One hundred and twenty patients with chronic hepatitis C were treated with a 6-month course of recombinant alpha-interferon (a daily dose of 6 MU i.m. for the first two weeks and 6 MU or 3 MU i.m. three times weekly thereafter). Serum levels of thyroxine (T4), triiodothyronine (T3), thyroid-stimulating hormone (TSH), antithyroglobulin antibody (TGHA) and antimicrosomal antibody (MGHA) were measured before and three month after treatment. Ten of 106 patients with normal thyroid function test before therapy developed thyroid dysfunction; five with hyperthyroidism, four with hypothyroidism and one with positive MCHA. Fourteen patients had thyroid function disorder before treatment. Seven of eight patients with positive MCHA, showed a rise in the titer during the treatment. These data showed that a small proportion of patients treated with interferon developed thyroid dysfunction during the treatment. The interferon-induced thyroid dysfunction appears to be caused via the immune system but also by acting directly on the thyroid gland.

Adult↗

PubMed1994

[A case of mediastinal cyst treated with percutaneous injections and drainage].

A 69-year-old woman visited our hospital for further investigation of a prominence at the right heart border. Chest X-ray, tomography, CT scan and ultrasonography revealed an anterior mediastinal cyst. After admission, we performed needle aspiration, injection of contrast material and drainage. Since the lesion was diagnosed as a benign mediastinal cyst, the patient has been followed up without surgery. CT scan after a two-year period revealed fatty tissue in the area of the lesion without evidence of recurrence.

Aged↗

PubMed1994

[A case of true thymic hyperplasia showing slow growth as revealed by chest X-ray].

A case of true thymic hyperplasia in a 33-year-old man is reported. Radiographic findings of the chest (including computer tomography and magnetic resonance imaging) showed a mass in the anterior mediastinum. Thoracotomy revealed an enlarged thymus. Histological examination identified true thymic hyperplasia. True thymic hyperplasia is a lesion rarely observed in adults. This case was reported because of the age of the patient.

Adult↗

PubMed1994

[An adult case of congenital esophagobronchial fistula complicated with pyothorax].

A 64-year-old woman with congenital esophagobronchial fistula complicated with pyothorax is reported. She was admitted to our hospital because of high fever and cough. Chest X-ray showed a cavity with niveau in the right lower lobe. The next day she noticed right chest pain. Chest X-ray showed right pleural effusion. The diagnosis of left esophagobronchial fistula with pyothorax was confirmed by esophagography, esophagoscopy, chest X-ray and chest CT. After treatment of the pyothorax with antibiotics and drainage, fistulectomy and right lower lobectomy were performed. The postoperative course was uneventful. Histologically, the fistula had esophageal epithelium with a submucosal muscle layer and demonstrated a transitional zone between squamous epithelium and bronchial epithelium.

Bronchial Fistula↗

PubMed1994

[Forms of an in vivo polymerization product, n-butyl-2-cyanoacrylate, within the gastric wall].

The in vivo morphology of sclerosants, n-butyl-2-cyanoacrylate (Histoacryl; referred hereinafter to briefly as HA) polymer formed within the gastric wall was investigated in an animal experiment. The results indicate that HA polymer formed after local injection of HA into the stomach wall with deliberate avoidance of contact with blood got scattered in an arboroid pattern, suggesting thus that when HA is injected into the gastric mucosa at an extravascular site, the resulting polymer is likely to get scattered and miss the target site. Polymerization products that were formed after injection of HA alone were deep purple, dense, firm, rounded in shape and lesser in adverse histologic influence upon the walls of stomach. On the other hand, those formed by injection of HA with Lipiodol were large-sized, light brown and oval-shaped ones with more irregular margins and less distinct boundaries as compared to those seen after injection of HA alone. These results of the study led us to conclude that at the present time it would seem wise to limit the use of HA for this particular therapeutic purpose only to those cases of bleeding gastric varices.

Animals↗

PubMed1994

Inhibition of ethanol-induced inositol phosphate formation and Ca(2+) mobilization by okadaic acid in rat hepatocytes: evidence for a role of protein phosphatases in the modulation of phospholipase C by ethanol.

