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Biomedical subjects

M Fujimoto

Publications and source records attributed to M Fujimoto.

At least 307 records · Page 17Linked to original sources
PubMed1994

Functional significance of K+ and Cl- channels in volume regulation in proximal tubular cells.

Using the patch-clamp technique to cultured opossum kidney (OK) cells, we measured the activities of K+ channel and Cl- conductance during hyposmotic stress. The results are as follows: 1) A 50% lowered osmolarity of bath media induced a biphasic change of the membrane potential (EM): early hyperpolarization and late depolarization. The former transient response was abolished by removing Ca2+ from the cellular media, whereas the latter slow response was blocked by DIDS. 2) The hyposmosis-induced change of EM was due to K+ channels activated by cytosolic Ca2+. 3) In hyposmotic media, Cl- current was effectively increased, and this effect was abolished by Cl- channel blockers. 4) The hyposmosis-induced Cl- conductance was inhibited in the cytosolic acid media. In the alkaline media, it was enhanced even without hyposmotic stress. We conclude that the hyposmosis-induced activation of Cl- conductance, being stimulated by alkaline cell pH and inhibited by acid cell pH, may contribute to the ion transport and cell volume regulation along with the Ca(2+)-activated K+ channel.

Animals↗
PubMed1994

Role of pH-sensitive ion channels in regulation of cell volume in opossum kidney cells.

Applying the patch-clamp technique to cultured opossum kidney (OK) cells, we investigated effects of pH on the activation of Cl- channels induced by a hyposmotic shock. The Cl- conductance of cell membranes was measured in 145 mM NMG-Cl solution with the whole-cell configuration. Under control conditions, the Cl- conductance was almost negligible. When the cell was exposed to a hyposmotic medium, the Cl- conductance was remarkably elevated. This conductance change was reversibly inhibited by Cl- channel inhibitors, such as DIDS. The activation (pHi) from 7.3 to 7.0, but not influenced by changing the bath pH (pHe). We conclude that the Cl- channel activation by a hyposmotic challenge is highly sensitive to pHi.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1994

A myomodulin-CARP-related peptide isolated from a polychaete annelid, Perinereis vancaurica.

Myomodulin-CARP-family peptides have been isolated only from molluscs. In the present study, a heptapeptide, Ala-Met-Gly-Met-Leu-Arg-Met-NH2, termed Pev-myomodulin, was isolated from a polychaete annelid, Perinereis vancaurica using the esophagus of the animal as the bioassay system. The sequence of the annelid peptide is highly homologous with those of the myomodulin-CARP-family peptides found in molluscs. The annelid peptide is regarded as a member of the myomodulin-CARP family, though all the molluscan peptides have a Leu-NH2 at their C-termini. The annelid peptide showed a potnet contractile action on the esophagus of the annelid. The peptide may be an excitatory neuromediator involved in the regulation of the esophagus. Among various myomodulin-CARP-family peptides and their analogues, the annelid peptide showed the most potent contractile action on the esophagus. Replacement of the C-terminal Met-NH2 of the annelid peptide with a Leu-NH2 decreased its contractile potency, while replacement of the C-terminal Leu-NH2 of myomodulin and CARP with a Met-NH2 increased their potency. The C-terminal Met-NH2 of the annelid peptide seems to be important, but not essential, for exhibiting its contractile activity on the esophagus. On the anterior byssus retractor muscle of the bivalve mollusc Mytilus edulis, the annelid peptide showed catch-relaxing and contraction-modulating effects qualitatively similar to those of the authentic peptide CARP, though the annelid peptide was less potent than CARP.

Amino Acid Sequence↗
PubMed1994

[Diagnostic strategy for malignancy and parenchymal invasion of so-called mucin-producing tumor of the pancreas].

This study investigated diagnostic indications of malignancy and parenchymal invasion of so-called mucin-producing tumor of the pancreas (MPT). We reviewed 40 patients with this type tumor. In diagnosis of malignancy, jaundice, mural nodule (EUS), displacement or compression of the portal vein (angiography), compression of the common bile duct (cholangiography) and Group IV-V in biopsy, Class III-V in brushing cytology were important. In diagnosis of parenchymal invasion, solid mass (US, EUS, CT), arterial encasement (angiography), defect in the common bile duct (cholangiography), stenosis or obstruction of the MPD (pancreatography) and elevation of serum CA19-9, CEA levels were important. By these findings, MPT diagnosed as benign can be observed without surgical treatment. On the other hand, MPT diagnosed as malignant must be treated by surgical resection, and operative procedure must be chosen according to whether the MPT was accompanied by parenchymal invasion or not.

