Toxicokinetics: its significance and practical problems.
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Animals↗
Biomedical subjects
R Kato
Publications and source records attributed to R Kato.
Immunofluorescent localization of platelet-activating factor (PAF) in the rat.
An immunofluorescent staining method for detecting platelet-activating factor (PAF) is described. This method employs a polyclonal anti-PAF rabbit antibody. When rat brain, heart, lung, liver or kidney tissue was stained using this method, the heart, lung and kidney exhibited PAF-specific staining. Analysis of the amount of PAF in different organs, either by immunofluorescence or by bioassay, showed that kidney tissue contains the greatest amount of PAF.
Animals↗
Bronchoplastic procedures for tuberculous bronchial stenosis.
Thirty-six patients underwent tracheobronchoplastic procedures for treatment of tuberculous tracheobronchial stenosis. The modes of operations were left upper sleeve lobectomy in 13 patients, sleeve resection of the left main bronchus in 12 patients (two underwent concomitant left upper lobectomy), right upper sleeve lobectomy in five patients, sleeve resection of the right intermediate bronchus in two patients, right sleeve superior segmentectomy of the lower lobe in one patient, sleeve resection of the trachea with concomitant left pneumonectomy in one patient, carinal resection with right upper sleeve lobectomy and middle lobectomy in one patient, and dilatation of the left main bronchus with a free skin graft reinforced with a steel wire in one patient. One patient died of pulmonary edema of unknown cause on the first postoperative day. Anastomotic stenosis occurred in seven patients. One of these patients underwent reoperation and six underwent endoscopic dilatation. One patient died in the hospital of massive bleeding during endoscopic dilatation 4 months after operation. Slight to moderate stenosis resulted in the remaining patients. Although there are some complications, we believe bronchoplastic operation is worthwhile for restoring pulmonary function in patients with tuberculous tracheobronchial stenosis.
Adult↗
[Adult case of aortopulmonary window with aortic regurgitation: a case report].
A 45-year-old woman was admitted to our hospital because of the evaluation of heart murmur. Her height was 152 cm and body weight was 46 kg. The physical examination showed a grade 4 continuous murmur widely audible on the anterior chest wall. The chest X-ray film was normal. The electrocardiogram showed premature ventricular contractions and left ventricular (LV) hypertrophy. The two dimensional echocardiogram demonstrated the presence of moderate aortic regurgitation (AR), however, aortopulmonary window could not be detected. The aortic valve showed neither atherosclerotic nor rheumatic changes. At cardiac catheterization, pulmonary artery (PA) pressure was 20/11 mmHg and aortic pressure was 133/60 mmHg, and a step-up of O2 saturation between right ventricule and pulmonary artery (PA) was demonstrated. The aortography revealed an aortopulmonary window between the proximal ascending aorta and the main PA, and grade 2 AR. The pulmonary to systemic flow ratio averaged 1.5:1. The coronary artery and the LV wall motion was normal. Aortopulmonary window is a very rare anomaly and often requires operation in childhood because of its large left-to-right shunt in most cases. Neither an asymptomatic adult case with this anomaly nor a case with AR has not been reported so far.
Aortic Valve Insufficiency↗
[Multidisciplinary treatment for a patient with recurrent thymoma associated with myasthenia gravis (MG), pure red cell aplasia (PRCA), and hypogammaglobulinemia].
The patient is 62-year-old female. When she was 43 years old, MG occurred. At age of 49 years thymoma was found and complete thymectomy (stage III) and postsurgical irradiation were performed. At age of 57 years pleural dissemination of the thymoma was found. Chemotherapy was effective but did not obtain total tumor cell kill. Though chemotherapy has been repeated for each tumor regrowth, the regimen used at first recurrence became ineffective and the interval between tumor regrowth became shorter. This year, when she is 62 years old, PRCA and hypogammaglobulinemia were accompanied with the forth tumor regrowth.
Agammaglobulinemia↗
[Tracheobronchial injury: clinical analysis of 17 consecutive cases].
Consecutive 17 tracheobronchial injury caused by blunt chest trauma were reviewed. 14 patients were injured by traffic accidents, 2 by fall from the high, and one by accident during play in the house. 16 were male and one was female. Patient's age range from 4 to 60 years (average 25). Site of tracheobronchial injuries were scattered and there were not found risky area. Several problem to rescue tracheobronchial injuries are discussed. To maintain the ventilation in the patient of carinal injury, it is supposed that jet ventilation may be a possible method. For the infant victims, it is difficult to evaluate the injury using bronchofiberscopy. It is recommended that repair of tracheobronchial injury may be undergone as soon as the general condition becomes enough for anesthesia. On a technical aspect, stay suture should be put at the healthy site because those injuries are larger than expected before operation. For the victims with cerebral injury or shock, respirator is necessary for ventilatory management. In those cases adequate sedation and muscle relaxation should be applied.