The effect of the protein phosphatase inhibitor okadaic acid on phospholipase C (PLC)-linked signal transduction processes was investigated in intact hepatocytes. A short (5 min) pretreatment of the hepatocytes with okadaic acid (1 mu M) markedly inhibited a subsequent stimulation of PLC by ethanol as well as by receptor-mediated stimuli (vasopressin and phenylephrine). Okadaic acid inhibited the agonist-induced hydrolysis of polyphosphoinositides, the accumulation of inositol trisphosphate (InsP(3)) and the increase in cytosolic Ca(2+) concentrations. The inhibition could be overcome by high concentrations of vasopressin or ethanol, but only partly so with phenylephrine. A comparison of the sensitivity of different agonists at similar rates of InsP(3) accumulation and Ca(2+) mobilization indicated that ethanol-induced PLC activation was more resistant to the effects of okadaic acid than the hormonal agonists. Moreover, the stimulation of PtdInsP kinase by ethanol, which accompanies PLC activation, was refractory to okadaic acid treatment. These findings suggest that receptor-mediated PLC activation is subject to multiple controls by phosphorylation-dephosphorylation, not all of which affect the actions of ethanol on this signal transduction system.

Animals↗

PubMed1993

Neuronal pathway involved in nitric oxide-mediated descending relaxation in rat ileum.

The neuronal pathway that initiates nitric oxide-mediated descending relaxation in rat ileum was studied. The descending relaxation, which was suggested to be mediated by nitric oxide from our previous study, was selectively inhibited by 5-HT3 receptor antagonists. It was also inhibited by a nicotinic acetylcholine receptor antagonist. Exogenous 5-hydroxytryptamine (5-HT) and a selective 5-HT3 receptor agonist induced dose-dependent relaxation of ileal circular muscle. 5-HT-induced relaxation was selectively inhibited by 5-HT3 receptor antagonists. Nicotine also induced relaxation of the circular muscle, and its effect was inhibited by 5-HT3 receptor antagonists. 5-HT and nicotine increased the cyclic GMP content of the ileal tissue. Nitro-L-arginine inhibited the increases induced by both compounds in the cyclic GMP content, and a 5-HT3 receptor antagonist also inhibited that induced by nicotine. These results indicate that activation of a cholinergic neuron-5-HT neuron pathway initiates nitric oxide-mediated descending relaxation in rat ileum.

Animals↗

PubMed1993

Processing of a fusion protein by endoprotease in COS-1 cells for secretion of mature peptide by using a chimeric expression vector.

The subtilisin-related proprotein convertase furin is expressed in various mammalian tissues. Expecting that COS-1 cells have a furin-like endoprotease, we constructed a fusion expression vector for production of a recombinant foreign protein having no signal peptide or a protein in truncated form into secreted mature protein. A cDNA fragment encoding N-terminal procalcitonin (pro-CT) of human calcitonin precursor was inserted into the mammalian expression vector pME18S. We used PCR techniques to generate four kinds of cDNAs encoding the C terminus of the pro-CT with Arg residues at P4 (Arg-Xaa-Lys-Arg), P6 (Arg-Xaa-Xaa-Xaa-Lys-Arg), or both (Arg-Xaa-Arg-Xaa-Lys-Arg), in addition to the Lys-Arg motif at the cleavage site, in order to determine the conditions for efficient processing in nonendocrine cells, such as COS-1 cells. The cDNA coding for the Fc fragment of human immunoglobulin G1 was fused in-frame to the cDNA encoding pro-CT at its C terminus. Upon transfection of the chimeric plasmids into COS-1 cells, almost all of the fusion protein with the Arg residues at both P4 and P6 were processed into secreted Fc product, even without cotransfection of furin. These results indicate that COS-1 cells have a furin-like endoprotease and suggest that pro-CT, with the Arg residues at both P4 and P6, can be used as a carrier peptide for expression of a foreign protein having no signal peptide or a protein in truncated form in COS-1 cells.

Amino Acid Sequence↗

PubMed1993

Orientation of erythrocytes in a strong static magnetic field.