Aged↗
PubMed1994

[A case of isolated vagus nerve palsy with herpes zoster].

A case of isolated vagus nerve palsy with herpes zoster was reported. A 31-year-old woman was admitted to our hospital with six days' history of difficulty of swallowing of fluid and hoarseness with a painful vesicle on the right ear. Neurological examination revealed poor elevation of soft palate on the right side, but the pharyngeal reflex was preserved. Herpetic vesicles were present on the right concha, within posterior wall of the external auditory meatus. No facial palsy, loss of hearing and mucosal lesions in the mouth or pharynx were present. This is the first case of isolated vagus nerve palsy due to varicella-zoster infection, showing the distribution of the auricular branch of the vagus (Arnold's nerve) in the ear.

Adult↗
PubMed1994

Myricerone caffeoyl ester (50-235) is a non-peptide antagonist selective for human ETA receptors.

OBJECTIVE: To assess the pharmacological profile of a novel non-peptide endothelin antagonist (50-235) at endothelin receptors in human vascular smooth muscle preparations using radiolabelled binding techniques and in vitro pharmacological assays. METHODS: The antagonist was investigated for its ability to inhibit specific [125I]-endothelin-1 binding to ETA and ETB receptors using cryostat sections of media of human coronary artery. Antagonism by 50-235 (1-30 mumol/l) of endothelin-1-induced vasoconstriction in isolated preparations of human coronary artery, saphenous vein and left internal mammary artery was also determined. RESULTS: In coronary artery 50-235 (10(-11) to 10(-4) mol/l) inhibited specifically bound [125I]-endothelin-1 (0.1 nmol/l) in a biphasic manner. The ratio of ETA:ETB receptor was 79:21. Increasing concentrations of 50-235 produced progressive rightwards displacements of the endothelin-1 dose-response curve in each of the three types of blood vessel. The dose-response curves were parallel and no attenuation of the maximum endothelin-1 response was observed suggesting that 50-235 was antagonizing endothelin-1 vasoconstriction in a competitive manner. The pA2 values determined by analysis of the Schild regression lines were 6.05 in coronary artery, 6.12 in saphenous vein and 6.18 in left internal mammary artery, and the slopes were not significantly different from unity. CONCLUSIONS: The antagonist 50-235 exhibits nanomolar affinity for human ETA receptors and 500-fold selectivity for ETA compared with ETB receptors. Its novel non-peptide structure demonstrates that the carbon-nitrogen bond is not crucial for endothelin antagonist activity, and might provide important information for the development of therapeutic agents for conditions in which endothelins may be pathophysiologically relevant.

Aged↗
PubMed1994

[Treatment with arbekacin of surgical infections by resistant strains of Staphylococcus aureus. Arbekacin Study Group].

The frequency of infection by methicillin-resistant Staphylococcus aureus (MRSA) is high in Japan and control of such strains is urgently needed. Arbekacin (ABK), a semisynthetic aminoglycoside, has potent activity against S. aureus, including resistant strains, and against Gram-negative bacteria as well. For this reason, in surgical infections (which are often caused by more than one bacterium), this drug might be particularly effective. We calculated the MIC and the decrease in the MIC when cultures of 59 resistant strains of S. aureus isolated in our wards at Osaka City University Hospital, contained arbekacin in the medium. We also used the drug to treat 12 infections caused by resistant strains of S. aureus. The MICs of vancomycin had a single peak at 0.5 microgram/ml, and those for ABK had double peaks at 0.5 and 4.0 micrograms/ml. The effect of arbekacin in lowering the MIC of minocycline (MINO) was slight because of the low MIC of MINO. Effects on fosfomycin (FOM), ampicillin, clavulanic acid/ticarcillin, cefotiam, cefuzonam, flomoxef, and imipenem/cilastatin were strong; the peaks were lowered by 1/2(7)-1/2(11). When 1.0 micrograms/ml ABK was present in the medium, the efficacy of FOM was increased enough that, by prediction from the pharmacokinetics of FOM (blood level when given at the usual dose), all but one (2%) of the 47 resistant strains would be eradicated clinically. If 2.0 micrograms/ml ABK were in the medium, all strain would be eradicated, by our calculations. We treated 11 infections and one colonization by resistant strains of S. aureus with ABK and evaluated the response in these cases of infection. Four infections were treated with FOM as well. The clinical efficacy was good in four infections (three patients), fair in four, and poor in three, for an efficacy rate of 36%. All presumed causative bacteria were eradicated in two (18%) of the 11 infections and S. aureus strains were eradicated in three (27%) of the 11 infections. No symptoms of side effects were reported, but blood urea nitrogen and creatinine rose in a 72-year-old woman with duodenal perforation and peritonitis. The MIC levels of ABK were satisfactory, but clinical efficacy for staphylococcal infections caused by resistant strains was unsatisfactory.

