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K Inoue

Publications and source records attributed to K Inoue.

At least 19 recordsLinked to original sources
PubMed1992

Release of 14-kDa group-II phospholipase A2 from activated mast cells and its possible involvement in the regulation of the degranulation process.

Group II phospholipase A2 was detected in appreciable amounts in rat peritoneal mast cells. The effect of several inhibitors specific to 14-kDa group-II phospholipase A2, including two proteinaceous inhibitors and a product of microorganisms with a low molecular mass, on mast-cell activation was examined. When rat peritoneal mast cells were sensitized with IgE and then challenged with antigen, the specific phospholipase-A2 inhibitors suppressed histamine release in a concentration-dependent manner. By contrast, these inhibitors showed no effect on prostaglandin generation under the same conditions. Histamine release from rat peritoneal mast cells subjected to non-immunochemical stimuli, such as concanavalin A, the Ca2+ ionophore A23187, compound 48/80 and substance P was also suppressed. When rat peritoneal mast cells were treated with 14-kDa-group-II-phospholipase-A2-specific inhibitors, washed and stimulated, histamine release was not affected appreciably. Similar suppressive effects of the inhibitors on histamine release were observed with mouse cultured bone-marrow-derived mast cells. When bone-marrow-derived mast cells were activated, they secreted both a soluble and an ecto-enzyme form of 14-kDa group-II phospholipase A2, although appearance of the enzyme associated with the external surface of cells was observed transiently. An appreciable amount of membrane phospholipids was degraded during activation of mast cells, which was decreased by treatment with 14-kDa-group-II-phospholipase-A2 inhibitor. These observations suggest that degranulation and eicosanoid generation in mast cells are regulated independently by discrete phospholipases A2 and that the 14-kDa group-II phospholipase A2 released from mast cells during activation may play an essential role in the progression of the degranulation process.

Animals↗
PubMed1992

Dopamine receptor agonists and antagonists enhance ATP-activated currents.

The effects of dopamine and related compounds on ATP-activated channels were investigated in pheochromocytoma PC12 cells. Dopamine (10 microM) enhanced an inward current activated by 100 microM ATP. A similar enhancement of the ATP-activated current was observed with apomorphine (10 microM), a non-selective dopamine receptor agonist, with (+)-SKF-38393 (10 microM), a selective dopamine D1 receptor agonist, and with (-)-quinpirole (10 microM), a selective dopamine D2 receptor agonist. Moreover, (+)-SCH-23390 (30 microM), a dopamine D1 receptor antagonist, and (-)-sulpiride (30 microM), a dopamine D2 receptor antagonist, also enhanced the ATP-activated current. The results suggest that ATP-activated channels are modulated by dopaminergic mechanisms, and that this modulation cannot be attributed to any single class of dopamine receptors.

Adenosine Triphosphate↗
PubMed1992

Immunohistochemical study on epidermal growth factor (EGF) receptor during carcinogenesis in the rat liver.

The expression and localization of epidermal growth factor (EGF) receptor were investigated immunohistochemically using anti-EGF receptor antibody in the normal rat liver and 3'-methyl-4-dimethylaminoazobenzen (3'-Me-DAB) induced tumors in rats. In 8 weeks after 3'-Me-DAB treatment, multiple nodules of cholangiocarcinoma were found in the rat liver, and atypical nodules of hepatocytes were also found 14 weeks later. Immunoreactive products against EGF receptor were only slightly positive in the normal liver, the nodule of cholangiocarcinoma, and atypical nodule of hepatocytes. It was noted that EGF receptor immunoreactivity was more intense in non-cancerous tissue adjacent to tumorous nodules than in the cancerous tissue. The present finding suggests that the expression of EGF receptor may be associated with regenerating as well as carcinogenetic processes in the rat liver.

Adenoma, Bile Duct↗
PubMed1992

Extracellular adenosine 5'-triphosphate-evoked glutamate release in cultured hippocampal neurons.

Characteristics of extracellular ATP-evoked electrical responses in rat hippocampal neurons were investigated. Extracellular ATP (100 microM) induced a rapid depolarization followed by repetitive firings of spikes in these cells under whole-cell current-clamp. In whole-cell voltage-clamp experiments, ATP activated 2 types of inward currents that were inhibited by P2-purinoceptor blocker suramin (300 microM). One is a small (about -20 pA) sustained current which is insensitive to tetrodotoxin (TTX), and the other is a large (-100 to -300 pA) transient current which abolished in the presence of 3 microM TTX. The ATP-induced transient current was blocked by 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX; 30 microM), a non-N-methyl-D-aspartate (non-NMDA) receptor antagonist. ATP failed to induce the transient current in the cell which showed the desensitization to quisqualic acid (QA; 10 microM), a non-NMDA receptor agonist. These findings suggest that ATP directly activates small sustained currents, and indirectly induces the transient currents by evoking glutamate release.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1992

Accuracy of the bronchoscopic DNA content analysis of non-small-cell lung carcinoma.

