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The incidences, distribution and histopathological findings of N, N'-dimethylnitrosourea (DMNU)-induced brain microtumors in Sprague-Dawley rats were studied. Subcutaneous injections of DMNU in young adult rats one a week resulted in the induction of 122 gliomas in 38 animals with an incidence of 69% after a time lapse of between 157 and 246 days from the first injection. Of these tumors, 66 were classified as microtumors (diameter less than about 1 mm) by detailed light microscopy observation of serial sections. The microtumors were of 3 types: 55 oligodendrogliomas, 8 astrocytomas and 3 mixed gliomas. As the tumors became larger in size, anaplasia appeared, especially in the central part of the tumors. The microtumors developed randomly throughout the brain. It was concluded that, in adult rat brains, the target cells of DMNU were well differentiated glial cells which had already migrated from the matrix layer.

Normal development of the human stapes footplate was investigated in serial sections by light microscopy. Materials were obtained from 35 Japanese embryos from the 6th to 32nd week of embryonal age. Eighteen embryos up to 16 weeks of age (3.5mm to 105mm in crown-rump length) were examined, focusing particularly on the lamina stapedialis of the otic capsule. The present study showed that primordial formation of the lamina stapedialis appeared in 16mm embryo and that the lamina was completely formed and fused to the base of the annular stapes in a 35mm embryo. In a 50mm embryo, the adult form of stapes was found with a rim and annular ligament. The results, therefore, seemed to essentially agree with the theory of dual origin and development of the footplate proposed by Cauldwell and Anson, and teratogenic agents might affect any stage of the process producing anomalies,

The correlation between the systolic time interval and abnormal contraction in ischemic myocardium was studied in anesthetized open-chest dogs. A strain-gauge was sutured on the surface of the left ventricular wall perfused by the left anterior descending coronary artery (LAD) for measuring segment-length. The left ventricular stroke volume decreased progressively after occlusion of LAD. The left ventricular ejection time (LVET) was progressively shortened in close correlation with the elongation of segment-length at the onset of isometric relaxation in 20 seconds after LAD occlusion when early systolic myocardial contraction and isometric contraction time (ICT) were not affected. ICT was gradually prolonged and closely related with the lengthening of the early systolic segment-length, while LVET recovered toward the control level in spite of further decrease in stroke volume. A close relationship was observed between ICT/LVET and stroke volume (gamma = 0.76, P less than 0.01). The results suggested the possibility that LVET was normalized even when the left ventricular function was impaired, and ICT/LVET ratio was the most sensitive index of LV dysfunction.

Binding of bacterial endotoxin to platelets, erythrocytes, lymphocytes and granulocytes was examined by using diffusion dialysis. Platelets, erythrocytes, lymphocytes and granulocytes were fractionated from normal human blood and the binding of endotoxin (LPS: Lipopolysaccharide of E. coli) to each cell fraction was measured at 4 degrees C and the binding efficiency was expressed as a binding index (%d4degreesC +/- SD). The binding index for each cell fraction was as follows; 10.2 +/- 1.6 for platelets, 1.0 +/- 0.9 for erythrocytes, 4.3 +/- 1.6 for lymphocytes and 10.0 +/- 1.5 for granulocytes (n = 11) respectively. Since a platelet possesses a small cell surface area compared with other cells, it was clear that the endotoxin bound preferentially to platelets in vitro. The binding mechanism to the platelet cell surface was suggested to be direct binding of endotoxin to the receptor on platelet cell membrane rather than through an immunologically activated mechanism.

Endotoxin (lipopolysaccharide, LPS) and LPS antibody in the blood were studied in 61 cases of ulcerative colitis (U.C.) by radioimmunoassay. Lysozyme (LZM) concentration was also studied by the turbidimetric method. As a result, it was found that the blood LPS value as well as serum LZM concentration reflects the clinical observations. The case of endotoxemia in the active phase group showed a positive correlation between the LPS value and LZM concentration. LPS antibody which could not be detected in many cases of the active phase, had a high titer in cases of remission with a long history of the disease. These results would suggest that in U.C. with damaged intestinal mucosal barrier, LPS originating from intestinal flora enters into the blood and aggravates the disease and further that this invading LPS releases LZM into the blood. The same studies were performed on 7 cases of Crohn's disease and the same result was obtained.

