Alterations of phospholipid and triglyceride metabolism in fatty liver caused by pyridoxine deficiency in rats.
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Biomedical subjects
Publications and source records attributed to M Okada.
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In rat liver, 90% of the aspartate aminotransferase is present as the holoenzyme. In pyridoxine deficiency, the ratio of holoenzyme activity to total activity is markedly reduced, but after pyridoxine injection it was found to rapidly increase, although the total enzyme activity remained low for a few days. The activities of aspartate aminotransferase isozymes in pyridoxine-deficient rat tissues and the effect of pyridoxine treatment on their activities were examined. The intestinal enzyme activities of pyridoxine-deficient rats were readily reconstituted in the presence of pyridoxal phosphate in vitro, but the enzyme activities in liver and muscle in the deficient rats required several days for complete recovery, suggesting that active enzyme was synthesized de novo in these tissues.
The effect of pyridoxine deficiency on cholesterol catabolism was studied in rats. The concentrations of bile lipid components were higher in pyridoxine-deficient rats than in controls. A decreased ratio of taurine to glycine conjugates was observed in the deficient rats. No change in the neutral sterol content, but an increase in the bile acid content of the feces was observed in the deficient rats. Increased cholesterol catabolism in pyridoxine-deficient rats was also shown by the shorter half-life of the [14C] cholesterol injected into these animals.
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A human helper T cell clone (d4), which showed its helper effect on the differentiation of both T and B cells, was established by MLC reaction of normal T cells against a B lymphoblastoid cell line (CESS) followed by cloning in the presence of IL2 and x-irradiated CESS and autologous non-T cells. d4 cells helped the induction of cytotoxic T cells against UV-treated CESS cells. Antigen-stimulated d4 cells secreted helper factor(s) involved in the induction of cytotoxic T cells (killer helper factor(s), KHF), and KHF activity could be separated into two fractions, one with the m.w. of 15,000 to 20,000 and the other with the m.w. of 45,000 to 50,000. The factor with 15,000 to 20,000 m.w. showed IL 2 activity; the other factor showed gamma-interferon activity without IL 2 activity, suggesting that both IL 2 and gamma-interferon exerted KHF activity. d4 cells or their culture supernatant showed helper activity in the induction of IgG in a B cell line (CESS). The helper activity of the supernatant (TRF) was absorbed with CESS cells but not with IL 2-dependent CTLL, whereas KHF activity was absorbed with IL 2-dependent CTLL but not with CESS cells. The results showed that TRF and KHF were distinct molecules and a single helper T cell clone could secrete helper factors for both B and T cells.
It is well recognized that only very low concentration of antibiotics is obtained from cerebrospinal fluid (CSF) despite its high blood concentration. It has been attributed to the blood-brain and blood-CSF barriers. Penetration of CTM into CSF was studied in 7 patients. Two of them were complicated with septic meningitis, and others were not infected. CTM was administered intravenously and samples were obtained from both serum and CSF from 15 minutes to 4 hours for determination of concentration of the antibiotics. In 2 patients with meningitis, the peak level of CTM in CSF after intravenous injection of 2 g and 1 g of CTM was 197 mcg/ml (46% of peak serum concentration), and 17.3 mcg/ml (38% of peak serum level), respectively. In noninfected patients the peak level of CTM in CSF after intravenous injection of 1g of CTM was from 0.3 mcg/ml to 1.9 mcg/ml (0.84% approximately 3.64% of peak serum concentration). We conclude that the percent penetration of CTM into CSF increases in the presence of the inflamed meninges and that prophylactic dosage of CTM for postoperative meningitis will be intravenous administration of 2 g of CTM in adults.
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Plasma aluminum levels of 17 patients with gastric and/or duodenal ulcers who had received four grams of sucralfate daily for eight to ten weeks were compared with those of six control subjects. Aluminum levels were determined by flameless atomic absorption spectrometry. Plasma of patients on long term sucralfate therapy contained 8.41 +/- 6.00 (SD) micrograms aluminum per liter and was not significantly different than that of the control subjects which contained 6.50 +/- 7.87 micrograms per liter. These values agreed well with normal values reported previously. In conclusion, long term ingestion of sucralfate in therapeutic doses does not result in an increase in plasma aluminum concentration.
