In Japan, many cases of muscle contracture as a sequela of injections have been reported. We studied the physico-chemical properties and muscle-damaging potential of many injectables which are commonly used in hospitals. Contrary to our expectations, the pH of the injectables was found to range widely from 1.4 to 12.8, and the osmotic ratio from 0.2 to 36. It was also found that their hemolytic potential was closely related to the severity of the muscle lesions in animal experiments and that there were many injectables with strong muscle-damaging potentials. Therefore, doctors should be informed of the physico-chemical properties and tissue-damaging potential of each injectable; pharmaceutical companies should exert all possible efforts to improve injectables; and doctors should keep the administration of intramuscular injections to a minimum and use them only in cases of actual need.
Oligosaccharides derived from chondroitin 4-sulfate (Ch4-S) and chondroitin were digested by canine liver lysosomes under acidic conditions. The degree of digestion of Ch4-S by hyaluronidase and β-glucuronidase was examined on the basis of types of the digestion products. Tetradeca- and dodecasaccharides derived from Ch4-S and chondroitin were first digested by hyaluronidase, while the octasaccharide was hydrolyzed by β-glucuronidase. Decasaccharide was degraded by both hyaluronidase and β-glucuronidase. The results showed that decasaccharide from Ch4-S served as the largest-molecular-weight substrate for β-glucuronidase in the degradation of Ch4-S by the enzymes of lysosomes in contrast to the results of the digestion studies of hyaluronic acid (HA). The contribution of β-glucuronidase to the depolymerization of chondroitin and HA by hyaluronidase was examined in the presence of saccharo-l, 4-lactone, a specific inhibitor of β-glucuronidase, in the reaction mixture. The depolymerization of chondroitin by hyaluronidase was significantly reduced by the addition of saccharo-1, 4-lactone. From the results, it is suggested that β-glucuronidase contributes to the degradation of the evennumbered oligosaccharides which inhibit the action of hyaluronidase in the depolymerization of Ch4-S.
A 14-year-old boy was found to excrete excessive amounts of acidic glycosaminoglycans which were predominantly chondroitin 4-sulfate and chondroitin 6-sulfate. Clinical features included dwarfism, mental retardation, coarse facies, deformities of the spine, hip joints and thorax, and granulations in leucocytes. The clinical and biochemical features found in this boy were compared with the known types of mucopolysaccharidosis and it has been concluded that this case is a new type of mucopolysacchariduria.
Topical instillation of Adriamycin, 40 mg in 20 ml sterilized distilled water, was performed in 20 cases of bladder tumors every day for two weeks. In 8 cases (40%) the tumors disappeared completely, while in 5 cases (25%) tumors were reduced in size, but in 7 cases (35%) there was no effect. Therefore, the rate of effectiveness was 65%. The local bladder reaction and urethral pain were noted in all cases, as a result of which the therapy was interrupted in 2 cases. Abnormal values of red blood cells, white blood cells and platelets were not observed. In 3 cases the serum level of Adriamycin was only trace 1 or 2 hr after instillation. In conclusion, Mitomycin C was thought to be superior to Adriamycin as far as the effectiveness and irritability on the normal bladder epithelium were concerned.
One hundred and sixty cases of acute leukemia observed at our Department between 1953 and 1977 were reviewed as to the presence and nature of the accompanying gastrointestinal hemorrhage. A massive gastrointestinal hemorrhage requiring blood transfusions occurred in 29 cases (18%). The most common lesion was hemorrhagic necrosis of the small intestines. There were three forms of hemorrhage: Type I: thrombocytopenia, hemorrhagic diathesis, diffuse hemorrhage of mucosa and submucosa, but no erosion nor ulceration. Type II: no specific pathologic findings. Diffuse hemorrhage, superficial erosions, bacterial and fungal invasions were observed. Type III: single and/or multiple ulcerations, necrosis and perforation of the small intestines and colon. Thrombocytosis was almost always present at the prebleeding phase in these cases. Intravascular microthrombi at the basis of ulceration were seen. Usually, more than one process were seen in each case. An appropriate approach to the severe gastrointestinal hemorrhage with a combination of anti-leukemic chemotherapy, anti-coagulant therapy, platelet transfusion, etc. would further add to the number of long-term survivors in acute leukemia.
