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Biomedical subjects

H Nishio

Publications and source records attributed to H Nishio.

At least 199 records · Page 11Linked to original sources
PubMed1991

Mechanism of transient increase in intracellular concentration of free calcium ions in HL-60 cell differentiation induced by vitamin D3 and phorbol ester.

A promyelocytic leukemia cell line, HL-60, was induced to differentiate into monocyte-macrophage lineage cells by treatment with active vitamin D3 and phorbol esters, and into granulocyte lineage ones by retinoic acid and dimethylsulfoxide. The changes in intracellular concentration of free calcium ions ([Ca2+]i) were measured and analyzed by calcium-imaging analysis with Fura 2-AM. A significant and transient increase in [Ca2+]i was observed in active vitamin D3 and phorbol ester systems; however, no change was detected with retinoic acid and dimethylsulfoxide. This increase was due to the influx of calcium ions from outside of the cells, and L-type calcium channels were shown to mainly contribute to this influx. Protein kinase C was also shown to be involved in the increase in [Ca2+]i.

Calcitriol↗
PubMed1990

A very small frame-shifting deletion within exon 19 of the Duchenne muscular dystrophy gene.

We report the molecular characterization of a Japanese Duchenne muscular dystrophy (DMD) patient. The analysis of genomic gene by polymerase chain reaction indicates that the individuals have a limited deletion within an amplified region, which encompasses exon 19 of DMD gene. The amplified region was sequenced. Comparison of the deletion joint sequence with the normal amplified region sequence indicates that both 5' and 3' deletion end points are present within exon 19 and the deletion removes total 52 bp out of 88 bp of exon 19. Both his mother and sister are carriers of the deletion-containing allele. The mutation introduces a termination codon at residue 791 in exon 20, and is predicted to result in the production of a severely truncated protein. This sort of deletion (designated as DMD-Kobe) might be classified as a new type of DMD gene abnormality.

Adolescent↗
PubMed1990

Cardiovascular effects of two disulfide analogues of sarafotoxin S6b.

Sarafotoxin S6b (STX-b), a peptide toxin isolated from the venom of the Israeli burrowing asp, Atractaspis engaddensis, consists of 21 amino acid residues with four cysteines at positions 1,3,11 and 15. In the present study, we compared the cardiovascular effects of two synthetic STX-b analogues with different disulfide bridge locations, i.e. STX-b type A (1-15, 3-11) and STX-b type B (1-11, 3-15). At doses of 0.3-3 nmoles/kg (i.v.), type A produced a sustained pressor effect with transient increase in pulse pressure. However, at 5 nmoles/kg, it produced a transient increase followed by decrease in blood pressure, heart rate and respiratory rate within 30 sec and 12 out of 13 mice died within 10 min. Various kinds of ECG changes, suggestive of myocardial ischemia and hyperkalemia, were observed. Type A also caused a significant increase in the plasma levels of K+, lactate dehydrogenase, creatine phosphokinase, inorganic phosphate and glucose. By contrast, type B did not kill any mouse at doses up to 50 nmoles/kg. In the rat aorta, type A caused a potent vasoconstriction which was dependent on extracellular Ca2+ and was partially inhibited by verapamil and H-7, a protein kinase C inhibitor. In the rat Langendorff heart preparation, type A produced coronary vasospasm with potency about 100 times higher than that of type B. A similar potency ratio was observed for the positive inotropic effect in rat atria. These results indicate that the location of disulfide bridges in sarafotoxin S6b markedly influences the pharmacological potency and the natural sarafotoxin S6b should be type A with the disulfide bridge locations at positions 1-15 and 3-11.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1990

Glucose, free fatty acid and ketone body metabolism in Duchenne muscular dystrophy.

