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S Yano

Publications and source records attributed to S Yano.

At least 289 records · Page 16Linked to original sources
PubMed1996

Systemic chemotherapy alters interleukin-1 beta and its receptor antagonist production by human alveolar macrophages in lung cancer patients.

The purpose of this study was to determine whether cytotoxic chemotherapy influences the number and function of alveolar macrophages (AM) in patients with lung cancer. AM were obtained by bronchoalveolar lavage from 24 patients with lung cancer and 17 control patients. The functional integrity of AM was determined by their ability to produce interleukin-1 beta (IL-1 beta) and interleukin-1 receptor antagonist (IL-1ra) before and after platinum-containing systemic chemotherapy. The productions of IL-1 beta and IL-1ra were quantitated by enzyme immunoassays. The proportions of multinucleated cells among AM were significantly decreased after systemic chemotherapy in lung cancer patients. No significant difference in spontaneous and lipopolysaccharide (LPS)-stimulated IL-1 beta or IL-1ra production by AM was observed between lung cancer patients and control patients. Significant increase of IL-1 beta and significant decrease of IL-1ra production by AM were demonstrated in patients with small cell lung cancer who experienced response to systemic chemotherapy. These results suggest that systemic chemotherapy may influence functional roles of AM in the lung, and consideration of influence of systemic chemotherapy on host functions is important in cancer treatment.

Adult↗
PubMed1995

Antithrombotic effect of a humanized anti-GPIIb/IIIa monoclonal antibody, YM207, in a photochemically induced thrombosis model in monkeys.

We investigated the antithrombotic effects of a F(ab')2 fragment of a humanized anti-platelet glycoprotein (GP) IIb/IIIa monoclonal antibody, YM207, in a platelet-rich thrombosis model. Thrombus was induced in a mesenteric venule of squirrel monkeys by irradiation with filtered light in combination with i.v. administration of a fluorescent dye (sodium fluorescein). Time to occlusive thrombus formation was significantly prolonged by i.v. bolus injection of 0.3 mg/kg of YM207. At doses of 1 mg/kg and 3 mg/kg, complete occlusion did not occur during 60 min of the observation. Platelet aggregation in platelet-rich plasma was inhibited by YM207 at doses 0.3 mg/kg or more. A good correlation was obtained between inhibition of platelet aggregation and the percentage of GPIIb/IIIa receptors blocked by YM207. Bleeding time was significantly prolonged at a dose of 3 mg/kg. Platelet counts showed no significant change. These results suggest that YM207 is effective in preventing platelet-rich thrombus formation without inducing the prolongation of bleeding time or a significant decrease in platelet count. YM207 may be a useful therapeutic agent for the treatment of thrombotic disorders.

Adenosine Diphosphate↗
PubMed1995

Anti-tumour effect of aromatase inhibitor, CGS16949A, on human breast cancer cells.

The growth inhibitory effect of a new non-steroidal aromatase inhibitor, CGS16949A (Fadrozole hydrochloride: [4-(5,6,7,8-tetrahydro-imidazo-[1,5a]-pyridin-5-yl) benzonitrile monohydro chloride]) was studied in human breast cancer cells MCF-7 and T47D. The aromatase activity of MCF-7 was inhibited by CGS16949A in a dose-dependent manner (IC50: 2.8 x 10(-9) M). The cells were incubated for 120 h in phenol red free RPMI 1640 containing 5% stripped foetal calf serum, 10(-8) M testosterone and various concentrations of CGS16949A. Testosterone-induced MCF-7 growth was inhibited by CGS16949A almost completely at the concentrations as low as 10(-9) M, but was not inhibited by antiandrogenic cyproterone acetate (6-chloro-1 beta,2 beta-dihydro-17-hydroxy-3'-H- cyclopropa[1,2]-pregna-1,4,6-triene-3,20-dione acetate: CPA). On the other hand, the growth of T47D stimulated by testosterone was not inhibited by CGS16949A, but was inhibited by CPA. These data suggested that the aromatization of androgens should participate in the growth of MCF-7 and that one of the growth inhibitory mechanisms of CGS16949A should be the inhibition of the intracellular aromatase activity.

Aromatase↗
PubMed1995

Natural antibodies against the immunoglobulin F(ab')2 fragment cause elimination of antigens recognized by the F(ab')2 from the circulation.

