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Biomedical subjects

S Yano

Publications and source records attributed to S Yano.

At least 253 records · Page 14Linked to original sources
PubMed1997

Case of propylthiouracil-induced vasculitis associated with anti-neutrophil cytoplasmic antibody (ANCA); review of literature.

A 39-year-old Japanese woman had been receiving propylthiouracil for 5 years for hyperthyroidism when she developed myalgia, scleritis, proteinuria, fever, and inflammation of the nose. Examination of a renal biopsy specimen showed focal segmental necrotizing glomerulonephritis. Indirect immunofluorescent staining showed a highly positive perinuclear pattern of anti-neutrophil cytoplasmic antibody (ANCA) in her serum. Enzyme-linked immunosorbent assay (ELISA) of the ANCA showed positivity for anti-proteinase 3, anti-myeloperoxidase, anti-leukocyte elastase, and anti-lactoferrin, but anti-cathepsin G and anti-lysozyme were negative. Because ELISA showed the titer of anti-leukocyte elastase antibody to be markedly elevated, we challenged this data by performing dot blot analysis. The patient's serum reacted with the native form, but not with denatured leukocyte elastase. Propylthiouracil-induced vasculitis was suspected. Symptoms abated within 2 weeks and all values of ANCA were reduced after the drug was withdrawn. Vasculitis is a rare side-effect of propylthiouracil therapy. Recently it was reported in association with ANCA. We present the findings of this patient and compare them with those described in 19 published cases of propylthiouracil-induced vasculitis associated with ANCA.

Adult↗
PubMed1997

[The significance of p21 expression in gastric cancer].

We examined the expression of p53, p21, cyclin D1, E, and PCNA in 75 cases of gastric cancer by immunohistochemical study and the expression of p21 RNA in cases by in situ hybridization. The rate of stage III, IV cases of p53(+) p21(-) group was significantly higher than that of any other groups. The apportinately 3-year survival rate of p53(+) p21(-) group was significantly lower than either that of p21(+) p53(-) or p53(-) p21(-) group. The 3-year survival rates of positive cases were significantly lower than those of negative cases on both cyclin D1 and E. The positive rate of cyclin E of the p53(-) p21(+) group was significantly lower than that of the p53(+) p21(-) group. The average PCNA Labeling. Index (LI) of the p53(+) p21(-) group was significantly higher than that of the p53(-) p21(+) group. The 3-year survival rate of cases with expression of p21 RNA was higher than that of cases without p21 RNA. Average PCNA L1 of cases with expression of mutant-type p53 was high and the number of poor prognostic cases in cases with expression of mutant-type p53 was large. In contrast, the average PCNA LI of cases with expression of p21 was low and the number of good prognostic cases with expression of p21 was large. These results suggest that p21 suppresses synthesis of DNA via cyclin E and PCNA.

Cyclin D1↗
PubMed1997

Model of malignant pleural effusion of human lung adenocarcinoma in SCID mice.

Malignant pleural effusion (PE) is a frequent problem in lung cancer. In this study, we established a model of malignant PE of human adenocarcinoma cells, PC-14, in SCID mice. Intravenously injected PC-14 cells formed colonies in the lungs as early as week 4 after tumor inoculation, and produced bloody PE in all recipient SCID mice by week 8. Pretreatment of SCID mice with anti-mouse IL-2 receptor beta chain antibody (TM-beta 1) to deplete natural killer (NK) cells markedly promoted the production of bloody PE and metastases to multiple organs, such as the lungs, liver, kidneys, and lymph nodes 4 weeks after tumor inoculation. Histological studies indicated that PC-14 cells formed colonies in the lungs, and then invaded the pleura and spread to the pleural cavity. To establish cell lines with a high potential to produce PE, we harvested PE, expanded the tumor cells in vitro, and injected them into SCID mice again. By four in vivo selection cycles in this way we obtained PC-14-PM4 cells, which produce lung metastases and PE earlier than PC-14 cells. The survival of SCID mice inoculated with PC-14-PM4 cells was significantly shorter than that of mice inoculated with PC-14 cells. The expressions of adhesion molecules, such as CD44, CD49d, ICAM-1, and MHC class I, on PC-14-PM4 cells tended to increase compared with PC-14 cells. These changes of adhesion molecules seem to be one of possible mechanisms involved in higher metastatic potential of PC-14-PM4 cells. PE models with PC-14 and PC-14-PM4 cells should be useful for biological and preclinical studies on malignant PE produced by human lung cancer.

