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Biomedical subjects

M Fujiwara

Publications and source records attributed to M Fujiwara.

At least 721 records · Page 40Linked to original sources
PubMed1983

Evidence for muscarinic cholinergic receptors in dog portal vein: binding of [3H]quinuclidinyl benzilate.

Muscarinic cholinergic receptor sites in dog portal veins were analyzed directly using [3H]quinuclidinyl benzilate (QNB) as a ligand. Specific [3H]QNB binding to crude membrane preparations from the isolated veins was saturable, reversible and of high affinity (KD = 15.5 +/- 2.8 pM) with a Bmax of 110 +/- 14.7 fmol/mg protein. Scatchard and Hill plot analyses of the data indicated one class of binding sites. From kinetic analysis of the data, association and dissociation rate constants of 1.91 X 10(9) M-1 min-1 and 0.016 min-1, respectively, were calculated. The dissociation constant calculated from the equation KD = K-1/K+1 was 8.3 pM, such being in good agreement with the Scatchard estimate of KD (15.5 pM). Specific binding of [3H]QNB was displaced by muscarinic agents. Nicotinic cholinergic agents, alpha-bungarotoxin, nicotine and hexamethonium, were ineffective in displacing [3H]QNB binding at 10 microM. Our findings provide direct evidence for the existence of muscarinic cholinergic receptors in dog portal veins.

Animals↗
PubMed1983

Enzymatic properties of phospholipid methylation in rabbit platelets.

The enzymatic properties of phospholipid methylation in rabbit platelets were examined using S-adenosyl-L-[methyl-3H]methionine as a substrate. pH optimum for the methylation was around 10.5 under Tris-HCl and glycine-NaOH buffer systems. When Tris-HCl buffer was replaced by phosphate buffer, pH optimum shifted to around 8.0 and the methylation was increased approximately threefold, compared with that in the case of Tris-HCl buffer at pH 8.0. The formation of the 3H-methylated phospholipids was increased by addition of exogenous phosphatidyl-N-monomethylethanolamine or phosphatidyl-N,N-dimethylethanolamine, intermediates of the biosynthesis of phosphatidylcholine from phosphatidylethanolamine. However, the increase in product formations by addition of exogenous intermediates was all but equal under Tris-HCl and phosphate buffer systems at pH 8.0. These results suggest that phosphate ion stimulates the first step of the successive methylation to form phosphatidyl-N-monomethylethanolamine from phosphatidylethanolamine. The methylation in platelets was inhibited to 30% of the basal value with Ca2+ (0.2 mM). However, Ca2+ showed different effects on the methylation in various tissues (activation to 150% of the basal value in the adrenal gland and slight inhibition to 82-88% of corresponding basal values in the liver, lung, kidney and brain).

Animals↗
PubMed1983

Characterization of alpha adrenoceptors in pial arteries of the bovine brain.

When attempting to characterize the nature of adrenoceptors in bovine pial arteries, we found specific 3H-yohimbine binding was saturable, reversible and of high affinity (KD = 18.3 +/- 1.2 nM) with a Bmax of 687 +/- 27 fmol/mg protein (N = 4). On the other hand, there was no specific 3H-prazosin binding in these tissues. Scatchard and Hill plot analyses of specific 3H-yohimbine binding indicated one class of binding sites. From kinetic analyses of the data, association and dissociation rate constants of 1.6 +/- 0.3 X 10(7) M-1min-1 and 0.51 +/- 0.04 min-1, respectively, were calculated (N = 3). The dissociation constant from the equation KD = K-1/K+1 was 35.7 +/- 7.6 nM, such being in good agreement with the KD value estimated from Scatchard plots. Specific binding of 3H-yohimbine was displaced effectively by alpha 2 adrenergic agents and less effectively by alpha 1 adrenergic agents or beta adrenergic agents. Ki values for adrenergic drugs of 3H-yohimbine binding were as follows: yohimbine, 25 nM; clonidine, 260 nM; methoxamine, 6.8 microM; propranolol, 8.7 microM; prazosin, 21 microM; phenylephrine, 22 microM; noradrenaline, 27 microM; adrenaline, 66 microM; isoproterenol, 3,300 microM. These results indicate that alpha adrenoceptors in the bovine cerebral arteries can be classified as the alpha 2 subtype.

Animals↗
PubMed1983

Alterations in neutral amino acid transport across the blood-brain barrier in hepatic failure.

