[A case of the aged man with acute onset autoimmune hepatitis].
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Acute Disease↗
Biomedical subjects
K Higashino
Publications and source records attributed to K Higashino.
[Long-term follow up of idiopathic thrombocytopenic purpura in childhood].
Sixty children with idiopathic thrombocytopenic purpura (ITP) were followed up for 15 to 208 months (mean 120 months) from their first visit. Of these 65% (39 cases) were suffering from acute ITP and 47% of the patients were male. Of the 21 patients with chronic ITP 43% (9 cases) entered remission within five years from the onset of the disease. Conversely patients with chronic ITP for more than five years did not enter remission. Four patients with chronic disease were diagnosed to be other diseases (i.e. three cases were aplastic anemia, the other was Evans' syndrome) after one to four years from the onset. Four patients with chronic ITP for more than five years from the onset are now doing well without any severe bleeding problems. The patients who recovered have had neither problems nor complications. None of the patients died of a cerebral hemorrhage or severe bleeding. We consider that long term outcome of ITP in childhood would be better than that of adult cases.
Child↗
IFN-gamma-inducing factor up-regulates Fas ligand-mediated cytotoxic activity of murine natural killer cell clones.
NK cells, non-T non-B immune effector lymphocytes, are localized in many organs, including liver, as well as in the circulation. To investigate the regulatory mechanism of killing apparatus in hepatic NK cells, we established IL-2-dependent NK cell clones from liver lymphocytes of BALB/c nude mice. To generate the NK cell clones, we incubated liver lymphocytes with a high dose of IL-2 in the presence of irradiated Kupffer cells, as feeder cells and as the source of IL-12, originally identified as NK cell stimulatory factor. Unless liver lymphocytes were incubated with both IL-2 and Kupffer cells, no cell growth was observed. Hepatic NK cell clones were established from this cell line by limiting dilution. The surface phenotypes of cloned NK cells were IL-2R beta-chain+ CD16+ CD3- IgM-. The clones did not express NK2.1, which is expressed by a half of NK-enriched spleen cells of BALB/c mice. Although the cells contained dense granules reactive to mAb against perforin, they exerted no conventional cytolytic activity against YAC-1. They constitutively expressed Fas ligand (FasL) and specifically killed Fas-positive target cells by fragmenting DNA. This Fas-FasL-mediated killing activity was enhanced by IFN-gamma-inducing factor, a recently identified novel cytokine produced by activated Kupffer cells, but was not affected by other Kupffer cell-produced cytokines, such as IL-12, IL-1beta, and TNF-alpha. Taken together, these findings suggest that hepatic NK cells participate in the immune response as effector cells through the Fas-FasL system in collaboration with cytokines from Kupffer cells.
Animals↗
Determination of human plasma xanthine oxidase activity by high-performance liquid chromatography.
An assay for human plasma xanthine oxidase activity was developed with pterin as the substrate and the separation of product (isoxanthopterin) by high-performance liquid chromatography with a fluorescence detector. The reaction mixture consists of 60 microliters of plasma and 240 microliters of 0.2 M Tris-HCl buffer (pH 9.0) containing 113 microM pterin. With this assay, the activity of plasma xanthine oxidase could be easily determined despite its low activity. As a result, it could be demonstrated that the intravenous administration of heparin or the oral administration of ethanol did not increase plasma xanthine oxidase activity in normal subjects, and also that plasma xanthine oxidase activity was higher in patients with hepatitis C virus infection than in healthy subjects or patients with gout. In addition, a single patient with von Gierke's disease showed a marked increase in the plasma activity of this enzyme, relative to that apparent in normal subjects.
Chromatography, High Pressure Liquid↗
Prevention of growth arrest-induced cell death of vascular smooth muscle cells by a product of growth arrest-specific gene, gas6.
We have purified Gas6 as a growth-potentiating factor for vascular smooth muscle cells (VSMCs) [Nakano, T. et al. (1995) J. Biol. Chem. 270, 5702-5705]. However, specific production of Gas6 in growth-arrested cells raises an intriguing question as to the physiological function of Gas6. In this study, we found that serum-starved VSMCs secreted some survival factors and depletion of the factors induced cell death of VSMCs. Finally, we demonstrated that cell death was prevented by the addition of Gas6, suggesting that one of the major biological activities of Gas6 is protection of growth-arrested VSMCs from death.
Animals↗
Immunohistochemical localization of aldehyde and xanthine oxidase in rat tissues using polyclonal antibodies.
