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Biomedical subjects

H Azuma

Publications and source records attributed to H Azuma.

At least 253 records · Page 14Linked to original sources

Clonal heterogeneity of anti-AKR/gross leukemia virus cytotoxic T lymphocytes. Evidence for two distinct antigen systems.

AKR/Gross leukemia virus-induced tumor reactive cytotoxic T lymphocyte (CTL) clones were derived from C57BL/6 spleen cells. Analysis of their specificity pattern was performed by using a panel of target cells such as E male G2 and AKR.H-2bSL1 (susceptible tumors to polyclonal anti-AKR/Gross virus CTL), and cl. 18-5 and cl. 18-12 (insusceptible variant sublines derived from AKR.H-2bSL1). Several of these CTL clones were selected for further study. Lysis of Gross cell surface antigen-positive tumor cells by these clones was restricted by the H-2Kb molecule. The cell surface phenotype of these clones was Thy-1.2+, Lyt-2.2+, L3T4-, a phenotype consistent with that of polyclonal anti-AKR/Gross CTL, suggesting that they were of conventional CTL origin. According to their fine specificity pattern, the CTL clones were divided into two major groups (A and B) which were further subdivided into five and three subgroups, respectively. The specificity of group A clones was essentially the same as that of the standard polyclonal CTL population except for a variable level of natural killer-like activity by some of the CTL clones. That is, group A clones did not efficiently lyse the insusceptible variant tumors nor any of Friend-Moloney-Rauscher-positive tumors tested, but they showed strong lytic activity to susceptible tumors and iododeoxyuridine-treated insusceptible variants. Thus, their CTL activity appeared to be strictly directed to Gross cell surface antigen-positive tumors that are susceptible to polyclonal anti-AKR/Gross virus CTL. In contrast, group B clones could lyse both susceptible and insusceptible variant tumors and also a Friend virus-induced tumor (FBL3). Therefore, as defined by these CTL clones, at least two distinct antigenic systems (A and B), each with several antigenic determinants, appeared to be present. Because recent findings suggested that most of the polyclonal anti-AKR/Gross virus CTL activity appeared to be directed to N-ecotropic proviral determinants, we further investigated the nature of these two antigenic systems by use of additional target cells including lipopolysaccharide (LPS)-stimulated spleen cell blasts from AKXL recombinant inbred strains and retrovirus-infected fibroblasts. Group A clones could lyse all LPS blasts derived from AKXL recombinant inbred strains containing the AKV-1 proviral genome, but lysed only very insufficiently or did not lyse AKV-1-negative blasts containing the AKV-3 and/or AKV-4 provirus.(ABSTRACT TRUNCATED AT 400 WORDS)

AKR murine leukemia virus↗

Metabolism of plasma fibronectin in rabbits with experimental hyperthyroidism and hypothyroidism.

We previously reported that the concentration of plasma fibronectin (pFN) is increased in patients with hyperthyroidism and decreased in those with hypothyroidism. In this work, labeled pFN was given intravenously to euthyroid, hyperthyroid, and hypothyroid rabbits to examine its metabolism in states of thyroid dysfunction. In euthyroid rabbits, the serum concentration of thyroxine (T4) was 2.94 +/- 0.59 micrograms/dL, and that of pFN was 24.2 +/- 1.2 mg/dL. With 125I-FN as tracer, the half life was estimated as 72.8 +/- 2.6 hours, the fractional catabolic rate (FCR) as 2.08 +/- 0.07%/h, the rate of synthesis (SR) as 3.84 +/- 0.20 mg/kg/day and j1/j2 (the ratio of the exchange coefficients between intravascular and extravascular compartments) of pFN as 0.295 +/- 0.051. With 3H-FN as tracer, these values were not significantly different. In hyperthyroid rabbits, obtained by treatment with I-thyroxine, the serum T4 concentration was increased to 5.73 +/- 1.58 micrograms/dL and the pFN concentration to 29.6 +/- 2.2 mg/dL. In these animals, the half life of pFN was shortened to 59.8 +/- 1.0 hour, the FCR was slightly increased to 3.07 +/- 0.52%/h and the SR was greatly increased to 7.13 +/- 1.17 mg/kg/d. In hypothyroid rabbits, obtained by treatment with methylthiouracil, the serum T4 and pFN levels were reduced to 1.50 +/- 0.36 micrograms/dL and to 20.7 +/- 1.7 mg/dL, respectively, the FCR and SR were also decreased to 1.39 +/- 0.04%/h and 2.26 +/- 0.14 mg/kg/d, respectively. The values of j1/j2 did not significantly change during this work.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Contractile and relaxant effects of jellyfish toxin on the vascular and intestinal tissues.

