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Biomedical subjects

M Koyanagi

Publications and source records attributed to M Koyanagi.

47 records · Page 3Linked to original sources
PubMed1991

Activation of a natural killer clone upon target cell binding via CD2.

The functional relevance of CD2-mediated signal transduction in triggering T cell receptor/CD3-independent natural killer cell cytotoxicity was investigated by introducing wild-type CD2 or signaling-deficient CD2 with truncated cytoplasmic region into a murine natural killer-like large granular lymphocyte clone lacking CD2 and T cell receptor/CD3. The introduction of wild-type CD2 led to CD2-dependent binding and cytotoxicity against P815 target cells. In contrast, the introduction of mutant CD2 with truncated cytoplasmic region led to comparable P815 binding but reduced cytotoxicity as compared with the wild type. These results provide a direct evidence for CD2-mediated triggering of NK cell cytotoxicity upon target cell binding.

Amino Acid Sequence↗
PubMed1990

A murine very late activation antigen-like extracellular matrix receptor involved in CD2- and lymphocyte function-associated antigen-1-independent killer-target cell interaction.

CD2 and lymphocyte function-associated antigen (LFA)-1 are well known as T cell adhesion molecules involved in killer-target cell interactions. However, our recent study revealed that molecule(s) other than CD2 and LFA-1 might be involved in the lymphokine-activated killer (LAK) cell cytotoxicity against certain target cells. In order to characterize such unknown molecules, we established a mAb (RMV-7) which could inhibit CD2/LFA-1-independent LAK cell cytotoxicity and binding to target cells at the effector site. The Ag identified by RMV-7 appeared on splenic T cells late after mitogenic stimulation and was a noncovalently linked heterodimer composed of a 140-kDa alpha-chain and a 95-kDa beta-chain. RMV-7 blocked LAK cell binding to fibronectin (FN), fibrinogen, and vitronectin but not that to laminin or type IV collagen, indicating that the RMV-7-defined molecule is a unique extracellular matrix receptor for FN, fibrinogen, and vitronectin. One of its ligand, FN, was found on the surface of several target cells, and LAK cell cytotoxicity against them was blocked by anti-FN antibody at the target site. Similarly, cytotoxicity of a H-2d-specific CTL clone was inhibited by RMV-7 and anti-FN antibody as well. These results indicate that a unique very late activation Ag-like extracellular matrix receptor on murine CTL and LAK cells contributes to target cell binding and cytotoxicity.

Animals↗
PubMed1990

Relative contribution of CD2 and LFA-1 to murine T and natural killer cell functions.

We have examined the functional property of murine CD2 as an intercellular adhesion molecule by using five anti-murine CD2 mAb which were classified into two groups according to their mutual competition in binding to cell surface CD2. Hamster fibroblasts transfected with murine CD2 cDNA exhibited increased conjugate formation with a murine mastocytoma P815 which expresses the putative murine LFA-3 mRNA detected by cross-hybridization with human LFA-3 cDNA under conditions of low stringency. This increase in conjugate formation was abrogated by both groups of anti-CD2 mAb, although some differences in the extent of inhibition were observed at lower concentrations of the mAb. We then examined the involvement of CD2 in several murine T cell responses by using these mAb to abrogate CD2-mediated cellular interactions. Anti-CD2 mAb significantly inhibited mitogenic T cell responses induced by suboptimal doses of Con A and PHA. In the allogenic MLR response and in the Ag response of two KLH/I-Ak-specific Th cell clones, the inhibitory effect of anti-CD2 mAb was also greatest under suboptimal conditions, i.e., with lesser doses of the Ag. These results indicate that the contribution of CD2 as an accessory molecule is variable, depending on the Ag dose used for stimulation, and they suggest that CD2 is involved in the Ag response of murine T cells under the physiologic conditions where only a limited amount of Ag is available. We next examined the contribution of CD2 to MHC-restricted cytotoxicity by CTL and to MHC-unrestricted cytotoxicity by NK and lymphokine-activated killer cells. Only a marginal inhibition by anti-CD2 mAb alone was observed. Anti-lymphocyte function-associated Ag (LFA)-1 mAb alone exhibited greater inhibitory effects than anti-CD2 mAb in all of the cases tested. In most cases, however, substantial levels of cytotoxicity remained, even in the presence of both anti-CD2 and anti-LFA-1 mAb. These results indicate a minor contribution of CD2, as compared with LFA-1, to cytotoxicity by murine CTL, NK cells, and lymphokine-activated killer cells, and they reveal the presence of undefined cellular interaction pathways other than those mediated by CD2 and LFA-1.

