Biomedical subjects

S Yano

Publications and source records attributed to S Yano.

At least 397 records · Page 22Linked to original sources

PubMed1991

Interleukin-2-activated murine cell lines with macrophage- and B-lymphoblast-lytic activity.

Interleukin-2 (IL-2)-activated murine killer cell lines with macrophage- and B-lymphoblastic-lytic activity were established, and their target specificity, surface markers, recognition-related structures, and requirements for optimal cell growth were characterized. Sustained growth of IL-2-activated lymphocytes was supported by the combination of IL-2 and IL-4-enriched T cell conditioned medium (CM), but was not supported by IL-2 alone or the combination of IL-2 and IL-3-containing CM in the presence of macrophages (M phi). The established line required continuous contact with M phi to maintain anti-M phi cytolytic activity. Flow cytometric analysis showed that the original line isolated by the first cloning was Thyl+, CD4-, and weakly CD8+, FcR+. The majority of these cells were CD3+ and TCR-V beta 8+. From this line, the CD3+, TCR-V beta 8+ and CD3-, TCR-V beta 8- clones were isolated by subcloning. The former clone showed Thyl+, CD3+, CD4-, CD8-, TCR-V beta 8+, FcR(+)-phenotype, and the latter clone showed Thyl+, CD3-, CD4-, CD8-, TCR-V beta 8-, FcR- phenotype. The original line and subclones showed a similar target specificity and killed resident or thioglycollate (TG)-induced peritoneal M phi and B-lymphoblasts, but did not kill T-lymphoblasts. Allogeneic M phi, M phi-like cell line P388D1, and B cell hybridoma were sensitive, whereas fresh lymphocytes, T cell lymphoma BW5147, natural killer (NK)-sensitive YAC-1, and NK-resistant P815 tumor cells were resistant to lysis by these cytotoxic lines. The addition of anti-H-2 heteroserum, anti-MHC class 1, anti-MHC class II, anti-CD3, or anti-TCR-V beta 8 monoclonal antibody (mAb) to assay cultures did not inhibit the anti-M phi cytolysis by these killer cells. In addition, the CD3- TCR-V beta 8- clone killed M phi and B lymphoblasts better than the CD3+, TCR-V beta 8+ clone. These results suggest that cytotoxic lines established in this study do not use the T cell receptor (TCR) molecules to recognize target cells and the MHC molecules are not involved in recognition. Anti-LFA-1 mAb partially inhibited anti-M phi-lysis, suggesting that the cell contact between targets and effectors is important in cytolysis. Our present data suggest that the culture condition containing IL-2, IL-4, and M phi may support the continuous growth of non-MHC-restricted killer cells with relative target specificity against M phi and B-lymphoblasts.

Animals↗

PubMed1991

Effect of eicosapentaenoic and docosahexaenoic acid on natural killer cell activity in human peripheral blood lymphocytes.

The effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on natural killer (NK) cell activity in human peripheral blood lymphocytes were studied. The direct addition of trieicosapentaenoyl-glycerol (EPA-TG) or tridocosahexaenoylglycerol (DHA-TG) emulsion to a cytotoxicity assay system significantly suppressed NK cell activity. The addition of lipoxygenase inhibitor AA861 also inhibited NK cell activity. The inhibition was proportional to the concentration of EPA-TG emulsion. DHA-TG emulsion, or AA861. The presence of both EPA-TG emulsion or DHA-TG emulsion and AA861 at the same time led to a greater inhibitory effect on NK cell activity than when these emulsions were used separately. The inhibitory effect caused by these lipids or lipoxygenase blockade could not be reversed by adding back exogenous leukotrienes to the assay system. Preincubation of effector cells with EPA-TG or DHA-TG emulsion resulted in a significant inhibition of their NK cell activity. NK cell activity of human lymphocytes was markedly decreased after the infusion of EPA-TG emulsion into healthy volunteers. Thus, in vivo use of EPA-TG or DHA-TG emulsion may influence immune reactivity of the host, although the mechanism has not yet been elucidated.