A toxic component (pCrTX) of jellyfish Carybdea rastonii (10(-8)-10(-6)g/ml) caused a contraction in both rat aorta and guinea-pig taenia coli which was partially inhibited by indomethacin or aspirin. pCrTX (10(-7)-10(-6)g/ml) relaxed the norepinephrine-induced contraction in rat aorta which was inhibited by removing endothelium or by adding methylene blue. These results suggest that a portion of the pCrTX-induced contraction is due to release of prostaglandin(s) and that the pCrTX-induced relaxation is due to release of an endothelium-derived relaxing factor.

Animals↗

An evaluation of fecal occult blood screening in automated multiphasic health testing and services.

In the present paper, the efficacy of fecal occult blood screening in automated multiphasic health testing and services (AMHTS) is evaluated, and some problems with it are also discussed. A total of 54,735 subjects were screened for occult blood by the Shionogi slide 1-day method. According to a follow-up survey of the 715 subjects judged (+ +), 42 cases of colorectal polyp and 13 of colorectal cancer were confirmed. Eight of the 12 cases of primary colorectal cancer, excluding a case of metastatic transverse colon cancer, were located in the colon's right-side. The result may have arisen from the fact that most subjects in AMHTS are relatively young and free of symptoms. This suggests that fecal occult blood testing in AMHTS may be useful for detecting colon cancers of the right side as well as of the left. Of the nine cases of primary colorectal cancer previously screened, five had been judged (+) in previous testing. This fact indicates an especially rigorous examination of subjects judge (+) to be necessary in AMHTS. Meanwhile, of the 45 cases of gastric cancer detected by enhanced X-ray testing, only eight (17.8%) subjects were judged (+) or (+ +). It is suggested that fecal occult blood testing may not, therefore, be too effective in screening for gastric cancer.

Adult↗

[Changes in plasma fibronectin levels in patients with thyroid disease and its mechanism].

Plasma fibronectin (FN) level was determined in normal subjects and patients with thyroid disease by the Laurell method. In vitro effect of triiodothyronine (T3) on FN synthesis by cultured human fetal skin fibroblasts was also studied. Plasma FN level was 32.2 +/- 5.5 mg/dl (mean +/- SD) in normal adults, and no sex difference was observed. The plasma FN concentrations were increased in patients with hyperthyroidism (63.3 +/- 15.2 mg/dl), decreased in patients with hypothyroidism (19.5 +/- 6.5 mg/dl), and in normal range in patients with simple goiter (30.2 +/- 7.0 mg/dl). These FN values have been normalized with a time lag of a short period after their thyroid function became normal. There was a positive correlation between plasma FN concentrations and serum T3 or T4 concentrations, but a inverse correlation between plasma FN concentrations and serum thyroxine binding globulin or cholesterol levels. In vitro studies revealed that the addition of T3 to the incubation medium stimulated FN synthesis by human fetal skin fibroblasts at the concentrations between 10(-8)M and 10(-6)M. These results indicate the usefulness of plasma FN determination in patients with thyroid disease for their management and studying pathophysiology of the disease, and suggest at the fluctuation of plasma FN concentrations in these patients may at least in part due to the effect of thyroid hormone on FN synthesis by the cells.

Adolescent↗

Platelet aggregation caused by a partially purified jellyfish toxin from Carybdea rastonii.