Adolescent↗
Interleukin-1 beta augments release of norepinephrine, dopamine, and serotonin in the rat anterior hypothalamus.
We investigated the effects of interleukin-1 beta (IL-1 beta), administered directly into the rat anterior hypothalamus (AHY), on monoamine release in the same region by using a brain microdialysis technique and an HPLC-electrochemical detection system. First, to study the local effects of IL-1 beta, we used a microdialysis probe equipped with a microinjection tube for administering IL-1 beta in the same region into which the probe had been inserted. IL-1 beta (1 ng) injected directly into the AHY elicited release of norepinephrine (NE), dopamine (DA), and 5-HT, as well as increases in their metabolites, 4-hydroxy-3-methoxyphenylglycol, 3,4-dihydroxyphenylacetic acid, 4-hydroxy-3-methoxyphenylacetic acid, and 5-hydroxyindole-3-acetic acid, in the AHY. Vehicle alone exerted no effect on monoamine release. Although the elevated levels of NE and DA persisted for more than 6 hr after injection of IL-1 beta, the elevated levels of 5-HT were transient. Second, in order to investigate whether this effect of IL-1 beta is a direct action in the AHY, we performed in vitro experiments using hypothalamus slices. IL-1 beta (0.1 and 1 nM) increased the levels of each monoamine released from hypothalamic slices in a dose-dependent manner. These findings suggest that IL-1 beta acts directly on the hypothalamus to induce release of NE, DA, and 5-HT. Third, the roles of prostaglandins (PGs) in NE release in the AHY elicited by direct injection of IL-1 beta were examined.(ABSTRACT TRUNCATED AT 250 WORDS)
6-Ketoprostaglandin F1 alpha↗
[Treatment of invasive thymoma using low dose and extended-field irradiation including hemi-thorax or whole-thorax].
The records of 10 patients treated for invasive thymoma with low-dose and extended-field irradiation including hemi-thorax or whole-thorax are reviewed. Six patients were in stage III. They were treated with up to 15 Gy hemi-thorax irradiation which was followed by shrinkage of the radiation field after removal of tumor. Five of them have lived 4 to 10 years, while one remaining patient died of uncertain cause. Four patients had stage IVa thymoma. Two patients in an earlier stage were treated with irradiation alone; whole-thorax irradiation of up to 20 Gy followed by local irradiation. Those two patients, however, developed severe pulmonary infection secondary to irradiation pneumonitis. Furthermore, local relapse was observed in one patient who died of respiratory insufficiency after 6 years. In the remaining 2 patients in stage IVa, intensive chemotherapy was administered before whole-thorax irradiation of up to 15 Gy. One of these patients is alive with no evidence of recurrence for 5 years, while the other died of a disease not related to thymoma. These facts indicate that whole-thorax irradiation combined with chemotherapy may be of value in preventing local relapse with stage IVa thymoma.
Adult↗
Species differences in stereoselective metabolism of mephenytoin by cytochrome P450 (CYP2C and CYP3A).
Stereoselective involvement of hepatic cytochrome P450 in the metabolism of mephenytoin was investigated in vitro by using livers of five different experimental animal species and humans. The rates of microsomal 4'-hydroxylation were 2 to 6 times higher with the R-enantiomer than the S-enantiomer in rabbits, dogs and rats, whereas the rates of the 4'-hydroxylation in female mice were not different between R- and S-enantiomers. Preferential S-mephenytoin 4'-hydroxylation was observed in monkeys as similar to that in humans. The rates of microsomal mephenytoin N-demethylation were approximately 2 times higher with the R-enantiomer than the S-enantiomer in male rats and both sexes of dogs. Antibodies raised against CYP2C11 (anti-CYP2C) clearly inhibited microsomal 4'-hydroxylation of S-mephenytoin and N-demethylation of R-mephenytoin in rats, monkeys and humans. Antibodies raised against CYP3A2 (anti-CYP3A) clearly inhibited microsomal 4'-hydroxylation of R-mephenytoin, but marginally S-mephenytoin, in rats. Anti-CYP3A, however, showed no clear inhibition on microsomal 4'-hydroxylation and N-demethylation of both enantiomers in monkeys and humans, except for slight inhibition of R-mephenytoin 4'-hydroxylation in male monkeys. The results suggest that stereoselective involvement of rat CYP3A and scant involvement of human CYP3A in R-mephenytoin 4'-hydroxylation are major determinants of the species differences between rats and humans in stereoselective mephenytoin 4'-hydroxylation.
