[Renal hypertension (author's transl)].
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Biomedical subjects
Publications and source records attributed to T Omae.
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The DNAase in human urine was purified about 30-fold with a recovery of 28%. This involved DEAE-cellulose and phosphocellulose chromatography steps and gel filtration on Sephadex G-75. The enzyme required divalent cations such as Co2+, Mg2+, Mn2+ and Zn2+ for activity, but Ca2+, Cu2+ and Fe2+ were ineffective. EDTA and G-actin inhibited the reaction. The maximum activity was observed at pH 5.5 in acetate buffer plus Co2+ or Mg2+ and Ca2+. It had a molecular weight of approximately 38 000, estimated by gel filtration on Sephadex G-75 and isoelectric point of around pH 3.9. The enzyme is an endonuclease which hydrolyzes native, double-stranded DNA about 3 to 4 times faster than thermally denatured DNA to produce 5'-phosphoryl- and 3'-hydroxyl-terminated oligonucleotides. The final preparation was free of non-specific acid and alkaline phosphatases, phosphodiesterase and ribonuclease activities.
Ultrastructural changes in the arterioles of the intestinal submucosa were observed in rats 20 to 24 hr after bilateral nephrectomy. Sham-operated rats served as controls. The changes of arterial pressure after the nephrectomy or sham operation was measured directly through carotid artery cannulation, and analysed by the paired t-test. Ferritin was injected intravenously into two rats in each group 60 min. before fixation in order to trace plasma insudation into the arteriolar wall. Mean blood pressure was 102 +/- 9 and 112 +/- 6 mm Hg (mean +/- S.E.), before and after the nephrectomy, respectively. The latter was significantly higher than the former, though it remained in the normotensive range. It was also higher than that in control rats after sham operation. In sham-operated rats, there were neither vascular lesions nor evidence of increased leakage of ferritin into arteriolar walls. Arterioles from the nephrectomised rats, on the other hand, exhibited foci of smooth muscle cell necrosis characterised by cellular fragmentation and the deposition of fibrinoid and electron-dense granules. The fibrinoid was of two types of axial periodicity, i.e., 20--23 nm and 16--17 nm, respectively. Dense granules, 13--90 nm in diameter, were encountered mainly between the basement membrane and plasma membrane of smooth muscle cells. Though scanty fibroblasts were seen, there was no infiltration of mononuclear cells in the adventitia accompanying medial necrosis. Ferritin particles accumulated in the necrotic foci of the media in high concentration, and were seen in endothelial gaps, within the cytoplasm and in palsmalemmal vesicles of the endothelial cells. The main pathway of ferritin insudation into the media was considered to be by way of endothelial gaps.
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An 18-year-old girl with von Gierke's disease associated with a lipid storage myopathy is reported. The diagnosis of von Gierke's disease was made from decreased activity in glucose-6-phosphatase in the jejunal biopsy specimen. Neurologically she showed generalized hypotonia of the muscles, atrophy of bilateral proximal muscles of the lower extremities, weakness in neck flexors, deltoid and lumbar girdle muscles, and a positive Gower's sign. Muscle biopsy from flexor femoris muscle revealed fatty deposition in type 1 fibers and atrophy of type 2 fibers and the diagnosis of an accompanying lipid storage myopathy was made. This case also had a ventricular septal defect confirmed by right cardiac catheterization.
Although impaired water diuresis in adrenocortical insufficiency is well-known, little attention has been paid to the diuretic pattern at night. In two cases of panhypopituitarism, the nocturnal diuretic pattern was found to be quite different from that in the morning, and marked diuresis did occur after water loading at night, without any significant change of serum cortisol which remained at a low level throughout the day. At the antidiuretic stage in the morning, urine osmolality continued to rise gradually, in spite of the water loading, to the level of 666 mOsm/liter. At the water restriction test, the urine was concentrated only to the same level of 600-700mOsm/liter. At the ascending stage of urine osmolality, exogenously injected pitressin showed little antidiuretic effect, although the kidney was able concentrate urine to the higher level later. In the morning, 3 liters of 5% glucose infusion failed to produce a marked diuresis in spite of extreme plasma dilution and expansion. Furosemide immediately induced diuresis even in the morning and the kidney recovered its ability to respond to pitressin. Glucocorticoid also improved the diuretic pattern in the morning, but a latent period of about 2 hr was always observed before the appearance of the effect. What happened during this latent period was unclear, but it was interesting to note that a mechanism similar to that which induces diuretic response seemed to occur without glucocorticoid at night.
As a tool with which to detect iodinated compounds in human thyroid specimens, we have reevaluated a nonincineration technique which has so far been employed in the determination of thyroxine-iodine in peripheral blood. The catalytic action of iodoamino acids in the Ce-As reaction was enhanced by a small amount of Cl2. On the contrary, a large amount of Cl2 inhibited the reaction unexpectedly. Among iodide, iodotyrosine and iodothyronine, iodide was the most effective catalyst in the Ce-As reaction and iodothyronine was the least effective one. Protein seemed to inhibit this reaction of thyroglobulin. But the result of iodine content in thyroglobulin by this technique agreed well with that by incineration when measured 127I was corrected by percent activity of dializable part of the total activity of 131I-thyroglobulin with the same protein concentration, after the NaClO treatment. The results of human thyroid specimens were as follows: the thyroglobulin content of five normal subjects was 8.0 +/- 1.5% of wet thyroid weight. That of Hashimoto's disease was significantly decreased which seemed compatible with the decrease in iodine content of thyroglobulin, whereas thyroglobulin content of Graves disease treated with 1-methyl, 2-mercaptoimidazole followed by a large dose of iodide was well preserved in spite of a lower degree of iodination of thyroglobulin. As for the distribution of iodoamino acids-iodine in normal thyroid, T4 was 20.5 +/- 0.7%. This technique ultimately looks promising as a tool with which to study intrathyroidal iodine metabolism in human.
