[Clinical studies on surgeries in hemophilia--report of 7 cases].
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Biomedical subjects
Publications and source records attributed to H Wada.
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Sympathetic nervous system may play an important role in the pathogenesis of essential hypertension. The present study was undertaken to evaluate the interaction between sodium intake and sympathetic nervous activity in the patients with essential hypertension. Plasma and urinary catecholamines (CA) were measured in 38 hypertensive patients (WHO 1-2 stage) and 24 age-matched normal subjects on regular (urinary sodium excretion (UNaV): 133 +/- 8 mEq/day; mean +/- SEM), high (UNaV 317 +/- 90 mEq/day), and low (UNaV 67 +/- 28 mEq/day) sodium diets for each 5 days at random. CA were analyzed by THI methods after HPLC separation. Twenty-four hour urinary norepinephrine (NE), epinephrine (E), and electrolytes (Na+, K+) excretion on the 5th day of each regimen were determined. In the 6th day morning supine and 5 min upright plasma NE(PNE), plasma E (PE), and plasma renin activity were determined after blood pressure and pulse rate measurement. The results were also analyzed according to the difference between salt-sensitive and non-salt-sensitive type of hypertensive patients. Plasma NE was 1.1 +/- 0.4 p mol/ml (supine), 1.5 +/- 0.4 p mol/ml (upright) in normotensive subjects and 1.8 +/- 1.1 p mol/ml (supine), 2.5 +/- 1.1 p mol/ml (upright) in the patients with essential hypertension, 24 hr urinary NE excretion were 116 +/- 54 micrograms/day in normotensive subjects and 138 +/- 88 micrograms/day in the patients with essential hypertension on regular sodium intake. Mean plasma NE levels in patients with essential hypertension were always higher than those in normotensive subjects on any sodium diets. Plasma NE and urinary NE were significantly reduced by high sodium intake and increased by low sodium intake in both normotensive subjects and the patients with essential hypertension. Percentile decrease in PNE when the diet was changed from low sodium to high sodium was much greater in normotensive subjects than the patients with essential hypertension. These tendency was observed in both salt-sensitive and non-salt-sensitive hypertensive patients. However, PNE in non-salt-sensitive hypertensive subjects tended to be higher than those in salt-sensitive hypertensive subjects. These results suggest that abnormal relationship between sodium intake and sympathetic nervous system may play an important role in the pathogenesis of essential hypertension.
A fluorometric method for the simultaneous analyses of phenethylamine, phenylethanolamine, tyramine and octopamine has been developed. The method involves ion-exchange chromatography, derivatization with fluorescamine, solvent extraction and then separation by thin-layer chromatography. The fluorescent spots are then quantitated by scanning. The detection limits of this method are about 10 pmoles for phenethylamine, phenylethanolamine and tyramine, and 20 pmoles for octopamine. The method was used for simultaneous analyses of putative neurotransmitter amines in whole rat brain.
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The contents of histamine in various tissues of mutant mice deficient in mast cells (W/Wv) and in congenic normal mice (+/+) were determined by high-performance liquid chromatography and were compared. In spite of the absence of mast cells in W/Wv mice, the histamine content of their whole bodies was about 5-10% of that of +/+ mice. The skin, heart and lungs of W/Wv mice contained negligible amounts of histamine (about 2% of that in +/+ mice), but the liver, kidneys and spleen contained appreciable histamine (8-15% of that in +/+ mice), and the brain and stomach contained much histamine (45 and 34%, respectively, of that in +/+ mice). These results indicate the presence of non-mast-cell histamine, especially in the brain and stomach, where it may play important physiological roles.
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Red blood cell lysates were applied to DEAE cellulose paper for detection of glucose-6-phosphate dehydrogenase. Glucose-6-phosphate dehydrogenase (G-6-PD) was separated from 6-phosphogluconate dehydrogenase (6-PGD) by DEAE-cellulose paper-chromatography and their activities were detected on the chromatogram by applying the reaction mixture. The fluorescence of NADPH formed by G-6-PD was not interfered with by 6-PGD activity. This is a sensitive procedure which detects slight loss of G-6-PD in red blood cells and could be applied to the detection of G-6-PD deficiency.