Adenocarcinoma↗
PubMed1996

An increase of acidic isoform of catalase in red blood cells from HIV(+) population.

A systemic oxidative stress of HIV (+) individuals has been recognized from a low glutathione level and a high level of inflammatory cytokines such as TNF alpha. Previously, we demonstrated that the catalase enzyme activity in HIV (+) population is significantly altered depending on the cell types; the level was significantly high in red blood cells while the enzymes in white blood cells were remarkably low (Res Commun Subs Abuse 16: 161-176, 1995). In this study, we further characterized the difference in RBC catalase molecules between HIV (+) and control population. We have found that RBC from HIV (+) population, whether they were asymptomatic or symptomatic, contained a significantly elevated catalase protein accompanied by the enzyme activities, and that the majority of the elevated protein were acidic pI of the molecules with an identical subunit mass of approximately 60 KDa. These results suggest that catalase is induced prior to and/or during erythroid differentiation lineage in HIV (+) population as a somatic defense to respond and compensate for a systemic oxidative stress and for an anemic condition.

Adult↗
PubMed1996

Regulation of CCAAT/enhancer-binding protein family members by stimulation of glutamate receptors in cultured rat cortical astrocytes.

Regulation of mRNA levels, DNA binding activities, and phosphorylation of CCAAT/enhancer-binding protein (C/EBP) family members by stimulation of glutamate receptors were studied in cultured rat cortical astrocytes. Indirect immunofluorescence and immunoblot analyses with specific antibodies to C/EBP family members revealed that both C/EBPbeta and C/EBPdelta but not C/EBPalpha are expressed in the nuclei of astrocytes. After exposure to glutamate, C/EBPbeta mRNA levels increased within 10 min, reached the maximal level at about 1 h, and returned to the basal level within 6 h. In contrast, C/EBPdelta mRNA levels decreased by 6 h and were recovered within 12 h. These changes in mRNA levels were accompanied by an increase and a decrease in proteins for C/EBPbeta and C/EBPdelta, respectively. Elevation of C/EBPbeta mRNA levels by glutamate treatment required an increase in intracellular Ca2+ concentration and depended on activations of protein kinase C and calmodulin-dependent protein kinases. Gel mobility shift analysis using nuclear extracts from the glutamate-treated cells showed increases in C/EBP site binding activities 2 h after the exposure to glutamate. Moreover, glutamate stimulated phosphorylation of C/EBPbeta in 32P-labeled astrocytes in a Ca2+-dependent manner. These results suggest that glutamate regulates functions of C/EBP family members in brain astrocytes through changes in mRNA levels of C/EBPbeta and C/EBPdelta as well as through phosphorylation of C/EBPbeta.

Animals↗
PubMed1996

T helper 2 cytokines differently regulate monocyte chemoattractant protein-1 production by human peripheral blood monocytes and alveolar macrophages.

Th2 cytokines, such as IL-4, IL-10, and IL-13, suppress proinflammatory cytokine production by monocytes/macrophages. Since monocyte chemoattractant protein-1 (MCP-1) is presumed to play an important role in monocyte recruitment and activation during inflammatory and immune responses, we examined here the effects of these Th2 cytokines on MCP-1 production by human blood monocytes and alveolar macrophages. Unstimulated, highly purified blood monocytes did not produce MCP-1 spontaneously, while LPS treatment induced the production of MCP-1 and its mRNA expression. All Th2 cytokines tested suppressed LPS-induced MCP-1 production and its mRNA expression, although the suppressive effect of IL-13 was weaker than that of IL-4 or IL-10. In contrast, IL-10, but neither IL-4 nor IL-13, induced unstimulated peripheral blood monocytes to produce biologically active MCP-1 protein within 4 h, reaching a maximal level at 12 h. IL-10-induced MCP-1 production was reduced by pretreatment of IL-10 with anti-IL-10 Ab, negating the involvement of contaminated endotoxin. Moreover, IL-10 induced MCP-1 mRNA expression in unstimulated monocytes, independent of de novo protein synthesis. Furthermore, human alveolar macrophages produced MCP-1 spontaneously, and the production was inhibited by IL-4 or IL-13, but was augmented by IL-10. These findings suggest that IL-10 regulates MCP-1 production by monocytes/macrophages in a different way from other Th2 cytokines, such as IL-4 and IL-13, and contributes to host defense responses.

