has been in complete remission for more than 6 years.

We report the successful treatment of a patient with plaque-stage mycosis fungoides with long-term and intravenous administration of recombinant human interferon-gamma (IFN-gamma) and discuss the possible mechanisms of this therapy. A 55-year-old female patient had been resistant to existing treatments and had suffered repeated exacerbations over a 5-year period. Four weeks after initiation of 2 x 10(6) U/day of IFN-gamma, a > 10% decrease in the affected surface area was noted. Twenty-two weeks after the administration of 228 x 10(6) U of IFN-gamma, complete remission (CR) was obtained. The CR continued for 13 weeks, but this was followed by an exacerbation. The second CR was obtained after the IFN-gamma dosage was increased to 16 x 10(6) U/week. The dosage was then gradually reduced by 2-4 x 10(6) U every 2 or 3 months. She was treated with a total dose of 2814 x 10(6) of IFN-gamma. She has been followed up for more than 6 years, and there has been no recurrence of mycotic skin lesions nor any visceral involvement. During therapy, no serious side-effects were noted. Long-term administration of IFN-gamma is useful for the treatment of patients with intractable mycosis fungoides. A gradual decrease in the dose of IFN-gamma is important for maintaining remission.

Antineoplastic Agents↗

PubMed1996

[Intensity of liver tumor promotion effects in rats given repeated oral administrations of benzimidazole compounds].

Liver tumor-promoting effects of anthelminthic agents, febantel (Feb), fenbendazole (Fen) or oxfendazole (Oxf), were investigated in a rodent 2-stage carcinogenesis model. Five-week-old male F344 rats were initiated with or without diethylnitrosamine (DEN) and one week later given diet containing Fen (3600, 1800, 600, 200 or 70 ppm), Feb (2000, 1000, 500 or 100 ppm) or Oxf (500, 250, 100 or 10 ppm) for 8 weeks. Induction of CYP1A1/2 was observed in treated groups of DEN + Feb and DEN + Oxf groups, and its induction was most marked in DEN + Oxf groups. CYP2B1 and CYP4AI were also induced in these treated groups. The number or area of Cx32 positive spots per hepatocyte was significantly decreased in treated groups except for DEN + Oxf 100 ppm group, as compared to DEN alone group. GST-P positive foci was significantly increased in DEN + Fen groups treated with 1800 ppm or more, DEN + Feb groups treated with 1000 ppm Feb or more and DEN + Oxf groups treated with 250 ppm Oxf or more. These results suggest that these three compounds have liver tumor promotion effects and the promoting action in Oxf is most strong among them.

Administration, Oral↗

PubMed1996

[Modifying effects of goitrogens on the tumor development in the liver and lung of rats].

In order to investigate whether goitrogens and liver enzyme-inducers modify the tumorigenesis in the liver or lung, 6-week old male F344 rats were given single subcutaneous injection of DHPN, and starting one week later received water containing goitrogens, namely sulfadimethoxine (SDM), propylthiouracil (PTU) and potassium thiocyanate (KSCN), or an enzyme-inducer, phenobarbital (PB), for 19 weeks ad libitum. Although the number of GST-P positive foci in the liver was significantly increased in the PB group as compared to the control group, there were no significant fluctuations in the SDM, PTU and PB groups. With respect to the lung, it is suggested that SDM, KSCN and PB may enhance the lung tumorigenesis, since the multiplicities of hyperplasias of alveolar epithelia were increased in groups treated with these compounds.

Animals↗

PubMed1996

[Effect of macrophage colony-stimulating factor on complement receptors and complement regulatory proteins on human peripheral white blood cells].

The effect of M-CSF and C5a on the expression of complement-related membrane proteins on the peripheral white blood cells was investigated. M-CSF or C5a was added into the suspension of the peripheral white blood cells. The expression of the complement receptors, CD35 (CR1) and CD11b/18 (CR3), and inhibitory membrane proteins, DAF and MCP, was measured by flow cytometry. M-CSF increased CR3 on polymorphonuclear cells (PMNs) and CR1, CR3, MCP and DAF on monocytes. C5a increased CR1, CR3 and DAF on PMNs, but did not affect the expression of those on monocytes. It is concluded that M-CSF possessed the activity of increase expression of both complement regulatory proteins and complement receptors of monocytes and C5a selectively affected the expression of those on PMNs.