Tissues from male Wistar rats, fixed with 4% paraformaldehyde and embedded in paraffin, were studied with immunoperoxidase techniques using polyclonal antibodies raised against aldehyde oxidase or xanthine oxidase purified from rat liver. Immunohistochemical studies demonstrated that aldehyde oxidase-bearing cells were strongly stained in renal tubules, esophageal, gastric, intestinal and bronchial epithelium as well as liver cytoplasm. Weak but positive immunoreactivity was observed on the pulmonary alveolar epithelial cells, gastric glands and intestinal goblet cells. In contrast, it was demonstrated that cells with xanthine oxidase were strongly stained in renal tubules, esophageal, gastric, and small and large intestinal and bronchial epithelia etc. Positive immunostaining was also found in adrenal gland, skeletal muscle, spleen and cerebral hippocampus. Immunoreactivity againt aldehyde oxidase was not found in adrenal gland, spleen, mesentery or aorta, while immunoreactivity against xanthine oxidase was not found in mesentery or aorta. Although the significance of this ubiquitous and similar localization of aldehyde and xanthine oxidase seems unclear at present, these results may provide a clue as to the full understanding of the pathophysiological role of these oxidases in tissues.
Adrenal Glands↗
A novel de novo mutation in HPRT gene responsible for Lesch-Nyhan syndrome (HPRT OSAKA).
A virtually complete deficiency of hypoxanthine guanine phosphoribosyltransferase (HPRT) causes Lesch-Nyhan syndrome. A novel mutation of HPRT gene in a Japanese Lesch-Nyhan family has been identified using mRNA and genomic DNA from peripheral blood cells. A single nucleotide substitution of T to C in exon 3 resulted in a mis-sense mutation, CTC (Leu) to CCC (Pro), at codon 65. Utilizing an Mn/I restriction site which was lost in the mutation as an indicator, a family study showed that the mother was normal not having the mutant gene. The mutation was a de novo event that had occurred in the germ cells of the mother or in the proband during the early phase of fetal development.
DNA↗
Effect of glucagon on the xylitol-induced increase in the plasma concentration and urinary excretion of purine bases.
To investigate whether glucagon affects the xylitol-induced increase in the production of purine bases (hypoxanthine, xanthine, and uric acid), the present study was performed with five healthy subjects. Intravenous administration of 300 mL 10% xylitol increased the plasma concentration and urinary excretion of purine bases, erythrocyte concentrations of adenosine monophosphate (AMP) and adenosine diphosphate (ADP), and blood concentrations of glyceraldehyde-3-phosphate (GA3P) + dihydroxyacetone phosphate (DHAP), fructose-1,6-bisphosphate (FBP), and lactic acid; it decreased the blood concentration of pyruvic acid and the plasma concentration and urinary excretion of inorganic phosphate. However, intravenous administration of 1 mg glucagon together with xylitol reduced the xylitol-induced changes in oxypurines, pyruvic acid, GABP + DHAP, and FBP, whereas it promoted the xylitol-induced increase in the urinary excretion of total purine bases and did not affect the xylitol-induced increase in the plasma concentration of total purine bases. In addition, in vitro study demonstrated that sodium pyruvate prevented the xylitol-induced degradation of adenine nucleotides in erythrocytes. These results suggested that gluconeogenesis due to glucagon increased the production of pyruvic acid, accelerated the conversion of NADH to NAD, and thereby prevented both the xylitol-induced degradation of adenine nucleotides in organs similar to erythrocytes and the inhibition of xanthine dehydrogenase in the liver and small intestine, resulting in decreases in the plasma concentration and urinary excretion of oxypurines. However, it was also suggested that in the liver storing glycogen, glucagon-induced glycogenolysis accumulated sugar phosphates, resulting in purine degradation, since the xylitol-induced increase in the NADH/NAD ratio partially blocked glycolysis at the level of GABP dehydrogenase. Therefore, administration of glucagon together with xylitol may synergistically increase purine degradation more than xylitol alone, despite decreases in the plasma concentration and urinary excretion of oxypurines.
Adult↗
Elimination of iomeprol by hemodialysis.
Iomeprol is commercially a relatively new type of contrast medium. There have been no reports concerning its dialysability and safety when administered to patients with end-stage renal failure undergoing regular therapeutic hemodialysis (HD). One hundred milliliters of iomeprol (350 mgl/ml) was injected intravenously at computed tomography in 10 patients suffering from chronic renal failure. HD was then performed within 30 min after the start of iomeprol injection. The duration of HD was 4 h and blood samples were taken at 15, 30 min, 1, 2 and 4 h after its start. Mean dialysance of urea was 176.0-182.9 ml/min, compared to 131.4-133.3 ml/min for iomeprol. Elimination rate of iomeprol was 821.4 +/- 4.6% 4 h after the start of HD. Two of the 10 patients had side effects. One of them complained of a heat sensation and the other of sneezing and rash. As 4-h HD effectively removed iomeprol from the body and there were no severe side effects, it is concluded that iomeprol is suitable for HD patients.