Cells, Cultured↗
PubMed1996

Novel metastasis model of human lung cancer in SCID mice depleted of NK cells.

Metastasis is a critical problem in the treatment of human lung cancer. Thus, a suitable animal model of metastasis of human lung cancer is required for in vivo biological and preclinical studies. In this study, we tried to establish a suitable model for this, using SCID mice. Neither human SCLC H69/VP cells (5 x 10(6)) nor squamous-cell carcinoma RERF-LC-AI cells (1 x 10(6)), injected through a tail vein, formed metastases in untreated SCID mice. Pre-treatment of SCID mice with anti-asialo GM1 serum resulted in only a few metastases of H69/VP cells, but pre-treatment with anti-mouse IL-2 receptor beta chain Ab (TM-beta 1) resulted in numerous lymph-node metastases 56 days after tumor inoculation. H69/VP-M cells, an in vivo-selected variant line, formed significant numbers of lymph-node metastases even in SCID mice pre-treated with anti-asialo GM1 serum. SCID mice depleted of NK cells by treatment with TM-beta 1 showed different patterns of metastasis when inoculated intravenously with the 2 different human lung cancer cell lines (H69/VP and RERF-LC-AI cells): H69/VP cells formed metastases mainly in systemic lymph nodes and the liver, whereas RERF-LC-AI cells formed metastases mainly in the liver and kidneys, with only a few in lymph nodes. A histopathological study showed that the metastatic colonies consisted of cancer cells. The numbers of metastatic colonies formed by the 2 cell lines increased with the number of cells inoculated. TM-beta 1 treatment of SCID mice efficiently removed NK cells from peripheral blood for at least 6 weeks, whereas, after treatment of the mice with anti-asialo GM1 serum, NK cells were recovered within 9 days. These findings suggest that NK-cell-depleted SCID mice may be useful as a model in biological and pre-clinical studies on metastasis of human lung cancer.

Animals↗
PubMed1996

Biochemical characterization of a new disintegrin, flavostatin, isolated from Trimeresurus flavoviridis venom.

We biochemically characterized a new disintegrin, flavostatin, isolated from Trimeresurus flavoviridis venom. Flavostatin inhibited ADP-, collagen-, and thrombin receptor agonist peptide-induced platelet aggregation in human platelet-rich plasma (IC50 range: 59 to 111 nM) and blocked the binding of biotinylated human fibrinogen to purified GPIIb/IIIa with an inhibitory potency 31,000-fold higher than that of Arg-Gly-Asp-Ser (RGDS). Flavostatin strongly inhibited high-shear-stress-induced platelet aggregation in platelet-rich plasma (PRP) with an IC50 value of 188 nM. Fluorescein isothiocyanate (FITC)-conjugated flavostatin saturably bound to unstimulated and ADP-stimulated washed platelets with high affinity (Kd values: 38 and 21 nM, respectively); the corresponding number of binding sites was 86460 and 79192 per platelet. In competition experiments with several glycoprotein IIb/IIIa antagonists, the binding of FITC-conjugated flavostatin to platelets was completely inhibited by ReoPro, triflavin, TP9201, MK383 and GR144053, but not by YM207, YM337 and B6A3.

Amino Acid Sequence↗
PubMed1996

Neurogenic stimulation of gastric acid secretion by the Na+, K(+)-ATPase inhibitor ouabain in mouse isolated stomach.