We examined how the substances, especially glucose, free fatty acids (FFA) and ketone bodies, and hormones associated with energy metabolism change with the disease progress in Duchenne muscular dystrophy (DMD). Serum creatine kinase (CK) activity was used as an index of the stage of DMD, because this activity is exponentially decreases with the progress of the disease. The glucose concentration in DMD patients with CK activity of less than 1,000 U/l (low CK) was significantly lower than that in controls, although there was no significant difference between that in DMD patients with CK activity of more than 1,00 U/l (high CK) and that in controls. The FFA concentration in both high CK and low CK patients was significantly higher than that in controls. The FFA concentration in low CK patients tended to be higher than that in high CK patients. The ketone body concentration in low CK patients was significantly higher than that in controls and that in high CK patients. The [glucagon]:[insulin] ratio in low CK patients was significantly higher than that in controls and that in high CK patients. It was also observed in a correlational study that the glucose concentration decreased with the age and the decrease in CK activity, i.e., with the progress of DMD. The FFA and ketone body concentrations increased with the decrease in the glucose concentration. The decrease in the glucose concentration may be due to a caloric shortage and/or degenerated muscle, which cannot supply enough gluconeogenic substrates, such as alanine. The kinetics of insulin and glucagon in DMD may help to maintain the glucose metabolism. Increased concentrations of FFA and ketone bodies may be helpful in the advanced stage of DMD, as energy sources and as substrates, sparing muscle protein.

Adolescent↗
PubMed1990

Beta-glucosidase activity in liver, spleen and brain in acute neuropathic Gaucher disease.

We examined the property of beta-D-glucosidase in normal child liver, spleen and brain tissues and in tissues affected by Gaucher disease using two different kinds of synthetic substrates, 2-hexadecanoylamino-4-nitrophenyl-beta-D-glucopyranoside (HN Glc) and 4-methylumbelliferyl-beta-D-glucopyranoside (MU Glc). HN glucosidase activity was noted only in the particulate fraction of each organ tissues of the normal child, and it was deficient in the tissue affected by Gaucher disease. MU glucosidase activity in the whole homogenate and the soluble fraction showed normal levels for the liver and brain tissue of the Gaucher patient. However, MU glucosidase activity in the particulate fraction, at the vicinity of pH 4.5, for the liver, spleen and brain tissue was deficient in the affected patient. HN Glc was a very easy and useful substrate for the diagnosis of Gaucher disease, but it was not very sensitive. While MU Glc was very sensitive, it was necessary to remove the non-specific beta-D-glucosidase for the diagnosis of Gaucher disease.

Brain↗
PubMed1990

Deficient activity of nucleotide binding regulatory protein coupled with PGE2 receptor in renal medulla of spontaneously hypertensive rats.

Prostaglandin (PG) E2 receptor-adenylate cyclase system was studied in the kidney of 12-week-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) to evaluate the role of this system in hypertension. PGE2 receptors were determined by a radioligand binding method using [3H]-PGE2. Adenylate cyclase responses to PGE2, sodium fluoride (NaF) and forskolin were also measured. The concentration of PGE2 receptor was increased in SHR compared with WKY. PGE2- and NaF-stimulated adenylate cyclase activities were significantly lower in SHR than WKY. There was no significant difference in forskolin-stimulated adenylate cyclase activity between SHR and WKY. NaF activates the nucleotide binding regulatory protein (G-protein) and forskolin directly activates the catalytic unit. These results indicate that the activity of G-protein coupled with renal PGE2 receptors is deficient in SHR. This defect may contribute to the elevation of blood pressure, through sodium retention.

Adenylyl Cyclases↗
PubMed1990

Urinary dicarboxylic acids in X-linked adrenoleukodystrophy.

The urinary excretion of dicarboxylic acids in X-linked adrenoleukodystrophy (X-ALD) was studied. The dicarboxylic acid profile in X-ALD did not show any specific pattern, unlike Zellweger syndrome and neonatal adrenoleukodystrophy. Medium-chain dicarboxylic acids with an even number of carbon atoms (adipic, suberic, sebacic) and an odd number of carbon atoms (pimelic, azelaic) were excreted within the normal ranges. Dicarboxylic acids with more than 10 carbon atoms were not found. These findings may be due to the normal beta-oxidation system of dicarboxylic acids in X-ALD.

