Biomedical subjects
Publications and source records attributed to N Ishida.
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'Per repeat is a rodent genomic DNA fragment which is homologous to the Gly-Thr repetitive amino acid sequence of the Drosophila clock gene period'. This study examined the temporal and spatial expression of the per repeat mRNA in rat brain. Northern blot analysis showed that the level of per repeat mRNA species fluctuates under light-dark cycle conditions in rat brain. Furthermore, the fluctuation of per repeat mRNA was clearly observed in the suprachiasmatic nucleus, but not so in other regions including the hippocampus as shown by in situ hybridization. The above results suggest that the Gly-Thr repetitive sequence also plays an important role in the circadian rhythm of mammals.
Phospholipase D (EC 3.1.4.4) of Streptomyces species was found to catalyze transphosphatidylation to L-ascorbic acid from phosphatidylcholine (PC) in a biphasic reaction system. The product was identified as 1,2-diacyl-sn-glycero-3-phospho-6'-L-ascorbic acid (PA-AsA) by mass spectrometry and nuclear magnetic resonance spectroscopy. The optimal pH of transphosphatidylation was 4.5 and the rate of PA-AsA formation increased as concentrations of L-ascorbic acid increased. The conversion of PC to PA-AsA was greater than 80%. PA-AsA was found to be more resistant to hydrolysis by phospholipase D than was PC.
The effects of (4R)-hexahydro-7,7-dimethyl-6-oxo-1,2,5-dithiazocine-4- carboxylic acid (SA3443), a novel cyclic disulfide compound, on the development of chronic liver injury were studied in rats, using two types of models, carbon tetrachloride (CCl4)-induced chronic liver injury and heterologous serum (swine serum)-induced liver fibrosis. SA3443 (30-100 mg/kg, p.o.) significantly suppressed increases in serum transaminase and alkaline phosphatase activity induced by CCl4-treatment for 10 weeks. This compound also inhibited increases in hepatic lipids and hydroxyproline content in CCl4-treated rats. In the histopathological studies, treatment with SA3443 resulted in a decrease in the degree of hepatic necrosis, fibrosis and steatosis. On the other hand, 8-weeks treatment with swine serum revealed hepatic fibrosis without appearance of necrosis or fatty accumulation. In this model, SA3443 (30 mg/kg, p.o.) reduced the hepatic hydroxyproline level, and diminished the formation of connective tissue in the liver. These findings indicate that SA3443 protects the liver against chronic liver injuries induced by CCl4 and heterogeneous serum.
OK-432, a streptococcal preparation with potent biological response modifying activities, had the ability to cure mice bearing BAMC-1 (fibrosarcoma) ascites when it was injected intraperitoneally five times, 2, 4, 6, 8, and 10 days after the tumor inoculation. Previously, it was shown that the OK-432 injection on day 2 was indispensable since only a minimal antitumor effect was obtained when an inflammation-inducing agent such as thioglycolate instead of OK-432 was injected on day 2, followed by four OK-432 injections on days 4, 6, 8 and 10. In the present study, the injection of OK-432 on day 2 and a subsequent injection of either IL-2 or IFN-gamma on day 4 or 6 showed a significant antitumor effect, achieving a complete cure in approximately 50% of mice treated, although none of the mice could be cured by a single injection of either OK-432, IL-2, or IFN-gamma on day 2. Interestingly, however, the mice treated with an injection of a lymphokine (IL-2 or IFN-gamma) on day 2 followed by OK-432 on day 4 were not cured either. Peritoneal cells on day 12 in mice treated with OK-432 and either of the lymphokines contained pantropic killer cells, which were Thy-1+ and asialo GM1+ (AsGM1+). Moreover, the antitumor effect of the combined treatment was abolished when mice were pre-treated with anti-AsGM1. No significant antitumor effect was observed in athymic nu/nu mice. Together with our previous findings, these results indicate that lymphokines induced by OK-432 administration may account for some of its therapeutic effects and that these lymphokines may also facilitate the subsequent induction of specific killer cells. These results warrant further investigation on possible effective therapeutic protocols with the combined use of OK-432 and lymphokines.
1. We measured haloperidol reductase activity in red blood cells in 87 samples collected from 50 Japanese psychiatric patients on HAL. HAL reductase activities in the patients were in a range of 7.9-26.1 pmol/hr/10(6) RBC (mean = 13.4, S.D. = 3.4). Interindividual variability was as large as 25.4% (CVs), while intraindividual CVs were small (8.9%). 2. Distribution of HAL reductase activities was normal but their values were slightly lower in the patients than those in the normal controls, though the difference between these two groups was not significant. 3. No significant correlations were found between HAL reductase activity in RBC vs dose of HAL per body weight, or plasma and RBC RHAL/HAL ratio.
