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Biomedical subjects

H Inoue

Publications and source records attributed to H Inoue.

At least 1,765 records · Page 98Linked to original sources

Novel reactions of 5-bromouracil derivatives with active methylene compounds.

5-Bromouracil derivatives (1) reacted with carbanions at room temperature to give 6-substituted uracils (6), 2,4-diazabicyclo[4,1,0] heptanes (8) and 2,4-diazabicyclo[4,3,0]nonane derivative (9), which depend largely upon the structure of the active methylene compounds employed for the generation of carbanions.

Alkanes↗

Surgical results for the treatment of primary carcinoma of the lung.

In order to examine the effectiveness of surgical therapy for primary lung carcinoma, 200 surgical patients were reviewed. Survival rates were compared to the initial operative approach, the tumor stage, and the histological type. The five year survival rate was 62% for Stage 1 tumors, 60% for Stage 2, 21% for Stage 3 and 32% for Stage 3 when metastases were confined to the ipsilateral hilar lymph nodes. The most profound influence on prognosis was exerted by the presence or absence of metastases to the mediastinal lymph nodes. Other factors such as tumor size, histological type, and degree of differentiation did not appear to affect prognosis. With extended resections of the adjoining organs, a 5 year survival rate of 37% was obtained in patients in whom the carcinomatous infiltration did not extend beyond the boundaries of the aortic adventitia, pleura, or pericardium. However, it was 0% when this boundary was broken. The CT scan was found to be helpful in the preoperative identification of carcinomatous infiltration. In some patients with preoperative CT scans demonstrating limited infiltration, the left atrium or aorta was resected and satisfactory long term survival was obtained. Finally we examined the effectiveness of the addition of radical lymphadenectomy of the right mediastinal nodes during the treatment of left lung carcinoma. This was performed by adding a median sternotomy to the standard left thoractomy and was well tolerated.

Adenocarcinoma↗

[Results of in vitro chemosensitivity assays: human tumor clonogenic and scintillation assay].

The authors reviewed their experiences to date with chemosensitivity testing of 629 tumors by human tumor clonogenic assay (HTCA) and of 199 tumors by scintillation assay (SA). HTCA and SA were both performed using a double-layer-soft-agar system with continuous exposure of cells to one concentration of standard anticancer drugs. Overall, 60% of specimens in HTCA and 58% in SA produced significant growth in vitro. HTCA was 52% (13/25) reliable for predicting in vivo sensitivity, and 95% (36/38) reliable for in vivo resistance, whereas SA was 40% (8/20) reliable for in vivo sensitivity and 88% (21/24) for in vivo resistance. The current results indicate that there is no particular difference in the success rate and in the predictive accuracy for in vivo sensitivity and resistance between HTCA and SA. Therefore, it is doubtful whether only clonogenic tumor cells among whole tumor cell populations should be selected in assessing the chemosensitivities of human tumors. In vitro success rates were variable, depending on the tumor histology. In vitro growth of gastric cancer specimens was characteristically lower than that of colon cancer specimens (48% and 60% in HTCA, and 46% and 68% in SA, respectively). (p less than 0.005). Optimal in vitro-in vivo drug concentrations and culture conditions are still being defined. Correlation studies of in vitro-in vivo responses of gastrointestinal cancers suggested that in vitro concentrations of 5-fluorouracil and mitomycin C used in this study were considerably higher than their optimal doses. Tumor cell heterogeneity poses significant problems in the clinical use of chemosensitivity assays. The question arises as to whether a single biopsy specimen is representative of a patient's disease. In this last study, we sought evidence of tumor heterogeneity by comparing chemosensitivity responses between: 1) different portions of a single tumor, 2) a primary and a metastatic biopsy taken from a patient on the same day, and 3) different metastases from a patient taken on the same day. The results demonstrated the presence of considerable heterogeneity of response to chemotherapy among different tumors from the same patient, and even within the same tumor. The reported discrepancies of in vitro and in vivo sensitivity may be due to such therapeutic heterogeneity among tumors.

Antineoplastic Agents↗

Transcriptional and post-transcriptional regulation of L-type pyruvate kinase in diabetic rat liver by insulin and dietary fructose.

