Biomedical subjects

T Mine

Publications and source records attributed to T Mine.

At least 73 records · Page 4Linked to original sources

PubMed1995

The effect of lansoprazole treatment on the healing and relapse of peptic ulcer and serum levels of IgG anti-Helicobacter pylori antibody.

In the present study, the effects of short-term treatment with lansoprazole on healing and recurrence of peptic ulcer were investigated. Complete healing (change to the S2 stage) after 3 or 4 weeks of treatment with lansoprazole was observed in 9.9% of gastric ulcers and 38.3% of duodenal ulcers. Complete healing was observed after 3 or 4 weeks of treatment with lansoprazole in gastric ulcers and was significantly related to the serum titer of IgG anti-Helicobacter pylori antibodies. This was not the case in duodenal ulcers. Complete healing after 6 or 8 weeks of treatment with lansoprazole was not dependent on serum levels of IgG anti-H. pylori antibodies. Short-term treatment by lansoprazole did not affect serum levels of IgG anti-H. pylori antibodies immediately after the end of lansoprazole treatment, but significantly reduced serum levels of IgG anti-H. pylori antibodies were found 9 months after treatment.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed1995

Attenuation of glycogenolytic action of activin A in intact rat liver.

Activin A stimulates glucose production by causing glycogenolysis in isolated hepatocytes. To determine the physiological significance of this effect, we examined the effect of activin A on glucose production in the perfused liver. Unlike the effect in isolated cells, activin A did not enhance glucose production nor did it cause radiocalcium efflux in the perfused liver. There was no effect of activin A in the liver perfused in the opposite direction. Although activin A did not promote glucose production, it was recovered from the hepatic vein in a bioactive form. When liver perfusion was performed in partially hepatectomized rats, activin A increased radiocalcium efflux. In isolated hepatocytes, activin A increased inositol phosphates, and the effect of activin A was attenuated by the plasma membrane fraction of hepatocytes. The inhibitory effect of the plasma membrane was abolished by digestion of the membrane with trypsin. These results indicate that the effect of activin A on glucose production is attenuated in the intact liver and that a protein factor(s) in plasma membrane may be involved in the inhibition.

Activins↗

PubMed1995

Conversion of amylase-secreting rat pancreatic AR42J cells to neuronlike cells by activin A.

When AR42J cells, an amylase-secreting pancreatic exocrine cell line, were treated with activin A, cells extended neuritelike processes, and, concomitantly, amylase-containing vesicles disappeared. Immunofluorescence and immunoelectron microscopy revealed that these processes had neurite-specific cytoskeletal architectures: neurofilaments and microtubule bundles with cross-bridges of microtubule-associated protein 2. In addition to such morphological changes, activin-treated cells exhibited a marked increase in cytoplasmic free calcium concentration in response to depolarizing concentration of potassium. Moreover, activin-treated AR42J cells expressed mRNA for alpha 1 subunit of the neuroendocrine/beta cell-type voltage-dependent calcium channel. In naive AR42J cells, a sulfonylurea compound, tolbutamide, did not affect free calcium concentration, while it induced a marked elevation of free calcium in activin-treated cells. Single channel recording of the membrane patch revealed the existence of ATP-sensitive potassium channel in activin-treated cells. These results indicate that activin A converts amylase-secreting AR42J cells to neuronlike cells. Given that pancreatic endocrine cells possess neuronlike properties and express ATP-sensitive potassium channel as well as neuroendocrine/beta cell-type voltage-dependent calcium channel, activin treatment of AR42J cells may provide an in vitro model system to study the conversion of pancreatic exocrine cells to endocrine cells in islets.

Activins↗

PubMed1995

External radiotherapy for biliary decompression of hilar cholangiocarcinoma.

