Role of thrombin in mesangial proliferative glomerulonephritis.
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Adult↗
Biomedical subjects
H Fukui
Publications and source records attributed to H Fukui.
Increased plasma levels of substance P and disturbed water excretion in patients with liver cirrhosis.
BACKGROUND: The pathogenesis of impaired water excretion in liver cirrhosis has not been fully elucidated. METHODS: We induced an intravenous water overload of 20 ml/kg body weight in 10 cirrhotics without ascites (CLC), 11 cirrhotics with ascites (DLC), and 10 normal subjects (N) and investigated the relationship of plasma levels of substance P (SP), norepinephrine (NE), and antidiuretic hormone (ADH) to impaired water excretion. RESULTS: Free water clearance (CH2O) was lower in DLC (mean, 2.7 ml/min) than in N (8.3 ml/min; P < 0.001) and CLC (6.9 ml/min; P < 0.001). In DLC the creatinine clearance (CCr), maximal urine flow rate/CCr, (CH2O + CNa)/CCr, and mean arterial pressure (MAP) were significantly lower than in N and CLC. There was a progressive increase in basal SP, from lowest in N to CLC, to highest in DLC. Basal NE increased in CLC and DLC. Basal ADH did not differ among N, CLC, and DLC. In cirrhotics CH2O was correlated positively with serum albumin and cholinesterase and negatively with the retention rate of indocyanine green at 15 min. Basal SP was negatively correlated with CH2O (r= -0.71: P < 0.001) and MAP (r= -0.56; P < 0.005). Basal NE was correlated positively with basal SP (r= 0.67, P < 0.01 ). CONCLUSIONS: Decreased CH2O is closely related to the severity of the liver disturbance. Decreased CCr and reduced delivery of filtrate to the ascending limb of the loop of Henle secondary to an increased sodium reabsorption in the proximal tubule may play an important role in the impairment of water excretion. The increase in SP, which has a potent vasodilatory action, and the associated enhanced activity of the sympathetic nervous system may be responsible for the mild or moderate impairment of water excretion in the absence of nonosmotic hypersecretion of ADH in cirrhotics with ascites.
Adult↗
Presence of atrial natriuretic peptide in rat thyroid medullary carcinoma cell line.
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Animals↗
Geranylgeranylacetone, an anti-ulcer drug, stimulates hexosamine production in a rat gastric mucosal cell line through binding to a specific cytosolic protein.
An anti-ulcer drug, geranylgeranylacetone (GGA), stimulates hexosamine production in a rat gastric mucosal cell line (RGM-1). The aim of this study was to elucidate the mechanism of this action. The role of protein kinase A, inositol phospholipid turnover and tyrosine kinase in the stimulatory action of GGA on hexosamine production in RGM-1 was determined by observing cAMP production, [3H]-inositol phosphate turnover and western blotting of tyrosine phosphorylation, respectively. Any trophic effect of GGA on RGM-1 was also checked by [3H]-thymidine incorporation. Our experiments showed that GGA has no effect on cAMP production, inositol phospholipid turnover, tyrosine phosphorylation or DNA synthesis in RGM-1. Finally, a [14C]-GGA competitive receptor binding assay was performed on RGM-1 and we found that [14C]-GGA specifically bound to RGM-1 cytosolic protein. Although retinoic acid (RA), another polyisoprenoid compound significantly stimulated hexosamine production in RGM-1, we confirmed that the [14C]-GGA binding site in RGM-1 is different from the RA binding site. In summary, GGA stimulates hexosamine production in RGM-1 and this action is probably mediated through its binding to a specific cytosolic protein in RGM-1.
Animals↗
Relationship between severity and symptoms of reflux oesophagitis in elderly patients in Japan.