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Alkaline phosphatase (ALP) activity of cultured Li-10 cells obtained from rat liver was found to be a function of cell population density. After the cells grew to confluence, the enzyme activity per cell increased about 100 times that at a low population density. The increase of activity was inhibited by the addition of actinomycin D or cycloheximide to the culture medium. When the cells that had gained high ALP activity after confluency were subcultured, ALP activity decreased to a low basal level after about 48 h. Under cytochemical examination using an electron microscope, the induced ALP activity was seen exclusively at the apical surface region of the cells but scarcely at cell-cell and cell-substratum contact regions.
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Using the H2 clearance method, spinal cord blood flow of the rabbit could be steadily measured. This allowed examination of blood flow problems using data analysis to provide informed decisions as to whether or not the blood flow through the gray and white matter was distinguishable. Spinal cord blood flow was also compared through the cervical, thoracic, and lumbar cord regions. The results were as follows: 1. The H2 clearance curves consisted of about 70% monoexponential curve (Mono), and 30% biexponenial curve (Bi), with a tendency toward higher values in the latter. 2. In Bi, a significant positive correlation was noted between the total flow values and the initial slope method values. The initial slope method was therefore used for subsequent data analysis. 3. By using a histogram to evaluate the data on each medullary segment, it was possible to separate a subgroup with a peak around 20 ml/100 g/min and another one with a peak around 40 ml/100 g/min. Based on the microangiographic findings, a more abundant vascular distribution was demonstrated in the gray matter than in the white matter. The first subgroup was noted corresponding to the blood flow through the white matter, and the latter through the gray matter. When the blood flow through the white and gray matter was calculated according to the subgroup data base, the flow ratio through the white and gray matter was 1:2. 4. Comparing the blood flow through each spinal cord segment revealed no significant difference at a p level of 0.01.
N-Nitroso-N-(hydroxymethyl)alkylamines, which are key intermediates in the metabolic activation of nitrosamines having a methyl group, were synthesized and their chemical and mutagenic properties were examined. Six N-nitroso-N-(hydroxymethyl)alkylamines (alkyl = methyl, ethyl, n-propyl, n-butyl, sec-butyl, tert-butyl) were prepared by the deoxygenation of N-nitroso-N-(hydroperoxymethyl)alkylamines. Their stability in aqueous solution was highly dependent on pH, being stable in acidic media, but unstable in neutral or alkaline media. The structure also exerted a profound effect on the stability. Thus a branched alkyl group accelerated the decomposition, although compounds with a normal alkyl group showed a similar response to the change of pH. The alkylating activity of the compounds toward deoxyguanosine and thymidine was demonstrated, and was dependent on the reaction solvent used. The overall alkylating activity was found to be highest with the compound ultimately yielding a methylating agent, while a more selective alkylation towards the oxygen, compared to the nitrogen, was observed with the ethylating, propylating and butylating species. Reactions with cysteine and histidine were also observed. A potent mutagenic effect of the N-nitroso-N-(hydroxymethyl)alkylamines was demonstrated in Salmonella typhimurium TA1535 and Escherichia coli WP2 and WP2 hcr-, in the absence of the S9 mix. A good correlation of the activities of the N-nitroso-N-dialkylamines and the N-nitroso-N-(hydroxymethyl)alkylamines with the same alkyl group was demonstrated.
The carcinogenicity of eleven alpha-oxidized nitrosamines (alpha-acyloxy, alpha-hydroperoxy and alpha-oxo nitrosamines) was tested in F-344 rats. All chemicals were dissolved in olive oil and rats received 10 weekly subcutaneous injections of these chemicals (10 x 5 mg/kg of N-methyl-N-(acetoxymethyl) nitrosamine or equimolar amounts of the other chemicals) at the interscapular region. Subcutaneous tumours were detected in many rats of all groups treated with the chemicals, although no tumour was detected at the injection site in the control group. Lung and thyroid tumours were also observed in many rats of the treated groups, especially those injected with N-alkyl-N-(acetoxymethyl)nitrosamines. Many other tumours developed in the experimental groups, but it is not certain that they were related to the treatment with the chemicals. The results indicate that the chemicals possess local as well as systemic carcinogenicity in F-344 rats. The potent carcinogenic effects at the injection site of the alpha-oxidized nitrosamines, coupled with their direct mutagenic activity, suggest that these derivatives are useful models for the ultimate form of the metabolically activated nitrosamines.