Aged↗
A phase II study of cisplatin, vindesine and continuously infused 5-fluorouracil in the treatment of advanced non-small-cell lung cancer. Osaka Lung Cancer Chemotherapy Study Group.
Fifty-two previously untreated patients with advanced non-small-cell lung cancer (NSCLC) were treated on a 14 day cycle with cisplatin (60 mg m-2 i.v.) and vindesine (3 mg m-2 i.v.) on day 1, followed by a 3 day continuous infusion of 5-fluorouracil (800 mg m-2 day-1) starting on day 8. An overall response rate of 40.4% was observed in 47 evaluable patients, which included one complete response and 18 partial responses. Responses were achieved in 61.1% of stage 3 patients and 27.6% of stage 4 patients. The median progression-free interval was 19.3 weeks, and median survival time was 41.6 weeks (47.1 weeks for patients with stage 3 disease and 38.7 weeks for those with stage 4 disease). Toxicity was well tolerated. Gastrointestinal and renal toxicities did not exceed WHO grade 2. Grade 3 or 4 leucopenia and anaemia occurred in nine (19%) and four (9%) patients respectively, but only grade 2 thrombocytopenia was observed. Phlebitis at the infusion site was observed in 24 patients (53%). This treatment programme achieved a response rate similar to other active combination regimens for the treatment of advanced NSCLC, and was less toxic.
Adenocarcinoma↗
IL-4 and anti-CD40 protect against Fas-mediated B cell apoptosis and induce B cell growth and differentiation.
Most Th2 clones, when activated, produce IL-4 and express CD40 ligand (CD40L) on their cell surface. Therefore, they can induce growth and differentiation of B cells by cognate help. In contrast, activated Th1 clones, which produce IFN-gamma and express both CD40L and Fas ligand (FasL) on their cell surface, often induce B cell apoptotic cell death. To understand the mechanism by which Th2 cells can induce B cell growth and differentiation in the presence of FasL-positive cells, we stimulated B cells with IL-4, anti-IgM and/or anti-CD40 in the presence of anti-Fas. We report here that addition of anti-Fas strongly inhibited anti-CD40-induced B cell proliferation without affecting anti-IgM-induced B cell proliferation. Furthermore we showed that stimulation of B cells with anti-CD40 induced the expression of Fas molecules on the B cells (approximately 30%) and rendered them highly sensitive to anti-Fas-mediated apoptotic cell death. Indeed, over 23% of anti-CD40-stimulated B cells showed hypodiploid DNA after being incubated with anti-Fas, while h2 cells could dominate over FasL-positive Th1 cells by production of CD40L and IL-4, which in combination induce antibody production and inhibit the Th1 cell-mediated immune response.
Animals↗
Effect of amino acids on the excretions of purine bases and oxypurinol.
To investigate whether or not amino acids affect the urinary excretion of purine bases and oxypurinol, a 12% amino acid solution was infused to 6 subjects who took allopurinol (300 mg) 6 h before the study. Amino acid infusion increased the urinary excretion and the fractional clearance of uric acid and oxypurinol and decreased the plasma concentration of oxypurinol. However, it affected neither the urinary excretion, the fractional clearance, the plasma concentration of oxypurines nor the plasma concentration of uric acid. These results indicate that amino acids affect the renal transport pathways of oxypurinol and uric acid but not those of oxypurines. In addition, it was suggested that the amino acid-induced increase in the urinary excretion of oxypurinol may be considered when allopurinol is administered to hyperuricemic patients with hypoproteinemia who have taken amino acids either orally or intravenously.
Adult↗
Uric acid transport in fanconi syndrome with marked renal hypouricemia: analysis using pyrazinamide and benzbromarone.
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Adolescent↗
A fetal intestinal-type alkaline phosphatase produced in Caco-2 cells.