Obstructive jaundice due to hilar cholangiocarcinoma is difficult to decompress because of the location of the tumor. We used external radiation alone for biliary decompression and reviewed its efficacy in this study. Subjects comprised 14 patients diagnosed as having inoperable hilar cholangiocarcinoma by ultrasonography, percutaneous transhepatic cholangiography, and CT scanning. The total bilirubin level on admission ranged from 0.4 to 34.6 mg/dl (mean: 11.0 mg/dl). These patients were irradiated with a 4MeV linear accelerator using parallel opposing fields measuring from 7 x 7 cm to 8 x 10 cm. The total radiation dose ranged from 50 Gy to 60 Gy and in fractions of 1.8-2.0 Gy per day. No patient underwent further biliary decompression after percutaneous transhepatic cholangiography, and irradiation was performed immediately after diagnosis. Eleven of the 14 patients received the full dose of external radiation. Three patients discontinued radiotherapy because of severe vomiting and nausea, pneumonia, and a hemorrhagic gastric ulcer. In 10 of the 11 patients, the serum total bilirubin level returned to normal (p < 0.005) and no cholangitis occurred. Obstructive jaundice recurred in one patient, and serum total bilirubin returned to normal again after further irradiation. Eight of the 11 patients could be discharged from hospital and returned to society. The survival time of the 11 patients ranged from 3 to 25 months and the 12-month survival rate was 50% (Kaplan-Meier method). This study suggests that external radiation therapy is an effective treatment for biliary decompression in patients with unresectable hilar cholangiocarcinoma.

Aged↗

PubMed1995

Human chronic gastric ulcer and connexin.

In this study we investigated the relationship between chronic gastric ulcers and the appearance of connexin 32 or connexin 43. Samples were taken endoscopically and the appearance of connexin 32 or connexin 43 was assessed by Western blotting using anticonnexin 32 or anticonnexin 43 antibodies. Normal gastric mucosa contained both connexin 32 and connexin 43. In contrast, gastric mucosa surrounding a chronic gastric ulcer lesion contained a smaller amount of connexin 32 and connexin 43. We also investigated the relationship between the appearance of connexins and ulcer healing. Antiulcer treatment for chronic gastric ulcer was administered. When ulcer healing was observed, connexins 32 and 43, which decreased at the active ulcer stage, had returned almost to levels observed in normal gastric mucosa. These data clearly indicate that disappearance of both connexin 32 and connexin 43 is closely related to the stage of chronic gastric ulcer lesions.

Anti-Ulcer Agents↗

PubMed1994

Inhibition by somatostatin of amylase secretion induced by calcium and cyclic AMP in rat pancreatic acini.

It has recently been shown that somatostatin inhibits amylase secretion from isolated pancreatic acini by reducing cyclic AMP (cAMP) production [Matsushita, Okabayashi, Hasegawa, Koide, Kido, Okutani, Sugimoto and Kasuga (1993) Gastroenterology 104, 1146-1152]. To date, however, little is known as to the other mechanism(s) by which somatostatin inhibits amylase secretion in exocrine pancreas. To investigate the action of somatostatin independent of cAMP generation, we examined the effect of somatostatin in isolated rat pancreatic acini stimulated by 1 microM calcium ionophore A23187 and 1 mM 8-bromo-cyclic AMP (8Br-cAMP). Somatostatin inhibited amylase secretion evoked by a combination of A23187 and 8Br-cAMP in a dose-dependent manner. The maximum inhibition was obtained by 10(-7) M somatostatin, and at this concentration somatostatin inhibited the effect of A23187 and 8Br-cAMP by approximately 30%. In electrically permeabilized acini, an elevation of free calcium concentration resulted in an increase in amylase secretion and cAMP enhanced the secretion evoked by calcium. cAMP shifted the dose-response curve for calcium-induced secretion leftwards and elevated the peak value of secretion. Somatostatin inhibited the effect of cAMP on calcium-induced amylase secretion by shifting the dose-response curve to the right. To determine the involvement of a G-protein(s), we examined the effect of somatostatin in acini pretreated with pertussis toxin. Pretreatment of acini with pertussis toxin completely blocked somatostatin-inhibition of amylase-secretion evoked by A23187 and 8Br-cAMP. These results indicate that somatostatin decreases amylase secretion induced by cAMP and calcium by reducing the calcium sensitivity of exocytosis. A pertussis toxin-sensitive G-protein is also involved in this step.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1994

Stimulation of follistatin production by epidermal growth factor in cultured rat hepatocytes.