Regulation of the expression of the hepatic L-type pyruvate kinase gene by insulin and dietary fructose was studied in diabetic rats. Insulin increased the levels of putative nuclear RNA precursor species of this enzyme in parallel with that of total cellular pyruvate kinase L mRNA. These changes occurred more slowly than those induced by dietary fructose. Insulin caused a 3-fold increase in transcription of the pyruvate kinase L gene after 6 h and a 6-fold increase after 16 h. The increase caused by insulin was inhibited by glucagon, but not by adrenalectomy. Cycloheximide inhibited the induction caused by insulin, suggesting that insulin may stimulate transcription of the pyruvate kinase L gene by stimulating synthesis of some unknown protein. On the other hand, feeding fructose had no effect on transcription of the pyruvate kinase L gene. We previously showed that increases in the levels of putative nuclear RNA precursor species of the pyruvate kinase L after fructose feeding preceded changes in the levels of cytosolic pyruvate kinase L mRNA (Inoue, H., Noguchi, T., and Tanaka, T. (1984) J. Biochem. (Tokyo) 96, 1457-1462). Thus, dietary fructose may increase the levels of pyruvate kinase L mRNA by stabilizing nuclear RNA species. Glucagon inhibited the increase in pyruvate kinase L mRNA caused by dietary fructose. However, plasma levels of glucagon and thyroid hormones were not decreased in diabetic rats after fructose feeding. In addition, treatment with triiodo-L-thyronine caused no change in the pyruvate kinase L mRNA level. Furthermore, adrenalectomy did not impair enzyme induction by fructose in diabetic rats. Thus, the effect of fructose on pyruvate kinase L seems to be directly on the liver.

Adrenalectomy↗

A genetic study of inositol trisphosphate involvement in phototransduction using Drosophila mutants.

Phosphatidylinositol 4,5-bisphosphate phosphodiesterase activity was found to be almost absent in the compound eyes of Drosophila visual mutant, norpA (no receptor potentials A). We compared the enzyme activities among independently isolated norpA alleles, each having a different degree of the vision defect. A close correlation was found between the size of receptor potentials (electroretinogram), phototactic behavior and the enzyme activity. The correlation exists not only among alleles, but also in a single, temperature-dependent allele under different temperature; the enzyme activity of flies kept at 18 degrees C (phototactic) was about five times higher than that of the ones kept at 28 degrees C (blind). These results suggest that hydrolysis of phosphatidylinositol 4,5-bisphosphate is involved in phototransduction process in Drosophila eyes.

Alleles↗

Synthesis and hybridization of dodecadeoxyribonucleotides containing a fluorescent pyridopyrimidine deoxynucleoside.

Partially self-complementary dodecadeoxyribonucleotides containing a fluorescent nucleoside, 3-beta-D-2'-deoxyribofuranosyl-2, 7-dioxopyrido[2, 3-d]pyrimidine (pyridopyrimidine deoxynucleoside, dF) were synthesized by the phosphotriester solidphase method. A dodecanucleotide d(GGGAAFGTTCCC) pairing the analog and guanine at the centre of the chain showed a higher melting temperature than the corresponding G-C paired duplex. A similar comparison between A-T and A-F suggested that weaker hydrogen bonds exist when adenine and pyridopyrimidine residues are paired.

Circular Dichroism↗

Immunohistochemical studies on mouse cerebral cortex grafted into the third ventricle of rats treated with cyclosporin A.

Newborn mouse cerebral cortex was transplanted into the third ventricle of an adult rat brain. After the operation, the immunosuppressant cyclosporin A was administered daily for two weeks, and the grafted tissue was examined immunohistochemically at the 4th week. Neurons, astroglias and oligodendroglias were positively stained by antibodies against neurofilament, glial fibrillary acid protein and 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase), respectively. The CNPase staining indicated that myelination had occurred in the grafted tissue. Thus both neuronal and glial elements in the grafted tissue could survive and mature in the third ventricle of the different species upon administration of cyclosporin A.

Animals↗

A distinct terminal structure in newly synthesized chondroitin sulphate chains.

A method was developed for the analysis of non-reducing terminal structure of radiolabelled chondroitin sulphate chains with the aid of N-acetylgalactosamine 4-sulphatase ('terminal 4-sulphatase'), N-acetylgalactosamine 6-sulphatase ('terminal 6-sulphatase'), beta-glucuronidase and beta-N-acetylhexosaminidase. Studies with this method on the non-reducing terminal structure of [35S]sulphate- and [3H]glucose-labelled chondroitin sulphate chains from rat and chick-embryo cartilages showed that the presence of a high proportion of 4-sulphated hexosamine residues is a common feature of the termini of newly synthesized chondroitin sulphate chains. Of the non-reducing terminal 4-sulphated hexosamine residues, about 14% (chick embryo) or 46% (rat) contained an additional sulphate group at position 6. The internal portion of the chondroitin sulphate chains, in contrast, contained little or no 4,6-bis-sulphated hexosamine residue, suggesting that 4,6-bis-sulphated structure may play a role in biosynthetic control at the level of chain termination.

Animals↗