Adolescent↗
PubMed1990

Metabolic risk factors in the normolipidemic male patients with angiographically defined coronary artery disease.

The relationship of plasma lipid and apolipoprotein (apo) concentrations and plasma insulin response to oral glucose load to angiographically determined coronary artery disease (CAD) was investigated in 65 normolipidemic (plasma cholesterol less than 230 mg/dl and plasma triglyceride less than 150 mg/dl) males. According to the results of coronary angiography, the patients were divided into 2 groups: patients with normal coronary artery, NCA group (n = 21); and patients with coronary artery disease, CAD group (n = 44). No significant differences in concentrations of plasma cholesterol and triglyceride were observed between the CAD and NCA groups. In the CAD group cumulative lifetime tobacco consumption was higher and high density lipoprotein (HDL) cholesterol concentration was lower than those in the NCA group. The variables that correlated with the severity of CAD, defined by the number of lesions and percent stenosis, were levels of plasma apo A-I and apo B. Prevalence of subjects with reduced oral glucose tolerance did not differ between 2 groups. However, hyperinsulinemic response to oral glucose load was present in the CAD group. HDL-cholesterol concentration, the sum of plasma insulin levels and the magnitude of the early insulin response during oral glucose challenge were accurate predictors of the presence of but not the severity of CAD. Multivariate analysis of the data confirmed the independent effect of plasma levels of apo A-I and apo B on the severity of CAD. The present data indicated that plasma levels of apo A-I and apo B were powerful discriminators in the normolipidemic CAD patients and that a high insulin response might be an indicator of enhanced susceptibility to the distinct coronary atherosclerosis.

Adult↗
PubMed1990

Effect of concanavalin A on serotonin transport into blood platelets: possible involvement of protein kinase C.

Possible involvement of protein kinases in the serotonin (5-HT) transport system in platelets and the inhibitory effect of concanavalin A (Con A) on platelet 5-HT uptake were investigated. Staurosporine and K-252a, highly active inhibitors of protein kinases, did not inhibit 5-HT transport, but they antagonized the inhibitory effect of Con A on 5-HT uptake. KT5720, a protein kinase A inhibitor that has no effect on protein kinase C, neither affected 5-HT transport nor antagonized the inhibitory effect of Con A on 5-HT uptake. The Con A effect on 5-HT uptake was also antagonized by LaCl3, a Ca++ entry blocker. When the activity of Ca++ transport into platelets was estimated, Con A was shown to have a stimulative effect, which was antagonized by alpha-methyl-D-mannoside, a specific antagonist of Con A binding to cell membrane glycoproteins. Furthermore, Con A was shown to stimulate the protein kinase C activity of platelets, which phosphorylates a 40-kDa platelet protein; the Con A effects were antagonized by alpha-methyl-D-mannoside, staurosporine and K-252a, but not by KT5720. We suggest that the activation of protein kinase C and phosphorylation of 40-kDa protein might be involved in the inhibitory effect of Con A on platelet 5-HT transport.

Alkaloids↗
PubMed1990

The biochemical and ultrastructural examinations in central cholinergic damage of the rat induced by the intraperitoneal administration of AF64A.

Ethylcholine mustard aziridinium ion (AF64A), a synthesized cholinergic neurotoxin, was administered via intraperitoneal injection to the rat to study its effect on the central cholinergic nervous system. A single or consecutive daily injection of AF64A for 10 days resulted in a persistent reduction of acetylcholine (ACh) content in the several tested regions of the brain in the following order: hippocampus greater than cerebral cortex = striatum, the degree was the greatest in the hippocampus. Both resting and K(+)-stimulated release of ACh from the hippocampus were also significantly reduced 24 hr after a single injection of AF64A. Furthermore, daily injection of AF64A for 10 days induced a significant reduction of choline acetyltransferase (ChAT) activity in the homogenate obtained from the hippocampus but not from the cerebral cortex and striatum. ChAT activity in the crude synaptosomal fraction of the cerebral cortex was also significantly decreased. These results suggest that intraperitoneal administration of AF64A could induce cholinergic hypofunction more selectively in the nerve terminals. The high affinity choline uptake, which is located mainly on cholinergic nerve terminals, was not affected by the administration of AF64A. Any notable changes of ultrastructure in the cholinergic nerve terminals after the administration were not observed in all three regions examined. The present findings suggested that intraperitoneal administration of AF64A induces a specific damage of cholinergic nerve terminals by inhibiting ChAT activity. The cholinergic damage was most prominent in the hippocampus.