Production of follistatin in cultured rat hepatocytes was studied by measuring follistatin release with a protein-binding assay using [125I]activin A. Follistatin was detected in conditioned medium of cultured hepatocytes. Ligand blotting using [125I]activin revealed that follistatin released into the medium consisted of two different forms with molecular weight of approximately 40 K-Da. Epidermal growth factor (EGF) elicited dose-dependent increases in DNA synthesis and follistatin release. Dose-response relationship for EGF-induced follistatin release correlated well with that for EGF-induced DNA synthesis. In EGF-stimulated cells, a marked increase in DNA synthesis occurred after 48 hrs. Similarly, follistatin release was markedly augmented after 48 hrs. Amount of cell-bound follistatin was not changed by the treatment with EGF. These results indicate that cultured hepatocytes synthesize and release follistatin. The activin-follistatin system operates in cultured rat hepatocytes and may modulate DNA synthesis by altering the action of activin A.

Activins↗

PubMed1994

Studies on the effect of parathyroid hormone (1-84) on glucose output in the liver: comparison of effects in isolated hepatocytes and in perfused liver.

This study was conducted to determine the action of parathyroid hormone (1-84) (PTH(1-84)) on glucose output both in perfused liver and in isolated hepatocytes. In isolated rat hepatocytes, PTH(1-84) stimulated glucose output in a concentration-dependent manner. The action was detected at 10(-11) M and, at 10(-9) M, PTH produced its maximal effect. The magnitude of the maximal effect of PTH(1-84) was about 65% of that of phenylephrine. In contrast, PTH(1-84) had no effect on glucose output in perfused rat liver. Concentration of PTH(1-84) in effluent of perfused liver was less than that in the inflow. However, when the effluent obtained from liver perfused with 10 nM PTH(1-84) was added to isolated hepatocytes, a considerable amount of glucose was released, which was reversed by PTH(7-34), a competitive inhibitor of PTH receptor. These results indicate that PTH(1-84) increases glucose output in isolated hepatocytes but not in intact liver. It is suggested that the action of PTH(1-84) is blocked in intact liver by a yet unknown mechanism.

Animals↗

PubMed1994

Activin A: negative regulator of amylase secretion and cell proliferation in rat pancreatic acinar AR42J cells.

Activin A, a member of the transforming growth factor-beta supergene family, exists in secretory granules of non-B-cells of rat pancreatic islet (H. Yasuda, K. Inoue, H. Shibata, T. Takeuchi, Y. Eto, Y. Hasegawa, N. Sekine, Y. Totsuka, T. Mine, E. Ogata, and I. Kojima. Endocrinology 133: 624-630, 1993). Because functions of exocrine pancreas are influenced by hormones in pancreatic islet, it is possible that activin A affects the function of pancreatic acinar cells. To examine this possibility, we studied the effects of activin A on amylase secretion and DNA synthesis in AR42J cells. In these cells, dexamethasone (Dx) induces increases in secretory organelles and secretion of amylase (C. D. Logsdon, J. Moessner, J. A. Williams, and I. D. Goldfine. J. Cell Biol. 100: 1200-1208 1985). Activin A did not change the rate of amylase release by itself nor affect the cholecystokinin-stimulated amylase release from Dx-treated differentiated AR42J cells. However, when activin A was added together with Dx, activin A inhibited Dx-induced increase in amylase content in a dose-dependent manner. In the presence of 1 nM activin A, the effect of Dx was abolished. In the absence of Dx, amylase content of the cells was also reduced by activin A in a dose-dependent manner. The maximum inhibitory effect was obtained by 10 nM activin A, and at this concentration amylase content became undetectable. In addition, activin A potently inhibited DNA synthesis as assessed by [3H]thymidine incorporation.(ABSTRACT TRUNCATED AT 250 WORDS)

Activins↗

PubMed1994

Pharmacological properties of the new stable prostacyclin analogue 3-Oxa-methano-prostaglandin I.

