[Experimental study on permeability and ototoxicity across the round window membrane].
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Biomedical subjects
Publications and source records attributed to T Harada.
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Mechanisms involved in the action of cholecystokinin octapeptide (CCK-8) on the isolated circular muscle of the guinea pig sphincter of Oddi were investigated. CCK-8 (10(-9) to 10(-6) M) caused a concentration-dependent contraction of the sphincter. Angiotensin II, bethanechol and serotonin also contracted this tissue. CCK-8 exerted the most potent effect. However, bradykinin, porcine motilin and norepinephrine failed to elicit any contraction. The CCK-8-induced contraction was inhibited by about 60% by atropine (3 X 10(-7) M) or tetrodotoxin (3 X 10(-7) M) but was not affected by hexamethonium (3 X 10(-5) to 10(-4) M) or phentolamine (3 X 10(-6) to 10(-5) M). Proglumide (3 X 10(-4) to 3 X 10(-3) M), a derivative of glutaramic acid, inhibited competitively the contraction by CCK-8. However, proglumide influenced neither the electrically elicited twitch contraction nor the bethanechol-induced contraction. CCK-8 evoked a concentration-related release of [3H]acetylcholine (ACh) from previously labeled stores. The CCK-8-evoked release of [3H]ACh was eliminated by tetrodotoxin and was inhibited, in a concentration-dependent manner, by proglumide. These results suggest that the contractile response to CCK-8 of the guinea pig sphincter of Oddi consists of a direct effect on the smooth muscle and an indirect effect mediated by ACh release from postganglionic parasympathetic neurons.
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Familial amyloidotic polyneuropathy (FAP) is a genetic disorder showing autosomal dominant inheritance. Amyloid fibrils of FAP patients from various origins have been shown to contain a prealbumin variant with Val30----Met30 substitution as a major component. However, the structure of the prealbumin gene responsible for the variation has not been characterized. We determined the complete nucleotide sequence of the prealbumin gene from a patient with the Japanese type of FAP. In comparison with a normal prealbumin gene sequence, the patient's gene was found to be carrying seven base substitutions. The substitution responsible for the Val----Met change was found in exon 2, as expected, and the others were in introns. Hybridization analyses of normal and FAP patient DNAs showed that the base substitution in exon 2 was specific for FAP but the others were polymorphic changes. It was concluded that the mutation responsible for the Val----Met change is the only base change specific for FAP in the prealbumin gene.
The antimanic effect of zotepine was investigated in 16 patients with manic-depressive psychosis or manic schizoaffective psychosis. Zotepine markedly improved manic symptoms in 75% and afforded at least slight improvement in all patients studied. However, in 50%, zotepine caused conversion from mania to depression. The most frequent side effects were dysarthria in 50%, parkinsonian symptoms in 33%, dry mouth in 28%, and sleepiness in 28%. EEG abnormalities were noted in 22% of patients. The antimanic effect of zotepine was enhanced by lithium carbonate; however, concomitant use of zotepine and lithium possibly increased the incidence of EEG abnormalities. The conversion-to-depression effect of zotepine was not inhibited by lithium. Overall, the concomitant use of zotepine and lithium may be important in the treatment of manic psychoses.
Iodinated proteins in normal thyroid tissue extracts were analyzed immunochemically, immunohistochemically and physicochemically after isoelectric focusing. An albumin-like protein ranging from pI 4.80 to 5.21 was found in normal human thyroid tissue extracts, and its pI range was not compatible with that of serum albumin ranging from pI 4.85 to 6.16. An immunodiffusion study suggests that T3 loosely combines with the albumin-like protein, and that this compound is so-called thyroid albumin. Amino acid analysis revealed a difference in the basic amino acid composition of thyroid albumin and serum albumin, and our immunohistochemical study showed that thyroid albumin and T3 were localized in follicular epithelial cells, but not in the colloid. Based on these results, thyroid albumin may be described as consisting of T3 and an albumin-like protein which is distinguishable from serum albumin and distinct from thyroglobulin immunochemically. It appears that a low molecular weight hormone like T3 can be detected when it combines with a protein molecule. Recently, DeGroot et al. (1975) suggested a collateral pathway of hormone metabolism through the thyroid albumin in thyroid follicular cells. Our results seem to support the existence of this pathway.