Benzoquinones↗

PubMed1991

An antibody reacting with splenic red pulp macrophages in the sera of patients with rheumatic diseases.

An antibody was detected in the sera of patients with certain rheumatic diseases that reacted with the cytoplasm of the splenic red pulp (SRP) cells of adult mice. This antibody was detected in the sera of all patients with mixed connective tissue disease (MCTD), 53% of patients with systemic lupus erythematosus (SLE), 42% with Sjögren's syndrome (SS), and 10% with rheumatoid arthritis (RA). However, this antibody was found neither in the sera from patients with other types of rheumatic diseases nor in healthy volunteers. The screening of this antibody may be useful in diagnoses of MCTD, SLE, and SS. In the present study, we also performed the characterization of the cells reacting with this antibody. The cells proved to be acid phosphatase positive phagocytes in the SRP, that is, red pulp macrophages. Moreover, a histochemical analysis of the reacting antigen in these cells has demonstrated that its antigenic activity is NaIO4 and RNase sensitive, suggesting that the antigen may be associated with RNA.

Aging↗

PubMed1991

Characterization of inhibitory effects of an anti-murine CD2 monoclonal antibody on the proliferation of T cell clones.

Though the functional roles of human CD2 are well characterized, murine studies have been lacking until very recent years. Our previous work showed that a mAb against the T11(1)-like domain of CD2 clearly inhibited T cell proliferation induced by mitogenic and allo-antigenic stimuli, but the degree of inhibition was much smaller than had been demonstrated in the human system. In the present study, we observed functional aspects of murine CD2 on CD4+ T cell clones. It was shown that all T cell clones tested were CD2-positive, and that proliferation induced by APC + Ag was inhibited by anti-CD2 mAb. The maximum inhibition was also partial (40-60% inhibition) but CD2-mediated inhibition was observed even at concentrations as low as 0.2 microgram/ml. In contrast to the APC + Ag stimulation, the proliferation induced by lymphokines or immobilized anti-CD3 mAb was not inhibited at all. Taken together, these findings indicate that: (1) CD2 is also involved in the interaction between HTL and APC in murine system; but (2) perturbation of murine CD2 does not influence TCD/CD3- and lymphokine-mediated signal transduction.

Animals↗

PubMed1991

The influence of FK-506 on the thymus and spleen in normal C3H/He mice: flow cytometric analysis of lymphocyte subpopulations.

Although FK-506 has been widely investigated as a potent suppressor of organ allograft rejection in animals, little is known about the effect of FK-506 on normal animals. In this study, we investigated the influence of FK-506 on the thymus and spleen in normal C3H/He mice at the age of 5 weeks. Mice were given dosages of FK-506 varying between 0.3 and 30 mg/kg/day intramuscularly for 5 days. After treatment with FK-506, the total number of lymphocytes in the thymus was significantly decreased in a dose-dependent manner; however, no change was evident in the total number of lymphocytes in the spleen. FK-506 also influenced the immunophenotypes in thymocytes, but not in splenocytes. The absolute number of CD4+ CD8- or CD4- CD8+ thymocytes decreased significantly in the 0.3 mg/kg/day-treated group. CD4+ CD8-, but not CD4-CD8+ thymocytes decreased further in the 1 mg/kg/day-treated group. Neither subpopulation decreased any further with continuing administration. On the other hand, the number of CD4+ CD8+ thymocytes did not decrease significantly in the 0.3 mg/kg/day-treated group, whereas it did decrease significantly in the 1 mg/kg/day-treated group, decreased further with the increase in dosage of FK-506, and decreased markedly in the 30 mg/kg/day group, The number of CD4-CD8-thymocytes did not show any change, even in the high-dosage groups. These results indicate that FK-506 influences the subpopulations of thymocytes according to its dosage. At a lower dosage, it affects mature CD4+ CD8- or CD4- CD8+ cells, but not immature CD4+ CD8+ and CD4-CD8- cells.2

Animals↗

PubMed1991

Ca2+ channel blocking effects of hirsutine, an indole alkaloid from Uncaria genus, in the isolated rat aorta.