Since information concerning reflux oesophagitis in the elderly is limited, particularly in Japan, the severity and symptomatic profiles of reflux oesophagitis in elderly patients were investigated. One hundred and nineteen patients with reflux oesophagitis found among 2278 endoscopy cases between 1993 and 1996 were investigated in this study. The patients were divided into two groups, elderly and non-elderly. The severity of reflux oesophagitis was estimated by the Los Angeles classification. The presence or absence of typical symptoms (heartburn and regurgitation) was determined by interview. Reflux oesophagitis was not only more frequently found in the elderly group, but was more severe than in the non-elderly. Although the degree of manifestation of typical symptoms was similar between the elderly and the non-elderly with high-grade oesophagitis, the elderly patients with mild reflux oesophagitis were less symptomatic than the non-elderly. Mild reflux oesophagitis in the elderly may be missed due to its rarity of typical reflux symptoms and a substantial number of elderly persons might have subclinical reflux oesophagitis.
Adult↗
Platelet and brain alpha 2-adrenoceptors and cardiovascular sensitivity to agonists in dogs suffering from endotoxic shock.
We examined the changes in alpha 2-adrenoceptor binding on platelet and brain membranes of dogs treated with a non-lethal dose of endotoxin (0.1 mg/kg intravenously), and the alpha 2-adrenoceptor mediated cardiovascular effects during endotoxin shock. At 2 h, 24 h, and 7 days after endotoxin administration, the number of binding sites (Bmax) of [3H]yohimbine binding decreased and equilibrium dissociation constants (Kd) increased in platelets, whereas both Bmax and Kd decreased in either cerebral cortex or medulla oblongata. After 30 days of endotoxin administration, there were no significant differences in Bmax or Kd between the treated and untreated animals in both platelets and brain tissues. Significant positive correlations were observed for Bmax values between platelets and brain tissues, although negative correlations for Kd values between platelets and brain were not significant. Significant negative correlations were also observed between plasma catecholamine concentrations and platelet alpha 2-adrenoceptor number, and between plasma noradrenaline and medulla alpha 2-adrenoceptor number. Pretreatment with E coli endotoxin diminished cardiovascular effects such as bradycardia, hypotension, and increase in systemic vascular resistance induced by either i.v. clonidine or xylazine. This suggests that alpha 2-adrenoceptor activity is impaired in the central nervous system as well as in the peripheral vascular system during endotoxin shock. Therefore, platelets may in part represent a good model which reflects the alpha 2-adrenoceptor changes in the central nervous system and peripheral vascular system during and after endotoxin shock.
Adrenergic alpha-2 Receptor Antagonists↗
Increased hepatocyte growth factor content in rat stomach during omeprazole treatment.
BACKGROUND AND AIMS: Hepatocyte growth factor (HGF) is a potent mitogen of gastric epithelial cells, and its production is stimulated during the healing of gastric mucosal lesions. In this study, the effect of a proton pump inhibitor, omeprazole, on the production and degradation of HGF in the stomach was examined to elucidate the mechanism of the omeprazole-induced acceleration of gastric mucosal healing. METHODS: Indomethacin-induced gastric mucosal lesions were induced in rats with or without omeprazole pretreatment. HGF gene expression and the content of HGF was investigated in the rat stomach. HGF degradation by gastric juice was also tested. RESULTS: In omeprazole-treated rats, the healing of gastric mucosal lesions was accelerated in comparison with those of untreated rats. Although omeprazole treatment did not enhance the indomethacin-induced increase in HGF gene expression, it significantly augmented the gastric HGF content. Furthermore, omeprazole increased the gastric content not only of the inactive but also of the active heterodimeric form of HGF, and this appeared to be due to the inhibition of the HGF degradation by gastric juice. CONCLUSION: Omeprazole-induced acceleration of gastric mucosal healing may be mediated at least in part by the reduced degradation of HGF in the stomach.
Animals↗
[Identification of protein kinase C phosphorylation sites involved in desensitization of the histamine H1 receptor].