Adult↗
PubMed1994

Nedocromil sodium acts directly on human B cells to inhibit immunoglobulin production without affecting cell growth.

The effect of nedocromil sodium (NES) on human immunoglobulin (Ig) isotypes, IgG subclasses and IgA subclasses was studied. NES inhibited IgM and IgA1 production from human lymphoblastoid B-cell lines CBL and GM-1056, respectively, in a dose-dependent fashion. This inhibition was not due to decreased cell growth as cell proliferation was not affected by NES and cell viability was always greater than 98%. Of the various cytokines tested, interleukin-4 (IL-4) reduced the NES-induced inhibition of Ig production, whereas other cytokines, including IL-1 beta, IL-2, IL-3, IL-5, IL-6, interferon-alpha (IFN-alpha), IFN-gamma, granulocyte-macrophage colony-stimulating factor (GM-CSF) and erythropoietin (Epo) failed to do so. The reducing effect of IL-4 was blocked by anti-IL-4 antibody but not by control IgG. Moreover, IFN-alpha and IFN-gamma, but not GM-CSF, overcame the reducing effect of IL-4. NES also inhibited production of IgM, IgG1, IgG2, IgG3, IgG4, IgA1 and IgA2 by tonsillar B cells stimulated with Staphylococcus aureus Cowan strain I (SAC) and IL-6 without affecting proliferation. This inhibition was reduced by IL-4 specifically. These results indicate that in addition to its anti-allergic function, NES may act as a B-cell regulatory reagent.

B-Lymphocytes↗
PubMed1994

Pharmacological characterization of a potent nonpeptide endothelin receptor antagonist, 97-139.

The endothelin (ET) receptor antagonist activity of 97-139 [27-O-3-[2-(3-carboxy-acryloylamino)-5-hydroxyphenyl]-acryloylo xy myricerone, sodium salt] was studied. In rat aortic smooth muscle A7r5 cells that express ETA receptors and human Girardi heart cells that express ETB receptors, 97-139 displaced specifically bound [125I]ET-1 with the Ki values of 1.0 +/- 0.2 and 1000 +/- 200 nM, respectively. The compound caused a concentration-dependent inhibition of ET-1-induced increases in intracellular Ca++ levels in A7r5 cells, but not in Girardi heart cells. 97-139 also inhibited ET-1-induced [3H]thymidine incorporation in A7r5 cells (IC50 = 0.92 +/- 0.48 nM). In rat aortic rings, 97-139 produced parallel rightward shifts in the ET-1 concentration-response curve without affecting the maximal contractile response (pA2 = 8.8 +/- 0.4). Administration of 97-139 (0.03-1.0 mg/kg) i.v. to pithed rats resulted in dose-dependent inhibition of the pressor response to ET-1. The in vivo potency of 97-139 was almost the same as that of BQ-123, although the potencies of 97-139 in binding assays and in vitro functional assays were about one order of magnitude higher than those of BQ-123. This discrepancy might involve high binding toward albumin in plasma because 95% plasma and 4% albumin reduced the apparent binding affinity of 97-139 by 22- to 24-fold, but not of BQ-123.(ABSTRACT TRUNCATED AT 250 WORDS)

Albumins↗
PubMed1994

[A study of the influence of gastric acid on the extension of regenerative epithelium of gastric ulcer].

To study the influence of gastric acid on the extension of the regenerative epithelium, 26 patients (28 ulcers) of gastric ulcer were examined by the stereo video-endoscope being able to measure the length and 24-hours intragastric pH monitoring. Extending speeds of the regenerative epithelium were measured from the time the regenerative epithelium of the ulcer was observed till the last examination, but which was limited 8 weeks after the first observation of the regenerative epithelium. The relationship was not observed between the extending speeds and the stages (A2-H1, H1-H2, H2-S1) of the ulcer. For 21 ulcers followed up by the stereo video-endoscope from active stage, the extending speed of the regenerative epithelium and the pH 3 holding time in a day were significantly correlated (r = 0.51, p = 0.014), and the same relationship (r = 0.56, p = 0.008) were observed in the nighttime. It was confirmed that the gastric acid regulated strongly the extending speed of regenerative epithelium of gastric ulcer. The intragastric circumstance of the low acid secretion induced by the antacid-drugs was considered to accelerate the extension of regenerative gastric epithelium.