1. We have previously found the stimulatory effect of ouabain on gastric acid secretion. In the present study, we further studied the ouabain-induced acid secretion in mouse isolated stomach. 2. In the resting stomach preparation, ouabain produced a transient increase in basal acid secretion, which was followed by a fall to the level lower than the initial basal level. 3. The ouabain-induced acid secretion was abolished by tetrodotoxin or atropine, and was partially inhibited by hexamethonium or famotidine. High K+ solution potentiated the ouabain stimulation. 4. Endogenous ouabain has been recently identified in plasma of humans, but the physiological roles of this compound have not yet been defined. The present study in mouse isolated stomach showed that ouabain induced a transient increase in gastric acid secretion through the release of endogeneous acetyl-choline, and subsequently inhibited acid secretion. It therefore seems likely that endogeneous ouabain modifies gastric acid secretion in physiological and pathological conditions.

Animals↗
PubMed1996

Comparison of the antiplatelet agent potential of the whole molecule, F(ab)2 and Fab fragments of humanized anti-GPIIb/IIIa monoclonal antibody in monkeys.

1. The potential antiplatelet agent use of the whole molecule, F(ab)2 and Fab fragments of humanized antiglycoprotein (GP) IIb/IIIa monoclonal antibody, hC4G1, were investigated in rhesus monkeys. 2. Fab completely inhibited platelet aggregation 1 hr after an i.v. bolus administration of 1 mg/kg without a decrease in platelet count or prolongation of bleeding time, and the duration of inhibition was much shorter than that of F(ab)2. 3. These results suggest that the Fab fragment of hC4G1 may be a more useful antiplatelet agent in patients with acute thromboembolic diseases than the whole molecule or F(ab)2 fragments.

Animals↗
PubMed1996

Palliative steroid therapy and serum interleukin-6 levels in a patient with lung cancer.

We report a patient with metastatic adenocarcinoma of the lung who had a detectable serum interleukin-6 (IL-6) level. Despite systemic chemotherapy, the tumor progressed, with elevation of serum IL-6 level. Palliative steroid therapy with 20 mg/day of prednisolone resulted in the decline of serum IL-6 level and, simultaneously, improved anorexia and oral intake. Although there was no weight gain or improvement in hypoalbuminemia, these results suggest that steroids may suppress the abnormal production of IL-6 in cancer patients and that this action affects symptoms. Further study is warranted to clarify the role of IL-6 in tumor-related symptoms and the effect of steroid therapy in relation to IL-6 production in cancer patients.

Aged↗
PubMed1996

Anti-ganglioside GM2 monoclonal antibody-dependent killing of human lung cancer cells by lymphocytes and monocytes.

Ganglioside GM2 (GM2) frequently appears on the cell surface of human cancers of neuroendocrine origin. A mouse-human chimeric monoclonal antibody (mAb), KM966, against GM2 was previously found to promote the lysis of various cancer cells by human blood mononuclear cells (MNC). In this study, we analyzed the effector cells responsible for the chimeric mAb-dependent cell-mediated cytotoxicity (ADCC) against small cell lung cancer (SCLC) cells and examined the enhancing effect of various cytokines on the ADCC activity. The ADCC activity was assessed by 4-h 51Cr release assay. Highly purified lymphocytes (> 99%) and monocytes (> 90%) were separated by centrifugal elutriation from peripheral blood MNC of the same healthy donor. KM966 induced lysis of SCLC cells mediated by both lymphocytes and monocytes to similar extents, in a dose-dependent manner. Pretreatment of lymphocytes with various cytokines [interleukin (IL)-2, IL-12 and interferon-gamma] and that of monocytes with macrophage-colony-stimulating factor significantly augmented the killer activity against SCLC cells in the presence of KM966 mAb. KM966 was also effective for the lysis of non-small cell lung cancer cells in direct proportion to the GM2 expression levels. These findings suggest that combined treatment of KM966 mAb with cytokines may be therapeutically useful for in vivo killing of lung cancer cells expressing GM2 through the ADCC reaction.

Adenocarcinoma↗
PubMed1996

Effect of circulating antigen on immunoscintigraphy of ovarian cancer patients using anti-CA125 monoclonal antibody.

