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Biomedical subjects

M Yamazaki

Publications and source records attributed to M Yamazaki.

At least 703 records · Page 39Linked to original sources
PubMed1988

Increased production of superoxide anion by neonatal polymorphonuclear leukocytes stimulated with a chemotactic peptide.

In order to assess the functional property of neonatal polymorphonuclear leukocytes (PMNs), we studied their chemoattractant-stimulated superoxide anion (O2-) production using a soluble chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) as a PMN stimulus. O2- production by neonatal PMNs was increased: when stimulated with 10(-7)M FMLP, O2- values (nanomoles; mean +/- SE) produced by 10(6) PMNs were 16.5 +/- 1.3 for neonatal PMNs and 12.6 +/- 0.6 for adult PMNs (p less than .02). When studied under various concentrations (10(-9) to 10(-6)M) of FMLP, neonatal PMNs produced more O2- than adult cells under the stimulation of a lower concentration (10(-8)M) as well as a higher concentration (10(-7)M) of FMLP. The increased O2- production by neonatal PMNs was also observed under their stimulation by phorbol myristate acetate. Neonatal and adult PMNs produced equal amounts of O2- when stimulated with a particulate stimulus of opsonized zymosan. To analyze further the mechanism for the increase in FMLP-induced O2- production by neonatal PMNs, we next studied whether there was some abnormality in their FMLP receptors. Neonatal PMNs had normal numbers of FMLP receptors; the receptor numbers (mean) per cell were 54,000 in neonatal PMNs and 56,000 in adult cells. Additionally, the FMLP receptors had normal affinity for the peptide. These results demonstrate that the increased production of O2- by FMLP-stimulated neonatal PMNs is not due to the abnormality of its binding to the receptors but is due to that of the subsequent events.

Adult↗
PubMed1988

Hepatic portal injection of glucose elevates efferent sympathetic discharges of interscapular brown adipose tissue.

Efferent sympathetic discharges of interscapular brown adipose tissue were recorded after three different concentrations of glucose (138, 277, and 416 mM) and 154 mM NaCl were injected into the portal vein or into the right jugular vein. When injected into the portal vein there was a significant increase in the discharge in response to both concentrations of glucose (277 and 416 mM), whereas only 416 mM glucose solution could cause an increase in the discharge when injected into the right jugular vein. There was no appreciable change in the discharge following the NaCl injections into the portal and jugular veins, and the portal glucose responses in the discharge were abolished by transection of the hepatic branch of the vagus nerve. Since stimulated sympathetic activity has been shown to elevate thermogenesis of the adipose tissue, these findings suggest that vagal glucose signals derived from the portal vein may be involved in the regulation of heat production of this tissue.

Adipose Tissue, Brown↗
PubMed1988

Inhibition of benzoyl peroxide/Cu2+-dependent lipid peroxidation by manganese.

1. Formation of peroxides by benxoyl peroxide (BPO) and CuCl2 was examined in the human red blood cell ghost. 2. Amounts of peroxides formed increased with the amount of the ghost solution added. 3. Of all the cations tested only manganese ion inhibited the formation of peroxides in BPO-CuCl2 reaction system. 4. The formation of peroxides was inhibited approx. 50% with 0.4 microM manganese. 5. The inhibitory manner of manganese was non-competitive against copper.

Benzoyl Peroxide↗
PubMed1988

Binding to prostaglandin (PG) receptors and activation of adenyl cyclase by 20-isopropylidene-PGS in rabbit platelet membranes.

20-Isopropylidene-PGE1 (Isop-PGE1) was about 10 times more potent than PGE1 in inhibition of thrombin-induced aggregation of rabbit washed platelets. Likewise, 20-isopropylidene-17(R)-methyl-carbacyclin (CS-570), a stable PGI2 analogue, was more potent than carbacyclin in the anti-aggregatory activity. In order to define the platelet-prostaglandin interactions, a binding assay was done using platelet membranes with [3H]-PGE1 as a radioligand. Isop-PGE1 (IC50 = 0.18 microM) bound to the PG receptors more potently than PGE1 (IC50 = 2.1 microM). CS-570 (IC50 = 0.39 microM) was more potent than carbacyclin (IC50 = 1.9 microM). These indicate that introduction of an isopropylidene group to the carbon 20 of PGs increases the binding ability to the receptors. These PGE1 and PGI2 analogues activated platelet membrane adenyl cyclase and increased intracellular cAMP levels with the same potency series obtained in the binding experiments. All these results suggest that the binding to the receptors by these PGs is coupled to the activation of adenyl cyclase, followed by the increase in cAMP levels in platelets and the inhibition of platelet aggregation. Thus, the increased anti-aggregatory activity of 20-isop-PGs may be explained by their increased affinity for the PG receptors and stimulation of adenyl cyclase. 15-Epimeric-20-isopropylidene-PGE1 (15-Epi-isop-PGE1), which has an unnatural configuration of the 15-hydroxyl group, was much less potent than isop-PGE1 in the binding experiment and the other three investigations. This indicates that the configuration of the 15-hydroxyl group is important for the binding to the PG receptors and the consequent activities in platelets.