Acetylcholine↗
PubMed1990

[A study on the psychological status of perioperative patients].

To evaluate the causes of psychic disturbances after operation, three different psychological tests, Spielberger's rating scale "The State-Trait Anxiety Inventory (STAI)", Maudsley Personality Inventory (MPI) and Baum test, were performed during perioperative periods in 25 patients who received simple total hysterectomy. The score of the A-Trait analyzed from STAI that is trait anxiety, did not change significantly, while the score of the A-State analyzed from that, that is state anxiety, decreased significantly in postoperative period. Especially, the score of the A-State showed gradual decreasing tendency during perioperative period in the patients, who were classified as N+ group in MPI, showing the tendency of nervousness. On the contrary, in the patients of N- group, showing no tendency of nervousness, the score of the A-State increased significantly immediately before operation. In Baum test, most of the patients showed some psychological disturbances even during the postoperative period. From the Baum test, it was shown that they had psychologic fragility and lability even postoperatively, in spite of stabilization of general status.

Adult↗
PubMed1990

[A case of miliary tuberculosis associated with acute respiratory failure during pregnancy].

A case of miliary tuberculosis associated with acute respiratory failure during pregnancy was reported. A 39-year-old, 29-week pregnant woman was admitted to our hospital with complaints of nonproductive cough and fever on June 12. On admission, her temperature was 38.2 degrees C; pulse rate was 90/min., and blood pressure was 120/76 mmHg. Physical examination revealed moist rales at right lung basis. Chest X-ray showed small nodular infiltrates in right lower lung field. Laboratory data revealed positive CRP, accelerated ESR and increased level of alpha 2-globulin. The number of T-cells was markedly decreased (14/mm3). The PPD skin test was negative, and the sputum smears for acid-fast bacilli were negative. Suspected of bacterial or viral pneumonia, the patient was treated with antibiotics (CPM, EM and CAZ), which had no effects for her. On June 16, the Chest X-ray showed infiltrates throughout bilateral lung fields, and the patient became increasingly dyspneic. On June 18, the results of arterial blood gas, analysis under room air were: PaO2 26.7 Torr, PaCO2 29.0 Torr, pH 7.505. Because of severe hypoxemia, she was intubated and placed on a volume-cycled respirator. Hydrocortisone (1000 mg, daily) was added to treatment because ARDS was suspected. Since the smears of tracheobronchial secretions showed acid-fast bacilli on June 24, she was diagnosed to have miliary tuberculosis. Then the intensive therapy with antituberculosis drugs (isoniazid 400 mg, rifampicin 450 mg, and streptomycin 1g, daily) was started. The non specific antibiotics were discontinued; hydrocortisone was tapered and stopped. The next week, she became afebrile and hypoxemia steadily improved.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1990

[Immunohistochemical studies of collagen types I, III and IV distribution and the expression of procollagen III peptide in papillary carcinomas of the thyroid].

Collagen types I, III and IV and procollagen III peptide (P III P) were examined immunohistochemically in 38 papillary carcinomas of the thyroid. The immunoreactivity to both type I and type III collagen was diffuse and abundantly observed in the fibrous stroma, where it displayed a fibrillar and/or granular pattern with little difference in the intensity of the staining. The immunoreactivity to collagen type IV was localized in the basement membrane of the vessels and partly in the tumor cell nests. A distinctive cytoplasmic immunoreactivity to P III P was observed in the cancer cells and the fibroblasts in all of the 38 papillary carcinomas, specifically an intense and extensive immunoreactivity by the cancer cells present in tumors having fibrosclerosing stroma and/or showing an extensive local invasion. Thus, it is conceivable that stromal collagen in a papillary carcinoma can be produced by not only the fibroblasts but also by tumor cells and its productivity could be affected by the degree of the tumoral invasion.