Correlation among age, concentrations of carboxyhemoglobin and hydrogen cyanide, oxygen density and hemolysis were studied in 120 house fire victims. Victims aged over 60 years comprised approximately 50% of the pooled subjects. Blood samples were mainly collected from the left ventricle, but sometimes from both the right and left ventricles. The concentration of carboxyhemoglobin ranged from 1-95%, of which 71 persons (59.7%) died with carboxyhemoglobin concentrations below 60%. Carboxyhemoglobin concentrations below 10% were found in 9 persons (7.5%). Most of these cases involved the elderly persons. In this paper, we report on the death of elderly victims as a result of low carboxyhemoglobin concentrations. A significant correlation of blood carboxyhemoglobin concentrations existed between the right and left ventricles. The concentration of carboxyhemoglobin in the left ventricle was significantly higher than that in the right. Two out of 31 victims whose hydrogen cyanide concentrations were determined, succumbed to hydrogen cyanide poisoning, having a high concentration of hydrogen cyanide and a low concentration of carboxyhemoglobin. On analysis, oxygen density was found to be low in 13 persons. A negative correlation was shown between carboxyhemoglobin concentration and hemolysis. Inasmuch as hemolysis may indicate the extent of heat dissociation, hemolysis should provide an index of carbon monoxide dissociation from carboxyhemoglobin. In the present study of victims, possible causes of death i.e., carbon monoxide gas poisoning, hydrogen cyanide poisoning, oxygen deprivation, burning, shock due to burns and others were estimated. The survival time for elderly victims was considered to be short.
The electrophoretic mobility of Staphylococcus aureus 209P treated with cefodizime or cefotiam was examined by microscopic electrophoresis, and the production of oxygen-derived radicals by human polymorphonuclear leucocytes (PMN) was measured by a luminol-chemiluminescence assay. S. aureus cells moved from the negative to the positive electrode. Treatment with more than 0.039 mg/L (1/256 MIC) cefodizime or 0.313 mg/L (1/4 MIC) cefotiam significantly reduced the mean mobility compared with the untreated bacterial cells. The decrease of the electrophoretic mobility of antibiotic treated bacteria indicated the decrease of the negative charge of the cell surface. Chemiluminescence of PMN when stimulated by S. aureus treated with more than 0.156 mg/L cefodizime (1/64 MIC) or 1.25 mg/L cefotiam (MIC) increased significantly compared with the untreated cells. These results suggested that the antibiotics caused a decrease of negative charge density on the cell surface of S. aureus, followed by an increase of phagocytic activity of PMN for S. aureus. Furthermore, cefodizime showed this effect even at the low drug-concentration which did not influence the growth of the bacteria cells.
Human preproendothelin-1 (prepro-ET-1) was transfected into an immortal human endothelial cell line that had been cultivated in a serum-free medium. Several transformants selected with Ecogpt selection were probed to have prepro-ET insert, express prepro-ET-1 mRNA, and secrete immunoreactive ET (ir-ET). One of the transformants, t-HUE2-1, secreted 30 times the amount of ET-1 and the ratio of mature ET-1 to big ET-1 was 11-fold higher compared with normal human endothelial cells. Thus, this transformant might be of use to study regulation of the posttranscriptional process of prepro-ET-1 in human cells.
The antihypertensive effect of SD-3211, a structurally novel type of nondihydropyridine calcium antagonist, was assessed using several types of experimental hypertensive rats. Oral administration of SD-3211 (10, 20, and 30 mg/kg) to conscious spontaneously hypertensive rats (SHR), deoxycorticosterone acetate-salt hypertensive rats (DHR) and 2-kidney, 1-clip renal hypertensive rats (RHR) resulted in a dose-dependent decrease in systolic blood pressure (SBP). The hypotensive effect of SD-3211 in these hypertensive rats was more pronounced than in normotensive rats (NR). The potencies of SD-3211 for the hypotensive effect in the hypertensive rats and NR were 5-7 times greater than that of diltiazem but 2-3 times less than that of nicardipine. Furthermore, SD-3211 showed longer-lasting hypotensive action than diltiazem and nicardipine, at the respective equihypotensive dose. During the course of hypotension, SD-3211 did not exert any influence on heart rate (HR) in any type of hypertensive rats or NR, in contrast to the appearance of tachycardia with nicardipine in SHR, DHR, and NR and of bradycardia with diltiazem in DHR. At doses of 10 and 30 mg/kg, the hypotensive doses, SD-3211 elicited a dose-dependent natriuresis but no kaliuresis in SHR. In the chronic study using SHR, SD-3211 at 10 mg/kg/day showed an antihypertensive effect during an administration period of 12 consecutive weeks. These results allow us to conclude that SD-3211 has a potent and long-lasting hypotensive action with little cardiac effect.
