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Biomedical subjects

Y Kano

Publications and source records attributed to Y Kano.

At least 307 records · Page 17Linked to original sources
PubMed1982

5-Methyltetrahydrofolate related enzymes and DNA polymerase alpha activities in bone marrow cells from patients with vitamin B12 deficient megaloblastic anemia.

The activities of 5-methyltetrahydrofolate (5-CH3THF) related enzymes and DNA polymerase alpha were determined in bone marrow cells obtained from patients with vitamin B12 deficient megaloblastic anemia and compared with those from healthy volunteers and patients with hemolytic anemia. 5-CH3THF homocysteine methyltransferase activity was significantly lower than that in the control subjects. 5,10-methylenetetrahydrofolate reductase activity was only slightly elevated to that in the control subjects. DNA polymerase alpha activity was significantly higher than that in the control. High deoxyuridine suppression test values in vitamin B12 deficient bone marrow cells were improved by tetrahydrofolate, but not by 5-CH3THF. These data indicate that, even though the reverse reaction catalyzed by 5,10-methylenetetrahydrofolate reductase may be operative in vitamin B12 deficiency, it is not sufficient to correct the disturbance in folate metabolism in vitamin B12 deficiency. Increased DNA polymerase alpha activity may be due to compensation for disarranged DNA synthesis.

5,10-Methylenetetrahydrofolate Reductase (FADH2)↗
PubMed1981

Vitamin B12-dependent methyltetrahydrofolate: homocysteine methyltransferase activity in normal and leukemic human hematopoietic cells.

The cyanogen bromide method was applied to the assay of vitamin B12-dependent methyltetrahydrofolate:homocysteine methyltransferase activity in normal and leukemic human hematopoietic cells. Normal peripheral lymphocytes and leukemia cells of lymphoid origin wuch as CLL and ALL, contained higher levels of enzyme activity than did normal human bone marrow cells. Normal granulocytes and leukemia cells of myeloid origin, such as CML in the chronic phase and AML, contained lower enzyme activity. Leukemia cells of CML in blast crisis showed higher mean activity than in the chronic phase of the disease.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed1981

Roles of DNA interstrand crosslinking and its repair in the induction of sister-chromatid exchange and a higher induction in Fanconi's anemia cells.

The roles of DNA crosslink and its repair in the induction of sister-chromatid exchanges (SCEs) were studied in normal, xeroderma pigmentosum (XP) complementation group A, and Fanconi's anemia (FA) fibroblasts after treatment with mitomycin C (MC) or decarbamoyl mitomycin C (DMC) for 1 h. FA strains were 5-30-fold more sensitive to MC killing than normal cells, but normally responded to DMC killing. XP group-A cells were twice and only slightly more sensitive to DMC and MC killings, respectively, than normal cells. The induction rate of immediate SCEs by MC was 1.7 times higher, despite a normal SCE rate by DMC, in FA strains than that in normal cells. Alternatively, SCE rates by DMC and MC were 6 times and only 1.3 times higher, respectively, in XP cells than in normal cells. In normal cells, the reduction of MC-induced SCEs as a function of repair time followed a biphasic curve of the first rapid (half-life, 2 h) and the second slow (half-life, 14 h) components. Such components corresponded exactly to the first half-excision and the second slow repair processes of molecular crosslink repair. In MC-induced SCEs, FA17JTO cells exhibited only the slow reduction component without the first rapid component and a higher saturation level in the time-dependent reduction in SCEs. This indicates that SCEs are produced by crosslinks remaining unrepaired for long times (24-48 h) after treatment of FA cells. Conversely, XP group-A cells capable of the first half-excision manifested the first rapid reduction in SCEs, although the second component declined at the slowest rate (half-life, 48 h) owing to a defect in the second mono-adduct repair. The reduction in DMC-induced SCEs followed only the slow component. Thus, these results demonstrate that crosslink can be the lesion leading to SCE, and the MC-induced SCE frequency is higher in FA cells than in normal cells. In the FA20JTO strain, such a repair defect seemed to be less than in FA17JTO cells, judged from the survival and SCE characteristics.

Anemia, Aplastic↗
PubMed1981

In vivo correlation between DNA supercoiling and transcription.

The superhelical density of pMT plasmid DNA in Escherichia coli cells was measured as a function of the transcriptional activity, which was reduced by treatment with coumermycin or oxolinic acid. Superhelicity was assayed by agarose gel electrophoresis of DNA extracted from cells gently lysed by sarkosyl. Coumermycin treatment reduced the proportion of supercoiled plasmid DNA in concert with a decrease in the rate of plasmid-coded synthesis of trp mRNA, implying a correlation between supercoiling of DNA and its suitability for transcription. On the other hand, the oxolinic acid-induced loss of supercoiled plasmid DNA was relatively small, while concomitant inhibition of trp mRNA synthesis was very severe. Treatment of the cells with these two drugs never removed all of supertwists from the pMT plasmids carried.

Aminocoumarins↗
PubMed1981

A new human photosensitive subject with a defect in the recovery of DNA synthesis after ultraviolet-light irradiation.