Enzymic, immunological and lectin-binding properties of alkaline phosphatase (AP) produced in Caco-2 cells, a human colon carcinoma cell line, were investigated. The enzyme was very similar to fetal intestinal (meconium) AP in the enzymic and immunological properties, but different from fetal intestinal AP in lectin-binding properties; expression of the galactose moiety was altered in AP of Caco-2 cells, compared to that of fetal intestinal AP. These results indicate that AP of Caco-2 cells can be used in place of fetal intestinal AP when the enzymic properties of an AP of unknown origin are investigated, but cannot be used instead of fetal intestinal AP in the structural study of AP.
Alkaline Phosphatase↗
Difference of the plasma concentration and urinary excretion of allopurinol, oxypurinol, and purine bases between dietary intake and fasting.
To investigate how much the metabolism of allopurinol, oxypurinol, and purine bases during dietary intake (total calorie 2,083 kcal, total protein 107.5 g, total lipid 74.1 g, total carbohydrate 228.3 g, total purine 180.5 mg) differs from that during fast, allopurinol (300 mg) was administered to 5 normal subjects after a 6-hour fast and then breakfast was taken. Four and 10 hours after the administration of allopurinol lunch and dinner were taken, respectively. Two weeks later the same protocol was performed, except for the intake of only water instead of diet. The fractional clearances and urinary excretions of oxypurinol, uric acid, and the clearance of creatinine were increased by dietary intake, compared with the respective ones resulting from fasting. At the same time the plasma concentrations of hypoxanthine, xanthine, and oxypurinol were decreased in dietary intake, compared with the respective ones in fasting, while the urinary excretion of neither allopurinol, hypoxanthine, nor xanthine was affected. These results suggest that the administration of allopurinol at bed time (during the nocturnal fast) may be more effective than that after breakfast in order to decrease the plasma concentration of uric acid.
Adult↗
[Gout and atherosclerosis].
Recently atherosclerotic diseases, such as coronary heart disease and cerebrovascular disease have been considered as an important complication of hyperuricemia and gout. However, it is still controversial whether or not hyperuricemia is an independent risk factor of atherosclerotic diseases. On the other hand, several risk factors for coronary heart disease, for example hyperlipidemia and hypertension, are frequently observed in the patients with gout. Atherosclerosis in relation to hyperuricemia was discussed in view of definite and probable risk factors.
Alcohol Drinking↗
[Pharmacological agents affecting uric acid metabolism].
A large number of pharmacological agents affect the serum concentration of uric acid. Some drugs raise serum uric acid level by an increase in uric acid production or a decrease in uric acid excretion, while others lower serum uric acid level by a decrease in uric acid production or an increase in uric acid excretion. In addition, some drugs show so-called biphasic effect; ie, hyperuricemic in lower doses but hypouricemic in higher doses. Hyperuricemic agents contribute to gout and/or urate nephropathy. Among them, pyrazinamide is often used to determine the defective site(s) of uric acid transport in renal tubules in conjunction with uricosuric agents, such as benzbromarone or probenecid. In contrast, the clinical significance of hypouricemic agents other than uricosuric agents has not been emphasized. However, some may induce acute uric acid nephropathy by a significant increase in uric acid excretion. In this review, drugs affecting uric acid metabolism are summarized with regard to their mechanism of action and clinical significance.
Allopurinol↗
Acyl-coenzyme A: cholesterol- acyl-coenzyme A:1,2-diacylglycerol acyltransferase and phosphatidate phosphorylase activities in liver microsomes from nephrotic rats.
The lipid components of very low density lipoproteins (VLDL) were significantly elevated in the nephrotic rats. Also the nephrotic VLDL particles had a significantly higher ratio of surface lipids (FC + PL) to core lipids (TG + CE) probably indicating production of smaller sized VLDL in the nephrotic rats. Electron microscopy showed VLDL particles with a reduced mean size in the nephrotic rats. The activities of VLDL core lipid synthesizing enzymes were evaluated in experimental nephrotic syndrome. In addition, the effects of exogeneous cholesterol, 25-OH-cholesterol and low density lipoprotein (LDL) on the acyl-coenzyme A: cholesterol acyltransferase (ACAT) activity were investigated as well. ACAT activity in nephrosis was normal, but stimulated to varying extents in the presence of these factors. On the other hand, the acylcoenzyme A:1,2-diacylglycerol acyltransferase (ADGAT) and phosphatidate phosphorylase-activities were significantly increased in the nephrotic rats. The microsomal cholesterol (free and ester) and phospholipid concentrations were normal but the triglyceride level was significantly reduced in the experimental group. We speculate that an excess production of smaller-sized VLDL particles due to altered activities of microsomal lipid synthesizing enzymes may occur in puromycin amino nucleoside induced-nephrotic rats.
Acyltransferases↗