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Biomedical subjects

N Okada

Publications and source records attributed to N Okada.

At least 523 records · Page 29Linked to original sources

[Protective effect of CoQ 10 administration on cardial toxicity in FAC therapy].

An unique combination treatment for cancer patients has been attempted in our department. The treatment consists of 500 rad irradiation of cobalt 60 on the first day and drip infusion of mixture of 50mg adriamycin, 500mg cyclophosphamide and 500mg 5-fluorouracil on the next day. This combination therapy was repeated every 3 weeks. The myocardial intoxication may be a great problem in this therapy. Investigation was performed in 40 cancer patients in order to clarify of Coenzyme Q10 (CoQ10) could show any protecting effect upon the possible myocardial intoxication. All patients were divided into 2 groups; one with CoQ10 of 20 patients, who received CoQ10 of 90mg/day orally and the other without CoQ10 of 20 patients. In the group without CoQ10, cardiothoracic ratio (CTR) and pulse rate increased significantly in all patients and on ECG low voltage of QRS complex was seen in 2 cases, changes of ST-segment, T-wave and appearance of arrhythmia were more than frequent in the group without CoQ10 than that with CoQ10. It is concluded that CoQ10 is effective for protecting the myocardium in this cancer therapy.

Adult↗

Nucleotide sequences of mouse genomic loci including a gene or pseudogene for U6 (4.8S) nuclear RNA.

We have isolated four clones which hybridize with U6 (4.8S) nuclear RNA, a mammalian small nuclear RNA(nRNA), from DNA of BALB/C mouse liver. Their restriction maps are totally different from each other, indicating that they derived from different loci in the mouse genome. The nucleotide sequences around the hybridizing region in the three clones have been determined. One clone gives a gene that is co-linear with the U6 RNA. There is a sequence TATAAAT beginning 31 nucleotides upstream of the gene, which may suggest that the U6 RNA is transcribed by RNA polymerase II. The other two clones contain a pseudogene for the U6 RNA which has 7 or 9 nucleotide changes from the RNA. The pseudogenes are surrounded by radically different sequences from those surrounding the gene, and they are closely linked to a pseudogene for another snRNA, 4.5S-I RNA, or a part of highly repetitive an interspersed sequence B1.

Animals↗

Heat-labile glucose-6-phosphate dehydrogenase in cultured fibroblasts from patients with De Sanctis-Cacchione Syndrome.

The normal senescent fibroblasts in culture accumulate a significantly high proportion of altered enzymes, and the alterations are considered to be the manifestation of ageing in molecular terms. To detect the possible molecular alterations in patients with De Sanctis-Cacchione syndrome, the severest form of xeroderma pigmentosum, in which repair processes to UV light-damaged DNA are defective and the neurologic abnormalities are considered to reflect accelerated ageing, we studied the heat stability of glucose-6-phosphate dehydrogenase (G6PD) in crude extracts of cultured skin fibroblasts. Three patients with the syndrome were the center of our investigation. Even at early passage in culture the heat-labile portion of G6PD was increased in the cells from patients in comparison to normal controls. The life span of the cells in culture from patients was not reduced below normal age-matched controls, and no appreciable senescent appearance was observed. The increase in the heat-labile portion of G6PD from cells of DeSanctis-Cacchione syndrome patients to reflect that defective repair of DNA damage occurs, rather than being a direct result of ageing of cultured cells.

Adult↗

Novel models for RNA splicing that involve a small nuclear RNA.

Nucleotide sequences of mammalian small nuclear RNAs (snRNAs) have been analyzed with a computer program for complementarity with sequences around a splice junction of various eukaryotic mRNA precursors (pre-mRNAs). A region in U2 RNA or some other snRNAs can form base pairs with both exons surrounding an intron of certain pre-mRNAs and, thereby, can align the two junctions leading to correct splicing of the pre-mRNA. These findings suggest that a snRNA such as U2 can be involved in splicing certain pre-mRNAs by pairing with exons, which we we call an "exon model" for splicing, as compared with the model involving U1 RNA presented by Lerner et al. [Lerner, M. R., Boyle, J. A., Mount, S. M., Wolin, S. L. & Steitz, J. A. (1980) Nature (London) 283, 220-224]. We constructed a secondary structure model of U1 RNA and studied the capacity of base pairing with pre-mRNAs on the basis of both primary and secondary structures of U1 RNA. We present an alternative model for splicing that involves U1 RNA, which assumes base pairing of noncontiguous regions of U1 RNA with an intron of a pre-mRNA. Pairing of an snRNA with exons could explain correct matching of the two junctions that bound one and the same intron, which is not explained by pairing with consensus sequences at the ends of an intron as proposed by Lerner et al. Pairing of an intron with U1 RNA and pairing of the surrounding exons with another snRNA such as U2 RNA could take place at the same time to insure specificity of splicing.