A humanized monoclonal IgG1 antibody, designated hC4G1, recognizes the fibrinogen receptor glycoprotein (GP)IIb/IIIa on platelets and inhibits platelet aggregation. When the F(ab')2 fragment of hC4G1 (F(ab')2 hC4G1) was administered to cynomolgus monkeys, all the monkeys showed inhibition of platelet aggregation ex vivo. Unexpectedly, a significant decrease in platelet count was observed in 5 of 18 monkeys. Antibodies against F(ab')2 hC4G1 were detected in the plasma of these monkeys by ELISA. Antibody activity in the plasma of these monkeys was significantly correlated with the intensity of platelet decrease (r = 0.84). The natural monkey antibodies to F(ab')2 hC4G1 were directed against the C-terminal region of F(ab')2 fragment common to all human and humanized IgG antibodies. Natural homo-reactive antibodies were also detected in human plasma from 15 of 40 healthy volunteers. Specificity was closely similar to that of the monkey antibodies. Affinity-purified human homoreactive antibodies enhanced phagocytosis of platelets treated with the F(ab')2 hC4G1. Monkey plasma with high homo-reactive antibody activity was confirmed to decrease platelet count when administered together with F(ab')2 hC4G1 to a monkey with low antibody activity. These results suggest that F(ab')2 of humanized and human antibodies causes elimination of the corresponding antigens from the circulation by homo-reactive antibodies.

Animals↗
PubMed1995

Differential effects of anti-inflammatory cytokines (IL-4, IL-10 and IL-13) on tumoricidal and chemotactic properties of human monocytes induced by monocyte chemotactic and activating factor.

The effect of recombinant human IL-4, IL-10, and IL-13 on the chemotaxis and antitumor activity of human blood monocytes induced by monocyte chemotactic and activating factor (MCAF) was examined. MCAF alone did not induce monocyte-mediated cytotoxicity against human melanoma (A375-M) cells whereas it significantly enhanced the cytotoxicity by norMDP-stimulated monocytes. MCAF, unlike IFN-gamma, had no priming effect on monocyte activation by norMDP. MCAF acted with norMDP or LPS to enhance the production of both IL-1 beta and TNF-alpha. Enhanced cytotoxicity of monocytes stimulated with MCAF plus norMDP was reduced by IL-1 receptor antagonist and anti-TNF-alpha antibody. IL-4, IL-10, and IL-13 suppressed the generation of antitumor activity and cytokine production (IL-1 beta and TNF-alpha) of monocytes stimulated with MCAF plus norMDP or LPS. Chemotaxis of monocytes induced by MCAF was not affected by norMDP or any of the anti-inflammatory cytokines (IL-4, IL-10, and IL-13). Moreover, the pretreatment of monocytes with anti-inflammatory cytokines did not suppress monocyte-chemotaxis. These findings suggest that in vivo recruitment and anti-tumor expression of blood monocytes induced by MCAF may be differently regulated by anti-inflammatory cytokines in vivo.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1995

Immunoscintigraphy of colorectal cancer using 111In-labeled monoclonal antibody to mucin.

A murine monoclonal antibody MLS102 recognizes sialosyl-Tn antigen in mucin and immunohistochemically reacts with more than 80% of colorectal cancer tissues. The purpose of this study was to assess the usefulness of this monoclonal antibody for the immunoscintigraphy of colorectal cancer. Planar and SPECT images were obtained on day 2 or day 3 after injection of 2 mg and 74 MBq 111In-labeled MLS102 antibody into 17 patients with colorectal cancer. Nine of 11 primary tumors and 4 of 6 locally recurrent tumors were detected. Positive images were obtained in all tumors larger than 4.5 x 2.7 cm. Three tumors of less than 2.5 cm and 1 recurrent tumor, which was missed by other imaging modalities, were negative. There were no adverse reactions. Human anti-(mouse Ig) antibody developed in 4 patients. Although improvement of detectability for smaller tumors needs to be pursued, the antibody MLS102 is potentially promising for use in immunoscintigraphy of colorectal cancer.

Adult↗
PubMed1995

Intracellular alkalinization by NH4Cl increases cytosolic Ca2+ level and tension in the rat aortic smooth muscle.