The murine monoclonal antibody (mAb) 145-9 recognizes an epitope present on CA125 but different from the epitope defined by the mAb OC125. To evaluate the clinical usefulness of the 145-9 antibody, immunoscintigraphy was performed in ovarian cancer patients and the effect of circulating CA125 on tumor imaging was investigated. Two milligrams (74 MBq) of 111In-labeled 145-9 was injected intravenously into 11 patients with ovarian cancer. Pre-injection serum CA125 concentrations were between 166 U/ml and 7414 U/ml. Tumors were visualized in 10 of 11 patients. In two patients, lymph nodes that were not detected by other imaging modalities but were clinically suspected as metastases were visualized. There was no correlation between serum CA125 level and antibody uptake in the tumors. Immune complexes between the antibody and circulating antigen were observed in sera of all the patients, but the fraction of radioactivity in complex form did not correlate well with serum CA125 levels. The immune complexes survived in the circulation and the circulating radiolabel, including immune complexes, was still bound to solid-phase CA125. The plasma clearance rate and hepatic uptake of the antibody were not significantly affected by circulating CA125. In conclusion, the antibody 145-9 formed complexes with CA125 in vivo but this did not Compromise the outcome of antibody imaging. The antibody 145-9 can be used in immunoscintigraphy of ovarian cancer irrespective of serum CA125 level.

Adult↗
PubMed1996

Transduction of the macrophage colony-stimulating factor gene into human multidrug resistant cancer cells: enhanced therapeutic efficacy of monoclonal anti-P-glycoprotein antibody in nude mice.

To develop a therapeutic modality for overcoming multidrug-resistant (MDR) cancer with anti-MDR1 antibody, we examined the effect of macrophage colony-stimulating factor (M-CSF) gene transfection into MDR AD10 cells on therapy of MDR cancer with anti-MDR1 antibody (MRK17) in nude mice. MDR human ovarian cancer (AD10) cells were transduced with the human M-CSF gene inserted into an expression vector to establish gene-modified cells capable of producing low (ML-AD10), intermediate (MM-AD10) nd high (MH-AD10) amounts of M-CSF. Systemic administration of MRK17 resulted in significant dose-dependent inhibition of subcutaneous growth of ML-AD10 tumors. In contrast, systemic administration of recombinant M-CSF in combination with MRK17 did not augment the therapeutic efficacy of MRK17 alone, but rather promoted the growth of the parent AD10 cells. To test the efficacy of in vivo M-CSF gene therapy combined with antibody, we mixed the parent AD10 cells with MH-AD10 cells producing a large amount of M-CSF, and inoculated the mixed cells subcutaneously. Treatment with MRK17 inhibited growth of the mixed cells more than that of the parent cells alone. Thus, combined therapy with anti-MDR1 mAb and M-CSF gene modification of MDR cancer cells may provide a new immunotherapeutic modality for overcoming MDR in humans.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Induction by interleukin-15 of human killer cell activity against lung cancer cell lines and its regulatory mechanisms.

Interleukin (IL)-15 is a novel cytokine with IL-2-like activity. In the present study, we examined IL-15-mediated induction of killer activity of peripheral blood mononuclear cells (MNC) against lung cancer cell lines, and the regulatory mechanisms of this induction by IL-15. Cytotoxic activity was measured by 51Cr release assay. IL-15 at concentrations of more than 10 ng/ml induced significant killer activity of blood MNC against a small cell lung cancer cell line (SBC-3), as well as Daudi cells, and 50 ng/ml was considered its optimal concentration. A time course study revealed that an incubation period of 4-6 days was optimal for induction of killer activity. MNC cultured with IL-15 also exhibited killer activity against other lung cancer cell lines (H-69, N-291 and PC-9 cells). IL-15 and IL-12 had additive effects on induction of killer activity against SBC-3 cells. On the other hand, IL-15 had no synergistic or additive effect on induction of killer activity by IL-2. Fresh human monocytes isolated by centrifugal elutriation augmented the development of killer activity of lymphocytes stimulated by IL-15. As a humoral regulatory factor, IL-4 had a suppressive effect on induction of killer activity by IL-15. IFN-gamma, IL-1beta, TNF-alpha, IL-6 or IL-10 had no effect on induction of killer activity by IL-15 at the optimal concentration. These results suggest that IL-15 has potential for the immunotherapy of lung cancers.

Antibody-Dependent Cell Cytotoxicity↗