Ca2+ channel blocking activity of hirsutine and its pharmacological features were studied. Hirsutine (10(-6) to 3 x 10(-5) M) produced a dose-dependent relaxation of the isolated rat aorta contracted by norepinephrine and high K+ concentration. This effect was exhibited in the aorta strips with or without the endothelium, suggesting an involvement of vasodilative mechanisms not dependent on the endothelium. Hirsutine also inhibited the contractions induced by serotonin and Ca2+ channel activator YC-170, but not by Ca2+ ionophore A23187. The pA2 value of hirsutine was 6.6 +/- 0.1 (mean +/- S.E.; n = 4) in antagonizing cumulative dose-response curve for Ca2+ in the depolarized aorta strips. It is concluded that hirsutine apparently exhibits Ca2+ channel blocking activity mainly through inhibition of the voltage-dependent Ca2+ influx.

Alkaloids↗

PubMed1991

Changes in fatty acid composition in rat blood and organs after infusion of docosahexaenoic acid ethyl ester.

An infusible emulsion of docosahexaenoic acid ethyl ester (DHA-EE) was prepared. One hundred milliliters of the emulsion contained 10 g DHA-EE (90% pure). Three milliliters of the emulsion was infused into tail veins of 22 Wistar rats weighing approximately 300 g. They were killed 1, 6, and 24 h and 3 and 7 d after the infusion, and fatty acid composition of various organs and plasma was analyzed along with that of control rats. DHA concentrations reached their peaks within 24 h after DHA infusion in plasma lipid fractions and in the phospholipid fraction of liver and lung. DHA did not increase at all in cardiac phospholipid fraction. However, DHA concentrations increased markedly (from 0.7% to 11%) in the free fatty acid fraction of heart 1 h after the infusion. DHA emulsion might be useful for patients in whom a rapid increment in DHA in tissues is beneficial.

Animals↗

PubMed1991

Lysis of murine macrophages by lymphokine-activated killer-like cells induced by BCG in vitro.

The lymphokine-activated killer (LAK)-like activity was found to be induced in mouse splenocytes cultured together with Bacillus Calmette-Guérin (BCG). The killer cells induced by BCG were capable of killing both NK-sensitive (YAC-1, P388D1) and NK-resistant (P815) tumor cells. As an important finding, they also lysed syngeneic macrophages (M phi). The anti-M phi killer activity appeared on day 2, and reached a peak on day 5 of culture. Phenotype analysis of the killer cells by depletion techniques using monoclonal antibody (mAb) and complement indicated that the majority of these anti-M phi killer cells were Thy-1+ and asialo GM1+. This M phi cytolysis could be inhibited by the addition of cold M phi, YAC-1 tumor cells, and P815 tumor cells, suggesting that the same population of the effector cells recognize M phi and tumor cells. The addition of anti-MHC class I, anti-MHC class II, anti-L3T4, or anti-Ly-2 mAb directly to assay cultures did not affect anti-M phi cytolysis, suggesting that the MHC molecules are not involved in the cytolysis of M phi by the BCG-induced killer cells. The addition of anti-LFA-1 mAb partially inhibited the cytotoxicity, suggesting importance of the contact between targets and effectors in the cytolysis. Our present data suggest that activation of murine lymphocytes with BCG induces LAK-like cells capable of killing a wide variety of tumor cells as well as M phi and this anti-M phi cytolysis is mediated by nonspecific killer cells.

Animals↗

PubMed1991

Quantitative assessment of quality of digitized portal images: receiver operating characteristic analysis applied to imaging in radiation therapy.

An objective and quantitative method for the evaluation of the quality of megavoltage portal images was developed by applying receiver operating characteristic analysis. On the basis of therapeutic use of portal images, setup errors were employed as "signals" in this experimental study that compared the original portal films with digitized images. Six readers observed 104 portal images of a chest phantom, half of which were "abnormal" (ie, had setup errors). Digital images (2,048 x 2,048 matrix) were enhanced by means of histogram equalization and then printed with a laser printer for observation. The readers showed a higher discrimination capacity with the digitally enhanced images, although a statistically significant improvement was not demonstrated. The present method of assessment of image quality proved to be both simple and clinically reasonable.

