Biomedical subjects
Publications and source records attributed to Y Moritani.
The low-temperature structure determination of the title compound, alternatively called ammonium hydrogen hydroxypropanedioate, NH(4)(+) x C(3)H(3)O(5)(-), has revealed that the H atom involved in a very short asymmetric O--H...O hydrogen bond [O...O = 2.448 (2) A at 240 K and 2.4393 (10) A at 20 K] is disordered.
A novel class of potent and selective phosphodiesterase 5 (PDE5) inhibitors, 4-aryl-1-isoquinolinone derivatives, which have been designed by the comparison of the structure of cGMP and a previously reported 1-arylnaphthalene lignan, was disclosed. Among these compounds, methyl 2-(4-aminophenyl)-1,2-dihydro-1-oxo-7-(2-pyridinylmethoxy)-4-(3,4,5-trimethoxyphenyl)-3-isoquinoline carboxylate dihydrochloride (36a) exhibited potent PDE5 inhibitory activity (IC(50) = 1.0 nM) with high isozyme selectivities (IC(50) ratio: PDE1/PDE5 = 1300, PDE2/PDE5 > 10 000, PDE3/PDE5 > 10 000, PDE4/PDE5 = 4700, PDE6/PDE5 = 28). Compound 36a also showed the most potent relaxant effect on isolated rabbit corpus cavernosum (EC(30) = 7.9 nM). Compound 63 (T-1032), the sulfate form of 36a, was selected for further biological and pharmacological evaluation of erectile dysfunction.
6,7-Diethoxy-1-[1-(2-methoxyethyl)-2-oxo-1,2-dihydropyridin- 4-yl]naphthalene-2,3-dimethanol [T-440, (1)] is a potential anti-asthmatic agent based on selective phosphodiesterase 4 inhibition. It was necessary for the further evaluation of 1 to develop an efficient synthetic route for 1, especially the construction of the 1-(2-methoxyethyl)-2-pyridone moiety. We examined an N-selective alkylation of pyridone derivative (2) in basic media. 2-Methoxyethylation of 2 with 2-methoxyethyl iodide utilizing LiH as the base gave predominantly an N-alkyl pyridone derivative (3a) in 82% yield (N/O-alkylation=92/8), which is compatible with an ab initio calculation of transition-state structures for the methylation of 2-pyridone. Single crystallization of a crude mixture of 3a and 4a furnished pure 3a, which is a key synthetic intermediate of 1.
A series of 1-aryl-2,3-bis(hydroxymethyl)naphthalene lignans have been synthesized and evaluated for their ability to selectively inhibit PDE IV isolated from guinea pig. Replacement of the 1-phenyl ring by a pyridone ring led to marked improvement of their selectivity for PDE IV over PDE III. The compounds that were most potent and selective involved those bearing an N-alkylpyridone ring at C-1. These compounds also showed potent antispasmogenic activity without causing significant changes in heart rate in the guinea pig. The most potent compound was 6,7-diethoxy-2, 3-bis(hydroxymethyl)-1-[1-(2-methoxyethyl)-2-oxo-pyrid-4-yl]nap hth alene (17f), ED50 values of histamine-induced and antigen-induced bronchoconstriction in the guinea pig being 0.08 and 2.3 mg/kg iv, respectively. This compound was chosen as a candidate for further pharmacological evaluation.
A 68-year-old man was referred to our hospital for further examination of a gingival mass. Chest radiographs and magnetic resonance imaging disclosed a bulky mass originating in the upper portion of the left lung, in contact with a chronic empyema lesion that first occurred after resection for pulmonary tuberculosis. Examination of a specimen obtained by percutaneous needle biopsy of the mass led to the diagnosis of large-cell carcinoma. Laboratory findings on admission showed marked leukocytosis (48,100/microliter) without evidence of severe a bacterial infection. The level of G-CSF in serum was abnormally high (246 pg/ml, normal value: < 30 pg/ml). Chemotherapy with vindesine, ifosfamide, and cisplatin resulted in shrinkage of the gingival mass, and a decrease in the G-CSF level to 66 pg/ml. Immunohistochemical staining with an anti-G-CSF monoclonal antibody to the primary lung tumor and the gingival mass obtained at autopsy was positive for cytoplasmic G-CSF.
We performed lung cancer resection in 721 patients between 1980 and 1989. Cancers were detected via mass screening programs by annual chest X-ray examination in the majority of cases. We evaluated the surgical results in patients with tumors detected by mass screening and compared them to those in whom the malignancy was detected by symptoms. Lesions in the mass screened group were T1 to T2 tumors in 90% of the cases, and NO in 73%. Stage I disease accounted for 65.3% in the mass screened group. The overall 5-year survival rate was 56.2% in the mass screened group, which was significantly better than the 25.3% for the symptom group (P less than 0.001). The surgical results in the lung cancer cases detected by the mass screening program had better results than the cases who presented with symptoms.