Using in vivo and in vitro experimental models, the uptake and excretion of 67Ga-citrate in tumor cells and normal cells were studied. The time-lapse accumulation of 67Ga in the tumor of rats bearing Yoshida sarcoma reached its peak 24 h after the administration of 67Ga and gradually decreased thereafter. However, the excretion of 67Ga from the tumor was less than that from normal lung. For culture cells in vitro, the uptake of 67Ga increased with lapse of contact time between 67Ga and the cells, but there was no distinct difference between the results of tumor cells and normal skin fibroblasts. The excretion of 67Ga from the cells tended to decrease with prolongation of the contact time, the excretion from tumor cell being only about 10% after a contact time of 24 h. This indicated a significant delay in excretion in comparison with that of normal skin fibroblasts. This delay in the excretion of 67Ga may be an important factor in the tumor accumulation of 67Ga.

Lymphocytes were highly purified from synovial fluid and peripheral blood of 10 rheumatoid arthritis patients and assessed for responsiveness to PHA-P and Con-A. In all cases, both synovial and blood lymphocytes showed a marked reduction in response to these mitogens compared with normal blood lymphocytes. The factors responsible for this low T cell responsiveness are discussed.

The covalently closed form of circular duplex SV40 DNA was separated from the open and linear form of SV40 DNA by agarose gel electrophoresis in a large-scale gel system. The closed circular DNA was recovered from agarose gels by re-electrophoresing the gel slices. The recovery of DNA was about 70%. Electron microscopic analysis showed that the recovered DNA did not have doube- or single-stranded breaks. The recovered DNA can be used without further purification for electron microscopy, as a substrate for experiments using restriction endonuclease and as a template for in vitro RNA synthesis.

Euchromatin specimen prepared by the usual method formed large clumps and had various shapes under electron microscopy. A method of separation of the euchromatin specimen into chromatin fractions having relatively homogeneous form was examined and partial characterization of these fractions was carried out. The heavy euchromatin fraction was a large network of thin fibrils (about 100 A in diameter) and various thick fibers. The intermediate euchromatin fraction consisted of relatively homogeneous networks of thick knobby fibers (about 250 A in diameter). The light euchromatin fraction had metworks of thick fibers. These chromatin fractions were quantitatively prepared from sonicated nuclei of mouse ascites sarcoma cells. Twenty-one or twenty-two bands of non-histone proteins besides histones were detected in these chromatin fractions by SDS-polyacrylamide gel electrophoresis. There were significant differences in the electrophoretic patterns of non-histone proteins among these chromatin fractions.

Levels of erythrocyte superoxide dismutase (SOD) activitiy in a sample of Japanese people were determined. Blood samples were taken from new-born infants, preschool children, young and old people who had no apparent diseases and also from three anemic patients. Erythrocyte SOD activities in different age groups had a nearly normal distribution. Females had slightly lower activities than males, although the difference was statistically insignificant. The distributions of SOD activities were 12.6 +/- 2.7 (m +/- SD) unit/mg Hb in young people and 11.4 +/- 3.0 in old people, indicating that erythrocyte SOD activity falls with aging. Because of low concentration of hemoglobin, SOD activities of old people expressed as unit/ml blood were much lower than in young people. Three anemic patients had slightly lower SOD activity.

The effect of Cd2+ on the respiration of rat liver mitochondria was investigated. The uncoupling effect of Cd2+ was partially restored by the addition of Mg2+. The influence of Cd2+ on adenine nucleotide concentrations in the reaction mixture consisting of mitochondria and ATP was also studied using high performance liquid chromatography. In the presence of added Mg2+, a two-fold increase in AMP concentration was brought about by the addition of Cd2+. There was a concomitant decrease in ATP. In the prence of added ADP, an increase in AMP concentration was also brought about by addition of Cd2+. The results are discussed in relation to ATPase and adenylate kinase activity in mitochondria.

