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Biomedical subjects

T Inagaki

Publications and source records attributed to T Inagaki.

At least 145 records · Page 8Linked to original sources

Neuronal cell loss in the dorsal raphe nucleus and the superior central nucleus in myotonic dystrophy: a clinicopathological correlation.

A quantitative study of neurons in the dorsal raphe nucleus (DRN) and the superior central nucleus (SCN) was performed in seven patients with myotonic dystrophy (MyD), five of whom showed hypersomnia, and in eight age-matched controls. The densities of neurons in the DRN and the SCN were significantly lower in MyD patients with hypersomnia than in MyD patients without hypersomnia and control subjects. There was an appreciable positive correlation in the density of neurons between the DRN and the SCN in all MyD patients. These data suggest that the neuronal loss of the DRN and the SCN is associated with the presence of hypersomnia in MyD.

Aged↗

Carbonic anhydrase isozyme VI in rat lacrimal gland.

Using monoclonal antibody specific to rat carbonic anhydrase isozyme VI (CA VI), the isozyme was localized in the lacrimal gland. A minority of acini (less than 10% of the total) contained a few immunoreactive acinar cells. Enzyme histochemistry indicated that the CA VI-positive cells were the only cells possessing CA in the lacrimal acini. In the acinar cells, the reaction product for CA VI was distributed in the secretory granules and cytosol between secretory granules. Except for mitochondrial enzyme (CA V) activity, the intracellular distribution of enzyme activity was similar to that of CA VI immunoreactivity, suggesting that rat lacrimal acinar cells contain only CA VI and CA V. CA VI in the secretory granules was discharged into the acinar lumen and is considered to carry out its function on the surface of the conjunctiva and cornea. The cytosolic CA VI may function in situ and be involved in electrolyte and water secretion by the acinar cells. Polyclonal antibody to rat erythrocyte CA (CA I and CA II) stained only the interlobular ducts. In contrast, all the ductal elements exhibited CA enzyme activity. This discrepancy between immunohistochemistry and enzyme histochemistry suggests the presence of CA isozyme(s) other than CA I, CA II and CA VI in the lacrimal duct.

Animals↗

Changes in the ratio of urinary alpha 1-microglobulin to ulinastatin levels in patients with Alzheimer-type dementia and vascular dementia.

Relationships between urinary levels of alpha 1-microglobulin (alpha 1M) and ulinastatin (UT) in patients with dementia were investigated. There were no significant differences in alpha 1M and UT levels and alpha 1M: UT ratios among three groups: age-matched control subjects, patients with either Alzheimer-type senile dementia (ATD) or vascular dementia (VD). Although a positive correlation was established between alpha 1M and UT levels in these groups, the regression of the demented patients differed significantly from that of controls (P < 0.05). A tendency towards a negative correlation between alpha 1M: UT ratios and the levels of severity or duration of the disease was displayed in the ATD group, whereas a tendency toward a positive correlation between alpha 1M: UT ratios and the levels of severity was observed in the VD group. These results suggest that changes in the relationships between urinary levels of alpha 1M and UT may provide a useful biochemical index for diagnoses of ATD and VD.

Aged↗

Factors affecting the occurrence of urothelial tumors in dye workers exposed to aromatic amines.

BACKGROUND: Past studies have analyzed individual jobs in dyestuff factories, materials manufactured and handled, age at exposure, and the duration of exposure in factories as factors related to the occurrence of urothelial tumors. None of these studies was based on long-term observation, and the factors involved in the occurrence of urothelial tumors remain controversial. In this study, various factors that may affect the occurrence of urothelial tumors in dye workers were assessed by multivariate analysis. METHODS: Three hundred and sixty-three workers in nine member factories of the Dyestuff Industrial Cooperative Association were included the study. Factory A is a large dyestuff chemical factory in Wakayama City with 218 dye workers. The other eight smaller factories employ a total of 145 dye workers. Correlations of tumor occurrence with a variety of factors, such as dyestuff intermediates manufactured and handled, types of job in the factory, age at the beginning of occupational exposure, and the duration of exposure were examined by multivariate analysis using multiple logistic models. RESULTS: Urothelial tumors were found in 58 (16.0%) of the 363 dye workers in the nine member factories of the Cooperative Association examined in the present study. The incidence in workers in Factory A, 5.5% (12 patients), was significantly (P < 0.01) lower than the overall incidence, while that in the eight small factories, 31.7% (46 patients), was significantly (P < 0.01) higher than the overall incidence. The risk factors significantly related to tumor occurrence in the 363 dye workers were benzidine (odds ratio, 8.302) as a dyestuff intermediate, manufacturing work (odds ratio, 4.631), and a long period of exposure (odds ratio, 1.018). Correlations of the tumor occurrence with the various factors were examined by multivariate analysis using multiple logistic models. In the total of 363 workers, benzidine as an intermediate (P < 0.05), manufacturing work (P < 0.01) and the duration of exposure (P < 0.01) were found to have contributed to the urothelial tumor occurrence. In Factory A, benzidine as an intermediate (P < 0.01) and duration of exposure (P < 0.05) contributed significantly to tumor occurrence. CONCLUSIONS: 1) The manufacturing and handling of benzidine and duration of exposure contribute significantly to the occurrence of occupational urothelial tumor, the former more strongly than the latter; 2) the contribution of different job types to tumor occurrence may be dependent upon the industrial health and safety practices in each factory.