Adult↗

PubMed1995

Distinct isoforms of the CD45 protein-tyrosine phosphatase differentially regulate interleukin 2 secretion and activation signal pathways involving Vav in T cells.

The CD45 family of transmembrane protein-tyrosine phosphatases plays a crucial role in the regulation of lymphocyte activation by coupling activation signals from antigen receptors to the signal transduction apparatus. Multiple CD45 isoforms, generated through regulated alternative mRNA splicing, differ only in the length and glycosylation of their extracellular domains. Differential distribution of these isoforms defines subsets of T cells having distinct functions and activation requirements. While the requirement for the intracellular protein-tyrosine phosphatase domains has been documented, the physiological role of the extracellular domains remains elusive. Here we report the generation of CD45-antisense transfected Jurkat T cell clones that lack CD45 or have been reconstituted to uniquely express either the smallest, CD45(0), or the largest, CD45(ABC), isoform. These cells exhibited marked isoform-dependent differences in IL-2 production and tyrosine phosphorylation of cellular proteins, including Vav after anti-CD3 stimulation. These results demonstrate that the distinct CD45 extracellular domains differentially regulate T cell receptor-mediated signaling pathways. Furthermore, these findings suggest that alterations in CD45 isoform expression by individual T cells during thymic ontogeny and after antigen exposure in the periphery directly affects the signaling pathways utilized.

Animals↗

PubMed1995

Effect of rat thyroid proliferative lesion development by intermittent treatment with sulfadimethoxine.

To determine whether production of thyroid proliferative lesions would be enhanced by intermittent rather than continuous treatment with a goitrogen, male F344 rats initiated with N-bis(2-hydroxypropyl)nitrosamine (DHPN, 2800 mg/kg body weight, single s.c. injection) were given water containing 0.1% sulfadimethoxine (SM) for 20 weeks (group 1) or 0.1% SM for the first 8 weeks followed by 2 cycles consisting of 2 weeks withdrawal and 4 weeks retreatment with 0.1% SM (group 2). Control rats (group 3) were untreated for 20 weeks after the DHPN initiation. Serum T3 and T4 levels were significantly decreased in groups 1 and 2 compared to group 3. Serum thyroid stimulating hormone level was significantly increased in all treated groups compared to group 3. The numbers of follicular cell hyperplasias were significantly increased in group 2 compared to group 1. BrdU labeling indices for follicular cells and hyperplasias were also significantly elevated in group 2 compared to group 1. Electron microscopic examination of thyrotrophs in the anterior pituitary in groups 1 and 2 revealed dilated rough ER cisternae with intracisternal dense granules. The number of intracytoplasmic secretory granules in group 2 was moderately decreased compared to group 1. Therefore, the results of the present study suggest that it may be possible to enhance production of thyroid neoplastic lesions by intermittent treatment.

Animals↗

PubMed1995

Calcium/calmodulin-dependent protein kinase II and protein phosphatase 2B (calcineurin) immunoreactivity in the rat hippocampus long after ischemia.

Calcium/calmodulin-dependent protein kinase II (kinase II) and protein phosphatase 2B (calcineurin) immunoreactivity in the rat hippocampus was studied 100 days after ischemic damage to hippocampal CA1 pyramidal neurons. One-hundred days after ischemia, only a few CA1 pyramidal neurons survived and they exhibited enhanced kinase II and calcineurin immunoreactivity in their basal and apical dendrites. The stratum lucidum of the CA3 (mossy fiber terminal area) had enhanced kinase II and calcineurin immunoreactivity. These results suggest activity-dependent regulation and redistribution of kinase II and calcineurin after intervention in neuronal circuitry.

Animals↗