A mixture with essential and nonessential amino acids high in branched chain amino acids and low in aromatic amino acids (Fischer solution), and another synthetic mixture of branched chain amino acids containing 3 amino acids associated with the urea cycle (Hep-OU) were infused to control subjects and patients with severe hepatic disease. Alterations in serum aminograms, blood ammonia levels and electroencephalograms following the infusion were studied and compared with those obtained by a commercially available amino acid mixture. Short-term or continuous infusion of a commercially available amino acid solution to cirrhotic patients caused an increase in methionine, phenylalanine and tyrosine and a decrease in branched chain amino acids. These post-infusion results were similar to the patterns seen in hepatic encephalopathy. In cirrhotic patients, infusion of Fischer solution which contains small quantities of methionine and phenylalanine produced an increase in the concentrations of these 2 amino acids, probably because of impaired utilization by the injured liver. No marked alterations in serum aminograms, however, were observed in cirrhotic patients either immediately after, or 3 h after, the end of the Hep-OU infusion. Reduction of methionine, tyrosine and phenylalanine levels and elevation of the molar ratio of (valine+leucine+isoleucine) / (phenylalanine+tyrosine) were significant. The infusion of Hep-OU to patients with liver cirrhosis or subacute hepatitis resulted in clinical and neurological improvements and the restoration of the molar ratio of branched chain amino acids/aromatic amino acids.

The authors attempted to determine if the organic sulfur compounds usually contained in a crude oil could serve as a marker of oil pollution in fish. Eels (Anguilla Japonica Temminck et Schlegel) were maintained in a controlled laboratory environment of water with a suspension of crude oil. Gas chromatography-mass spectrometry and mass chromatography of eel flesh extract showed the presence of organic sulfur compounds of alkyl-(from mono- to pentametyl) benzothiophenes, dibenzothiophene and alkyl-(from mono- to trimethyl) dibenzothiophenes, and other organic sulfur compounds of alkyl-(from mono- to pentamethyl) naphthalenes.

The homovanillic acid (HVA) concentrations in the lumbar cerebrospinal fluid (CSF) were determined in 38 epileptic and 39 control patients. The mean concentration of HVA was 23.9 ng/ml +/- 2.8 SEM for the epileptic group and 30.2 ng/ml +/- 2.1 SEM for the control group, respectively. Thus, HVA was significandly reduced in the patients with epilepsy compared with the controls. The mean HVA in the female patients was higher than in the male patients in both groups but this failed to reach statistical significance. There was no apparent relationship between the degree of reduced HVA concentration and other clinical indexes of the epilepsy (age, type and frequency of seizures, and anticonvulsant medication). For the determination of concentration gradient of HVA three fractions of the spinal CSF were obtained from 11 patients. A pronounced gradient of HVA concentration was found with a ratio of 1 : 1.46 : 1.97 for the first, second and third fractions. This suggests that a standardized conditions for collecting CSF should be employed to study HVA levels in humans.

Since 1903, 744 cases of megaloblastic anemia have been reported in Japan: 490 cases of pernicious anemia; 95 cases associated with pregnancy; 66 cases after gastrectomy; 22 cases of megaloblastic anemia of infants; 21 cases of folic acid deficiency other than pregnancy and 19 cases of vitamin B12 malabsorption after ileal resection. It is generally agreed among hematologists in Japan that pernicious anemia is relatively rare, as in other Asian countries. The diagnosis of pernicious anemia in Japan is usually made by stained marrow films, radioisotopic assay of serum vitamin B12, Schilling test and good response to vitamin B12 therapy. Serum folate level, intrinsic factor or its antibody, methylmalonic acid excretion, formiminoglutamic acid excretion and deoxyuridine suppression test are performed only at a small number of laboratories. The drugs of choice are hydroxocobalamin, deoxyadenosylcobalamin and methylcobalamin. Cyanocobalamin has nearly disappeared from commercial sources in Japan. Vitamin B12 administration is common in patients with neurological disorders. Megaloblastic anemia due to folic acid deficiency is extremely rare in Japan. Low serum folate levels are frequently observed among patients receiving anticonvulsants or in pregnant women, but in such samples megaloblastic anemia is almost never detected. The folic acid content of hospital diets indicates that satisfactory amounts of folate are taken in Japan. The intake of folic acid from rice is well over the minimum daily requirement of folate. Other factors in folic acid deficiency, such as food taboos, severe alcoholism and malabsorption syndrome are not frequently found in Japanese. The inadequate intake of folate was the critical factor in most reported cases.