To assess the accuracy of the bronchoscopic DNA content analysis, samples of non-small-cell lung carcinomas (NSCLC) were investigated by means of flow cytometry. Samples were dissociated using the detergent Triton X-100. In 58 NSCLC cases, 39 (67%) had DNA aneuploid tumors. We compared the DNA indices of bronchoscopic brushing samples with 21 corresponding surgical samples. In 16 (76%) cases, DNA ploidy of both bronchoscopic and surgical samples were in concordance. In 3 (14%) cases, both bronchoscopic and surgical sample showed DNA aneuploidy, but the number of the DNA aneuploid stem cell lines was different. The cause of these differences was ascribed to the intratumor DNA heterogeneity. In 2 (10%) cases, the bronchoscopic sample showed DNA diploidy, but the surgical sample showed DNA aneuploidy. In these cases, tumor cells obtained by bronchoscopic brushing were so few that the small DNA aneuploid peak was undetectable in the DNA histogram. But the tumor DNA ploidy was evaluated correctly in 90% of 21 cases using bronchoscopic samples. Consequently, despite some drawbacks, the DNA ploidy diagnosis using bronchoscopic samples in this relatively small study, was almost as reliable as surgical samples.

Adenocarcinoma↗
PubMed1992

Argentophilic intracytoplasmic inclusions in multiple system atrophy.

Argentophilic intracytoplasmic glial inclusions were recently reported in olivo-ponto-cerebellar atrophy (OPCA). We examined the brains of 3 cases of OPCA [2 with striato-nigral degeneration (SND) and 1 without SND], 1 case of pure autonomic failure (PAF) without pathology of OPCA or SND, as well as 36 controls including 2 cases of Holmes' type cerebellar cortical atrophy and 2 cases of Joseph's disease. Although the inclusions were tubulin-positive, the immunoreactivity was different from that of the dendrites. Electron microscopically, the microtubular structures composing the inclusion were fuzzy with granular material. These findings may indicate that the microtubules composing the inclusions are modified. Inclusion-bearing cells appeared to be oligodendrocytes while many of them had larger and lighter nuclei than those of normal-looking oligodendrocytes without the inclusions. The inclusions were widely distributed in a characteristic fashion beyond the typical lesions of OPCA, SND and PAF. The distribution pattern was essentially the same in the case of PAF and 3 cases of OPCA irrespective of the presence or absence of OPCA or SND lesions. In contrast, argentophilic inclusions were not observed in other types of spinocerebellar degeneration, in Holmes' type cerebellar cortical atrophy or in Joseph's disease. It is suggested, in line with other studies, that the inclusion may be specific to OPCA and related disorders which include PAF and a useful marker to distinguish OPCA from other neurodegenerative diseases.

Adult↗
PubMed1992

Neurochemical and histological analysis of motor dysfunction observed in rats with methylnitrosourea-induced experimental cerebellar hypoplasia.

Histological and neurochemical changes related to motor dysfunction observed in rats after neonatal treatment with nitrosoureas were examined. Neonatal rats received subcutaneous injections of methylnitrosourea (MNU: 0.125 mmol/kg, s.c.) or ethylnitrosourea (ENU: 0.25 mmol/kg, s.c.) daily at 4,5,6 and 7 days post partum, a period of cerebellar granule cell, stellate cell and basket cell formation. At 14 days and 45 days after birth, MNU-treated rats displayed a lowering in motor coordination skills measured by tests of retainment ability on a rod of 26 mm diameter, chinning-climbing ability on parallel rods or retainment ability on a rotating rod. Histological examination at 14 days after birth showed a cerebellar hypoplasia with reduced cellularity of the internal granule cell layer and a disperse disposition of Purkinje cells in the granule cell layer. Cerebellar growth and cerebellar content and concentration of DNA were remarkably reduced in the MNU-treated rat. The degree of the reduction in cerebellar content of glutamic acid paralleled the degree of the cerebellar hypoplasia at 14 and 45 days after birth. In contrast, the concentrations of gamma-aminobutyric acid, acetylcholine, 5-hydroxytryptamine and norepinephrine were significantly increased by MNU treatment. ENU treatment control did not exert any significant changes in the neurotransmitters and motor coordination. These results suggest that the motor dysfunctions observed in MNU treated rats are induced by unbalanced output activities from Purkinje cells to motor neurons.