Adolescent↗

Effects of normal and their branched alcohols with structurally minimal variation on kinetic parameters in thermolysin-catalyzed peptide hydrolysis and synthesis of N-(benzyloxycarbonyl)-L-phenylalanyl-L-phenylalanine and its methyl ester.

When higher alcoholic solvents were added to the reaction medium, and the enhancement of the enzyme activity, followed by its reduction then inactivation, were observed in thermolysin-catalyzed peptide hydrolysis and synthesis. The organic solvent content used was less than the saturating concentration in the buffer (i.e., water-organic one-phase system). The kinetic parameters, Km and kcat, at the alcoholic concentration giving maximal enzyme activity in these reactions changed linearly with increasing logP values of the alcohols and consequently kcat/Km as well. When the branched isomers of alcohols with structurally minimal variation of which logP was equivalent theoretically, were used as annexments, the kinetic parameters were also changed. The results, especially the changes of Km for each organic solvent, suggested that each alcohol should act at the active site of the enzyme in its own effective mode.

Alcohols↗

Squamous cell carcinoma of the pancreas with massive invasion of the retroperitoneum.

A 79-year-old woman with a rare form of pancreatic carcinoma with massive invasion of the retroperitoneum presented with upper abdominal pain and vomiting. Although examination (computed tomography, barium enema, upper gastrointestinal series) suggested peritonitis carcinomatosa due to pancreatic cancer, a primary lesion of the pancreas was not confirmed by endoscopic retrograde pancreatography. Autopsy ultimately revealed a small tumor (5 x 8 mm) of the uncinate process of the pancreas near the duodenum with peritonitis carcinomatosa. Microscopically, the tumor and its metastasis consisted of poorly differentiated squamous cell carcinoma without adenocarcinomatous change, a rare form of pancreatic tumor.

Aged↗

[A 115-year-old woman: the oldest individual in Japan].

The purpose of this study was to assess the background to the longevity of a 115-year-old woman who was the oldest individual in Japan as of September, 1994. The secrets of her social and medical profile appeared to be hereditary factors, well-balanced meals, no smoking or drinking, sufficient sleep and adequate exercise. From the viewpoints of psychological aspects and comprehensive functional assessment of the elderly, she clearly has a tenacious personality. Furthermore, she has maintained independence in her activities of daily living, and did not suffer from senile dementia until 107 years of age. From the medical standpoint, she has suffered from transient hypertension, but her left ventricle function has remained within the normal echocardiography range and no greatly abnormal values have been observed in blood chemistry tests. She has suffered from pneumonia and urinary tract infection many times since the age of 109, and on these occasions she was promptly admitted to our hospital and received appropriate medical treatment. We consider that this also played an important role in her longevity.

Activities of Daily Living↗

CJ-12,371 and CJ-12,372, two novel DNA gyrase inhibitors. Fermentation,isolation, structural elucidation and biological activities.

A fermentation broth of an unidentified fungus (N983-46) was found to produce DNA gyrase inhibitors, CJ-12,371 (1) and CJ-12,372 (2). Following isolation by solvent extraction and silica gel and ODS (reverse phase) chromatographies, the structures were determined to be novel spiro-ketal compounds with S-configuration at position C-1. CJ-12,371 and CJ-12,372 inhibit both DNA supercoiling and relaxation mediated by Escherichia coli DNA gyrase. The interaction of these compounds with DNA gyrase appears to be novel in that the compounds inhibit supercoiling and relaxation without blocking religation; thus, no cleavage intermediate of double strand DNA is observed. Both compounds have antibacterial activity against several species of pathogenic Gram-positive bacteria, with MICs between 25 and 100 micrograms/ml. These results suggest that the antibacterial potency of CJ-12,371 and CJ-12,372 is attributed to the inhibition of DNA gyrase. However, the compounds did not inhibit DNA gyrase selectively, as they also inhibited eukaryotic topoisomerase II-mediated relaxation. Semi-synthetic modifications to the dihydroxy motif in CJ-12,371 altered both gyrase- and topoisomerase II-inhibitory activities, but did not enhance selectivity.