Humans↗

PubMed1991

Importance of administration method in high-dose anticancer chemotherapy from toxicological standpoint in rats.

We examined death rates in Fisher rats when chemotherapeutic drugs were administered in a prescribed amount by either a single or divided dose. Lower death rates were observed when nimustine hydrochloride (ACNU) was given in a divided dose, or when cyclophosphamide (CY), vindesine sulfate (VDS) or vincristine (VCR) was administered as a single dose. Lower hematological toxicity was observed when ACNU was administered in 2 doses and CY in a single dose. With etoposide, we did not observe any significant difference between the two administration methods. In a combination study with ACNU and VDS, we observed lower toxic death rates when the dose of ACNU was split and VDS was given as a single dose. ACNU-induced death was substantially reduced by syngeneic bone marrow support or granulocyte colony-stimulating factor treatment. Our experiments indicate that the toxicity of the administration of chemotherapeutic agents may be significantly modified by altering the time course of administration. This would hopefully result in reducing the chemotherapy-related mortality associated with high-dose anticancer chemotherapy.

Animals↗

PubMed1991

The role of capsaicin-sensitive afferent nerves in protective effect of capsaicin against absolute ethanol-induced gastric lesions in rats.

The role of capsaicin-sensitive afferent nerves in gastroprotection by capsaicin was investigated in the absolute ethanol-induced gastric lesion model in rats. Capsaicin (0.1 and 0.5 mg/kg, p.o.) inhibited the lesion formation dose-dependently. The protective effect of capsaicin was attenuated by indomethacin-pretreatment and disappeared in capsaicin-sensitive nerve degenerated rats. Capsaicin did not induce the distension of gastric mucosal folds. These results suggested that stimulation of capsaicin-sensitive afferent nerves by capsaicin would enhance the prostaglandin formation, leading to an inhibition of gastric lesions.

Animals↗

PubMed1991

Gastric bleeding and increased gastric vascular permeability induced by platelet activating factor (PAF): effect of drugs that affect arachidonate metabolism.

The injurious effect of platelet activating factor (PAF) on gastric mucosa was studied by measuring bleeding in the acid perfused stomach of anesthetized rats. The effect of PAF on gastric mucosal vascular permeability (GMVP) was assessed by dye-leakage in the saline perfused stomach of anesthetized rats. Intravenous infusion of PAF (100 ng/kg/min for 20 min) apparently caused gastric bleeding under the gastric luminal perfusion with 150 mM HCl solution,, with the peak response at 50-70 min; biopsy indicated the presence of mucosal lesions. GMVP was markedly increased with the peak response at 20-40 min. Pretreatment with CV-3988 (1 or 10 mg/kg, i.v.), a PAF antagonist, dose-dependently blocked the PAF-induced gastric bleeding and increase in GMVP. Pretreatment with hydrocortisone acetate (20 or 40 mg/kg, s.c.) reduced PAF-induced gastric bleeding and increase in GMVP, in contrast to the aggravation by caffeic acid (1 or 5 mg/kg, s.c.). Indomethacin (1 or 5 mg/kg, s.c.) prevented PAF-induced gastric bleeding, and it depressed the increase in GMVP in the case of the lower dose. Prostaglandin E2 (50 or 500 micrograms/kg, s.c.) significantly reduced PAF-induced gastric bleeding, but had little effect on PAF-induced increase in GMVP. 1-Benzylimidazole (10 or 50 mg/kg, s.c.) also inhibited PAF-induced gastric bleeding and depressed the increase in GMVP at the higher dose. These results suggest that increased GMVP plays a significant role in producing the gastric damage by PAF. Changes in the mucosal level of cyclooxygenase products, especially thromboxanes, by drugs modifying the arachidonate metabolism would be closely associated with their prevention or aggravation of gastric damage induced by PAF.