Animals↗

Biological and structural differences between tRNAVal species isolated from rat ascites hepatoma cells and normal rat liver.

On RPC-5 column chromatography, the main valine acceptor activity of tRNA (tRNA2Val) from rat ascites hepatoma cells was eluted later than that of normal rat liver tRNA (tRNA1Val). The tRNA2Val was aminoacylated by E. coli amino-acyl-tRNA synthetase, while tRNA1Val from normal rat liver was not. Rat fetal liver tRNAVal was also aminoacylated by E. coli aminoacyl-tRNA synthetase. tRNA1Val (rat liver) and tRNA2Val (ascites hepatoma) were each purified to a homogeneous state by RPC-5 column chromatography and two-dimensional polyacrylamide gel electrophoresis, and their sequences were determined by post-labeling techniques. Ascites hepatoma tRNA2Val differed from rat liver tRNA1Val in that Gm18, C32 and an unknown modified nucleoside, N34, in the latter tRNA were mostly replaced by G, Cm, and inosine, respectively. In addition, 3'-terminal adenosine was not present in tRNA1Val (normal rat liver), but was in tRNA2Val (ascites hepatoma). Other modifications and the primary structures of the two tRNAValS were found to be the same. Thus it was concluded that the new iso-acceptor species of tRNA Val in ascites hepatoma cells is due to a change of post-transcriptional modification, not to a change of tRNA transcription. The unique feature of the change of post-transcriptional modification in tRNA2Val (ascites hepatoma) is that both hypo- and hyper-modification take place simultaneously in the tRNA molecule depending the locations of nucleotide residues.

Amino Acids↗

Pulsatile venous flow in extracorporeal circulation.

Effects of pulsatile venous flow upon the microcirculation were investigated in conditions with different venous pressures by using regional perfusion in dog's hind legs. In animals with venous pressure of -18 cmH2O (Collapsed stage), venous pulsation brought about a significant increase in mean oxygen consumption ratio and suppressed a rise of mean resistance ratio significantly. In animals with venous pressure of +2 cmH2O (normal venous pressure stage), the venous pulsation was effective in a rise of mean oxygen consumption ratio but was not effective in suppression of mean resistance ratio. In animals with venous pressure of +10 cmH2O (congestive stage), no effect of venous pulsation was recognized. We suppose that the intermittent elevation of venous pressure by venous pulsation is effective for opening some capillaries in animals with venous pressure below +2 cmH2O.

Animals↗

The course of culture of human keratinocytes: increase of heat-labile fraction of glucose-6-phosphate dehydrogenase.

Human epidermal keratinocytes in cell culture are unique in reorganizing the formation of a stratified cellular sheet and performing terminal differentiation. The course of keratinocytes in culture was delineated over 50 days in the primary culture. The rapid increase in total DNA content commencing 2 weeks after plating corresponded to the appearance of small polygonal keratinocytes in groups. The DNA content reached its maximum after 25 days of cultivation, decreasing gradually thereafter. The protein content increase slowly until 16 to 18 days of cultivation, and then increased rapidly, though slightly behind the rapid increase in DNA. The maximum value of protein content was reached at 32 days, after which the value decreased when the keratinized cells of the uppermost layer began to detach. The heat-labile fraction of glucose-6-phosphate dehydrogenase was increased in 33- and 43-day cultures, when the DNA content was decreasing.

Cell Division↗

Sendai virus infected cells are readily cytolysed by guinea-pig complement without antibody.

HeLa cells infected with Sendai virus (SV) acquired the ability to activate the alternative pathway (AP) of guinea-pig complement without antibody reaction. For induction of complement activating ability (CAA), at least 2 hr incubation of the infected cells was required. However, ultraviolet (UV)-irradiation (8400 erg/mm2) of SV did not impair the inducibility of CAA and 51Cr-labelled HeLa cells infected with UV-irradiated SV (UV-SV) became readily cytolysed by C4-deficient guinea-pig complement without antigen-antibody reaction. This phenomenon may represent a primary in vivo defence mechanism against SV infection by eliminating the virus-infected cells via activation of complement on the cell surface. Although SV-infected HeLa cells activated the AP of guinea-pig complement, they did not activate the AP of human or mouse complement. The species restriction in the CAA induced by SV infection may result in different pathological manifestations in virus-infected animals and may affect their susceptibility to this type of infection.

Animals↗