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Neocarzinostatin (NCS), an antitumor protein antibiotic, is composed of apo-neocarzinostatin (apo-NCS) and neocarzinostatin-chromophore (NCS-chr), the principle of the biological activities of NCS. Apo-NCS having two tryptophan (Trp) residues at positions (39 and 83) was chemically modified by N-bromosuccinimide in a study on the correlation of the binding site(s) of NCS-chr. Selective oxidation of Trp residues was observed when NCS was titrated with N-bromosuccinimide. In contrast, non-selective oxidation of the two Trps on apo-NCS was observed and both Trp (39 and 83) of apo-NCS were titrated with N-bromosuccinimide. After selective oxidation, the remaining Trp residue of NCS was assigned as Trp (83). These results clearly indicate that the Trp (83) residue of apo-NCS changed from the "reactive type" to the "non-reactive type" after the binding of NCS-chr with apo-NCS. The fluorescence emission intensity of apo-NCS generated from the Trp (39) residue was quenched by NCS-chr. These data suggest that NCS-chr directly interacts with the Trp (39) residue and that a beta-sheeted loop containing the Trp (83) residue of apo-NCS changes the high-order structure upon binding with NCS-chr.
We studied the importance of reflow after reperfusion for myocardial salvage. In 19 open-chest dogs, the left anterior descending coronary artery was occluded for 3h and then reperfused. Non-radioactive colored microspheres were injected into the left atrium to measure regional myocardial blood flow (RMBF). Immediately after occlusion, RMBF was reduced to 23 +/- 2% (of control) in the inner layer and 32 +/- 2% in the outer layer. Five minutes after reperfusion, RMBF was increased to 170 +/- 20% and 156 +/- 11% of control in the inner and outer layers, respectively. One week later, RMBF in the inner layer was reduced to 63 +/- 4% but it was not reduced (100 +/- 6%) in the outer layer. There was a roughly positive correlation between the inner/outer flow ratio measured 5 min after reperfusion and myocardial creatine kinase activity. Myocardial necrosis determined by triphenyl tetrazolium chloride stain varied inversely with the inner/outer flow ratio. These results indicate that good reflow in the inner layer 5 min after reperfusion is a favorable indicator for myocardial salvage.
The effects of SA3443, a novel cyclic disulfide compound, on acute liver injuries induced by carbon tetrachloride (CCl4), D-galactosamine and DL-ethionine were studied in rats or mice. SA3443 (100-300 mg/kg, p.o.) significantly suppressed the increases of serum transaminase activity and liver triglyceride content in the CCl4 or DL-ethionine-induced model. Furthermore, SA3443 (300 mg/kg, p.o.) clearly reduced the formation of hepatic lipid peroxide in CCl4-treated rats. These results indicate that SA3443 protects the liver against acute liver injury.
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Immortal vascular endothelial cell lines were established and utilized for the production of an endothelium-derived contraction factor (EDCF) in a serum-free medium. After the discovery of Endothelin (21 amino acid peptide, ET) as an EDCF, a prepro ET cDNA isolated from human tissue was used to examine the expression of ET and its regulation in human endothelial cells. A gene family of ET was shown in mouse by using prepro ET cDNA as a probe. Thus, a novel peptide, Vasoactive Intestinal Contractor (VIC) homologous to ET was deduced from the sequence of one of these genes. VIC was confirmed to induce vasocontraction as well as intestinal contraction. Northern blot analysis indicated that this gene was expressed in the intestine but not in endothelial cells. A cloning and sequencing of prepro VIC cDNA from mouse intestine suggest that a VIC-like peptide, as well as VIC, are co-synthesized by cleavage from prepro VIC with 160 amino acids.
The detection of boric acid in the tissue is of significance in investigating its toxicity. Because of this, we have devised a histochemical staining method to detect the presence of boric acid. The outline of this method follows. Frozen 12-14 microns sections, cut by a cryostat, are fixed in anhydrous ethanol and stained for 20 minutes in a protonated curcumin solution. Washing in acetic acid follows, and a red stain results if boric acid is present. This method causes a reaction, in which rosocyanin is formed by the reaction of boric acid and the protonated curcumin, and this principle is now used when an analysis of boric acid is needed. As to procedure, a 1 N concentration of sodium hydroxide is dropped onto a part of the stain to be tested, and the presence of rosocyanin is confirmed if the stain turns blue. Consequently, this staining confirms the presence of boric acid.
Daily physical activity levels of severely disabled persons were assessed by means of a statistical analysis of their heart rate during a 24-h period. A non-Gaussian probability density function of the heart rate was calculated and separated into two levels of heart rate distributions, i.e. a relatively lower heart rate for basic daily activity and a relatively higher heart rate relating to vigorous activity. Disabled persons with low ambulatory ability showed daily activity levels similar to normal subjects in the length of time and the level of the heart rate. Their daily activity satisfied their needs for maintaining good health. However, more prolonged vigorous activity in daily living was necessary to improve cardiovascular fitness. For severely disabled persons without ambulatory ability, almost all of the heart rates during daily activity were categorized into the lower heart rate distribution. Their low level of physical activity may lead to a serious decrease in cardiovascular function with its attendant risk of cardiopulmonary disease.