The pharmacological characteristics of the 3-oxamethano-prostaglandin I1 compound (+)-methyl [2-[(2R,3aS,4R,5R,6aS)-octahydro-5-hydroxy-4- [(E)-(3S,5S)-3-hydroxy-5-methyl-1-nonenyl]-2-pentalenyl]etho xy] acetate (SM-10902, CAS 139403-31-9), a novel stable analogue of prostacyclin and its free acid, SM-10906, were studied. SM-10902 was rapidly deesterified to its free acid in rabbit and human serum. SM-10902 and SM-10906 exhibited antiplatelet potency against ADP-induced aggregation in rabbit and human platelets. In the presence of diisopropyl fluorophosphate, an esterase inhibitor, the antiplatelet activity of SM-10902 was markedly reduced, to much less than that of SM-10906. SM-10906 inhibited platelet aggregation induced by various inducers in several species and enhanced the cyclic AMP (cAMP) level in human platelets. These activities were nearly equal to those of prostaglandin (PG) E1 and less than those of PGI2. SM-10906 relaxed isolated rabbit mesenteric and bovine coronary arteries, and elevated the cAMP level in bovine coronary arteries. SM-10906 given intravenously exhibited a sustained reduction in blood pressure based on vasodilation in ganglion-blocked, angiotensin II-supported rats. SM-10902 applied to the guinea-pig auricles increased the skin temperature, but SM-10906 and PGI2 showed no such effect. In conclusion, SM-10902, which is considered to be a prodrug of SM-10906, was suggested to exert its anti-platelet and vasodilator activities through the increase of cAMP. Since SM-10902 penetrates well into the skin, it may be useful as an external preparation to improve peripheral circulatory insufficiency.

Adenylyl Cyclase Inhibitors↗

PubMed1994

Healing of chronic gastric ulcer depends on gastric mucosal prostaglandin synthesis.

In the present study, the role of endogenous prostanoid synthesis in gastric mucosa in the healing of chronic gastric ulcers was investigated. Nineteen patients were divided into two groups in accordance with healing state after one month of treatment with cimetidine only: "healed group" and "unhealed group". Biopsy specimens taken from the mucosa around the ulceration (damaged gastric mucosa) and at a distance from the ulceration (normal gastric mucosa) at endoscopy prior to treatment were homogenized, and the mucosal prostanoid synthesis was determined using [14C]arachidonic acid. The mean value of prostaglandin E2 synthesis in the normal gastric mucosa of the healed group was 60% higher than in that of the unhealed group, but the difference was not significant. However, prostaglandin E2 synthesis in the damaged gastric mucosa of the healed group was 117% higher than in that of the unhealed group. The same tendency was observed for prostaglandin D2 and 6-keto prostaglandin F1 alpha synthesis as for prostaglandin E2. In our study it was demonstrated that there is a good correlation of prostaglandin synthesis in the damaged mucosa with healing of chronic gastric ulceration. Furthermore, our study indicated that prostaglandin synthesis, especially in damaged mucosa, might be important in the healing of gastric ulceration.

6-Ketoprostaglandin F1 alpha↗

PubMed1993

Activin A increases intracellular free calcium concentrations in rat pancreatic islets.

Activin A stimulated insulin secretion in rat pancreatic islets, an effect that was attenuated by reduction of extracellular Ca2+ and abolished by either nitrendipine or verapamil. Activin A increased intracellular the free Ca2+ concentration, [Ca2+]i in fura-2-loaded islets. Activin A-mediated elevation of [Ca2+]i was abolished by the reduction of extracellular Ca2+ or the addition of nifedipine. In addition, activin A did not increase [Ca2+]i in the presence of diazoxide, an opener of ATP-sensitive K+ channels. These results suggest that activin A increases insulin secretion by stimulating Ca2+ entry.

Activins↗

PubMed1993

The pedicled venous flap. An experimental study.