Intracellular pH (pHi) is elucidated to be an important regulator of various cell functions, but the role of pHi in smooth muscle contraction remains to be clarified. The purpose of the present study is to examine the effects of cell alkalinization by exposure to NH4Cl on cytosolic Ca2+ level ([Ca2+]i) and on muscle tone. We attempted simultaneous measurements of both [Ca2+]i and contractile force in rat isolated thoracic aorta from which the endothelium was removed. NH4Cl (10-80 mM) increased both [Ca2+]i and muscle tone in the presence of external Ca2+. These responses were reproducible. The removal of Ca2+ from the nutrient solution partially inhibited the rise in [Ca2+]i and the smooth muscle contraction induced by NH4Cl. In addition, the Ca2+ channel blocker verapamil also partially attenuated the responses to NH4Cl. The NH4Cl-induced responses were gradually reduced as NH4Cl was repeatedly added in a Ca(2+)-free solution. Norepinephrine (NE, 1 microM) induced a transient increase in [Ca2+]i and sustained contraction in the absence of external Ca2+, and the subsequent application of NE had little effect on [Ca2+]i. After internal Ca2+ stores were depleted by exposure to NE, the subsequent application of NH4Cl induced increases in [Ca2+]i and tension of the aorta in a Ca(2+)-free solution. These results suggest that NH4Cl mainly evokes Ca2+ release from the internal Ca2+ stores that are not linked with adrenergic alpha-receptor and causes Ca2+ influx through voltage-dependent Ca2+ channels in the vascular smooth muscle.

Ammonium Chloride↗
PubMed1995

Serum levels of interleukin 6 in patients with lung cancer.

Serum interleukin 6 (IL-6) levels were measured in 75 patients with lung cancer and in 20 patients with benign lung diseases. IL-6 was detectable in 29 patients with lung cancer (39%), but was not detectable in any of the patients with benign lung diseases. Serum C-reactive protein levels and plasma fibrinogen levels were significantly higher and serum albumin concentration was significantly lower in lung cancer patients with detectable serum IL-6 levels than in those without detectable serum IL-6 levels and in patients with benign lung diseases. On the other hand, no significant difference was observed in blood platelet counts in these three groups. Moreover, serum IL-6 levels were not significantly different in lung cancer patients with or without clinically demonstrated distant metastasis. These results suggest that IL-6 may be a mediator of various reactions including an inflammatory response in lung cancer patients.

Adult↗
PubMed1995

Immune complex transfer enzyme immunoassay that is more sensitive and specific than western blotting for detection of antibody immunoglobulin G to human immunodeficiency virus type 1 in serum with recombinant pol and gag proteins as antigens.

Antibody immunoglobulin G (IgG) to human immunodeficiency virus type 1 (HIV-1) in serum was detected by ultrasensitive enzyme immunoassays (immune complex transfer enzyme immunoassays) with recombinant reverse transcriptase (rRT), p17 (rp17) and p24 (rp24) of HIV-1 as antigens and beta-D-galactosidase from Escherichia coli as the label. The immune complex, comprising 2,4-dinitrophenyl-bovine serum albumin-recombinant protein conjugate, antibody IgG to HIV-1, and recombinant protein-beta-D-galactosidase conjugate, was trapped on polystyrene beads coated with affinity-purified (anti-2,4-dinitrophenyl group) IgG, eluted with epsilon N-2,4-dinitrophenyl-L-lysine, and transferred to polystyrene beads coated with affinity-purified (anti-human IgG gamma-chain) IgG. Bound beta-D-galactosidase activity was assayed by fluorometry. The assays were highly reproducible with no serious serum interference, and they were much more sensitive than Western immunoblotting for the corresponding antigens. Signals with rRT, rp17, and rp24 for asymptomatic carriers were at least 56,000-, 680-, and 22-fold higher, respectively, than those for seronegative individuals, and neither indeterminate nor false-positive results were observed, whereas some serum samples were false negative or false positive by Western blotting for p17 and/or p24 antigen. In some cases, seroconversion was detected earlier than by conventional methods. Therefore, these assays are suggested to be more useful than conventional methods not only for the confirmation of antibody IgGs to RT, p17, and p24 of HIV-1 in serum but also for the detection of seroconversion.

Antigen-Antibody Complex↗
PubMed1995

The kinetics of the pathogenic pronase-digested renal proximal tubular antigen and antibody in rat active Heymann nephritis.