Acetylcholine↗
PubMed1992

Immunohistochemical and ultrastructural studies of intraluminal crystalloids in human prostatic carcinomas.

Intraluminal crystalloids (ICr) observed in 19 cases of incidental or invasive human prostatic carcinoma (PCa) and in a case of benign prostatic hyperplasia were examined extensively by immunohistochemistry and electron microscopy. They were brilliantly eosinophilic with haematoxylin and eosin, manifesting needle-like, triangular, rectangular, hexagonal and irregular lump-like in shape. They were strongly positive, dark blue, with phosphotungstic acid -haematoxylin (PTAH) stain in all cases examined. Among the human antibodies tested, epithelial membrane antigen (EMA) gave specifically positive immunostainability with ICr in all cases. Annual ring-like lamellar or concentric structures were detected by electron microscopy. Positive staining of ICr with PTAH and anti-EMA antibody is very useful as a diagnostic marker for PCa in human prostatic tissues.

Aged↗
PubMed1992

A comparative study on immunosuppressive effects of cyclosporin A and FK 506 on peripheral blood lymphocytes in dogs.

Immunosuppressive effects of cyclosporin A (CsA) and FK 506 (FK) on peripheral blood lymphocytes were studied in dogs in respect to mixed lymphocyte reaction, proliferative responses to recombinant interleukin-2 (rIL-2), phytohemagglutinin (PHA) and concanavalin-A (Con-A); phenotypes of OKIa1, CD3, CD8 and surface IgM; cytotoxic activity against xenogeneic tumor cells. CsA (2.0 or 5.0 mg/kg, intravenously) or FK (0.16 mg/kg, intramuscularly) was given to mongrel dogs every morning for serial 21 days. The blood concentrations of CsA, measured as trough levels by fluorescence polarization method, ranged from 37 to 350 ng/ml in dogs administered at 2.0 mg/kg and from 170 to 894 ng/ml in dogs administered at 5.0 mg/kg during treatment, respectively. In dogs treated with FK at a dose of 0.16 mg/kg, the drug concentrations in the plasma during treatment ranged from 0.16 to 1.8 ng/ml. Mixed lymphocyte reaction and proliferative responses to rIL-2, PHA and Con-A, which were declined by CsA, were not affected by FK. In contrast, the proportion of OKIa1+ cells was not affected by CsA, whereas FK decreased the proportion of OKIa1+ cells progressively during the course of treatment. Cytotoxic activity was suppressed by both CsA and FK. These results possibly indicate that CsA and FK exert their immunosuppressive effects via different mechanisms.

Animals↗
PubMed1992

Heavy chain binding protein (BiP/GRP78) and endoplasmin are exported from the endoplasmic reticulum in rat exocrine pancreatic cells, similar to protein disulfide-isomerase.

Previously we found that in rat exocrine pancreatic cells, protein disulfide-isomerase (PDI), one of the major resident proteins in the lumen of the endoplasmic reticulum (ER) of many cells, is localized not only in the ER but also in the Golgi apparatus, secretory granules, plasma membranes, and even in the glandular lumens, despite possessing the ER retention signal KDEL (Lys-Asp-Glu-Leu) at the carboxyl terminus. In this report, we examined whether other ER luminal proteins bearing the KDEL signal at their C-termini, such as BiP/GRP78 and endoplasmin/GRP94 are also exported from the ER. We prepared two kinds of affinity-purified polyclonal antibodies; one against a synthetic peptide with 12 amino acids which is identical to the carboxyl terminus of BiP and another against purified endoplasmin. Immunoblot analysis using these two antibodies showed that BiP and endoplasmin exist in both the plasma membrane and the microsomal fractions, similar to the intracellular distribution of PDI in rat exocrine pancreas. The ratios of the amount of the three proteins in the two fractions, however, were variable, suggesting that the KDEL-bearing proteins such as PDI, BiP, and endoplasmin are exported from the ER with different efficiencies. Postembedding protein A-immunogold electron microscopy revealed that endoplasmin was exported from the ER and secreted to the extracellular space. The secretion of PDI in rat pancreatic lobules was inhibited by Brefeldin A (BFA) and by guanidino acid esters (FOY-305), which are known to be the inhibitors of the intracellular transport. Taken together with the previous immunogold electron microscopic analyses by Akagi et al. (1988), it is strongly suggested that in rat exocrine pancreatic cells PDI and the other KDEL-bearing proteins found in the extracellular space were not artificially released by cell damage during incubation but were secreted via the normal secretory pathway.