Six patients with asymptomatic primary pulmonary Cryptococcosis are reported. In all of the patients, the disease was detected by annual chest X-ray during mass screening for lung cancer or during follow-up for pulmonary tuberculosis or gastric cancer. The chest X-ray findings consisted of a solitary pulmonary nodule in 4 patients and multiple pulmonary nodules in 2. Only one patient who could not be histologically diagnosed by bronchofiberscopy underwent surgical resection. However, the other 5 patients were histologically diagnosed by transbronchial biopsy with bronchofiberscopy. They were treated with oral antifungal agents, namely flucytosine (5-FC) and/or fluconazole, with marked improvement of chest X-ray findings. These results indicate that transbronchial biopsy with bronchofiberscopy and oral administration of antifungal agents instead of initial surgical resection are useful in the diagnosis and treatment of primary pulmonary cryptococcosis.
Cyclosporin-induced gingival enlargement was presented. Enlargement was noted at several sites in the mouth of five patients taking Cyclosporin following liver transplantation. Papillary gingival enlargement was observed to affect the entire maxilla and mandible. Enlargement was particularly marked in the interdental papillary region on the labial side of the anterior teeth of the maxilla. Discoloration of the teeth was observed. Radiographic findings were unremarkable. Oral management of these patients is the prevention of dental caries and infection originating in the area of gingival enlargement. It is important to begin proper brushing as early as possible for suppressing progression of gingival enlargement. For prevention of dental caries, prophylaxis is more important in the case of liver transplantation than with normal patients. It should be stressed to the patients or their parents that periodic examination, topical application of fluoride and pit and fissure sealants are of special importance.
A case of pulmonary atresia with intact ventricular septum in a 4-year-4-month boy, whose dental treatment was performed under general anesthesia, was reported. For the general anesthesia, the medication Digoxin was stopped 24 hours before the treatment. For the prevention of bacterial endocarditis, medication consisting on antibiotics of the penicillin series was administered 24 hours before the treatment. The anesthesia was administered with the modified N.L.A. method with Ketamine and Diazepam. The dental treatment went smoothly, and was finished within 1-hour-15 mins from the start. Anesthesia was administered for 1-hour-45 mins. The prognosis was good, and the patient was discharged the next day. It should be noted that as for performing dental treatment under anesthesia or not using anesthesia, there are some different opinions. We think that it must be discussed from the point of view of the effect of the dental treatment on the patient versus the danger of the anesthesia. In this case, we found that, under general anesthesia, stress of the patient was reduced, and the dental treatment was able to be performed smoothly and safely.
In order to evaluate the efficacy of X-ray signs for the differential diagnosis of small lung cancer from tuberculoma, a cooperative study was carried out. X-ray films of 64 cases (lung cancer 35, tuberculoma 29) were read by 11 experienced chest physicians independently. The positivity of various X-ray signs were assessed respectively and obtained data were analysed with ROC analysis method. "Ill defined contour", "unevenness of density", "paleness" were proved to be relatively useful as a diagnostic tool, but "notch", "pleural indentation" were not useful in differentiating lung cancer from tuberculoma. It was also noted that great interindividual variations existed on the judgements of X-ray signs among chest specialists, and the conquest of which may be a crucial key for the universal validity of these signs.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Natural killer activity of lymphocyte against M-HeLa or MKN-28 cells was measured in the gastric cancer tissue, regional lymph nodes, spleen and peripheral blood, and also the influences of injection of Nocardia CWS into the tumor was studied. Tumor infiltrating lymphocyte showed higher rates of T and T gamma cells than the lymphocyte of normal gastric tissue, nearly the same value as the lymphocyte in peripheral blood. NK activity of the lymphocyte in the peripheral blood of the gastric cancer patient showed a significant decrease compared to that of the normal subject. NK activity of the tumor infiltrating lymphocyte was markedly lower than that of the lymphocyte in peripheral blood, and was at the same level as that of the normal stomach and the lymph node. Endoscopic injection of N-CWS into the gastric cancer tissue intensified the cytotoxicity of lymphocytes in the cancer tissue and regional lymph nodes to MKN-28 cells derived from gastric cancer 5 to 17 days later, however, the activity against M-HeLa did not augment. Human fibroblast interferon (interferon beta) increased NK activity of lymphocytes in peripheral blood and spleen, but showed no influence on the activity of lymphocytes in the gastric cancer tissue and the regional lymph nodes.