Musculocutaneous pedicled venous flaps on the dorsum of rats survived at a statistically significantly higher rate than musculocutaneous composite grafts (p < 0.01). With a Silastic sheet (Dow Corning) beneath, both composite grafts and pedicled venous flaps necrosed. When a Silastic sheet with holes in it to allow some revascularisation from the bed was placed beneath, the survival rate was significantly better than with a complete Silastic sheet (p < 0.01). These results demonstrate that pedicled venous flap survival depends both on the draining vein, and revascularisation from the underlying bed.

Animals↗

PubMed1993

Role of calcium fluxes in the action of glucagon on glucose metabolism in rat hepatocytes.

The aim of the present study was to assess the role of calcium fluxes in the action of glucagon on glycogenolysis and gluconeogenesis in isolated rat hepatocytes. Calcium influx was blocked by two ways: by use of the compound tetramethrin and by reduction of extracellular calcium to 1 microM. The minimal concentration of tetramethrin that inhibited glucagon-mediated calcium entry was 7.5 x 10(-7) M. In the presence of 7.5 x 10(-7) M tetramethrin, glucagon-induced glycogenolysis was markedly attenuated when glucagon concentration was 10(-9) M or higher. In contrast, tetramethrin had no effect on glucogenolysis evoked by lower concentrations of glucagon. Similarly, tetramethrin greatly reduced gluconeogenesis induced by high concentrations of glucagon without affecting the effect of low concentrations of glucagon. The same results were obtained in the presence of 1 microM extracellular calcium. To abolish glucagon-induced elevation of cytoplasmic free calcium concentration, we heavily loaded quin2 into hepatocytes. In these cells, glycogenolysis evoked by low concentrations of glucagon was completely abolished. Glycogenolysis caused by high concentrations of glucagon was markedly inhibited. These results indicate that glucagon action on hepatic glucose metabolism is mediated by two different mechanisms, which depend on concentrations of glucagon.

Aminoquinolines↗

PubMed1993

Activin A: an autocrine inhibitor of initiation of DNA synthesis in rat hepatocytes.

The present study was conducted to examine the effect of activin A on growth of rat hepatocytes. EGF induced a 10-fold increase in DNA synthesis as assessed by [3H]thymidine incorporation in cultured hepatocytes. When activin A was added together with EGF, DNA synthesis induced by EGF was markedly inhibited. Inhibition was detected at a concentration of 10(-10) M, and 5 x 10(-9) M activin A almost completely blocked EGF-mediated DNA synthesis. Similarly, activin A completely blocked DNA synthesis induced by hepatocyte growth factor/scatter factor. Activin A was capable of inhibiting EGF-mediated DNA synthesis, even when added 36 h after the addition of EGF. With the same time interval, TGF-beta also blocked EGF-induced DNA synthesis. Although both activin A and TGF-beta inhibited growth of hepatocytes in a similar manner, either activin A or TGF-beta did not compete with each other in their binding when assessed by competitive binding using an iodinated ligand. When hepatocytes were incubated with EGF, release of bioactivity of activin A into culture medium was detected after 48 h or later. Activity of activin A was released from parenchymal cells but not from nonparenchymal cells. mRNA for beta A subunit of activin was detected only slightly in unstimulated hepatocytes, but markedly increased at 48 h after the addition of EGF. To determine whether endogenously produced activin A affects DNA synthesis, we examined the effect of follistatin, an activin-binding protein that blocks the action of activin A. An addition of follistatin significantly enhanced EGF-induced DNA synthesis. Finally, in partial hepatectomized rat, expression of mRNA for beta A subunit in liver was markedly increased 24 h after the partial hepatectomy. These results indicate that activin A inhibits initiation of DNA synthesis in hepatocytes by acting on its own receptor and that activin A acts as an autocrine inhibitor of DNA synthesis in rat hepatocytes.

Activins↗

PubMed1993

Existence of activin-A in A- and D-cells of rat pancreatic islet.