The accelerated transport of the blood neutral amino acids into the brain in encephalopathic patients with fulminant hepatitis and advanced liver cirrhosis was demonstrated not only by determining the cerebrospinal fluid (CSF) aminogram but also by calculating the predicted velocity of the amino acid transport through the blood-brain barrier. Significant elevation in CSF aromatic amino acid (AAA) and methionine levels was observed in the encephalopathic patients. Arousal from hepatic encephalopathy by drip infusion of a branched chain amino acid (BCAA)-enriched solution was obtained coincidentally with the elevated BCAA levels and diminished concentrations of AAA and methionine in CSF. These clinical observations were confirmed experimentally in rats treated with carbon tetrachloride (CCl4) and D-galactosamine by obtaining the elevation of neutral amino acid contents in the brain and the slight increase in the brain uptake index (BUI) of a radiolabeled amino acid.

Amino Acids↗
PubMed1983

Autonomic drug effects and gastric secretion in a new experimental model of stress ulcers in rats.

A psychological procedure which does not involve the application of physical stimulation was used to produce gastric ulcers experimentally. Ulceration was induced in rats by exposing the animals to the aggressive attacks of rats treated with 6-hydroxy-dopamine (6-OHDA). Gastric secretion and the effects of autonomic drugs on ulcer formation were investigated. Atropine methylbromide did not significantly inhibit the occurrence of erosions. Phentolamine or hexamethonium bromide significantly inhibited the production of erosions, and combined administration of an anticholinergic agents and alpha-blocking agent led to a complete inhibition, with no notable behavioral change. In case of pylorus ligation, gastric secretion during exposure to attack of 6-OHDA-treated rats was significantly less than that in the controls. We suggest that the sympathetic nervous system plays an important role in the production of gastric erosions, as induced by the methods reported in this study.

Animals↗
PubMed1983

Attack stress and IgE antibody production in rats.

The effect of stress on production of immunoglobulin E (IgE) in rats was investigated, the IgE being titrated by passive cutaneous anaphylaxis (PCA) reactions. In rats, exposed to attack by other rats made aggressive by intraventricular injections of 6-OHDA for one hour per day for three consecutive days before the first immunization, there was no difference in the titer of IgE as compared to the control rats, but, in the rats exposed to stress procedure before the second immunization, the production of IgE was significantly suppressed.

Adrenal Glands↗
PubMed1983

Augmentation of 12-lipoxygenase activity of lymph node and spleen T cells in autoimmune mice MRL/1.

To investigate the relationship between development of autoimmune disease and arachidonic acid metabolism, we compared lipoxygenase and cyclooxygenase activities of lymphoid cells in MRL/1 mice during the development of the disease. Lipoxygenase activity per cell of lymph mo mice, although cyclooxygenase activity was low in both cases. These phenomena did not depend on aging since age-matched MRL/n mice lacking the lpr gene (congenic with MRL/1 mice), and BALB/c mice did not exhibit any change in the enzyme activity with aging. The lipoxygenase activity of 4 mo MRL/1 lymph node cells came mainly from nylon wool nonadherent cells. Lipoxygenase activity of nylon wool nonadherent spleen cells in MRL/1 mice was also higher in 4 mo mice than that in 1.5 mo mice, whereas we could not detect any difference in nylon wool adherent cells. The major lipoxygenase product was 12-hydroxyeicosatetraenoic acid (12-HETE), which was identified by a high performance liquid chromatography (HPLC). Our data suggest that change in arachidonic acid metabolism in T cells may be related to development of autoimmune disease in MRL/1.

Age Factors↗
PubMed1983

Primary malignant melanoma of the esophagus.

The case of a 54-year-old man with primary malignant melanoma of the esophagus is described. The results of morphologic examination are presented, and the histogenesis of the tumor and the classification of melanomas are briefly discussed. Histologic examination suggested that this was a case of primary malignant melanoma of the esophagus arising from melanosis of the esophageal mucosa. Like melanomas from the oral mucosa, vagina, anus, and vulva, the tumor had lentiginous radial components.

Esophageal Neoplasms↗
PubMed1983

Rectification of immunological abnormalities and lupus nephritis by the transfer of bone marrow cells.

Two-month old MRL/1 mice, which spontaneously develop lymphoproliferative syndrome and severe lupus nephritis at 4-5 months of age, were irradiated and reconstituted with bone marrow cells from a congenic strain MRL/n mice. In the chimeric (n----1) mice, the early onset of the lupus nephritis was prevented as evidenced by decrease in the degree of proteinuria, diminished intensity of immune deposits in glomeruli, and milder histopathologic changes in kidneys. Lymph node swelling as well as generation of a large number of splenic IgSC was also prevented. Anti-ss DNA antibody response in the chimeric mice, however, varied tremendously from one animal to another.