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Histidine decarboxylase (HisDCase, EC 4.1.1.22) activity in mouse skin increased by a factor of more than 10 after a single application of phorbol 12-myristate 13-acetate. The cell type that was responsible for the increase in HisDCase activity was examined by using (WB X C57BL/6)F1-W/Wv mice, which are genetically deficient in tissue mast cells. In contrast to a report that increase of ornithine decarboxylase (EC 4.1.1.17) activity occurs in the epidermis [O'Brien, T. G., Simisiman, R. C. & Boutwell, R. K. (1975) Cancer Res. 35, 2426-2433], the HisDCase activity was found to increase in the dermis. Although most of the histamine in the dermis was present in mast cells, the increase in HisDCase activity in the skin in W/Wv mice was comparable with that in congeneic +/+ mice. This increase of HisDCase activity in the skin of W/Wv mice was abolished by prior x-ray irradiation (800 rads; 1 rad = 0.01 gray) but was restored by subsequent bone marrow transplantation. Because mice, in general, are known to lack basophilic leukocytes, the present results suggest the existence of histamine-producing cells without basophilic granules that are derived from the bone marrow.
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Previously we reported that the heart norepinephrine concentration was markedly increased in diabetic rats. To further study the relationship between a disturbance in the autonomic nervous system and catecholamine metabolism in diabetes mellitus, the plasma catecholamine response to stress and catecholamine concentration of heart and adrenals were measured. Wistar male rats were made diabetic by streptozotocin and kept for 13 weeks. A silicon catheter was placed in the superior V. cava 1 week prior to the experiment. Insulin was injected subcutaneously for 3 days once daily. After an overnight fast and without anesthesia, 1 ml of blood, a control sample, was obtained and then the animals were exsanguinated. The blood was mixed with 1 mM EGTA at a final concentration and centrifuged. The tissue was homogenized with 0.4 N perchloric acid containing 1 mM EGTA and centrifuged at 10,000 x g for 20 minutes. Catecholamines were determined by high performance liquid chromatography. Normal rats responded to blood withdrawal stress, and plasma catecholamines were markedly increased, but almost no increase or an actual decrease was observed in diabetic rats. These abnormal responses were improved by insulin treatment. Heart norepinephrine was increased significantly in the diabetic rats compared with the control rats and was reduced significantly by insulin injections. Adrenal epinephrine was also significantly increased in the diabetic rats compared with the control rats, but was not significantly reduced by insulin. These result suggest a possible disturbance of catecholamine secretion in the diabetic rats.
A comparative study on the localization of enzyme activities in the 3 individual layers of the femoral artery of albino rabbits and the grafted artery revealed. 1) Very active energy metabolism was observed histochemically even in the grafted vessels, tissues usually regarded merely as a duct. 2) On a long-term observation, the enzyme activity in the grafted vessels never returned to normal. 3) All enzyme activities decreased after 3 to 6 months follow the grafting.
Escherichia coli L-asparaginase modified with monomethoxypolyethylene glycol, which has no ability to bind to the antibody and almost no immunogenicity, had a longer plasma half-life (32.9+/-2.5 hr) in normal mice than the native enzyme (3.35 +/- 0.45 hr). Preimmunization of mice with the native enzyme greatly shortened the plasma half-life of the native L-asparaginase (less than 0.1 hr) but did not change that of the modified L-asparaginase (32.2 +/- 2.1 hr). Treatment of mice bearing asparaginase-sensitive Gardner lymphoma (6C3HED) with L-asparaginases at various doses showed that the modified enzyme had a greater therapeutic effect than the native enzyme. In addition, preimmunization with the native enzyme prevented the antitumor activity of the native enzyme but did not affect the therapeutic efficacy of the modified L-asparaginase against the lymphoma.
Three alkaline RNases were purified from human pancreatic juice to near homogeneity as judged by sodium dodecyl sulfate and native polyacrylamide gel electrophoreses. The molecular weights of these RNases determined by sodium dodecyl sulfate electrophoresis were 27,000, 19,000, and 13,000. The activities of these three RNases were increased by addition of Mg2+, Ca2+, Co2+, K+, Na+, spermine, and spermidine and decreased by the addition of heparin, Cu2+, and Zn2+. These RNases showed higher hydrolytic activity toward polycytidylic acid than toward polyguanylic acid, polyuridylic acid, or polyadenylic acid. The three human pancreatic RNases were immunologically identical but differed from human liver RNase, as shown by Ouchterlony double-diffusion test. Radioimmunoassay of human pancreatic RNase showed that immunologically similar RNases are present in human saliva, and serum.
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