Amino Acid Sequence↗
PubMed1992

Developmental changes of fucosylated glycoconjugates in rabbit dorsal root ganglia.

Developmental changes of the fucosylated glycoconjugates in the dorsal root ganglia (DRG) of the rabbit were investigated histochemically using anti-fucosyl GM1 antibody and Ulex europaeus agglutinin 1 (UEA-1) lectin. Neither anti-fucosyl GM1 antibody nor UEA-1 lectin bound to the neural tubes or to the neural crest on embryonic day 14 (E14). Anti-fucosyl GM1 antibody binds diffusely to the DRG of E25. Large neurons unreactive with anti-fucosyl GM1 antibody appeared at 1 month and increased within 6 months after birth. Schwann cells immunoreactive with anti-fucosyl GM1 antibody came to be limited to the satellite cells surrounding the positive neurons. No staining with UEA-1 lectin was observed in the DRG of E25. Some small neurons became reactive with UEA-1 lectin within 1 month and remained to be so at 6 months after birth. Schwann cells including satellite cells were unreactive with this lectin. Since fucosyl GM1 was detected in the lipid fraction of DRGs from 1-month-old and 6-month-old rabbits, fucosyl GM1 itself should be the antigen molecule recognized by the anti-fucosyl GM1 antibody. Further study is necessary to elucidate the association between these developmental changes of the fucosylated glycoconjugates in DRG and their possible functional roles.

Animals↗
PubMed1992

The preclinical safety evaluation of human monoclonal antibody against cytomegalovirus.

The human monoclonal antibody against cytomegalovirus (Mab C23) was examined pharmacokinetically and toxicologically as part of the preclinical studies prior to approval for human use. Rats given repeated intravenous administrations of Mab C23 produced no antibodies against Mab C23 and maintained a blood Mab C23 level in a dose-dependent manner. However, pregnant rabbits produced antibodies against Mab C23. The half-life of Mab C23 in plasma was 15.9 days in rats, which was similar to that of normal human serum gamma-globulin (NHSG). Neither behavioral effects nor circulatory disturbance was found in mice, rats, and dogs even after a single intravenous injection of 100 or 200 mg/kg, which corresponds to 50 or 100 times the intended clinical dosage. The repeated doses of 2, 10, or 20 mg/kg of Mab C23 on six occasions with 1- or 2-week intervals elicited a transient decrease in leukocyte counts in rats given 10 or 20 mg/kg, but no adverse effects in cynomolgus monkeys. Mab C23 did not cause any reproductive or developmental toxicity when administered to rats and rabbits at dose levels of 20 mg/kg or less. However, pregnant animals showed lower plasma levels of Mab C23 than non-pregnant animals. The chromosomal aberration test disclosed no clastogenicity in human lymphocytes. An immunostaining for Mab C23 revealed no localizations in several tissues of cynomolgus monkeys given intravenous doses of Mab C23.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Ion channels on synaptic vesicle membranes studied by planar lipid bilayer method.

An anion selective channel and three types of cation selective channels were found in planar lipid bilayers incorporating synaptic vesicles from rat brains. In asymmetric KCl solutions (cis: 300 mM/trans: 150 mM), the anion selective channel showed a single-channel conductance of 94 pS and was inactivated by negative voltages and by 4-acetoamido-4'-isothiocyanostilbene-2,2'-disulfonic acid disodium salt (SITS). In the same solution, single-channel conductances of three types of cation selective channels were 250 pS (Type 1), 248 pS (Type 2), and 213 pS (Type 3), respectively. These channels resembled one another in single-channel conductances but were different in gating behaviors. Type 1 channel, which was most frequently observed, had a remarkable subconducting state (175 pS). Type 2 channel had a flickering state that increased as the potential became more positive, and a long inactive state that increased as the potentials were more negative. Type 3 channel, which was also sensitive to the potentials, had the open-channel probability increased as the potential became more positive.

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗
PubMed1992

Effects of exogenous somatostatin and insulin on islet amyloid polypeptide (amylin) release from perfused rat pancreas.

This study examined the effects of exogenous somatostatin and insulin on the release of islet amyloid polypeptide (IAPP), or amylin, from the isolated perfused rat pancreas. Somatostatin inhibited the release of both amylin and insulin from the perfused pancreas to the same extent. The infusion of 10 nM somatostatin resulted in 40% inhibition of the secretion of both amylin and insulin induced by 11.1 mM glucose and 10 mM arginine, and this inhibition was significantly increased to 70% by the infusion of 100 nM somatostatin (p less than 0.05). The amylin/insulin molar ratios remained constant at 0.8% and were not changed by the infusion of somatostatin. On the other hand exogenous insulin at a concentration of 1.8 nM did not affect the release of amylin induced by 11.1 mM glucose and 10 mM arginine, whereas 180 nM insulin slightly, although not significantly, inhibited the release of amylin by 15%. These findings suggest that the release of amylin may be negatively regulated by somatostatin and that circulating insulin may have no direct effect on the release of amylin at least at a physiological concentration.