Adenylyl Cyclases↗
PubMed1988

An investigation of the immune suppression induced by some saikosaponin derivatives.

The relationship between lymphocyte activation by purified plant glycoside and the suppression of antibodies against sheep erythrocytes was investigated by an adoptive cell transfer system. Glycosides are one of the main components of Shôsaikotô--famous hematopoietic remedies of oriental medicine. In earlier reports, BALB/c mice treated with these drugs, suppressed the plaque-forming cell (PFC) response to T-dependent antigens. In contrast, the PFC response was enhanced for T-independent antigens. In this communication, an experiment was designed to determine the nature of the suppressive factor(s) produced in treated mice. Mice were orally or intraperitoneally administered 1 mg/kg of five types of purified SS derivatives every other day on five consecutive occasions. Spleen cells and serum were prepared from SS-treated mice and were then passively transferred to recipient mice. On the spleen cells (and not any of the sera) from drug-treated hosts effectively suppressed the PFC in recipients. The spleen cells of treated mice were further divided into adherent and non-adherent cells; each cell type was transferred into recipient animals. The observed suppressive activity was clearly detected in the non-adherent cell population. A subsequent analysis of the lymphocyte subpopulation revealed that Lyt.1.1 negative and Lyt.2.2 positive cells were responsible for this suppression. It was concluded that some SS derivatives elevate the activities of the major immunocyte population, with suppressor cell activity predominating.

Animals↗
PubMed1988

Local induction of a cytotoxic factor in a murine tumour by systemic administration of an antitumour polysaccharide, MGA.

When an antitumour mannoglucan prepared from Microellobosporia grisea, MGA was administered i.v. to C3H/He mice bearing the solid MH134 hepatoma, a cytotoxic factor was induced that was detectable in the tumour homogenate by an 8 h cytolysis assay against L-929 fibroblasts. Without MGA treatment, the cytotoxic factor was not detectable in the tumour homogenate. MGA induced the cytotoxic factor in tumour tissue specifically, its level reaching a maximum (24 U ml-1) 3 h after administration of MGA: little if any cytotoxic factor was detectable in homogenates of normal tissues or sera after MGA-treatment. The molecular size of the cytotoxic factor was estimated to be 70-80 kD by gel filtration. It seemed to be a type of tumour necrosis factor because its activity was inhibited by antiserum against murine tumour necrosis factor. From these results, the selective induction of the cytotoxic factor was concluded to be important in the mechanism of the antitumour activity of MGA.

Animals↗
PubMed1988

Cytolytic heterogeneity of polymorphonuclear leukocytes in killing of murine tumor cells.

Murine inflammatory polymorphonuclear leukocytes (PMN) and inflammatory ascitic fluid were found to contain cytotoxin. This cytotoxin was not oxygen metabolites, but a protein with a molecular weight of 70 kilodaltons as determined by high-performance liquid chromatography. However, the cytolytic activity was completely neutralized by anti-murine tumor necrosis factor (TNF) antibody, suggesting that PMN cytotoxin is a TNF-like molecule or TNF itself. Cytolytic heterogeneity of PMN was also demonstrated: immature PMN obtained from ascitic fluid 6 hr after caseinate injection showed stronger cytotoxicity than mature PMN obtained 3 hr after the injection. However, mature PMN (3 hr) contained more cytotoxin than immature PMN (6 hr). This discrepancy may be due to differences in the abilities of these PMN to synthesize and release cytotoxin. These results indicate that not only macrophages, but also inflammatory PMN can produce a TNF-like cytotoxin and that cytolytic heterogeneity of PMN exists in tumor killing.

Animals↗
PubMed1988

A possible role of glucocorticoids: an intrinsic inhibitor of the cytotoxic activity of tumor necrosis factor.

The cytotoxic activity of tumor necrosis factor (TNF) against L929 fibroblasts in vivo was noncompetitively inhibited by physiological concentrations of glucocorticoids such as hydrocortisone (10(-7) M), corticosterone (5 X 10(-8) M) and dexamethasone (5 X 10(-9) M). The inhibition was abolished by the addition of actinomycin D (0.5 microgram/ml) or cycloheximide (4 microM). A phospholipase A2 inhibitor, quinacrine (2 X 10(-6) M), also inhibited the TNF cytotoxicity. These findings suggest that the antitumor cytotoxic reaction by TNF is regulated by glucocorticoid through some mechanism involving de novo transcription and translation and that this regulatory mechanism may involve inhibition of phospholipase A2 activity.

Animals↗
PubMed1988

Miconazole and amphotericin B alter polymorphonuclear leukocyte functions and membrane fluidity in similar fashions.