A partially purified toxin (pCrTX) was obtained from the tentacles of the jellyfish, Carybdea rastonii. When pCrTX (3 X 10(-8) - 3 X 10(-7) g/ml) was added to citrated platelet-rich plasma, aggregation was produced in a concentration-dependent manner. Scanning electron microscopic examination revealed that both pCrTX and collagen produced aggregates of platelets possessing many pseudopods. The concentration which produced 50% aggregation for pCrTX was 1.8 X 10(-7) g/ml, as compared to 2.3 X 10(-6) g/ml for collagen. The pCrTX-induced aggregation was only slightly inhibited by indomethacin and quinacrine in concentrations sufficient to inhibit arachidonic acid- and collagen-induced aggregation. pCrTX was less active in washed platelets suspended in Ca2+ free medium, whereas the pCrTX-induced aggregation was significantly augmented in the presence of Ca2+. The augmentation of aggregation by Ca2+ was only slightly attenuated by pretreatment with 100 microM verapamil. pCrTX significantly increased the concentration of cytoplasmic free Ca2+ ([Ca2+]i) and depolarized the platelet membrane in concentrations that produced aggregation. The increase in [Ca2+]i caused by pCrTX was little affected by verapamil. The depolarization by pCrTX was unchanged in the presence or absence of Ca2+, or by sodium or potassium transport inhibitors. The movement of 22Na+ into platelets was significantly increased by pCrTX. This increase in the movement of 22N+ into platelets was unaffected by tetrodotoxin. On the other hand, pCrTX-induced aggregation, depolarization and the increase in [Ca2+]i were all significantly attenuated in low Na+ medium. These results suggest that pCrTX causes a massive depolarization by increasing cation permeability indiscriminately and this generalized depolarization permits an inward movement of calcium down an electrochemical gradient which, in turn triggers platelet aggregation.

Animals↗

Comparative study of four arginine ester hydrolases, ME-1, 2, 3 and 4 from the venom of Trimeresurus mucrosquamatus (the Chinese habu snake).

Four arginine ester hydrolases, ME-1, 2, 3 and 4 from the venom of Trimeresurus mucrosquamatus had been isolated and characterized by Sugihara et al. (1980, 1981, 1982, 1983). Immunologically, ME-1, 2, 3 and 4 are identical. The four enzymes hydrolyzed Pro-Phe-Arg-MCA and z-Phe-Arg-MCA. Furthermore, ME-2 slightly hydrolyzed Boc-Val-Pro-Arg-MCA, Boc-Phe-Ser-Arg-MCA and Boc-Ile-Glu-Gly-Arg-MCA. ME-1 cleaved almost simultaneously the Arg(22)-Gly(23) and Phe(25)-Tyr(26) bond of oxidized insulin B chain. ME-2 and 3 also hydrolyzed the same bond of insulin B chain, but the activity was not as potent as ME-1. ME-4 did not cleave the substrate. The four enzymes hydrolyzed C-terminal of arginine in the biologically active peptides. Four arginine ester hydrolases showed fibrinogenolytic activity. ME-1 and 2 first cleaved B beta-chain and then A alpha-chain. On the contrary, ME-3 and 4 cleaved A alpha- and B beta-chain simultaneously. The four enzymes also hydrolyzed fibrinogen in plasma cleaving B beta- and gamma-chain and slightly digesting A alpha-chain. The various inhibitors affected TAME (tosyl-arginine-methylester) and the fibrinogen hydrolytic activity of the four enzymes. All four enzymes had fibrinolytic activity.

Amino Acid Sequence↗

Endothelium-dependent inhibition of platelet aggregation.