Animals↗
PubMed1990

Activity of platelet-activating factor (PAF) acetylhydrolase in plasma from healthy habitual cigarette smokers.

The activity of platelet-activating factor acetylhydrolase, a specific metabolizing enzyme of platelet-activating factor (PAF), in plasma of 39 male subjects was determined radiochemically by the method of Stafforini et al., (1987) J Biol Chem 262: 4223-4230, to clarify to what extent PAF affects atherosclerotic disorders induced by habitual smoking. The subjects examined included 18 habitual smokers (mean age: 62 +/- 10.6 years) and 21 age-matched nonsmokers. Plasma PAF acetylhydrolase activity was higher in the smokers than in the nonsmokers. There was no difference between smokers and nonsmokers in platelet aggregability in response to PAF or ADP. A higher apoprotein B/apoprotein A-I ratio in smokers as compared to nonsmokers was the only manifestation of abnormal lipoprotein metabolism in the former group. In the smokers, plasma PAF acetylhydrolase activity was directly proportional to total cholesterol, LDL-cholesterol, triglyceride, apoprotein B, LDL-cholesterol/HDL-cholesterol or apoprotein B/apoprotein A-I, and inversely proportional to HDL-cholesterol or apoprotein A-I. The results obtained suggest that alterations in PAF acetylhydrolase levels result from a slightly abnormal lipoprotein metabolism. Determination of plasma PAF acetylhydrolase activity is useful to study the role of PAF in atherosclerotic changes induced by smoking.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1990

Magnetic detection of sleep spindles in normal subjects.

The magnetoencephalogram (MEG) and electroencephalogram (EEG) were recorded simultaneously from 3 normal subjects during light sleep. The extracranial magnetic field patterns associated with the ionic currents within the brain (MEG) were measured using a SQUID magnetometer in a magnetically shielded room. Although a previous report indicated that there are few sleep spindles in MEG records, we observed many in all 3 subjects. We believe this is because measurements were made vertically at the vertex region.

Adult↗
PubMed1986

Possible active tubular secretion of sulfamonomethoxine and its metabolites in pigs.

The effect of probenecid on the plasma kinetics of sulfamonomethoxine (SMM) was examined in conscious pigs. A linear kinetic dose of SMM (10 mg/kg) was injected with or without probenecid. Probenecid (25 mg/kg, i.v.) was injected immediately before SMM injection and against at 1, 2, 3, 4 and 6 h later. The AUCs of SMM and of the acetylated compound of SMM (AcSMM) in probenecid injected animals were significantly larger when compared with those of non-injected animals (p less than 0.05). Next, possible active secretion from the renal tubule of SMM and its metabolites was examined using probenecid and pyrazinoate. Ten commercial pigs with ureter cannulae were used under anesthesia. The plasma concentration of SMM and AcSMM was maintained at a steady state by a priming dose of SMM (5 mg/kg, i.v.) followed by sustaining infusion (4 micrograms/kg/min). Renal clearance of AcSMM was suppressed by bolus injection of probenecid (25 mg/kg), but that of SMM was not. The renal excretion of a water soluble metabolite was suppressed by probenecid. No marked changes in renal excretory kinetics were found by pyrazinoate injection (12.5 mg/kg, i.v.). Consequently, the saturation in the active tubular secretion of AcSMM may play an important role in the nonlinear pharmacokinetics of SMM in pigs.

Acetylation↗
PubMed1985

Effects of atomic bomb radiation on the differentiation of B lymphocytes and on the function of concanavalin A-induced suppressor T lymphocytes.

The differentiation of peripheral blood B lymphocytes into immunoglobulin-producing cells (Ig-PC) by pokeweed mitogen (PWM) and the function of concanavalin A (Con A)-induced suppressor T lymphocytes were examined to elucidate the late effects of atomic bomb radiation. A total of 140 individuals, 70 with an exposure dose of 100 rad or more and an equal number with an exposure dose of 0 rad matched by sex and age, were selected from the Nagasaki Adult Health Study (AHS) sample. Both the differentiation of peripheral blood B lymphocytes into Ig-PC by PWM and the function of Con A-induced suppressor T lymphocytes tended to be more depressed in the exposed group than in the control group, but a statistically significant difference could not be observed between the two groups. The function of Con A-induced suppressor T lymphocytes tended to decrease with age, but a statistical significance was detected only for percentage suppression against IgM-PC.

Adult↗