Animals↗

PubMed1991

A reliable method for the production of antral gastric ulcer by a combination of 2-deoxy-D-glucose, aspirin and ammonia in rats.

In order to establish a reliable method for the production of gastric antral ulcer in rats, combined treatments with three factors: a vagal stimulant, a mucosal barrier breaker and a necrotizing agent were investigated. By the combined administration of 2-deoxy-D-glucose (2-DG; 200 mg/kg, i.v.), aspirin (100-400 mg/kg, p.o.) and hydrochloric acid (0.15 and 0.35 N, 0.5-1.5 ml/100 g, p.o.) or ammonia solution (0.5-1.0%, 0.5-1.5 ml/100 g, p.o.), gastric lesions were prominently induced in sites of both the corpus and antrum on day 2. The largest antral ulcer was induced by the combination of 2-DG (200 mg/kg), aspirin (200 mg/kg) and ammonia solution (1%, 10 ml/kg); and the mean antral ulcer index (mm2) was 43.1 +/- 4.4 and the incidence was 100%. The antral ulcer was found to penetrate the muscularis mucosae and still observed on day 21 and day 28 after ulcer induction in a few cases. From these findings, it was indicated that this antral ulcer would be a useful model for studying the etiology and therapy of gastric ulcer disease.

Administration, Oral↗

PubMed1991

Aggravation by the capsaicin-treatment of gastric antral ulcer induced by the combination of 2-deoxy-D-glucose, aspirin and ammonia in rats.

The effect of capsaicin-sensitive nerve degeneration (capsaicin-treatment) was investigated on the antral ulcer induction by the combined administration of 2-deoxy-D-glucose (2-DG; 200 mg/kg, i.v.), aspirin (200 mg/kg, p.o.) and 1% ammonia solution (10 ml/kg, p.o.) in male Sprague-Dawley rats. On the 2nd day after ulcer induction, erosive lesions were seen in the corpus, and ulcers penetrating into the muscularis mucosae were also seen in the antrum. In the capsaicin-treated rats, the antral ulcer was significantly aggravated as compared with that in capsaicin non-treated rats, although no difference was noted in the formation of corpus lesions between capsaicin-treated rats and non-treated rats. Acid output was investigated in pylorus ligated rats. 2-DG significantly increased the acid output. A significant increase in acid output was also observed in capsaicin-treated rats, and this increase tended to be augmented by the additional treatment with 2-DG. Atropine sulfate inhibited the significant increase in acid output of the capsaicin-treated rats. In all rats, both capsaicin-treated and pylorus-ligated, 2-DG induced antral ulcers that penetrated into the muscularis mucosae. From the above results, it was suggested that capsaicin-sensitive nerve degeneration modifies the gastroprotective ability in the antral mucosa to a greater extent than in the fundic mucosa, and this aggravation may be caused by activation of the vagus nerve, although the role of acid is not completely excluded.

Ammonia↗

PubMed1991

Effect of antiallergic agents and bronchial hypersensitivity in short-term bronchial asthma.

The effect of antiallergic agents with no antihistamine activity on bronchial hypersensitivity to histamine inhalation was studied in 37 asthmatic patients. Improvement in bronchial hypersensitivity to histamine was observed in 11 out of the 24 (46 percent) antiallergic agents-treated patients, but in none of the 13 (0 percent) untreated patients. The 11 patients whose bronchial hypersensitivity improved with antiallergic agents consisted of eight short-term cases of less than one year's duration and three long-term cases of more than one year's duration. Thus, improvement in bronchial hypersensitivity was observed in 8 of 11 (73 percent) short-term cases, and 3 of 13 (23 percent) long-term cases. A significant improvement in %FEV1 was observed only in the short-term cases treated with antiallergic agents, but the improvement of baseline FEV1 did not seem to explain entirely the improvement in bronchial hypersensitivity seen. The decrease in bronchial hypersensitivity was in parallel with that of other asthmatic symptoms. These results suggest that antiallergic agents might be most effective in the treatment of asthmatic patients with a short-term disease duration.