Activin-A, a member of the transforming growth factor-beta supergene family, stimulates insulin secretion in rat pancreatic islets and causes glycogenolysis in isolated rat hepatocytes. These observations prompted us to determine whether activin-A existed in rat pancreas by using an immunocytochemical method. Cells in pancreatic islets were stained by antibody against activin-A, whereas no immunoreactivity was observed in exocrine pancreas. Cells localized in the mantle of the islets were densely stained by the antibody. Immunoelectron microscopic study showed that activin-A existed in secretory granules in both A- and D-cells. Furthermore, studies using a double labeling method revealed that activin-A coexisted with glucagon in secretory granules in A-cells and with somatostatin in D-cells. Antibody against inhibin-A weakly stained cells in both the core and mantle of the islets only when the rat was pretreated with colchicine. Subtypes of activin subunit in islets were identified to be beta A by a reverse transcription-polymerase chain reaction method. In addition, mRNA for inhibin alpha-subunit was expressed in islets. However, mRNA for these inhibin subunits was not detected in exocrine pancreas. To further examine the action of activin-A on insulin secretion, we examined the effect of activin-A in a flow-through perifusion system. Activin-A induced a biphasic insulin secretory response in the presence of 2.8 mM glucose, and a low concentration of activin-A, which does not stimulate insulin secretion by itself, markedly enhanced glucose-mediated insulin secretion at concentrations above 2.8 mM glucose. Inhibin-A did not affect insulin secretion. These results suggest the existence of activin-A in A- and D-cells of rat pancreatic islets and raise the possibility that activin-A acts as a physiological regulator of carbohydrate metabolism.

Activins↗

PubMed1993

Metabolism of a tetrahydroaminoacridine derivative (SM-10888) in rat: structural analysis of an N-glucuronide of SM-10888 and an O-glucuronide of hydroxylated SM-10888 by FAB-MS/MS.

1. The metabolism of 9-amino-8-fluoro-1,2,3,4-tetrahydro-2,4-methanoacridine citrate (SM-10888), a cholinesterase inhibitor was studied in rat. 2. The phase I metabolite (designated M3) was isolated from urine and identified as 1-hydroxylated SM-10888 by 1H-n.m.r. and EI-MS. 3. Two glucuronides (designated SMG and M3G) were isolated from bile and urine and their structures examined by FAB-MS/MS and beta-glucuronidase hydrolysis. 4. FAB-mass spectra of SMG and M3G showed molecular ions ([M+H]+) at m/z 405 and 421, respectively. In their daughter spectra, fragment ions of aglycones (SM-10888 and M3), generated by the loss of glucuronic acid (176 amu) were observed. The daughter spectra of these aglycones were essentially similar to those of the corresponding synthetic standards. 5. SMG was hydrolysed non-enzymically at pH 5 as is often the case with N-glucuronides of arylamines. M3G could be hydrolysed by beta-glucuronidase but proved stable at pH 5. 6. From these results, SMG and M3G were concluded to be the N-glucuronide of SM-10888 and the O-glucuronide of M3, respectively.

Aminacrine↗

PubMed1992

Pertussis toxin blocks activin A-induced production of inositol phosphates in rat hepatocytes.

The present study was conducted to examine an involvement of G protein in the action of activin A in rat parenchymal liver cells. Activin A induced a dose-dependent increase in inositol phosphates in cells prelabelled with [3H]inositol. The effect of activin A was completely blocked by pretreatment of the cells with pertussis toxin. In contrast, pertussis toxin had little effect on angiotensin II-induced production of inositol phosphates. Both activin A and angiotensin II inhibited glucagon-mediated production of cAMP. Pretreatment of the cells with pertussis toxin blocked the inhibition induced by both activin A and angiotensin II. In permeabilized cells, activin A augmented production of inositol phosphates. Activin-mediated production of inositol trisphosphate was enhanced by GTP-gamma S and was attenuated by GDP-beta S. These results suggest that a pertussis toxin-sensitive G protein(s) may be involved in the action of activin A in hepatocytes.

Activins↗