In cascade perfusion and superfusion experiments on rabbit tissues, when acetylcholine (ACh) was introduced into the circuit so as to perfuse the aorta under perfusion with noradrenaline (NA), the effluent relaxed the transverse aortic strip which had been denuded of endothelium. The effluent from the perfused aorta which was capable of relaxing the transverse aortic strip also significantly inhibited platelet aggregation induced by arachidonic acid (AA) in a volume-related manner. The inhibitory activity was decreased by the prolongation of transit time before addition of the effluent to platelet-rich plasma. Neither the inhibition of AA-induced aggregation nor the relaxation of the transverse strip by the effluent could be observed after the removal of endothelium from the aorta, or after pretreatment of aorta with mepacrine or nordihydroguaiaretic acid (NDGA). The AA-induced platelet aggregation was unaffected by pretreatment of platelets with mepacrine or NDGA at the concentration tested. Pretreatment of aorta with indomethacin failed to modify the relaxation of the transverse strip induced by the effluent. These results strongly suggest that endothelium-derived vascular relaxant factor (EDRF) possesses inhibitory activity on AA-induced aggregation in addition to its vasodilator activity.

Acetylcholine↗

Calcium-dependent contractile response of arterial smooth muscle to a jellyfish toxin (pCrTX: Carybdea rastonii).

The purpose of the present experiments was to investigate the pharmacological mechanisms of the vasoconstriction caused by the toxin (pCrTX) which had been partially purified from the tentacles of the jellyfish Carybdea rastonii ('Andonkurage'). pCrTX (0.1 to 10 micrograms ml-1) produced a tonic contraction of rabbit aortic strips, which was nearly abolished in Ca2+-free medium and was significantly reduced by verapamil or diltiazem. pCrTX stimulated 45Ca2+-influx and this effect was markedly attenuated by verapamil. pCrTX-induced vasoconstriction was significantly attenuated by phentolamine, 6-hydroxydopamine (6-OHDA) and in low Na+-medium, but not by bretylium, guanethidine, reserpinization or tetrodotoxin (TTX). pCrTX continuously and significantly increased the 3H-efflux from [3H]-noradrenaline preloaded aortic strips and this effect was completely inhibited by pretreatment with 6-OHDA and in Ca2+-free medium, but not by phentolamine, bretylium, guanethidine or TTX. A single exposure to pCrTX for 30 min greatly reduced the contractile responses to tyramine, nicotine and transmural electrical stimulation, but not those to noradrenaline or KC1. In addition, incorporation of [3H]-noradrenaline was reduced. Pretreatments with chlorphenylamine or indomethacin failed to modify the contractile response to pCrTX. These results suggest that the pCrTX-induced vasoconstriction is caused by a presynaptic action, releasing noradrenaline from the intramural adrenergic nerve terminals, and by a postsynaptic action, which consists at least in part of stimulation of the transmembrane calcium influx. Both pre- and postsynaptic actions depend on the external calcium concentration. The data further suggest that pCrTX damages the noradrenaline uptake and/or storage mechanisms without damaging postsynaptic contractile systems.

Animals↗

Activities of novel polyhydroxylated cardiotonic steroids purified from nuchal glands of the snake, Rhabdophis tigrinus.

Seven novel polyhydroxylated steroids were isolated from the nucho-dorsal glands of the snake, Rhabdophis tigrinus. Biological activities of these steroids in inhibiting (Na+ + K+)ATPase and in producing positive inotropic action were examined in comparison with those of ouabain and gamabufotalin. Gamabufotalin was approximately 10 times more potent than ouabain in inhibiting (Na+ + K+)ATPase. Two compounds, compounds III and XIII, of the seven, produced nearly equipotent enzyme inhibitory activity to ouabain. The activity of the remaining five was relatively low among the compounds tested. All compounds exhibited more or less positive inotropic action in the papillary muscle preparations. The ranking order of the potency was: gamabufotalin greater than ouabain and compound IV greater than compound III and XIII greater than compound I, II, XII and XIV.

Amphibian Venoms↗

Delayed flare-up reactions caused by jellyfish.

Four patients had a recurrence of cutaneous lesions 1 week after being stung by jellyfish. Three patients had flare-up lesions after only one exposure to jellyfish. All of the recurring lesions were vesicular erythema, and the histological findings of case 3 corresponded to that of allergic contact dermatitis.

Adult↗

Contractile effects of jellyfish toxin extracted from Carybdea rastonii on isolated rabbit aorta.