Amyloid↗
PubMed1992

Bilateral internal drainage of biliary hilar malignancy via a single percutaneous track. Role of percutaneous transhepatic cholangioscopy.

Strictures of the hepatic bifurcation were bilaterally drained via a single percutaneous tract in 24 patients with hilar cholangiocarcinoma. This was achieved under percutaneous transhepatic cholangioscopic (PTCS) guidance which allowed for an excellent manipulation of the guidewire. Placement of two guidewires, one in the contralateral hepatic duct and the other in the common duct, was successful in 19 (79%) of patients at the first attempt. In the remaining cases the better accessible stricture was dilated, followed by negotiation of the other stricture under direct cholangioscopic control. After placement of guidewires into both hepatic ducts, bilateral drainage with a single Y-shaped catheter could be achieved in all 24 patients. There were no procedure-related complications. We conclude that this technique might be useful also for application of other intraluminal adjuvant treatment modalities.

Adenoma, Bile Duct↗
PubMed1992

Effects of FK506 on exocrine pancreas in rats.

The efficacy of FK506 on exocrine pancreas was studied in rats. Male Sprague-Dawley rats (230-250 g) received an i.m. daily injection of FK506 (0.1, 0.5, or 5.0 mg/kg), cyclosporine (CS; 25 mg/kg), or saline for 2 weeks. Isolated dispersed pancreatic acini were prepared from rats, and enzyme content of the cells and secretory response to cholecystokinin (CCK) were determined. Amylase and trypsin contents were increased in a dose-related manner by FK506 (p less than 0.01) and by CS at 25 mg/kg (p less than 0.01). The release of amylase in response to CCK was reduced by FK506 in a dose-related manner (p less than 0.01) and by CS at 25 mg/kg (p less than 0.01). Histologic examination showed that treatment of rats with FK506 at 0.1 mg/kg did not affect morphology of the acinar cells. FK506 at 0.5 mg/kg induced a minimal number of small vacuoles in cytoplasm of acinar cells and FK506 at 5.0 mg/kg, and CS at 25 mg/kg induced numerous cytoplasmic vacuoles and pyknotic nuclei. Increased enzyme storage and suppressed responsiveness of amylase release may have an association with the histologic changes. Therefore, the results of this study suggest that FK506, even when used in a low dose, may have adverse effects on the exocrine pancreas. Understanding of the mechanism of action of FK506 on pancreas will provide essential basic information that will allow transplant practitioners to more fully explore the benefits of this drug.

Amylases↗
PubMed1992

Qualitative and quantitative changes in islet cells of autotransplanted pancreas in dogs in relation to glucose metabolism.

This study was conducted to clarify the quantitative and qualitative changes in the cells of the islets of Langerhans in the autotransplanted pancreas in dogs and to correlate these changes with alterations of glucose tolerance. The left lobe of a canine pancreas was transplanted into the left iliac fossa. The splenic vessels were anastomosed to the left iliac vessels. The pancreatic duct was left open to the peritoneal cavity. Open biopsies of the autotransplanted pancreas were performed 3, 7, 11, and 14 weeks after transplantation. The islets in the transplanted pancreas were examined ultrastructurally; B-cells, A-cells, and D-cells were identified immunohistochemically and their percentages were determined. Intravenous glucose tolerance tests were performed 3, 5, 7, 11, and 14 weeks after operation, and several indexes (K values and integrated response and increased values for baseline serum and immunoreactive insulin) were calculated. Fibrosis of the transplanted pancreas progressed after transplantation. The percentage of B-cells fell significantly (p < 0.01), whereas that of A- and D-cells did not have significant changes. The ultrastructural study revealed an increase in collagen bundles, degranulation of B-cells, and marked preservation of A-cell granules 3 weeks after transplantation. B-Cells with dark cytoplasm were found 7 weeks after operation. In contrast, clusters of immature B-cells were seen in some sections of the pancreas 14 weeks after autotransplantation. The integrated response in baseline serum was increased significantly (p < 0.01), and the K value was decreased significantly (p < 0.01) 11 weeks after autotransplantation when compared with the initial posttransplant period.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