Anti-Bacterial Agents↗

Generation of novel rapamycin structures by microbial manipulations.

A new rapamycin producing culture was isolated and designated as Actinoplanes sp. N902-109. The addition of a cytochrome P-450 inhibitor and precursor feeding using this culture, and biotransformation approaches generated new rapamycin analogs with modifications at C-4, C-9, C-16, C-27, C-28 and/or C-39. The immunosuppressive activity of the resulting analogs was established in the mixed lymphocyte reaction assay.

Actinomycetales↗

[Combined hormone and chemotherapy for the patients with advanced prostate cancer].

From November 1984 to December 1993, 72 patients with newly diagnosed, stage C or D prostate cancer were treated with chemohormonal therapy consisting of CDDP, CPM, diethylstilbestrol diphosphate and orchiectomy. Forty-four of 72 patients (61%) had partial response 3 months after the initiation of the treatment. A good response rate was observed in prostate gland and tumor markers (63% and 81%), but the response rate was poor in bone and other soft tissure metastasis (17% and 18%). Subjective symptoms improved in 82% of the pain, 70% of the infravesical obstruction, 65% of the performance status, and 5% of the body weight. The 5-year survival rate was 66%. The prognosis of the patients with poorly differentiated carcinoma or high Gleason score tumor was poor. Survival rate was no different between stage C and D. Relapse occurred in 16 patients (22%) and tended to occur in the patients with poorly differentiated carcinoma, high Gleason score tumor, stage D2 or stable disease. The survival rate was better, and the relapse rate lower than in the 35 patients with hormonal treatment alone during the same period, but no significant difference was observed between the two groups.

Aged↗

Establishment of human oral-cancer cell lines (KOSC-2 and -3) carrying p53 and c-myc abnormalities by geneticin treatment.

Two cultured cell lines derived from human squamous-cell carcinomas were established through xenografted tumors in nude mice by "Geneticin" treatment, which allows to eliminate contaminated mouse fibroblasts and obtain enriched tumor cells at the early stage of cultivation. Line KOSC-2 and KOSC-3 were each derived from a squamous-cell carcinoma of the oral floor and of the lower gingiva, respectively. Both lines grew in a cobblestone pattern, demonstrating their epithelial heritage. Giemsa-banding patterns by chromosome analysis confirmed that both lines are of human origin. Molecular analysis of cancer-related genes, including the Ha-ras, c-myc and p53 genes, was performed. KOSC-3 cells showed co-over-expression of p53 and c-myc mRNA, in addition to p53 point mutation at codon 248 with transition from CGG to TGG. However, loss of heterozygosity (LOH) on chromosome 17 was detected in both lines by Southern blotting. These cell lines provide a model for elucidating the mechanism involving p53 inactivation and c-myc-gene over-expression.

Aged↗

The mutant Eisai hyperbilirubinemic rat is resistant to bile acid-induced cholestasis and cytotoxicity.

We investigated bile flow and biliary excretion of bile acids in the Eisai hyperbilirubinemic rat, a Sprague-Dawley mutant rat with conjugated hyperbilirubinemia, using both in vivo and in vitro models. In vivo bile flow was lower in Eisai hyperbilirubinemic rats than in the control rats before and after taurocholate was infused. After taurocholate was infused, bile acid output was similar in the Eisai hyperbilirubinemic rats and control rats. In the isolated perfused rat liver, biliary excretion of bile acids was higher in the Eisai hyperbilirubinemic rats than in the control rats after a high-dose infusion of taurocholate (0.33 mumol/min/gm liver). Infusion of taurochenodeoxycholate (0.22 mumol/min/gm liver) did not produce cholestasis and did not reduce the biliary excretion of bile acids in the Eisai hyperbilirubinemic rats. Taurochenodeoxycholate significantly increased the phospholipid/bile acid molar ratio and slightly reduced bile acid-induced alkaline phosphatase output into bile. The release of lactate dehydrogenase from the perfused liver 30 min after the start of the taurochenodeoxycholate infusion was 10 times lower in the Eisai hyperbilirubinemic rats than in the control rats (2.0 +/- 0.8 vs. 28.7 +/- 6.8 mU/min/gm liver). When the isolated perfused rat liver was infused with a 1-min pulse of horseradish peroxidase (25 mg), we observed an early and late peak of biliary excretion of horseradish peroxidase. The Eisai hyperbilirubinemic rats showed a significant increase in the late peak.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline Phosphatase↗