We studied whether direct phosphorylation plays a key role in protein kinase C-activating phorbol ester-mediated H1 receptor desensitization. Several potential protein kinase C-mediated phosphorylation sites were located in the third cytoplasmic loop form our cloning studies of H1 receptors. Ser396 and Ser398 were determined to be the phosphorylation sites by in vitro phosphorylation studies using synthetic peptides corresponding to the partial amino acid sequence of the third cytoplasmic loop. Mutant H1 receptors whose Ser396 or Ser398 were displaced by alanine were expressed in Chinese hamster ovary cells by site-directed mutagenesis. Characterization of these receptors revealed that Ser398, but not Ser396, was primarily responsible for protein kinase C-mediated H1 receptor desensitization.
Amino Acid Sequence↗
Histamine-induced calcium mobilization in single cultured cells expressing histamine H1 receptors: a relationship between its sensitivity and the density of H1 receptors.
Stimulation of histamine H1 receptors initiates the hydrolysis of phosphatidylinositides and results in the production of inositol (1, 4,5)-triphosphate and intracellular Ca2+ mobilization. Although the mechanism for signal transduction via the H1 recptor has been extensively investigated, little is known about the correlation between the sensitivity of histamine-induced Ca2+ mobilization and the density of H1 receptors in cultured cells. Cytosolic free Ca2+ concentration ([Ca2+]i) after stimulation by histamine was monitored in single CHO and rat C6-glioma cells stably expressed with H1 receptors and astrocytoma 1321N1 cells using the Ca2+-sensitive dye Indo-1 and dynamic single cell imaging techniques (ACAS 570 laser cytometer). Both of the H1 receptor-expressed CHO cells and C6-glioma cells were over 10 times more sensitive to histamine than astrocytoma 1321N1 cells in which H1 receptors were naturally present. The density of H1 receptors in the transfected cells was also more than 10-fold that of 1321N1 cells. In addition, inhibition of intracellular Ca2+-ATPase by thapsigargin elicited an increase in [Ca2+]i in H1 receptor-overexpessed cells and astrocytoma 1321N1 cells with similar sensitivity. These data suggest that the sensitivity of Ca2+ mobilization by histamine in these cells was correlatively augmented with the increase in the density of H1 receptors.
Animals↗
Dihydropyridine type calcium channel blocker-induced turbid dialysate in patients undergoing peritoneal dialysis.
We previously reported that manidipine, a new dihydropyridine type calcium channel blocker, produced chylous peritoneal dialysate being visually indistinguishable from infective peritonitis in 5 patients undergoing continuous ambulatory peritoneal dialysis (CAPD) [Yoshimoto et al. 1993]. To study whether such an adverse drug reaction would also be elicited by other commonly prescribed calcium channel blockers in CAPD patients, we have conducted postal inquiry to 15 collaborating hospitals and an institutional survey in International Medical Center of Japan as to the possible occurrence of calcium channel blocker-associated non-infective, turbid peritoneal dialysate in CAPD patients. Our diagnostic criteria for drug-induced turbidity of dialysate as a) it developed within 48 h after the administration of a newly introduced calcium channel blocker to the therapeutic regimen, b) absence of clinical symptoms of peritoneal inflammation (i.e., pyrexia, abdominal pain, nausea or vomiting), c) the fluid containing normal leukocyte counts and being negative for bacterial and fungal culture of the fluid, and d) it disappeared shortly after the withdrawal of the assumed causative agent. Results showed that 19 out of 251 CAPD patients given one of the calcium channel blockers developed non-infective turbid peritoneal dialysis that fulfilled all the above criteria. Four calcium channel blockers were suspected to be associated with the events: benidipine [2 out of 2 (100%) patients given the drug], manidipine [15 out of 36 (42%) patients], nisoldipine [1 out of 11 (9%) patients] and nifedipine [1 out of 159 (0.6%)] in descending order of frequency. None of the patients who received nicardipine, nilvadipine, nitrendipine, barnidipine and diltiazem (25, 7, 2, 1 and 8 patients, respectively) exhibited turbid dialysate. In conclusion, we consider that certain dihydropyridine type calcium channel blockers would cause turbid peritoneal dialysate being similar to that observed in patients developing infective peritonitis. To avoid unnecessary antibiotic therapy the possibility of this adverse reaction should be ruled out whenever a CAPD patient receiving a dihydropyridine type calcium channel blocker develops turbid dialysate.