Effects of the toxic component of jellyfish (Carybdea rastonii) (pCrTX) on the smooth muscle tension of isolated rabbit thoracic aorta were examined. pCrTX, at concentrations higher than 10(-7) g/ml, caused slowly developing tension that reached its maximum after about 1 hr. This contraction was partially inhibited by pretreatment of the tissue with phentolamine (5 X 10(-6) M) or indomethacin (10(-5) M). The contraction induced by pCrTX was partially inhibited by nicardipine (10(-7) M) and markedly augmented by Bay k8644 (10(-6) M). In low-Na+ solution, the rate of rise of the pCrTX-induced contraction was significantly reduced. Removal of external Ca2+ inhibited the pCrTX-induced contraction by about 30%, while chlorpromazine, trifluoperazine, prenylamine and papaverine (10(-4) M) completely inhibited the contraction. pCrTX itself did not cause any contraction in saponin-skinned smooth muscle and had no effect on the Ca2+-induced contractile tension. It has been reported that pCrTX-induced contraction is attributable to the release of endogenous catecholamines and also to the increase in Ca2+ influx in smooth muscle (Azuma et al., 1986). The present results confirmed the previous suggestion and further suggested that a portion of the contraction is due to release of prostaglandin(s) and also to the direct effect on smooth muscle which is not dependent on Ca2+ influx.

Animals↗

Additive effects of isoproterenol-phenylephrine aerosol following ipratropium bromide on airway obstruction in older patients with intrinsic asthma and chronic bronchitis.

The additive bronchodilating effect of isoproterenol-phenylephrine aerosol following ipratropium bromide was examined in seven intrinsic asthmatic patients and seven chronic bronchitic patients. FVC, FEV1 and Zrs were measured before and 30 min. after inhalation of ipratropium, 40 micrograms. Then inhalation of isoproterenol, 600 micrograms and phenylephrine, 570 micrograms was added and the pulmonary functions were measured 30 min. later. The age, baseline values of FVC and FEV1, and the increases in FEV1 and 1/Zrs with ipratropium did not differ between the two. Isoproterenol-phenylephrine aerosol following ipratropium produced further increases in FEV1 and 1/Zrs in asthmatic patients but no additive increases in bronchitic patients. These findings indicate that the role of autonomic nervous system, especially adrenergic system, on airway obstruction may be different between asthmatic and bronchitic patients and the method applied in this study may be helpful in differentiating these airway disorders.

Aerosols↗

Platelet aggregation caused by Carybdea rastonii toxins (CrTX-I, II and III) obtained from a jellyfish, Carybdea rastonii.

The pharmacological mechanisms of platelet aggregation induced by highly toxic proteins (CrTX-I, CrTX-II, and CrTX-III) obtained from tentacles of a jellyfish, Carybdea rastonii, were investigated. When the partially purified toxin (pCrTX) and CrTXs were added to the citrated platelet-rich plasma (PRP), aggregation was produced in a concentration-dependent manner. The activity of CrTXs was approximately 100 times more potent than pCrTX. The CrTXs-induced aggregation was little affected by indomethacin and quinacrine at concentrations sufficient to inhibit arachidonic acid- and collagen-induced aggregation. The CrTXs-induced aggregation in washed platelets was significantly augmented in the presence of Ca2+. The pretreatment with verapamil failed to modify this augmentation of aggregation. The concentration of cytoplasmic-free calcium ([Ca2+]i) of platelets was increased by CrTXs at the same concentrations that produced aggregation. This effect of CrTXs was again little affected by verapamil. CrTXs at the same concentrations as those that produced aggregation and increased [Ca2+]i caused depolarization of platelets, which was unchanged after pretreatment with sodium or potassium transport inhibitors. CrTX-I significantly increased the 22Na flux into platelets and this effect of CrTX-I was unaffected by tetrodotoxin. The CrTX-I-induced aggregation, depolarization, and increase in [Ca2+]i were all significantly attenuated in the low Na+ medium. These results suggest that CrTXs cause a massive depolarization by increasing cation permeability and this generalized depolarization permits an inward movement of Ca2+ down its electrochemical gradient which, in turn, triggers platelet aggregation.

Animals↗