To determine the effect of aldosterone antagonist on renal prostaglandin E synthesis, the rate of urinary excretion of immunoreactive prostaglandin E was measured radioimmunologically before and during the oral administration of an aldosterone antagonist, spironolactone, in 5 patients with essential hypertension, 3 with primary aldosteronism and 2 with postoperative primary aldosteronism. Spironolactone was administered at an oral dose of 25mg 4 times daily for about 1 week. In the control state, the rates of urinary prostaglandin E excretion ranged from 151ng/day to 4, 527ng/day in essential hypertension. The rates were not augmented in primary aldosteronism but decreased after the removal of an aldosterone producing adenoma. No obvious relationship was observed between plasma aldosterone concentration and the rate of urinary prostaglandin E excretion. On the first day of spironolactone administration, the excretion rates of urinary prostaglandin E were markedly increased independently of basal plasma aldosterone level in all cases except one case of essential hypertension. Urinary prostaglandin E excretion was increased with the concominant increase of urinary Na/K ratio in essential hypertension and primary aldosteronism. After the second day, the augmented urinary prostaglandin E excretion was decreased and the changes of urinary prostaglandin E excretion varied from case to case. These results suggest that synthesis of renal prostaglandin E is not mainly regulated by aldosterone in essential hypertension and primary aldosteronism.
The metabolisms of lecithin and phosphate-dylglycerol in the surfactant and residual fractions of rat lung were compared using the in vitro system where tissue slices and radioactive precursors such as [14C] palmitic acid, [14C] palmitoyl lysolecithin and [14C] stearoyl lysolecithin were incubated. The incorporation of precursors into the residual lecithin proceeded linearly during the incubation time, while the time curve on the incorporation into the surfactant lecithin exhibited a lag period before the incorporation increased significantly. A similar tendency was also observed in the incorporation into phosphatidylglycerol. These findings suggested a precursor-product relationship between the corresponding lipids in both the fractions. The turnover time of lecithin was approx. 340-370min and that of phosphatidylglycerol was 118min in the intracellular surfactant fraction. The turnover rates of lecithin and phosphatidylglycerol were approx. 0.6and 2nmoles/g of wet tissue, respectively. The transfer of lecithin from the residual fraction to the surfactant fraction was hardly influenced by the difference of fatty acid moiety at the 2-position of 1-palmitoyl-lysolecithin. However, the turnover time of 1-palmitoyl lecithin (360min) was distinctly shorter than that of 1-stearoyl species (730min). The turnover time of the saturated lecithin was also shown to be 328min. On the other hand, polyenoic species showed the shorter turnover time; 182min for the tetraenoic species.
Both riboflavin-2', 3', 4', 5'-tetrabutyrate and flavin adenine dinucleotide (FAD), especially the latter, could inhibit H2O2-induced platelet aggregation. FAD enhanced the glutathione reductase activity of platelets. FAD might exert its inhibitory effect on the H2O2-induced platelet aggregation via the glutathione reductase and peroxidase system.
A single injection of carboquone at a dose of 0.1mg/kg body weight induced damage of DNA of AH-109A cells as revealed by alkaline and neutral sucrose density gradient centrifugation. A significant decrease in the sedimentation velocity of DNA on alkaline sucrose density gradient centrifugation was observed 15min after the injection, and it returned to that of control after 60min. Thereafter, the size of DNA decreased progressively. When the cells were lysed with 2% sodium dodesyl sulfate solution and analysed on neutral sucrose density gradient centrifugation, a similar change in the sedimentation velocity was observed. The results obtained from the studies of intraperitoneal growth of AH-109A cells pretreated with carboquone in vivo and the survival of host animals well corresponded to the extent of the damage of DNA as revealed by alkaline and neutral sucrose density gradient centrifugation.
Two cell lines, T24 and MGH-U1, established from human urinary bladder carcinoma showed typically epithelial features. Although the proliferating cell population presented a polymorphic appearance including polygonal and elongated cells, ultrastructural studies failed to identify different types of cells in each cell line. Extensive cytoplasmic organelles, microvilli on the cell surface and cell continuity with the junctional complex were common findings in both the cell lines. Virus-like particle was not detected. Chromosome numbers of these cell lines were distributed from hypertriploidy to hypertext-raploidy. T24 cell line contained a large number of elongated cells and well-developed microvilli as compared with MGH-U1 cell line. The present results suggest that T24 cell line has been transformed to a relatively uniform cell population during the long-term culture as referred to in a previous report.