Adult↗
PubMed1993

Cyclic GMP phosphodiesterase inhibitors. 1. The discovery of a novel potent inhibitor, 4-((3,4-(methylenedioxy)benzyl)amino)-6,7,8-trimethoxyquinazoline.

A newly synthesized compound, 4-((3,4-(methylenedioxy)benzyl)amino)-6,7,8-trimethoxyquinazoline (6), had a potent (IC50 = 0.36 microM) inhibitory action on cyclic GMP phosphodiesterase (cGMP-PDE) isolated from porcine aorta; its inhibitory activities toward other PDE isozymes were at least 10-fold weaker. In addition, 6 relaxed porcine coronary arteries precontracted with PGF2 alpha (EC50 = 1.96 +/- 0.58 microM). At the concentration of 30 microM, 6 caused elevation of the intracellular cGMP level in porcine coronary arteries without any change in cAMP level. Various other 4-substituted 6,7,8-trimethoxyquinazolines were also synthesized and evaluated for cGMP-PDE inhibitory activity. From their structure-activity relationships, we concluded that the 4-((3,4-(methylenedioxy)benzyl)-amino) group is essential for potent inhibition of cGMP-PDE.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1993

Dermatofibrosarcoma protuberans: increased growth response to platelet-derived growth factor BB in cell culture.

Dermatofibrosarcoma protuberans (DFSP) is a malignant tumor originating in the dermis. Although it is locally aggressive and recurs unless completely excised, it only rarely metastasizes. In the present study, we established 4 cultured DFSP cell strains, which were almost identical to normal skin fibroblasts when observed under a phase-contrast-microscope, and we observed their responses to various growth factors. DFSP cells showed significantly greater response to platelet-derived growth factor BB(PDGF BB) and transforming growth factor beta 1(TGF beta 1) than normal fibroblasts. We also determined upregulation of PDGF beta receptors in DFSP cells by both 125I PDGF-BB binding assay and immunoblotting analysis. These findings suggest that the interaction between the PDGF-B chain and the overexpression of PDGF beta receptors might play a role in the development of DFSP tumors.

Cell Division↗
PubMed1993

Structure-activity relationships of an endothelin ETA receptor antagonist, 50-235, and its derivatives.

27-O-Caffeoyl myricerone (50-235) is a nonpeptide endothelin receptor antagonist which is highly selective for the endothelin ETA receptor subtype. In order to determine which functional groups in 50-235 are essential for its activity, we examined the potencies of 50-235 and its derivatives to inhibit [125I]endothelin-1 binding and endothelin-1-induced increase in the cytosolic Ca2+ concentration in rat aortic smooth muscle A7r5 cells. The results suggest that the 3-keto, 17-carboxyl and 27-caffeoyl groups in 50-235 are important for ETA receptor blocking activity. Modifications of the catechol ring of the 27-caffeoyl group influenced the affinity and the functional antagonist activity, but the effects were not parallel.

Animals↗
PubMed1993

The endothelin ETA receptor-specific effect of 50-235, a nonpeptide endothelin antagonist.

We characterized the endothelin receptor antagonist 27-O-caffeoyl myricerone (50-235), isolated from the bayberry Myrica cerifera, using rat aortic smooth muscle A7r5 cells that express ETA receptors and human Girardi heart cells that express ETB receptors. 50-235 concentration-dependently inhibited 125I-ET-1 binding to A7r5 cells with Ki of 51 +/- 12 nM, while it had no effect on 125I-ET-1 and 125I-ET-3 bindings to Girardi heart cells. Also in affinity cross-linking studies with 125I-ET-1, 50-235 inhibited labeling of a protein of M(r) = 67,000 in A7r5 cells, but did not inhibit labeling of two proteins with M(r) values of 70,000 and 46,000 in Girardi heart cells. Functionally, 50-235 inhibited the ET-1-induced increase in cytosolic free Ca2+ concentration ([Ca2+]i) in a dose-dependent manner (IC50 = 11 +/- 2 nM) in A7r5 cells. On the other hand, this compound had no effect on the basal level of [Ca2+]i and the high K(+)- and bombesin-induced increases in [Ca2+]i in A7r5 cells, nor on the ET-1-induced increase in [Ca2+]i in Girardi heart cells. Also, 50-235 inhibited ET-1-promoted mitogenesis of A7r5 cells. Thus, we conclude that 50-235 is a specific endothelin A receptor antagonist that could be very useful for elucidating the physiological and pathophysiological significance of ET.

