The authors have an opinion that changes of glycoprotein metabolism of many tissues, especially those of connective tissues, relate intimately to aging changes and arteriosclerosis as a causative factor, and that changes of serum glycoproteins indicate, more or less, those of tissues. In this paper, we estimated serum level of seromucoid (Winzler's mucoprotein), protein-bound hexose (PBH), total protein and fraction of serum glycoproteins (Schiff positive substances) and proteins in normal, arteriosclerotic and obese people to find the relationship between changes of glycoprotein metabolism and aging or arteriosclerosis. The reason to estimate those substances in obese people was that obesity was considered as a condition preparing arteriosclerosis. The results were as follows: 1) The mean level of seromucoid and PBH were increased with aging. The differences between the young group (year range 18-35) and the middle aged (36-59 years) were statistically significant. However, those between the middle aged and the aged (over 60 years) were not. Glycoprotein fraction showed statistically significant decrease of albumin and increase of α1-globulin in the aged group compared with those in the young. Those in the middle aged were intermediate. 2) In the middle aged obese group, seromucoid and PBH were significantly elevated. Each value showed a lineal positive correlation with obesity index calcurated from body weight and height. Glycoprotein fraction in this group were not significantly different from control. 3) In the arteriosclerotic group, seromucoid and PBH were significantly elevated. However, comparing each corresponding group, the increase of PBH in middle aged arteriosclerotic group and increase of seromucoid in the aged were statistically significant. In both the middle aged and the aged arteriosclerotic group, α1-globulin was significantly increased. The decrease of albumin was significant only in the middle aged group. 4) The morning and afternoon levels of PBH and seromucoid of the same individual were not different.
The Parathyroids were dissected out from 71 autopsy cases, fixed in 10% formalin, embedded in paraffin, sliced to a thickness of 6 microns and stained with Haematoxylin-Eosin. Photomicrograms of 50 fold magnification were used to calculate the relative areas of fatty infiltration and oxyphil cell islands, while a 400 fold magnification was used to estimate the total nuclear area (TNA) and total number of nuclei (TNN) in a unit area occupied entirely of chief cells, and also the average nuclear area (ANA) which may be obtained by dividing TNA by TNN. Twenty-five of the 71 cases had renal insufficiency as the main disease process leading to the fatal outcome, while the other 46, who died from various other causes, were used to calculate the correlation between age and histometrical values of the parathyroids. Above the age of 60, a marked increase in fatty infiltration and oxyphil islands was observed. TNA and ANA were found to decrease with advancing age showing a significant negative correlation, whereas TNN failed to show a significant correlation, indicating a decrease in size of individual nuclei, although the size of the cell as a whole did not change significantly. In renal disease, on the other hand, hyperplasia of each cell seemed to take place. Cases with aortic atherosclerosis showed changes similar to those caused by aging. TNA, TNN, and ANA also showed a significant negative correlation with systolic and diastolic blood pressure, suggesting that a decrease in size of individual nuclei and hyperplasia of each chief cell occurs as the blood pressure is elevated. These results might suggest some relationship between the function of the parathyroid gland and the aging process, especially the elevation of blood pressure and development of atherosclerosis.
Out of 583 autopsied cases in Yokufukai (Old people's home) during the last 6 years, pulmonary tuberculosis was found in 59 cases. Clinico-pathological study was carried out to clarify the factors responsible for the disturbances in pulmonary circulation and right heart enlargement in these cases. 1. The incidence of pulmonary atherosclerosis and of right heart enlargement in the cases with pulmonary tuberculosis complicated by pulmonary emphysema was higher than that in the cases with pulmonary tuberculosis alone. 2. In the cases with pulmonary tuberculosis alone, the incidence of pulmonary atherosclerosis was increased with the extent of tuberculous foci, and that of the right heart enlargement was the highest in far advanced group. As the clinical course was prolonged, moreover, the incidence of right heart enlargement was further increased in far advanced cases. 3. In the post-mortem study, obliteration and narrowing of the pulmonary arteries due to the intimal fibrosis with infiltration of round cells and the increase in elastic fibers in the media were found in the tuberculous foci or in the neighboring area. 4. These results suggested that the anatomical factor played an important role in the development of pulmonary heart disease in pulmonary tuberculosis.
After synthesizing Oxidized Starch Sulfates (OS-S) with various chemical properties (molecular weight and sulfur content), investigations were made on the relationships between chemical properties of OS-S and their several biological properties in order to use them for medical purposes such as hypercholesteremia and atherosclerosis. Outlines of the experimental methods used and the conclusions obtained were as follows. Clearing activity: In order to demonstrate the different behaviours of clearing activity induced by heparin or OS-S, samples were administered intravenously to rabbits and blood samples were drawed repeatedly at appropriate time intervals to analyze clearing activity. The lipemia clearing activity of OS-S was then compared with that of heparin and it was observed that maximal activation of clearing activity by OS-S occurred within 60 to 90 minutes after administration and duration of the activity was prolonged while the maximum was reached within 15 to 30 minutes and the activity declined rapidly in the case of heparin. Relationships between the clearing activity of OS-S and molecular weight (viscosity) or degree of sulfation of it was studied. It was recognized that the lipemia clearing activity of OS-S was parallel with their sulfur content but not with molecular weight (viscosity). It was also revealed that there was no direct correlation between clearing activity and blood anticoagulant activity of OS-S. Hypocholesteremic aciton: Hypocholesteremic action of the OS-S which has strong clearing activity, was examined using hypercholesteremic rabbits. It was observed that OS-S reduced turbidity and serum total cholesterol significantly and this hypocholesteremic action of OS-S was more effective than that of heparin. Since the peak of the decrease of cholesterol occurred slower than that of turbidity, it was considered that the decrease of the former was induced indirectly by clearing factor which hydrolyzes the triglycerides in β-lipoprotein and produced umballance in β-lipoprotein. Inhibition of Atherosclerosis: Simultaneously with the beginning of cholesterol feeding the treatment of these animals with 5mg/kg of OS-S (sulfur content 16.00, [η] 0.0078) twice daily was begun and continued for fifty days. OS-S prevented significantly the rises of serum turbidity and serum total cholesterol. The values of serum turbidity and cholesterol treated with OS-S were less than half of the values untreated controls at the end of the experiment. OS-S also inhibited the development of atherosclerosis as judged by naked eyes. The average aorta of the animals treated with OS-S presented less than one sixth the atheroma area of the untreated control aorta. The differences between the mean blood clotting time of the rabbits treated with OS-S and untreated control were not significant. From the above experiments it is concluded that OS-S which have sulfur content ranging from 13 to 16% and molecular weight about 3, 000 are suitable for clearing action of hyperlipemia, hypocholesteremic action, and inhibition of atherosclerosis.