The influence of miconazole on polymorphonuclear leukocytes (PMN) was investigated and compared with that of amphotericin B (AmB). Human PMN were preincubated in vitro with miconazole or AmB at therapeutically attainable concentrations in plasma, and their chemotactic functions were assessed with the synthetic chemotactic peptide N-formylmethionyl-leucyl-phenylalanine (FMLP). Changes in membrane fluidity of PMN were examined by an excimer-forming lipid technique. Adherence of PMN was measured by a nylon fiber column method. Miconazole and AmB pretreatment irreversibly depressed PMN random migration and chemotaxis under agarose but did not influence superoxide anion production. Both miconazole and AmB increased PMN adherence. Miconazole and AmB lowered the binding affinity of FMLP receptors on PMN and decreased the membrane fluidity in a similar manner. These results demonstrate that miconazole and AmB alter selected in vitro membrane properties of human PMN.

Amphotericin B↗
PubMed1988

Pharmacokinetic and pharmacodynamic interactions between furosemide and hydrochlorothiazide in nephrotic patients.

We examined the response of 8 patients with nephrotic syndrome (creatinine clearance 70.4 +/- 16.0 ml/min) to oral furosemide (F; 40 mg) in the absence (control) and in the presence of oral hydrochlorothiazide (HCT; 100 mg). In the 24-hour period after oral F, HCT was shown to increase urine volume and urinary sodium and chloride excretion. Increment was most significant during the 12- to 24-hour period. Enhancement of the diuresis with HCT was associated neither with a significant increase in the area under the curve of plasma F concentration nor an increase in urinary F excretion. Urinary excretion of glucuronidated F, one of the main metabolites of F, however, was decreased with HCT. In summary, HCT significantly enhanced the response to F in nephrotic patients.

Drug Interactions↗
PubMed1988

Abnormal membrane fluidity as a cause of impaired functional dynamics of chemoattractant receptors on neonatal polymorphonuclear leukocytes: lack of modulation of the receptors by a membrane fluidizer.

Membrane properties associated with chemoattractant-mediated cellular responsiveness of neonatal polymorphonuclear leukocytes (PMN) were analyzed using n-formylmethionyl-leucyl-phenylalanine. Inasmuch as aliphatic alcohols as a membrane fluidizer can enhance the chemoattractant binding and affect subsequent cellular responsiveness in adult PMN, neonatal PMN were studied for such properties by their treatment with iso-propyl alcohol, an aliphatic alcohol. The alcohol (less than 2.5%) treatment enhanced the N-formylmethionyl-leucyl-phenylalanine binding to adult PMN, but there were no changes in the N-formylmethionyl-leucyl-phenylalanine binding to neonatal PMN. Although the N-formylmethionyl-leucyl-phenylalanine-induced subsequent responsiveness including migration, lysosomal enzyme release and superoxide anion production were modulated by the alcohol treatment in adult PMN, there was no such modulation in neonatal PMN. Because membrane fluidity is largely involved in the regulation of the receptor functions, the membrane fluidity of neonatal PMN was next measured by an excimer-forming lipid technique in flow cytometry. The membrane fluidity value (0.45 +/- 0.037) of neonatal PMN was lower than that (0.74 +/- 0.072) of adult PMN (p less than 0.01). Although the aliphatic alcohol enhanced the membrane fluidity of adult PMN, it did not affect the membrane fluidity of neonatal PMN. We conclude that there is abnormal membrane fluidity as a cause of impaired functional dynamics of the chemoattractant receptors, which appears to underlie the defective modulation of cell functions by the membrane fluidizer in neonatal PMN.

1-Propanol↗
PubMed1988

Local induction of a tumor necrosis factor (TNF)-like cytotoxic factor in murine tissues with tumorous and nontumorous inflammation after systemic administration of antitumor polysaccharides.

Local induction of a cytotoxic factor (CF), which was reported by us to be a tumor necrosis factor (TNF)-like molecule, in murine tumor tissues by i.v. administration of antitumor polysaccharides was studied. The CF was measured by cytolysis assay against L929 fibroblasts in vitro. The antitumor polysaccharides mannoglucan polyalcohol (MGA), lentinan, carboxymethyl-(1----3)-beta-D-linear glucan DP540 (CM-TAK) and yeast mannan induced the CF in MH134 hepatoma tissues inoculated intradermally, with MGA inducing the highest level of the CF. MGA induced the CF in MM46 mammary carcinoma, Ehrlich carcinoma, and MH134 hepatoma, the growth of which were all inhibited by MGA, but not in Lewis lung carcinoma and EL-4 lymphoma, which are therapeutically resistant to MGA. MGA induced the CF in solid MH134 hepatoma tissues inoculated subcutaneously or intramuscularly as well as intradermally, but not in ascitic fluids with intraperitoneal MH134 hepatoma on which MGA is ineffective. These findings suggest that CF induction is correlated with the antitumor activity of polysaccharides. CF induction in tumor tissues was detectable 6 h after i.d. inoculation of MH134 hepatoma. Even in nontumorous inflammatory skin tissues produced by injection of TAK, the CF was induced by MGA. Thus, the early inflammatory reaction with accumulation of host cells and MGA treatment act cooperatively in local induction of the CF.

Animals↗