Calcium Channel Blockers↗
[Diagnostic usefulness of magnetic resonance cholangiopancreatography (MRCP) in comparison with retrograde cholangiopancreatography (ERCP) for cholelithiasis].
PURPOSE: To elucidate MRCP diagnostic usefulness compared to ERCP. PATIENTS, METHODS: 29 MRCP performed patients diagnosed by ERCP were studied. RESULTS: MRCP showed 92%, 67% sensitivity and 73%, 100% specificity in choledocholithiasis (CBD) and cholecystolithiasis (GB), respectively. MRCP revealed 4.0 false positive and 1.5 false negative in CBD and GB, respectively. MRCP could detect 22 stones out of 33 in CBD and 13 out of 42 in GB. As for the maximal diameter, MRCP depicted 31% for less than 5 mm and 100% for over 6 mm in CBD. In GB, 7% for less than 5 mm, 83% for 6-10 mm and 100% for over 11 mm. CONCLUSION: Although the depection of tiny stone is limited, MRCP is a useful diagnostic tool for cholelithiasis, especially choledocholithiasis.
Adult↗
[Findings of MR and MR cholangiopancreatography in acute cholecystitis].
We retrospectively reviewed magnetic resonance cholangiopancreatography (MRCP) of 25 patients with acute cholecystitis based on clinical, sonographic and surgical findings. Intramural high signal intensity on MRCP was demonstrated in 22 of the 25 patients (88%), and pericholedochal high signal intensity was observed in 6 of the 25 patients (24%). Pericholecystic or perihepatic fluid was demonstrated in 6 of the 25 patients (24%). Gallbladder stones were identified in all 21 patients (100%) by sonography, in 19 of the 21 (90%) by MRCP and in 11 of 18 patients by CT (CT was not performed in other 3 patients). Common bile duct calculi were detected in all 6 patients (100%) by MRCP, in 2 of the 6 (33%) by sonography, and in 5 of the 6 (50%) by CT with confirmation of surgical finding or endoscopic retrograde cholangiography (ERC). MRCP had a high accuracy in diagnosing acute cholecystitis with the finding of intramural high signal intensity. MRCP is an excellent method to evaluate acute biliary disease and may replace CT and ERC in the preoperative evaluation of acute cholecystitis.
Acute Disease↗
Cationic Surfactant Adsolubilization of 2-Naphthol and Naphthalene with Titanium Dioxide Having Dodecyl Chain
Adsolubilization of 2-naphthol and naphthalene by cationic surfactant-adsorbed layers formed on titanium dioxides with or without a dodecyl chain was investigated. The cationic surfactants used were dodecyltrimethylammonium bromide and 1,2-bis(dodecyldimethylammonio) ethane dibromide (2RenQ). It was found that the adsolubilized amounts of 2-naphthol and naphthalene increase and reach a maximum and then decrease for both surfactants and titanium dioxides with or without the dodecyl chain, where in the absence of surfactants the incorporated amount of naphthalene on the titanium dioxide with the dodecyl chain is markedly large. The adsolubilized amounts of 2-naphthol and naphthalene were enhanced with the titanium dioxide with the dodecyl chain by adsorption of surfactants, in particular 2RenQ. The admicellar partitioning coefficients also showed that naphthalene is adsolubilized preferentially rather than 2-naphthol and the surface treatment with the dodecyl chain enhances the adsolubilization for two adsolubilizates. Copyright 1997 Academic Press. Copyright 1997Academic Press
Journal Article↗
Developmental gene expression of gastrin receptor in rat stomach.
