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N Domae

Publications and source records attributed to N Domae.

52 records · Page 3Linked to original sources

Ultrastructural and purification studies on human tumor nucleolar antigens and nucleolar particles.

The presence of common nucleolar antigens in a broad array of human malignant tumors has led to several lines of investigations. In addition to studies on an increasing number of benign and malignant neoplasms with a variety of antibodies designed to statistically evaluate the presence of nucleolar antigens, purification procedures and chemical analyses are being used to characterize the specific antigens. The localization of the nucleolar antigens in HeLa cells was studied by the postembedding immunoelectron microscopic procedure employing rabbit antibodies to nucleoli or nuclear Tris extracts of these cells. The products of the peroxidase-antiperoxidase complexes visualized by the reaction with diaminobenzidine in nucleoli were mainly found in the nucleolonemas which contain the dense nucleolar RNP components. When these nucleoli became compact after treatment of HeLa cells with adriamycin, the distribution of the immunoreactive products was altered along with distribution of the dense nucleolar components. The human nucleolar antigens were mainly localized to nucleolar regions containing the nucleolar RNP components. Improved purification of the antigens made it possible to provide a satisfactory amino acid analysis of one pI 6.3 antigen. Interestingly, some of the nucleolar antigen was found in miniparticle undescribed until now.

Amino Acids↗

Donut-shaped "miniparticles" in nuclei of human and rat cells.

Donut-shaped "miniparticles" were extracted from nuclei of various types of human and rat cells. Electron-microscopic investigation showed these particles were predominantly in sucrose density gradient fractions that had an approximate sedimentation coefficient of 21S. These particles were 113 +/- 8A in diameter and had an electron dense center of 29 +/- 6A. They appeared to be composed of 8 subunits. Quantitative analysis of the number of these particles by electron-micrographic field counting showed nuclei of tumor samples had a larger amount of the particles than the cytosol. However, normal cell cytosol had a larger number of particles than the nuclei. A group of proteins in the 25,000-33,000 molecular weight range was shown to be the main protein component by two dimensional gel electrophoresis.

Animals↗

Lipopolysaccharide responsiveness of malignant lymphoid cells in a patient with hairy cell leukemia.

The malignant cells in a patient with hairy cell leukemia responded most evidently to lipopolysaccharide (LPS) in in vitro culture for 3 1/2 days when the conventional tritiated thymidine uptake method was used. Since the malignant cells from patients with several other forms of leukemia and the peripheral blood mononuclear cells from healthy individuals did not show a comparable degree of responsiveness to LPS, we could exclude the possibility that this response was due to effects on contaminating normal mononuclear cells or to the nonspecific conditioning effect through LPS-affected contaminating normal monocytes. Morphological changes were observed with photo- and electronmicroscopy. It is likely that the hairy cells from the patient did respond to LPS, and whether or not this phenomenon may be confined to this type of lymphoid leukemia is not being investigated.

Adolescent↗

Reverse effect of guanine on the inhibitory action of mycophenolic acid during nucleic acid synthesis.

Mycophenolic acid (MPA) was demonstrated to inhibit DNA and RNA synthesis in L1210 cells strongly; however these effects were remarkably reduced by guanine. The presence of MPA in the medium decreased the guanine nucleotide contents (GMP, GDP, GTP) of the cells, but the addition of guanine reversed this effect. We have reported previously that MPA had no inhibitory effect on hypoxanthine guanine phosphoribosyltransferase (HGPRTase) activity. Together these findings suggest that the decrease of guanine nucleotides induced by MPA is restored by GMP, which is formed from guanine by HGPRTase in the cells. It is speculated that a suppressor of HGPRTase activity, such as 6-mercaptopurine, may protect the antitumor activity of MPA by preventing the conversion of guanine to GMP.

Animals↗

Cardiomyopathy and other chronic toxic effects induced in rabbits by doxorubicin and possible prevention by coenzyme Q10.

Cumulative dose-dependent toxic effects, particularly cardiomyopathy, induced by doxorubicin and the possible prevention by coenzyme Q10 (CoQ10) were studied in rabbits. In rabbits given doxorubicin alone, there was considerable body weight loss, alopecia, pancytopenia, significant increase in serum creatine phosphokinase and LDH, and ECG changes characterized by tachycardia, flat and inverted T wave, the premature ventricular contractions. In rabbits given doxorubicin plus CoQ10, the only change was pancytopenia. In rabbits treated with doxorubicin alone, the most prominent histologic changes were observed in mitochondria of myocytes, and these changes were characterized by loss of outer membrane, disarrangement of cristae, and formation of numerous concentric lamellae. In addition to mitochondrial changes, there were numerous vacuolizations and extensive depositions of both electron-dense and membranous laminated bodies in the sarcoplasm and disarrangement of Z-band and filamentous changes of myofibrils. Numerous vacuolizations in the capillary endothelial cytoplasm in the myocardium were also conspicuous. On the other hand, few significant morphologic changes were seen in the nuclei of myocytes. There were few ECG and histopathologic changes in rabbits treated with both doxorubicin and CoQ10. These findings suggest that the cardiomyopathy of doxorubicin may be prevented or is at least inhibited by CoQ10. The mechanisms of both doxorubicin-induced cardiomyopathy and its prevention by CoQ10 are discussed.

Animals↗

Evaluation of oral aclarubicin treatment for tumors of the gastrointestinal track.

Aclarubicin (ACR), a drug useful for the treatment not only of tumors of the hematopoietic system but also of those of the gastrointestinal tract, has been administered invariably by the intravenous route. We attempted oral administration of ACR to increase its specificity in the treatment of gastrointestinal tumors. Oral administration resulted in a much higher intratumor concentration but lower peripheral blood cell or bone marrow cell concentration of the drug as compared with intravenous administration. The reduced peripheral cell inhibition and bone marrow suppression permits the administration of the drug in higher doses, and the absence of the drug in the plasma suggests a reduced likelihood of myocardial cell injury and hepatocyte impairment. These favorable findings are considered to warrant early clinical trial of the treatment.

Aclarubicin↗