Five pairs of immature, non-hemopoietic femur and tibia from 17-day-old gestating female rat fetuses, whose sex was determined by chromosomal analysis of liver cells, were transplanted into subcutaneous tissues of adult male rats. The original bones were about 3 mm in length and they grew to about 17 mm length at 4 wereks after transplantation. Bone deformation was not evident after transplantation and bone marrow hemopoiesis developed. Bone marrow cytohistologic observations were made on smears, and chromosome analyses were performed on bone marrow cells. Active erythro-, myelo- and megakaryopoiesis were conducted by cells of recipient adult rats. Sex chromosome analysis of cartilage cells from the epiphyses of transplanted bones demonstrated that the growing bones were composed of cells from the grafted embryo. The results thus strongly suggest that the transition of hemopoiesis from liver to bone marrow in late embryonic development is conducted by stem cells migrating through circulating blood and settling in the bone marrow and not by in situ cells differentiating in the bone marrow stroma.

Phosphorylase activities (total and a form) were determined in the livers of experimental hepatic injuries with carbon tetrachloride or galactosamine and the livers of patients with liver diseases. Experimental liver injuries caused a slight decrease in total activity in later stages and a marked increase in a form activity in earlier stages. In human livers, low values of total activity were found in acute hepatitis and cirrhosis of the liver with no consistent alteration in a activity. Phosphorylase activities in hepatocellular carcinomas were also low. The importance of the altered phosphorylase activities in hepatic injuries is discussed in relation to the disorder in glycogen metabolism in the injured liver.

Respiratory syncytial (RS) virus can be purified without losing its infectivity provided that each step of purification is carried out using NT buffer containing over 20% sucrose. Firstly, the virus grown on HES cells is efficiently removed from the culture fluid by precipitating with polyethylene glycol (PEG) 6,000, and the precipitate is suspended in a small amount of 20% sucrose-NT buffer, which results in about a 24-fold concentration of the original material. Then this suspension is centrifugated through 30% sucrose-NT buffer to obtain pellets, which are again suspended in 20% sucrose-NT buffer. This suspension is further centrifuged by discontinuous and linear sucrose density gradient. Finally, the specific infectivity of the purified virus was increased about 3,000-fold over that of the original material.

The female patient initially showed the acquired type of total lipoatrophy at about 8 years of age. At 12 years of age, the onset of diabetes mellitus was speculated from advanced pyodermia and dedentition. At 29 years of age, glucosuria was found, and she developed proteinuria, ascites, and pretibial edema. The physical examination revealed: hepatosplenomegaly, complete absence of subcutanous fat, cutaneous xanthomas, and emaciated facies with pronounced zygomatic arches. Diabetic retinopathy was revealed in the ophthalmological examination, and nephropathy was evident in renal biopsy specimens. She also had peripheral diabetic neuropathy. No adipose tissue was found in the mesenterium under peritoneoscopy. The hepatic biopsy specimen revealed advanced portal liver cirrhosis. Laboratory findings included: hyperlipidemia, elevation of BMR without evidence of hyperthyroidism, impaired renal function, and undetected anti-insulin antibodies and anti-insulin antibodies. Endocrinological examinations revealed normal value, except for an impaired hGH response in the arginine test. C-peptide immunoreactivity was high. Her condition was fairly well controlled by 140 units of insulin injection daily.

Effects of synthetic neurotensin on the endocrine pancreas were studied in nine normal and six hypophysectomized (10th to 14th day post-hypophysectomy) dogs. Synthetic neurotensin was administered into the superior pancreaticoduodenal artery, and plasma insulin and glucagon concentrations were measured radioimmunologically. In normal dogs, ten microgram/kg neurotensin administration brought about a mild hyperglycemic response and sharp and rapid increase of plasma insulin and glucagon concentrations in the superior pancreaticoduodenal vein. A biphasic insulin response was noted in the pancreatic vein. The results suggest that a large dose of neurotensin acts directly on the endocrine pancreas causing secretion of these hormones. In hypophysectomized dogs, basal levels of plasma insulin and glucagon were decreased and neurotensin had little effect on the endocrine pancreas even with the administration of a large dose.