Asthma, aspirin intolerance and nasal polyps form a triad of aspirin-induced asthma (AIA). Eighteen cases, 6 males and 12 females, who complained of asthma attacks and/or rhinorrhea after ingestion of non-steroidal anti-inflammatory drugs were encountered over several years. The mean age of onset was 32.1 for asthma and 25.4 for rhinitis. Asthma was found in all of the 18 cases and nasal polyps in 13 cases (72.2%). The polyps were recurrent and 7 patients had undergone polypectomies. Urticaria was seen in 44.4% and sinusitis diagnosed by X-ray in 81.8%. Sensitivity to at least one allergen was found in 7 out of 9 cases (77.8%) and 6 out of 11 cases (54.5%) gave results positive for RAST. Eosinophilia was seen in 14 out of 16 patients (87.5%). The pathogenesis of AIA is obscure but is probably related to inhibition of prostaglandin biosynthesis. We concluded that AIA is not a rare disease in Japan either, and the studies for eosinophilia may be useful for elucidation of the pathogenesis of AIA and nasal polyps.
The immunological response of 30 patients with acute sinusitis was examined by using an enzyme-linked immunosorbent assay (ELISA) designed to detect antibodies against outer membrane vesicles of Haemophilus influenzae. Using this ELISA, we found that 15 patients had slight increases in specific antibody in their convalescent serum. Maxillary sinus secretions from 15 patients had specific antibodies. IgG and IgA antibodies were detected with equal frequency, but IgA antibody was often found in maxillary sinus secretions while it was absent from serum. Thus it appears that patients with acute sinusitis respond systemically and locally with the specific antibody to H. influenzae.
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A simplified technique of the liver transplantation under hypothermia has been studied in dog. An immersion hypothermia was used in both the donor and the recipient. The temperature of the graft at excision was lowered to 20 degrees C with supplemental use of topical cooling. The temperature of the recipient was lowered at 27 degrees C when the transplantation was attempted. Chlorpromazine and dopamine were employed beneficially in hypothermia. No perfusion or irrigation of the graft was performed. The use of heparin was avoided. Anastomoses were carried out in turn of the proximal vena cava, portal vein, distal vena cava and the hepatic artery with a stem shaped aorta. Reperfusion was established after the completion of anastomosis between the proximal vena cava and portal vein. The anhepatic phase of the recipient was uneventfully lasted without heparinization. All dogs, 5 out of 11 without early surgical troubles survived more than 5 days. Immunosuppressive therapy was not employed except one which died of pneumonia on the 19th postoperative day. Histologically, these dogs were free from ischemic injury and/or thrombotic lesion throughout transplantation procedure.
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Five cases of iridocorneal endothelial syndrome have been examined with grand angle specular microscope. The first case presented normal appearance unlike the second case which showed diminution of the cellular density with 1.060/mm2 in comparison with 3,487/mm2 in the fellow eye. Pleomorphism and irregular size of endothelial cells associated with excrescences were noted in case 3 and 4. No endothelial cell could be observed in case 5: the authors introduce the possibility that time changes in corneal endothelium could be masked by a predescemetic membrane.
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Sixty-two patients with squamous cell carcinoma of the head and neck were administered a mean total dose of 75.9 g carmofur (HCFU) in combination with a mean total dose of 49.0 Gy irradiation therapy. The primary sites of cancer were: larynx 29 cases, oral cavity 11 cases, nasal and paranasal cavity 7 cases, hypopharynx 5 cases, nasopharynx 5 cases, epipharynx 3 cases, and others 2 cases. The clinical stages were: stage I II cases, stage II 15 cases, stage III 17 cases, and stage IV 19 cases. In 57 evaluable patients having measurable lesions, overall response rate, including 26 complete responses (CR) and 16 partial responses (PR), was 73.7%. Average doses of HCFU were 13.1 g at PR, 27.8 g at CR, and those of irradiation were 27.7 Gy at PR, 48.5 Gy at CR. The median duration of PR was 44.8 weeks and that of CR was 47.0 weeks, the overall response interval being 47.7 weeks. Of the 62 patients, 25 (40.3%) complained of side effects including pollakisuria (9 cases), appetite loss (6 cases), stomatitis (5 cases), and so on.