It is wellknown that postheparin plasma lipase appears rapidly in the blood. when heparin is injected intravenously. On the other hand, it has been recognized when epididymal adipose tissue or heart tissue are incubated in vitro with heparin, lipoprotein lipase (LPL) is rapidly released in the medium. After experimental conditions were determined referring to the method of Cherks et al., in vitro studies were made in order to investigate the effect of addition of heparin, Oxidized Starch Sulfate (OS-S) which was demonstrated to have lipemia clearing action in our previous paper and some other natural and synthetic polysaccharide sulfates on the rate of increase of LPL activity which appears in the medium when rat heart tissue is incubated with them. Experimental methods: Male albino rats weighing about 200g were killed by blow on the head and the heart excised and trimmed, rinsed quickly with cold Krebs Ringer phosphate buffer (pH 7.4) and then sliced or homogenized. Slices or homogenate, each weighing approximately 100mg, were placed in Warburg flasks which contained 1.0ml of Krebs Ringer phosphate buffer. To each flasks was added 200μg of heparin (Dai-ichi Chemicals, Japan), OS-S or other polysaccharide sulfates and preincubated for 60 minutes at 37°C under shaking and under air. After preincubation, medium was centrifuged at 15, 000g for 10 minutes and 0.5ml of the supernatant solution was added to centrifuge tube which contained 0.5ml of artificial lipoprotein substrate which was made by mixing one part of 10% bovine serum albumin (pH 8.7), two parts of 5% coconut oil emulsion and equal parts of fresh rat serum with final adjustment of pH to 8.5 with diluted ammonia and incubating the mixture at 37°C for 30 minutes. Incubation was carried out at 37°C and after 30 minutes reaction was stopped and deprotenized by adding 5% trichloroacetic acid. Mixture was centrifuged and glycerol in the supernatant was measured by means of Lambert-Neish method. Lipoprotein lipase activity was expressed as μg glycerol per 100mg of fresh tissue liberated in one hour. Results: From the data obtained, specific activities of the rate of increase of LPL activity of the other polysaccharide sulfates were calculated and expressed in terms of heparin having an arbitrary value of 100. Chondroitin Sulfate=-19, Carrageenin=44, Fucoidin Sulfate=-39, Dextran Sulfate B.P.=41, Dextran Sulfate=70, and OS-S I-V which have same viscosities about 0.026 and S% 3.7, 6.5, 8.0, 10.1, and 12.7 respectively showed the rates of increase of LPL activity 17, 28, 50, 61, and 70, and these results are parallel with their sulfur content. Further investigations on the increasing action of LPL activity in the medium by heparin or the other polysaccaride sulfates revealed that the action contains the action to activate LPL as well as that to release the enzyme from tissue.
In view of the importance of obtaining informations concerning the metabolic response to surgical stress in the early stage at individual organs. The authors have studied the influences of aging on the metabolism of nucleic acids, situating at the crossroad of the energy metabolism and protein biosynthesis. Metabolic response of nucleic acids under surgical stress was studies in male mice of DDY-strain, with the superficial burn on the hind limbs and tail. 1. DNA and RNA content in the liver and skeletal muscles were estimated quantitatively by the Schmidt-Thannhauser procedure. In the skeletal muscles of mice (6 weeks old, 20g of body weight), total nitrogen, total creatinine and RNA per gram of wet tissue, were considerably reduced during the period from 8 to 15 hours after the burn. In the liver, on the other hand, the quantity of total nitrogen per gram of wet tissue was not markedly changed after the burn, and the quantity of RNA was increased (p<0.1), associated with the definite increase of tissue transaminase activity (p<0.01). 2. The control (pre-burn) value of RNA per gram of wet liver tissue was reduced in aged mice group of 10 months of age than in younger mice group of 6 weeks of age (p<0.01). Although the quantity of RNA was increased even in aged mice during the period of 16 hours after the burn, each RNA value was lower at any period after the burn in aged mice compared with the correspondine values in younger mice. 3. 32P incorporation in-vivo was estimated in the liver 15 hours after the burn. 50μc of 32P per 20g of body weight was injected intraperitoneally 3 hours after the burn, and the specific activity in liver of the burned mice was compared with the specific activity in the control group. Definite increase of 32P incorporation of ribonucleic acids (both s-RNA and r-RNA) was revealed even at 11 hours after the burn in the liver of younger mice (6 weeks old), but the increase of 32P incorporation was slower up to 15 hours after the burn in the liver of aged mice (10 months old). The quantity of upper ribonucleic acids per gram of wet tissue seemed to be decreased in the liver of patients above the sixth decades who underwent upper abdominal operation. Although further studies would be necessary to get more precise information, the increased turnover of nucleic acids metabolism in response to surgical stress appears to be more pronounced in young individuals than in the aged.