Low molecular sialoglucides were isolated from the urines of normal human male and two patients with lysosomal disease (mucopolysaccharidosis type II and a new type of mucolipidosis) by charcoal adsorption method. Urinary sialoglucides were fractionated into two fractions (SC-1 and SG-2) by Sephadex G-25 gel filtration, and considerable increase in excretion of SG-1 was observed in the patients with lysosomal diseases: two to three-fold increase in mucopolysaccharidosis type II and seven to eight-fold increase in mucolipidosis. SG-1 was further fractionated into 18 to 19 fractions by Sephadex C-50 gel filtration and ion exchange chromatography. Comparison of the amounts and the chemical compositions of these fractions suggested that the increase in SG-1 was dependent upon the increase in excretion of low molecular sialoglucides rich in mannose and N-acetylglucosamine.
A mannose-containing sialooligosaccharide has been isolated from the urine of a patient with a newly recognized mucolipidosis which showed a low liver β-galactosidase activity and hyperglycopeptiduria. The chemical structure has been determined by glycosidase digestion, Smith degradation and permethylation studies. The following structure has been given for the oligosaccharide: NANAα2-6Galβ1-4GlcNAcβ1-2Manβ1-3Manβ1-4GlcNAc. This compound appears to be derived from an incomplete catabolism of glycoproteins with aspartylglucosylamine type side chains.
A method for simultaneous measurement of 11-deoxycorticosterone (DOC), 18-hydroxy-11-deoxycorti-costerone (18-OH-DOC) and aldosterone using 1.0-2.0ml of plasma has been developed. The present method consists of extracting plasma with dichloromethane, separating the DOC, 18-OH-DOC, and aldosterone from other steroids on a Sephadex LH-20 column, and quantitating each steroid by radioimmunoassay. This method was demonstrated to be sensitive, accurate and precise. In 20 normal male subjects, the mean recumbent level of DOC was 9.1±3.1ng/100ml, on random diet, at 0800h. The corresponding levels of 18-OH-DOC and aldosterone were 8.2±3.9ng/100ml, and 6.7±2.6ng/100ml, respectively. Plasma levels of these three steroids were measured in several types of adrenocortical disorders associated with hypertension and hypokalemia. Patients with Cushing's syndrome due to adrenocortical hyperplasia, and 17α-hydroxylase deficiency had elevated DOC and 18-OH-DOC levels, but showed normal or lower aldosterone levels. Hypersecretion of DOC and 18-OH-DOC may cause the symptoms of hypertension and hypokalemia. Patients with primary aldosteronism had elevated levels of DOC and 18-OH-DOC as well as aldosterone. The former two steroids may be hyperproduced as a precursor of aldosterone.
Three cases of congenital type of lipoatrophic diabetes were treated with oral antidiabetic agents or insulin for high blood sugar. The plasma triglyceride levels, determined after overnight fasting, were elevated following administration of oral agents or injections of insulin. On these medications, plasma phospholipid and cholesterol also tended to elevate. Paper electrophoresis of plasma revealed an increment of pre-β-lipoprotein. The levels of plasma triglyceride were reduced when doses of oral antidiabetic agents or insulin were kept constant for several days, and further reduction was observed after withdrawal of these therapeutics. These observations suggest that insulin enhances production and secretion of triglyceride in the liver.
Lethally irradiated mice received a transfusion of normal bone marrow cells from the same strain mice. The transfused colony-forming cells (stem cells) were settled in the spleen of the recipient and proliferated in it into erythroblast colonies. Some of these mice were given chloramphenicol or thiamphenicol for 7 days after marrow cell transfusion. Annulate lamellae were frequently observed exclusively in the erythroblasts of the mice received a injection of thiamphenicol.
A study was made of latent hepatic diseases in university students. 1.4% to 1.6% of the students were positive for hepatitis B surface antigen (HBsAg), and 10.3% for anti-HBs. Of 28 students with HBs-antigenemia, 2 had chronic persistent hepatitis, and 3 minimal hepatitis, 23 being healthy carriers. Hepatitis B e-antigen (HBeAg) was detected in 44% of the students with HBsAg, and anti-HBe in 13%. Anti-HBe was significantly more frequently found in female students with HBsAg than in male students. Though most of the students with HBsAg had high titer of antibody to hepatitis B core antigen (anti-HBc), there were a small number of cases showing low titer. HBsAg and anti-HBs was detected in the same serum specimens of 2 carrier students. Liver damage was also found in 3 students without HBs-antigenemia.
Klebsiella oxytoca was isolated from the blood of a leukemic patient. The typical pathogenicity of Klebsiella oxytoca was observed in the patient. The pathogenicity of several Klebsiella oxytoca strains isolated from blood, urine and sputum of different patients was examined in mice, and it was found that Klebsiella oxytoca isolated from the blood had a higher toxicity than the others.