Adult↗
[Transjugular intrahepatic portosystemic stent shunt (TIPSS) with use of Rösch-Uchida transjugular liver access set--evaluation by CT and its clinical application].
Appropriateness of the Rösch-Uchida transjugular liver access set designed for TIPSS procedure was confirmed, especially about the catheter angle and effective length of the 20 G puncture needle, by CT analysis on three dimensional vascular anatomy of the liver. Clinically, TIPSS using the set was successfully made for two patients, connecting superior right hepatic vein with right portal vein in one patient and middle hepatic vein with left portal vein in another patient with hypoplastic right portal vein. Prior to TIPSS procedure, verification of vascular anatomy on CT images is the key to success of TIPSS in safe.
Evaluation Studies as Topic↗
[Gianturco expandable metallic stents in the treatment of tumor thrombus in portal vein--preliminary clinical experience].
Two cases of hepatocellular carcinoma with protal vein invasion (Vp3) were successfully treated by Gianturco expandable metallic stents (GEMS). Each case was treated through the different approach, i.e. the percutaneous transhepatic or ileocolic venous route. GEMS was easily expanded within the protal vein and carcinoma thrombi were pushed against the walls, resulting in increase of portal blood flow. The GEMS might improve the impaired portal blood flow with hepatic failure and esophagogastric varices, in spite of the possibilities of dissemination and ingrowth of carcinoma thrombi.
Aged↗
Hormonal regulation of rat renal cytochrome P450s by androgen and the pituitary.
The hormonal regulation of rat renal cytochrome P450s, P450 4A2 (K-5) and K-2, was investigated. The level of P450 4A2 in male rats was five times that in female rats and accounted for some 90% of total cytochrome P450, measured photometrically. Lauric acid omega- and (omega-1)-hydroxylation activities of renal microsomes of male rats were also higher than those of female rats. The sex differences in lauric acid hydroxylation activity seemed to arise from the differences in P450 4A2 concentrations, according to an immunochemical study. P450 K-2 was a female-dominant form in rat kidneys. The level of P450 K-2 in renal microsomes of male rats was one-tenth that of P450 4A2. Castration of male rats decreased the levels of P450 4A2 and treatment of castrated male rats with testosterone reversed the decrease. The castration of male rats decreased the lauric acid hydroxylation of the renal microsomes to the level of female rats. The administration of testosterone to castrated male rats reversed the decrease. Hypophysectomy of male rats decreased the level of P450 4A2 and the administration of growth hormone reversed the decrease when intermittent injections mimicking the male secretory pattern were given, although continuous administration mimicking the female secretory pattern did not. Castration of male rats did not affect the level of P450 K-2, but testosterone decreased its level. Hypophysectomy of male rats increased the level of P450 K-2 and growth hormone decreased its level in hypophysectomized rats. These results suggested that the expression of P450 4A2 was regulated by androgen or growth hormone and regulation of P450 4A2 was different from that of P450 K-2. To explore the regulation of renal cytochrome P450 further, testosterone was given to control (intact) or hypophysectomized adult female rats. P450 4A2 was induced in the kidneys of both control and hypophysectomized female rats to close to the level of male rats. Thus, P450 4A2 was directly regulated by testosterone as well as growth hormone, and the regulation of the male-dominant form in rat kidneys was different from that of the male-specific form in the rat liver, which is regulated mostly by growth hormone.
Animals↗
Protein kinase C-dependent and -independent actions of a potent protein kinase C inhibitor, staurosporine.
12-O-Tetradecanoylphorbol 13-acetate (TPA), an activator of protein kinase C (PKC), induced ornithine decarboxylase (ODC) in primary cultured mouse epidermal cells. Staurosporine, a potent protein kinase C inhibitor, also induced ODC activity. Both TPA- and staurosporine-caused ODC inductions were markedly suppressed in the PKC-down-regulated cells. Another PKC inhibitor, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7), inhibited both TPA- and staurosporine-caused ODC inductions. H-7 by itself never induced ODC activity. Under our experimental conditions, staurosporine induced no detectable phosphorylation of endogenous proteins. TPA induced a translocation of PKC from cytosol to membrane whereas an optimal concentration of staurosporine to induce ODC did not induce an obvious translocation of PKC. Indomethacin, a cyclooxygenase inhibitor, inhibited staurosporine-caused ODC induction, but not TPA-caused ODC induction. Staurosporine induced specific morphological changes of epidermal cells both in normal and in PKC-down-regulated cells. These results indicate that staurosporine induces ODC activity in a PKC-dependent manner and morphological changes possibly through a PKC-independent mechanism. The mechanism of ODC induction caused by staurosporine may be in some way different from that caused by TPA.