Carcinoma, Papillary↗
PubMed1989

Structure-activity relationship of endothelin: importance of charged groups.

Endothelin (ET)-related peptides including ET-1 (1-39) were synthesized, and their constricting activity in rat pulmonary artery rings and pressor activity in unanesthetized rat were measured to elucidate their structure-activity relationship. The vasoconstrictor activities of ET-2, ET-3 and sarafotoxin S6b were one-half, one-60th and one-third that of ET-1, respectively. Such differences in biological activities should mainly arise from sequence heterogeneity at the N-terminal portion, especially at positions 4 to 7. All of the blocked ETs at the amino or carboxyl termini showed greatly decreased activities. A monocyclic analog, in which Cys3 and Cys11 were replaced by Ala, showed one-third the activity of ET-1; however, its deamino dicarba analog was almost completely inactive. Significant activities were retained even with replacement of amino acids at positions Ser4, Ser5, Leu6, Met7, Lys9, Tyr13, and Trp21 by Ala, Ala, Gly, Met(0), Leu, Phe, and Tyr or Phe, respectively. On the other hand, replacement of Asp8, Glu10 and Phe14 by Asn, Gln and Ala, respectively, resulted in complete loss of the biological activity. These results indicated that two disulfide bonds in ET molecule were not essential for the expression of vasoconstricting activity. Both terminal amino and carboxyl groups, carboxyl groups of Asp8 and Glu10, and the aromatic group of Phe14 seemed to be contributing, more or less, to the expression of the biological activities.

Animals↗
PubMed1989

[Development and clinical application of double catheter system for angiography].

Simultaneous double angiography of the two main branches of the aorta usually requires bilateral puncture of the femoral arteries. A double catheter system was devised to avoid this inconvenience. This system is composed of a 7F sheath with a valve of two small holes and two 3.5F catheters. Using this system and DSA, simultaneous double angiography of the two main branches of the aorta was performed with only one puncture site of a femoral artery in five cases. In four cases the splenic vein, superior mesenteric vein and portal vein were all opacified simultaneously. This system promises to be useful for visualization of the portal venous system and can be used for other simultaneous double angiography.

Angiography↗
PubMed1989

Synthesis of endothelin-1 analogues, endothelin-3, and sarafotoxin S6b: structure-activity relationships.

Two disulfide analogues (types A and B) of endothelin-3 (ET-3; formerly, rat ET), sarafotoxin S6b, and apamin, were synthesized to determine their disulfide structures as in the case of endothelin-1 (ET-1; formerly human and porcine ET). The disulfide structures of ET-3 and sarafotoxin S6b were found to be identical with that of ET-1 (type A) but distinct from that of apamin (type B). The vasoconstricting activities of ET-3 and sarafotoxin S6b were about one-60th and one-third that of ET-1, respectively. Such different biological potencies between endothelins and sarafotoxin S6b could be largely attributed to the sequence heterogeneity at the N-terminal portion. ET-1 analogues were also synthesized to clarify the structure-activity relationships. The opening of any disulfide bond in the ET-1 molecule extremely decreased the activity, while oxidation of the Met residue did not alter it. Amidation of the terminal COOH group and extension of the Lys-Arg sequence to the N-terminus led to 16- and 540-fold decreases in activity, respectively. Removal of the C-terminal Trp residue resulted in complete loss of the activity. The other disulfide analogues (type B and C) of ET-1 showed markedly lower activity than the parent molecule (type A). These results indicated the importance of the whole molecule with the proper double cyclic structure for determining its active conformation.

Amino Acid Sequence↗