Adult↗

PubMed1991

Effect of oral administration of glycyrrhizin on the pharmacokinetics of prednisolone.

The pharmacokinetics of total and free prednisolone (PSL) in six healthy men, with or without pretreatment with oral glycyrrhizin (GL), was investigated to confirm whether oral administration of GL influences the metabolism of PSL in man. Each subject received an intravenous administration of 0.096 mg/kg of prednisolone hemisuccinate (PSL-HS) with or without pretreatment with 50 mg of oral GL four times. Blood samples were taken from a peripheral vein at 5, 10, 15, 30, 45 min and 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 h after the start of PSL-HS infusion. The concentrations of total PSL in plasma were analyzed by high-performance liquid chromatography, and the free PSL was measured by an isocolloidosmolar equilibrium dialysis method. The pharmacokinetic parameters of PSL were determined by non-compartment analysis. Oral administration of GL was found to significantly increase the concentrations of total PSL at 6, 8 h, and of free PSL at 4, 6 and 8 h after PSL-HS infusion. Moreover, oral administration of GL was also found to modify the pharmacokinetics of both total and free PSL. After oral administration of GL, the area under the curve (AUC) was significantly increased, the total plasma clearance (CL) was significantly decreased, and the mean residence time (MRT) was significantly prolonged. However, the volume of distribution (Vdss) showed no evident change. This suggests that oral administration of GL increases the plasma PSL concentrations and influences its pharmacokinetics by inhibiting its metabolism, but not by affecting its distribution.

Administration, Oral↗

PubMed1991

Effect of diabetes mellitus on levels of atrial natriuretic hormone in plasma and the right atrium in the non-obese diabetic mouse.

Atrial natriuretic hormone (ANH) levels in plasma and the right atrium of non-obese diabetic mice in the decompensated diabetic state were investigated by radioimmunoassay and histological examination. Severely diabetic mice, with blood glucose levels over 33.6 mmol/l showed significantly higher hematocrit, plasma sodium and calculated plasma osmolarity than the age-matched normoglycemic mice. The plasma ANH levels in diabetic mice were significantly lower (17.5 pmol/l) than those in normoglycemic mice (43.6 pmol/l). The ANH concentrations in the right atrium were 26.6 mg/g protein in the diabetic and 11.2 mg/g protein in the normoglycemic mice. The right atrium in the diabetic mice showed much wider immunohistochemical staining by anti-human ANH antiserum compared with the normoglycemic mice. An increase in the number of atrial specific granules in the diabetic mice was observed by transmission and scanning electron microscopy. Morphometrical analysis indicated that the number of granules increased to more than twice that in the normoglycemic mice. These findings indicate that plasma ANH decreases in diabetic mice. The store of right atrial ANH may be increased to compensate for the marked dehydration in severe diabetes.

Animals↗

PubMed1991

Prevention of bacterial infection and LPS-induced lethality by interleukin-1 alpha in mice.

In order to make clear the characteristic biological properties of IL-1 alpha, its protective capabilities on bacteria-induced and LPS-induced lethality were compared with other BRMs in BALB/c mice. Pretreatment with IL-1 alpha (i.p., s.c.) or OK-432 (i.p.), could protect mice from the lethality of a K. pneumoniae infection (i.p.), and pretreatment with IL-1 alpha or TNF alpha could protect mice from LPS (i.p.) lethality. IL-1 alpha could protect mice from both bacteria- and LPS-induced lethality. There was no difference in serum corticosterone levels after the LPS injection between the IL-1 alpha pretreated and untreated groups. However, a more rapid clearance of LPS from the serum and a stronger LPS-neutralizing activity in serum were observed with the LAL assay in IL-1 alpha pretreated mice than in untreated mice. The enhanced LPS-clearance was suggested to be partly responsible for the increased protection against LPS-lethality. IL-1 alpha was indicated to be a unique BRM and to become a useful tool for the prevention of life-threatening bacterial infections and subsequent endotoxin shock.

Animals↗