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
Endothelium-accelerated hyporesponsiveness of norepinephrine-elicited contraction of rat aorta in the presence of bacterial lipopolysaccharide.
The role of the endothelium in the hyporesponsiveness of alpha-adrenoceptor-mediated contractions of the rat aorta was investigated. The norepinephrine-induced maximal contraction was diminished after repeated addition of the agonist. The hyporesponsiveness of the maximal contraction was endothelium dependent, being prevented by NG-monomethyl-L-arginine (0.5 mM), L-argininosuccinic acid (0.5 mM), puromycin (IC50 = 100 microM), actinomycin D (IC50 = 80 nM) but not by indomethacin, which suggests that nitric oxide (NO) synthase is induced. The sensitivity of the rings to NO-induced relaxation remained unchanged. The above-mentioned hyporesponsiveness of norepinephrine-induced maximal contractions of aorta rings was also observed after a 5-h incubation without norepinephrine. The agonist-independent hyporesponsiveness was also prevented by NG-monomethyl-L-arginine, puromycin and actinomycin D, which suggests that NO synthase is induced. Moreover, the norepinephrine-independent hyporesponsiveness was prevented by polymyxin B (10 micrograms/ml), which suggests that bacterial lipopolysaccharide (LPS) might be involved. The concentration of contaminating LPS was 89 +/- 11 ng/ml. When the concentration of contaminating LPS was reduced to 40-70 pg/ml, the hyporesponsiveness of the maximal contraction did not occur after repeated addition of norepinephrine or alter a 5-h incubation without the agonist. An addition of 30 or 100 ng/ml of E. coli lipopolysaccharide to the organ bath reproduced the hyporesponsiveness of the maximal contraction. After a 5-h incubation of aortic rings with 30 ng/ml LPS, only the endothelium-intact ring showed a reduced contraction. However, a 24-h incubation reduced the contraction even in the absence of endothelium.(ABSTRACT TRUNCATED AT 250 WORDS)
Amino Acid Oxidoreductases↗
[Transjugular intrahepatic portosystemic stent shunt (TIPSS)].
Our first clinical experience of TIPSS made for a 52-year-old patient with recurrent life threatening variceal bleeding is described. Although shunt-making between the right hepatic vein and the right portal vein and placement of Gianturco-Rösch Z stents were successfully made without significant complication related to the procedure, sufficient decompression of the portal vein pressure was not obtained because of compression on these stents at the tortuous portion of the shunting tract. Some technical problems of the procedure are also discussed, especially about choice of metallic stents and puncture technique.
Esophageal and Gastric Varices↗
Neurotransmitter release from synaptotagmin-deficient clonal variants of PC12 cells.
Synaptotagmin (p65) is an abundant synaptic vesicle protein of neurons and contains regions similar to the regulatory domain of protein kinase C. These domains are thought to be involved in calcium-dependent interaction with membrane phospholipids during exocytosis. To assess the functional role of synaptotagmin, synaptotagmin-deficient clonal variants of PC12 cells were isolated. All of the variant cells released catecholamine and adenosine triphosphate in response to elevated intracellular concentrations of calcium, which suggests that synaptotagmin is not essential for secretion of catecholamine and adenosine triphosphate from PC12 cells.
Adenosine Triphosphate↗
Transmural pressure inhibits nitric oxide release from human endothelial cells.
We examined the effect of transmural pressure on histamine-stimulated nitric oxide release from cultured endothelial cells prepared from human umbilical cord veins. PO2 and pH were kept constant throughout the experiments. Various levels of transmural pressure and atmospheric pressure (40, 80, 120 and 160 mm Hg) were applied. Nitric oxide release was inhibited in a pressure-dependent manner. The inhibitory effects were reversible, and nitric oxide had no effect on the morphology of the cells. Our results suggest that transmural pressure-mediated inhibition of nitric oxide release contributes to pressure-induced vasoconstriction and reduced endothelium-dependent relaxation in patients with hypertension.
Atmospheric Pressure↗
Copper valence fluctuation in the organic conductor (dimethyl-N,N'-dicyanoquinonediimine)2Cu studied by x-ray photoemission spectroscopy.
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Journal Article↗