Animals↗
PubMed1993

Effect of vasoactive intestinal peptide, somatostatin, and substance P on spontaneous IgE and IgG4 production in atopic patients.

The effect of vasoactive intestinal peptide (VIP), somatostatin (SOM), and substance P (SP) on spontaneous human IgE and IgG4 production in atopic patients was studied. In cultures of mononuclear cells (MNC), VIP inhibited both IgE and IgG4 production without affecting IgM, IgA, IgG1, IgG2, or IgG3 production. In contrast, SOM inhibited only IgE production whereas SP inhibited only IgG4 production without affecting production of other isotypes or other IgG subclasses. The effect of neuropeptides was specific because each was specifically blocked by a corresponding neuropeptide antagonist. To achieve the effect noted above, neuropeptides must be added at the start of the culture. IFN-alpha and IFN-gamma were found to inhibit both IgE and IgG4 production whereas prostaglandin E2 (PGE2) inhibited only IgE production. However, the inhibition of IgE and IgG4 production by neuropeptides could not have been mediated by IFN-alpha, IFN-gamma, or PGE2 because the addition of anti-IFN-alpha, anti-IFN-gamma, and indomethacin, respectively, did not reverse the inhibition. In contrast to their effects on MNC, neuropeptides did not affect production of either IgE or IgG4 by purified B cells; the addition of either T cells or monocytes to B cells had no effect on this. However, neuropeptides were effective in inhibiting IgE and IgG4 production by B cells cultured together with both T cells and monocytes. Depletion of sIgE+ and sIgG4+ B cells resulted in abrogation of IgE and IgG4 production, respectively. However, stimulation of sIgE- B cells with IL-4 plus anti-CD 40 mAb induced IgE production, which was inhibited by VIP and SOM, but not SP, in the presence of both T cells and monocytes. These results suggest that neuropeptides inhibited spontaneous IgE and IgG4 production by interaction with sIgE+ and sIgG4+ B cells in a T cell- and monocyte-dependent fashion. In addition, VIP and SOM also inhibited IgE production by modulating switching induced by IL-4 plus anti-CD 40 mAb in a T cell- and monocyte-dependent fashion.

Humans↗
PubMed1993

Molecular cloning and characterization of the angiotensin receptor subtype in porcine aortic smooth muscle.

A cDNA encoding porcine aortic smooth muscle angiotensin II (AII) receptor has been isolated using the homology screening approach and sequenced. Specific binding of [125I]AII was found in COS-7 cells transfected with the cDNA (Kd = 0.37 nM, Bmax = 1 approximately 3 x 10(4)/cell) and was displaced with unlabeled AII-related peptides and DUP753 in the order of [Sar1,Ile8]AII = AII > des-Asp1-[Ile8]AII = DUP753 > angiotensin I = angiotensin III. EXP655 had no effect on [125I]AII binding. COS-7 cells transfected with the cDNA responded to AII by only a small increase in the concentration of intracellular free Ca2+. However, electrophysiological study of the receptor expressed in Xenopus laevis oocytes provided strong evidence that it could functionally couple to a second messenger system leading to the mobilization of intracellular stores of Ca2+. Northern blot analysis in cultured porcine aortic smooth muscle cells demonstrated that the expression of this gene varies with the culture media. These results indicate that the cDNA encodes the functional and regulated AT1 subtype of AII receptors.

Amino Acid Sequence↗
PubMed1993

Neuropeptide Y stimulates DNA synthesis in vascular smooth muscle cells.

Neuropeptide Y (NPY) stimulated DNA synthesis in porcine aortic smooth muscle cells in a concentration-dependent manner. [Leu31, Pro34]NPY, a Y1-specific agonist, was several hundred times more potent than NPY(13-36), which preferentially bound to Y2 receptors, for stimulating DNA synthesis. On the other hand, human pancreatic polypeptide had no effect. The potency of NPY and related peptides for stimulating DNA synthesis paralleled their potency for increasing the cytosolic free Ca2+ concentration in the cells. Pertussis toxin treatment completely blocked both effects of the peptides. Thus, NPY may induce Ca2+ mobilization and stimulation of DNA synthesis in vascular smooth muscle cells via Y1 receptors whose signal transduction system involves pertussis toxin-sensitive GTP-binding protein(s).

Animals↗