The frequency of exposure to strong magnetic fields has increased as the magnetic-resonance image-diagnostic technique (MRI) and passenger transport systems based on the principle of magnetic levitation have come into wider use. Accordingly, it has become necessary to more systematically assess their influence on the body and set strict guidelines on acceptable limits of magnetism exposure. Therefore, we have assessed the influence of an uniform static magnetic field (8 T in maximum) on normal erythrocytes. The erythrocytes were oriented with their disk plane parallel to the magnetic field direction. These erythrocytes were influenced even by 1 T and almost 100% of them were oriented when exposed to 4 T. Furthermore, the degree of orientation was not influenced by the state of hemoglobin (oxy: diamagnetic, deoxy and met: paramagnetic). The dependence of the measured degree of orientation on the intensity of the magnetic field was in good agreement with the theoretical equation for the magnetic orientation of diamagnetic substances. As a result of a numerical analysis based on the equation, the anisotropic diamagnetic susceptibility of erythrocytes was found to be delta chi = 8 x 10(-22) electromagnetic units/erythrocyte. It was almost in agreement with the calculated value delta chi = 6 x 10(-22) emu/erythrocyte estimated from the diamagnetism of the membrane constituents of erythrocyte.

Cell Polarity↗

PubMed1993

Modulation of acetylcholine release from the myenteric plexus of guinea-pig ileum by 5-lipoxygenase metabolites of arachidonic acid.

Eicosatetraenoic acid, an inhibitor of 5- and 12-lipoxygenase, and AA861, a selective inhibitor of 5-lipoxygenase, dose dependently inhibited acetylcholine release from the myenteric plexus of guinea-pig ileum induced by electrical field stimulation. Metabolites of arachidonic acid produced by the 5-lipoxygenase pathway, such as 5-hydroxyeicosatetraenoic acid (5-HETE), leukotriene C4, D4 and E4, reversed the inhibitory effect of AA861. Among them, leukotriene D4 was the most potent, having an EC50 value of about 3 nM. The present study shows for the first time that 5-lipoxygenase metabolites may have a modulatory effect on acetylcholine release in the myenteric plexus of guinea-pig ileum.

Acetylcholine↗

PubMed1993

Spin trapping of superoxide released by opsonized asbestos from human promyelocytic leukemia cell line, HL60.

By ESR using 5,5-dimethyl-1-pyrroline-1-oxide as a spin trap, superoxide (O2-) production was proved upon stimulation of dimethyl sulfoxide-differentiated HL60 by crocidolite opsonized with fresh or refrigerated serum, as well as by phorbol myristate acetate (PMA). Crocidolite, unopsonized or opsonized with frozen-thawed or heat-inactivated serum, did not induce O2- release. Addition of iron chelators or superoxide dismutase inhibited O2- release completely. Neither undifferentiated nor PMA-differentiated HL60 released O2- upon stimulation with opsonized crocidolite.

Asbestos↗

PubMed1993

Successful treatment with a novel immunosuppressive agent, deoxyspergualin, in type II collagen-induced arthritis in mice.

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Animals↗

PubMed1993

Role of prostacyclin in acetylcholine release from myenteric plexus of guinea-pig ileum.

The roles of metabolites of arachidonic acid in spontaneous and agonist-induced acetylcholine release from a longitudinal muscle preparation with myenteric plexus of guinea-pig ileum were studied. Indomethacin significantly decreased both spontaneous acetylcholine release and its release induced by nicotine and substance P. We had found that prostaglandin E2 (PGE2) partly reversed this inhibition. We now found that a stable prostacyclin analog, OP-41483 at 100 nM, completely reversed the inhibition of acetylcholine release by indomethacin. On the other hand, PGD2, PGF2 alpha and ONO-11113, a thromboxane A2 analog, did not have any significant effect on the inhibition by indomethacin. OP-41483 had no effect on acetylcholine release induced by nicotine or substance P in the absence of indomethacin. To confirm the modulatory role of endogenous prostaglandins on acetylcholine release, we also studied the release of 6-keto-PGF1 alpha, a metabolite of prostacyclin, and PGE2 from longitudinal muscle preparations. The preparations released appreciable amounts of 6-keto-PGF1 alpha continuously during the experiments. Indomethacin inhibited release, while nicotine did not affect it so significantly. Our results suggest that endogenous prostacyclin modulates acetylcholine release from cholinergic nerve terminals in the myenteric plexus of guinea-pig ileum.

Acetylcholine↗

PubMed1993

Synthesis of low-toxicity, 5-deoxy-5-fluoro and 5-deoxy-5,5-difluoro derivatives of arbekacin and its analogs, and study of structure-toxicity relationships.

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Aminoglycosides↗