The tumor-inhibitory effect of injections of allogeneic tumor cells was observed. Established autochthonous sarcomas induced in the subcutaneous tissue of rats by 3-methylcholanthrene (MCA) were treated with immunization by using allogeneic Hirosaki sarcoma cells. When MCA-induced sarcomas grew to approximately 1 cm in mean diameter, Hirosaki sarcoma cells were inoculated into various tissues of primary tumor-bearing rats. Immunizing procedures consisted of intraperitoneal and subcutaneous injections in one experimental group, and of intradermal and intraperitoneal injections in another. Significantly inhibitory effect on the growth of autochthonous sarcomas was observed in the initial stage up to 2 cm in diameter as compared with that of control sarcomas. No significant inhibition was seen in the course of the growth of sarcomas larger than 2 cm in diameter. This results may indicate that immunotherapy by using allogeneic tumor cells should be considered to be valuable for the treatment of human cancer.
The development of glomerular lesions associated with ageing was investigated electron microscopically in rats with spontaneous diabetes. In young diabetic rats at eight weeks of age, there was no particular difference in ultrastructure from age-matched control rats showing an even contour of glomerular basement membrane, whereas in the diabetic rats at 12 weeks of age thickening of basement membrane with irregular protrusion of the epithelial side of lamina densa and accumulation of basement membrane-like materials in the mesangial regions could be observed. After 16 to 24 weeks of age in the diabetic rats, hemispherical thickening in addition to diffuse thickening of glomerular basement membrane was noted. The thickening of basement membrane was due to widening of lamina densa consisting of accumulation of basement membranematerials on the epithelial side of the lamina densa, all the way along the peripheral capillary loops. These features of glomerular lesions in the diabetic rats were progressively accentuated accompanying ageing. The early glomerular ultrastructural alterations in the diabetic rats were very compatible with those seen in the elder control rats. The results indicated that the development of diabetic glomerulopathy might be destined very early in life of the spontaneously diabetic rats supposedly by their diabetic genes.
Proteohyaluronic acid was extracted from human umbilical cord with 0.2% NaCl, then purified by cetylpyridinium chloride (CPC)-precipitation, DEAE-cellulose column chromatography, gel-filtration on Sephadex G-200 and on Sepharose 4B, in succession. The purified preparation contained glucosamine (40.1%), glucuronic acid (45.7%) and protein (2.6%). Glutamic acid, glycine, alanine, serine and aspartic acid were the major amino acids of the protein moiety. The result of the gel-filtration suggested that an average molecular weight was more than 1×106. Although analytical data for the constituent sugars and infrared spectra were similar before and after pronase digestion of this proteohyaluronic acid, the mobilities in electrophoresis and the elution patterns of gel-filtration differed remarkably from one another. Since the protein content decreased from 2.6% to 0.3% by the proteolytic digestion, it is evident that the degraded protein moiety played an important role in maintaining the macromolecular structure of this proteohyaluronic acid.
Arginine synthetase activity and ammonia removal in liver slices were determined in rats with obstructive jaundice or acute carbon tetrachloride (CCl4)-induced liver dysfunction and the following results were obtained: (1) Urea synthesis and ammonia removal in liver slices progressively decreased with prolonged biliary obstruction. The effects of ATP and/or ornithine addition were also markedly decreased, particularly in the group with 6 weeks of biliary obstruction. (2) Arginine synthetase activity also fell with prolongation of biliary obstruction and the fall was most pronounced in the 6-week group. (3) The CCl4-induced liver dysfunction group showed a significantly higher level of arginine synthetase activity than the group with 6 weeks of biliary obstruction, but ammonia removal was markedly decreased and the effects of ATP and ornithine addition were prominent. From the results, it is concluded that, due to a fall in the enzyme activity of the urea cycle in obstructive jaundice, liver dysfunction can easily occur with prolongation of the obstruction, while hepatic urea cycle dysfunction is brought about by severe metabolic disruption in the liver damaged by CCl4.
To reveal the regulatory function in uteroplacental blood flow we measured, using the method of double tracer microspheres, the rates of uteroplacental blood flow (UPBF) and uteroplacental shunt (UP-shunt) in SD-strain rats of normal and prolonged pregnancy. (1) In the group of rats of normal pregnancy, the rate of UPBF attained a peak on the 20th day of gestation, while the UP-shunt rate was highest on the 18th day of gestation. (2) In the progesterone-induced prolonged pregnancy group, the rate of UPBF remained at an 8% level until the 22nd day, i.e., the first day of prolonged pregnancy, and dropped to 6.6% on the 23rd day. The UP-shunt rate in the progesterone-administered group was about 27% on the 20th day, more favorable than the corresponding rate in the normal group, but thereafter rapidly decreased. The rate of increase in fetal body weight in this group became lower, showing a fetal death rate of 4.6%. (3) The decreases in placental alkaline phosphatase and leucine aminopeptidase examined as markers of placental function lagged behind the fall in the UP-shunt rate. On the 23rd day of gestation when the rates of UPBF and UP-shunt dropped, the decreases in their placental enzyme activities were remarkable.