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An interesting case of iodide induced goitre with immunological abnormalities is described. The patient who was sensitive to synthetic penicillin had previously been treated for exudative pleuritis, congestive heart failure and acute renal failure. Following recovery, he began to ingest large amounts of seaweed after which he developed goitrous hypothyroidism. It was of interest that the serum level of gamma-globulin increased, and subsequently the antithyroid microsomal antibody became strongly positive, suggesting that thyroidal autoimmune processes had been precipitated. Biopsy of the thyroid gland revealed chronic thyroiditis, with evidence suggesting extreme stimulation by TSH. Hight thyroidal uptake of 131I, positive perchlorate discharge test and biochemical analysis of the thyroidal soluble protein showed severe impairment of hormone synthesis following continuous accumulation of excess iodide. While there is evidence suggesting that increased iodide may be an important factor in the initiation of Hashimoto's thyroiditis, this may result from the marked increased sensitivity of Hashimoto's gland to the effects of iodine. Thus an occult lesion could be unmasked in this manner. The mechanism by which iodide mediates this effect is not clear.
In order to identify the nature of the substance(s) that causes pancreatic edema, pleural effusion, hematolcrit increase, and vascular lesion upon administration of renal extracts, effects of a pure preparation of submaxillary gland renin of mouse on blood vessels were studied. This enzyme was administered intraperitoneally to conscious anehpric rats. Blood pressure elevation recorded under unrestricted conditions was proportional to pancreatic edema, pleural effusion, hematocrit increase, and vascular lesions in small arteries and arterioles. Since the renin administered does not contain any substances and since the function of this enzyme is quite analogous to renal renin, these results have been interpreted to indicate that renin possesses both pressor and permeability activities and that the action of renin alone can account for the vascular lesions and the increased vascular permeability.
Peripheral neuropathy was not found even six to ten years after the onset of visual symptoms in a family with primary amyloidosis, except in the propositus at the terminal stage. The propositus had mainly ocular and CNS involvement. An ocular manifestation, the vitreous opacity, was the only involvement in the family members, in spite of the long clinical course. This family may have a different type of familial primary amyloidosis from that previously reported.
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The effects of bilateral common carotid artery occlusion on brain metabolism and arterial acid-base balance were studied in normotensive and experimental renovascular hypertensive rats. One hour after carotid occlusion in hypertensive rats, supratentorial lactate increased to 383% and lactate-pyruvate ratio to 280% of the controls, while adenosine triphosphate (ATP) decreased to 69%. These metabolic changes were thought to be due to cerebral ischemia. Arterial pCO2 was lowered and the pH was raised in the hypertensive animals due to cerebral ischemia induced hyperventilation. In the normotensive rats, carotid occlusion had minimal effects on cerebral metabolism and arterial acid-base balance. These results suggest that hypertensive rats are more susceptible to cerebral ischemia caused by carotid occlusion than normotensive rats. Increased cerebrovascular resistance in hypertension is discussed as a causal factor in cerebral ischemia.
Acid RNase was purified from normal human serum about 2400-fold by chromatography on phosphocellulose and Sephadex G-75 and rechromatography on Sephadex G-75. Assayed with yeast RNA as substrate, the enzyme showed the maximal activity at about pH 6.5 with sodium phosphate buffer. The reaction was activated by Na+, K+, and spermine, but it was not affected greatly by Mg2+, Co2+, and EDTA. Ca2+, Fe2+, Zn2+, and Cu2+ inhibited the reaction. Among the synthetic substrates examined, the enzyme preferentially hydrolyzed pyrimidine nucleotides, with a higher affinity for polycytidylate than for polyuridylate. The enzyme was thermolabile, but it stabilized with bovine plasma albumin. The molecular weight was approximately 15,000, estimated gel filtration on Sephadex G-75, and its isoelectric pH was above 11.0. From normal human leukocytes, acid RNase was purified about 400-fold by the same procedure described previously except that rechromatography on Sephadex G-75 was omitted. The properties of leukocytic RNase were found to be similar to those of serum acid RNase, but the latter enzyme differed in substrate specificity substantially from leukocytic RNase, preferring polyuridylate to polycytidylate. This evidence shows that serum RNase is not of leukocytic origin under normal physiological conditions.
Acid and alkaline RNase activities in serum were measured with yeast RNA as the substrate in normal subjects and in leukemic patients pretreatment and posttreatment, and the acid/alkaline ratios of activities were 0.63 +/- 0.08 (S.D.) (N, 12), 2.28 +/- 0.82 (N, 8), and 0.60 +/- 0.13 (N, 9), respectively. The mean value for the ratio in the pretreated leukemia was significantly higher than that in the other 2 groups (p less than 0.01). By separating these acid and alkaline RNases from normal and leukemic sera by phosphocellulose chromatography, it was further confirmed that acid RNase alone increased markedly in leukemic serum. From serum and leukocytes of leukemic patients, acid RNases were purified about 2000-fold and 300-fold, respectively, by phosphocellulose and Sephadex G-75 chromatography. Both enzymes displayed properties nearly identical with those of normal serum and leukocytes, except that leukemic serum acid RNase had about a 2.4-fold greater affinity for polyuridylate than for polycytidylate as substrate, in contrast to normal serum acid RNase that degraded polycytidylate exclusively. On the other hand acid RNases from serum leukocytes of leukemia showed a similar substrate preference. These results suggest that the high RNase levels of leukemic sera are due to an excessive leakage of acid RNase into the blood stream from abnormal leukocytes.
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