Animals↗
PubMed1983

Effect of azathioprine and carbon tetrachloride on induction of hyperplastic liver nodule and hepatocellular carcinoma by diethylnitrosamine and N-2-fluorenylacetamide in rats.

The enhancing or inhibitory action of the hepatotoxic agents, carbon tetrachloride (CCl4) and azathioprine (AZP), on the evolution of hyperplastic liver nodule (HN) and hepatocellular carcinoma (HCC) in diethylnitrosamine (DEN)- and N-2-fluorenylacetamide (FAA)-treated rats (control group) was tested. The area of gamma-glutamyl transpeptidase(gamma-GTP)-positive HN and/or foci in the eighth week was remarkably small in rats fed on a diet containing FAA and AZP (the AZP group), but was quite large in rats fed a diet containing FAA in addition to repeated CCl4 injections (the CCl4 group). HCC was first detected in the 21st week and the incidence of HCC within the 36 weeks of the experiment was very high in the CCl4 group. However, no tumor, including HCC, was detected in the AZP group during this observation period. No essential differences in the biochemical characteristics of HCC between the control group and the CCl4 group were observed with respect to several enzyme activities. The increased activity of liver aniline hydroxylase observed 12 hr after the administration of FAA, AZP, or DEN decreased when AZP was administered simultaneously with FAA to rats treated with DEN in advance. The mechanisms of the enhancing of inhibitory effect observed are discussed with special reference to the drug-drug interactions.

2-Acetylaminofluorene↗
PubMed1983

Vasorelaxing actions of molsidomine and its metabolites, in comparison with nitroglycerin.

The effect of a novel antianginal agent, molsidomine (N-ethoxycarbonyl-3-morpholinosydnonimine) (SIN-10) and its metabolites, 3-morpholinosydnonimine (SIN-1) and N-nitroso-N-morpholinoaminoacetonitrile (SIN-1A) on isolated dog blood vessels were investigated. SIN-1 and SIN-1A elicited a concentration-dependent relaxation of prostaglandin F2 alpha, contracted strips, while SIN-10 was without effect even in a concentration of 10(-4) M. The mean effective concentration (EC50) values of SIN-1A were much lower than SIN-1 and other vasodilators including nitroglycerin. The time course of relaxation was more rapid and transient in response to SIN-1A than to SIN-1. Adrenergic and cholinergic blocking agents did not affect the relaxing responses to SIN-1 and SIN-1A. SIN-1A also attenuated the norepinephrine-, KCl-, Ca2+-, or electrical transmural stimulation-induced contractile response, but SIN-1A increased the [3H]norepinephrine release from the adrenergic nerve terminals in response to transmural stimulation. Methemoglobin, which reportedly binds nitric oxide, or methylene blue, an inhibitor of guanylate cyclase, attenuated the relaxing response to SIN-1A. These results indicate that the vasodilating action of molsidomine results from the direct action on the vascular smooth muscle and suggest that the action is caused by its metabolites, probably SIN-1A, which contains a nitric oxide-moiety in the molecule. The possible mechanism of vasorelaxing action of SIN-1A is discussed in comparison with that of nitroglycerin.

Animals↗
PubMed1983

Effect of continued drinking on prognosis of alcoholic liver cirrhosis.

The prognoses of patients with alcoholic liver cirrhosis were compared between those who continued to drink and those who stopped. Clinical criteria were strictly set so as to control other variables affecting the prognoses. Four-year survival was significantly higher in the patients who stopped drinking than in those who continued to drink. Continued drinking worsens the prognosis of patients with alcoholic liver cirrhosis.

Adult↗
PubMed1983

Effects of Met-enkephalin on the substance P-ergic and cholinergic responses in the rabbit iris sphincter muscle.

In the rabbit iris sphincter muscle, transmural electrical stimulation produces a substance P-ergic response, in addition to a cholinergic one. The substance P-ergic response was selectively attenuated or abolished by (D-Pro2, D-Trp7,9) substance P or trigeminal denervation. In the present work, the effects of Met-enkephalin on these two neurogenic responses were examined. Met-enkephalin (10(-7) to 10(-5) M) inhibited the substance P-ergic and cholinergic responses, in a dose-dependent manner and the inhibitory action of Met-enkephalin was greater in the case of low frequency stimulation. These inhibitory effects of Met-enkephalin were antagonized by naloxone (10(-5) M). On the other hand, Met-enkephalin had no effects on the responses to exogenously applied substances P and carbachol. These results suggest that the trigeminal, substance P-ergic neurons as well as cholinergic nerves have opiate receptors and that enkephalin inhibits the neuronal responses presynaptically, probably the release of substance P or acetylcholine, through such opiate receptors.

Animals↗