We investigated the pathogenesis of active Heymann nephritis in the rat by conducting immunofluorescent and immunoblotting studies of the pathogenic antigen and the autoantibody, and by detecting this antigen-bound IgGs. Rat IgG was detected along the glomerular basement membrane (GBM) and significant proteinuria was observed 6 weeks after the injection of rat pronase-digested tubular brush border antigen. Circulating antibody which bound only to the brush border of proximal tubules of normal rat, appeared 2 weeks after antigen injection. Eluted antibody from nephritic kidney 6 weeks after immunization bound exclusively to the brush border of the proximal tubules of normal rat kidney. Monoclonal antibody against the nephritogenic 0.3 M antigen, which bound exclusively to the brush border in the normal rat, bound to the GBM in a fine granular fashion, as well as to the brush border from nephritic rats, indicating the deposition of nephritogenic 0.3 M antigen in the GBM of nephritic rats. On immunoblotting, both the circulating antibody and eluted antibody obtained from the nephritic kidney 6 weeks after immunization recognized the 0.3 M antigen. This antigen-bound IgG appeared in circulation at 2 weeks, becoming smaller in size at 4 weeks and disappearing 12 weeks after immunization. Thus, it is suggested that active Heymann nephritis in rats was induced by deposition of the circulating 0.3 M antigen-bound IgG complexes in the subepithelial space of GBM.

Animals↗
PubMed1995

Increased intraplatelet and urinary transforming growth factor-beta in patients with multiple myeloma.

The concentrations of transforming growth factor-beta (TGF-beta) in platelets, plasma and urine from 27 patients with multiple myeloma (MM) and from 22 normal controls were measured by sandwich enzyme-linked immunosorbent assay using a monoclonal antibody specific for human TGF-beta 1+2+3. A significantly increased intraplatelet TGF-beta (24.6 +/- 9.6 vs. 17.8 +/- 8.8 ng/10(5) platelets, p < 0.01) and urinary TGF-beta (1.4 +/- 0.8 vs 1.0 +/- 0.4 ng/mg Cr, p < 0.02) were observed in MM patients compared with normal controls. The mean platelet TGF-beta level in MM patients with osteolytic lesions was more increased than in those without osteolytic lesions (29.6 +/- 7.7 vs 18.4 +/- 8.2 ng/10(5) platelets, p < 0.001). In this study, we evaluated the possible role of TGF-beta in the pathogenesis of myeloma, especially in osteolytic lesions.

Aged↗
PubMed1995

Contrasting effect of interleukin-13 on interleukin-1 receptor antagonist and proinflammatory cytokine production by human alveolar macrophages.

We investigated the effect of interleukin-13 (IL-13) on production of IL-1 receptor antagonist (IL-1ra) and proinflammatory cytokines by human alveolar macrophages (AM). AM were obtained by bronchoalveolar lavage from healthy donors. The production of IL-1ra and proinflammatory cytokines, such as IL-1 beta, IL-6, and tumor necrosis factor-alpha (TNF-alpha), were quantitated by enzyme immunoassays. AM spontaneously produced IL-1ra, and this production was significantly augmented by IL-13. On the other hand, IL-13 alone did not affect production of proinflammatory cytokines by freshly isolated AM. Upon stimulation with lipopolysaccharide (LPS), AM produced a significantly amount of proinflammatory cytokines as well as IL-1ra, but this production was suppressed by IL-13 in a dose-dependent manner. In contrast, IL-13 caused a small but reproducible increase in LPS-induced IL-1ra production. These regulatory effects of IL-13 were also observed in blood monocytes and macrophages generated in vitro by maturation of blood monocytes with granulocyte/macrophage colony-stimulating factor. These observations suggest that IL-13 may act as an anti-inflammatory cytokine through regulation of cytokine production by AM in the lung.

Adult↗
PubMed1995

3-Monoglucuronyl-glycyrrhetinic acid is a major metabolite that causes licorice-induced pseudoaldosteronism.

18 beta-Glycyrrhetinic acid (GA) has been thought to be one of the major metabolites that causes licorice-induced pseudoaldosteronism. However, we found no difference in the blood level of GA between the patients with and without pseudoaldosteronism. We measured the blood concentration of 3 beta-D-(monoglucuronyl)18 beta-glycyrrhetinic acid (3MGA), another metabolite of 3 beta-D-diglucuronyl-18 beta-glycyrrhetinic acid (glycyrrhizin), by high performance liquid chromatography and found an increased concentration of 3MGA in 10 patients with licorice-induced pseudoaldosteronism, but not in 11 patients without pseudoaldosteronism. To investigate whether 3MGA can inhibit 11 beta-hydroxysteroid dehydrogenase, we incubated rat renal microsome with or without 3MGA and measured the conversion rate of [3H]cortisol to [3H]cortisone. 3MGA was found to be a potent inhibitor of 11 beta-hydroxysteroid dehydrogenase, allowing cortisol to exert its full mineralocorticoid effects. These results suggest that licorice-induced pseudoaldosteronism is due to an increased concentration of 3MGA, but not GA, in the circulating blood of these patients.

11-beta-Hydroxysteroid Dehydrogenases↗