Gastrin, which is present in fetal plasma, may have important roles in the development of gastric mucosa, since it is not only a potent stimulator of gastric acid secretion but also a growth promoting factor. Gastrin regulates various cellular functions via its receptors on cell membrane. Therefore, in order to elucidate a role for gastrin in the development of gastrointestinal system during gestation, Northern blot analysis was performed. The results of the study suggested that gastrin receptor is mainly present on parietal cells. Furthermore, proton pump and gastrin receptor gene expressions in parietal cells were strongly stimulated by the administration of exogenous gastrin. In conclusion, gastrin may be involved in the developmental change of parietal cells through its receptors.
Animals↗
Tissue-specific expression of HSV-tk gene can induce efficient antitumor effect and protective immunity to wild-type hepatocellular carcinoma.
The efficacy of expression of the herpes simplex virus thymidine kinase (HSV-tk) gene under the transcriptional control of the liver-specific albumin gene promoter, followed by ganciclovir treatment, was investigated both in vitro and in vivo. Murine and rat hepatocellular carcinoma (HCC) cells infected with retroviruses carrying the HSV-tk gene under the control of the murine albumin gene promoter were selectively killed by ganciclovir treatment in vitro, whereas non-HCC cells, such as murine mammary tumor cells and fibroblast cells, which were infected with the same retroviruses, were not. Susceptibility of the retroviral-infected HCC cells to ganciclovir was more than 100-fold higher than that of the retroviral-infected non-HCC cells. When mice bearing a bulky HCC mass consisting of the retroviral-infected HCC cells were treated with systemic ganciclovir administration, complete regression of the tumors was observed without any signs of overt toxicity. Profound antitumor effects on preestablished murine HCCs were observed when wild-type HCC cells were implanted into animals with a small percentage of the retroviral-infected counterparts. When only 5% of the cells were infected with retroviruses carrying the HSV-tk gene, significant inhibition of tumor development was observed with systemic ganciclovir treatment. Importantly, animals that were treated with implantation of mixtures of the retroviral-infected and parental HCC cells, followed by ganciclovir administration, did not exhibit tumor formation and resisted subsequent rechallenge with wild-type HCC cells. Our results indicate the feasibility of combination therapy with the HSV-tk gene and ganciclovir for the treatment of HCC.
Animals↗
Radical esophagogastrectomy for unshuntable extrahepatic portal hypertension with bleeding varices: report of a case.
A 29-year-old woman with idiopathic portal hypertension was referred to our department for the surgical management of repetitive bleeding from esophageal and gastric varices. At the age of 16 years she had undergone a splenectomy with esophageal transection followed by endoscopic sclerotherapy which had been performed a total of 24 times. Although vericeal hemorrhage was prevented for several months, bleeding from gastric varices and portal hypertensive gastropathy was not able to be controlled readily by endoscopic sclerotherapy from when she was 26 years old. On admission, angiographic studies showed a complete obstruction of the portal vein; however, a portosystemic shunt operation was not able to be performed due to her previous splenectomy. To control her repetitive bleeding, we decided to perform a total gastrectomy and distal esophagectomy with reconstruction by a Roux-en-Y esophagojejunostomy. Her postoperative course was uneventful, and no episodes of recurrent bleeding or other complications have developed, indicating that her quality of life has dramatically improved. Thus, we conclude that distal esophagectomy and total gastrectomy constitute an effective surgical treatment for unshuntable extrahepatic portal hypertension.
Adult↗
Regenerating gene expression in normal gastric mucosa and indomethacin-induced mucosal lesions of the rat.
Regenerating (reg) gene expression was tested in rat gastrointestinal mucosa to investigate the role played by this gene in the healing of mucosal lesions. Expression of reg mRNA was higher in the stomach than in any other region of the gastrointestinal tract. The gastric cells that expressed reg mRNA were located in the deepest mucosal layer and were small in diameter. In an injured state following indomethacin treatment, reg gene expression was markedly augmented, accompanied by an increase of c-fos expression and healing of the mucosal lesions. These results suggest a role of the reg gene in the healing of gastrointestinal mucosal lesions.
Animals↗