A non-sensitive, 8-yr-old male patient (termed UV81KO) with only acute recurrent sunburns and without any other physical or neuromental retardations was studied. The patient's skin exhibited lowered minimal erythema doses between 280 and 300 nm monochromatic wavelengths without delayed peaking of erythema. UV81KO skin fibroblasts in culture was 5-fold more sensitive to 254 nm UV killing than normal cells, though the response of obligatory heterozygotes was normal. UV81KO cells were also more sensitive to killings by fluorescent sunlamp (295-300 nm UV-B) radiation, 4-nitroquinoline-1-oxide, and N-hydroxy-acetyl aminofluorene, but not by monofunctional decarbamoyl mitomycin C, bifunctional mitomycin C, and alkylating agents (methyl methanesulfonate, ethyl methanesulfonate, N-methyl-N-nitrosourea). Assays for unscheduled DNA synthesis, T4 endonuclease V-susceptible sites (pyrimidine dimers), endogenous excision-break accumulation by arabinofuranosyl cytosine-plus-hydroxyurea, single-strand-break rejoining, and molecular-weight increase of pulse-chased DNA in irradiated cells indicated no apparently detectable defects in nucleotide-excision repair processes and in replicative bypass in UV81KO cells. Despite the repair proficiency as such, UV81KO cells showed the defective recovery of DNA synthesis after 254 nm UV irradiation with 1 and 5 J/m2, at which dose the recovery occurred in normal cells. The base line level of sister-chromatid exchanges (SCEs) was higher in UV81KO cells (10-12 SCEs/cell) than in normal cells (5 SCEs/cell), although the induction rate of SCEs by 254 nm UV in UV81KO cells was the same as in normal cells. Such clinical, cellular and molecular characteristics and comparison to those in the other photodermatoses (xeroderma pigmentosum, Cockayne's syndrome, the 11961 disorder, Bloom's syndrome) can make a clear distinction of UV81KO from the others. Thus, the UV81KO disorder is put forward as a new photodermatosis with a defect in the recovery of post-UV DNA synthesis.

Cell Survival↗
PubMed1981

Vincristine and prednisolone therapy in blast crisis of chronic myelogenous leukaemia in childhood.

6 cases of chronic myelogenous leukaemia (CML) blast crisis in childhood were treated with vincristine and prednisolone (V-P). In 3 terminal transferase ((TdT)-positive cases, blast cells were lymphoid in appearance. All 3 TdT-positive patients entered a complete remission but developed meningeal leukaemia. The mean duration of survival from the onset of blast crisis was 32 months. In 3 TdT-negative cases, V-P therapy was ineffective. The results of this study suggest that V-P therapy is more effective for CML blast crisis in childhood with TdT positive blast cells and that prophylactic central nervous system treatment is necessary to prevent meningeal leukaemia.

Adolescent↗
PubMed1981

[Rearing trial of a feed for Shiba goats].

Shiba goats are among the widely used for research purposes as laboratory animals and there is an increasing need for development of a suitable feed of reasonably constant nutrient composition and quality in pellet form for them. Preliminary studies yielded a pellet feed satisfactorily palatable and adequate as a maintenance ration for this species. The present experiments were conducted to assess the pellet feed for usefulness in rearing Shiba goats, in comparison with a conventional ration which has long been used at the Stock Farm of Tokyo University. No significant intergroup differences were observed as to VFA proportions in the rumen fluid, hematologic parameters or blood chemical constituents between the pellet feed and conventional ration. Animals maintained on the experimental pellets ad libitum displayed a significant decrease in apparent digestibility.

Animal Feed↗
PubMed1981

Two cases of acute myelogenous leukemia with high terminal deoxynucleotidyl transferase activity responding to vincristine-prednisolone treatment with complete remission.

Increased TdT activity was demonstrated in 2 cases of AML. One of them had Ph1 positive chromosome due to a standard translocation of t(9:22). Treatment with cytosine arabinoside, daunorubicin, 6-mercaptopurine and prednisolone was ineffective or only partially effective. Switching to the vincristine and prednisolone therapy resulted in a complete remission in both cases.

Adult↗
PubMed1981

Sister-chromatid exchanges are not directly related to 6-thioguanine-resistant mutations induced by ultraviolet radiation in V79 Chinese hamster cells.

A comparison of the effects of caffeine on ultraviolet (UV)-induced sister-chromatid exchanges (SCEs) and 6-thioguanine-resistant (6-TGr) mutations was attempted in order to study how the SCE mechanism correlates with mutagenesis. The linear UV dose-mutation relation indicated that the presence of 1mM caffeine during the 6-day expression period prior to the 6-TG selection did not alter the 6-TGr mutation induction rate. However, 1mM caffeine synergistically elevated the rate of UV-induced, immediate SCE formation, but did not alter the delayed SCE frequency in the 6-day survivors. These results indicate a clear dissociation of SCE from mutation, and suggest that SCE formation may not primarily involve the mutagenic process, but may rather be an error-proof mechanism that can tolerate some of DNA lesions.

Animals↗
PubMed1981

Effect of nitrous oxide on human bone marrow cells and its synergistic effect with methionine and methotrexate on functional folate deficiency.

5-Methyltetrahydrofolate homocysteine methyltransferase activity in human bone marrow cells obtained from patients undergoing surgical operation became low after about 4 hr of nitrous oxide (N2O) anesthesia. The deoxyuridine suppression test performed on these bone marrow cells also became abnormal after about 6 hr of N2O anesthesia. The incorporation of [3H]thymidine into DNA in the bone marrow cells preincubated with methionine or methotrexate was much higher after N2O anesthesia than before anesthesia. Since N2O and methionine or methotrexate have a synergistic effect on depletion of functional folate, N2O alone or in combination with methionine or methotrexate might be of value for cancer treatment and deserve clinical trials.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