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Biomedical subjects

T Shiomi

Publications and source records attributed to T Shiomi.

At least 145 records · Page 8Linked to original sources
PubMed1983

UV- and X-ray-sensitive double mutants of mouse L5178Y cells are synergistically more sensitive to 4-nitroquinoline-1-oxide than is either of the single mutants.

The X-ray-sensitive mutant M10 and the UV-sensitive mutant Q31 of mouse lymphoma L5178Y cells are both sensitive to killing by 4-nitroquinoline-1-oxide (4NQO). Since cell hybridization experiments showed that the 4NQO sensitivities in M10 and Q31 cells behaved as codominant traits (Shiomi et al., 1982c), it is not possible to determine by complementation test whether the M10 and the Q31 mutations responsible for 4NQO sensitivities are allelic. We have obviated this difficulty by selecting double mutants that are sensitive to both X-rays and UV. From X-ray-sensitive M10 cells, two UV-sensitive mutants (XU 1 and XU 2) were isolated by a cell-suspension spotting method. XU 1 and XU 2 were found to belong to the same complementation group as Q31 (group I). Double mutants XU 1 and XU 2 were 30-37-fold more sensitive to 4NQO than parental L5178Y cells, whereas the single mutants M10 and Q31 were only 6-8-fold more sensitive to 4NQO than L5178Y cells in terms of D10 values (dose required to reduce survival to 10%). These results show that the M10-Q31-double mutations enhance 4NQO sensitivity synergistically, indicating that the M10 and the Q31 mutations relevant to 4NQO sensitivities are non-allelic. The implications of this finding are discussed.

4-Nitroquinoline-1-oxide↗
PubMed1983

Isolation and characterization of mitomycin-C-sensitive mouse lymphoma cell mutants.

26 mutants with increased sensitivity to the lethal effects of mitomycin C (MMC) were isolated from mouse lymphoma L5178Y cells by a replica-plating technique. Most of them were about 5-10 times more sensitive in terms of D37 values to MMC than were parental cells. 5 of the MMC-sensitive mutants isolated from independently mutagenized cell populations were further analyzed. They were highly sensitive to the killing by decarbamoyl (DC) MMC, a monofunctional derivative of MMC, but were not sensitive to ultraviolet radiation, X-rays, 4-nitroquinoline-1-oxide or methyl methanesulfonate. These 5 mutants were classified into at least 2 genetic complementation groups. The implication of these mutations in cross-link and mono-adduct repair of DNA damage induced by MMC and DCMMC is discussed.

4-Nitroquinoline-1-oxide↗
PubMed1983

Human chromosome 13 compensates a DNA repair defect in UV-sensitive mouse cells by mouse--human cell hybridization.

A human chromosome responsible for excision repair of UV-induced DNA damage has been identified by studying somatic cell hybrids between an UV-sensitive mutant of mouse lymphoma L5178Y cells and normal human lymphocytes. An autosomal recessive mutant, Q31, of complementation group I is deficient in excision repair of UV-induced DNA damage. Somatic cell hybrids between Q31 and human lymphocytes exhibited the same UV resistance as did parental L5178Y cells. In addition, both the levels of UV-induced unscheduled DNA synthesis and chromosomal sensitivity were recovered from the UV-resistant hybrid clones. Segregation of the hybrid cells gave rise to UV-sensitive clones. The segregation of UV sensitivity was not correlated with the loss of human X chromosome. Karyotype analysis of the segregants gave evidence that a gene on human chromosome 13 compensates for UV hypersensitivity of Q31 mutant.

Animals↗
PubMed1983

Enhancement of antibody-independent phagocytosis by N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7).

A low-molecular weight compound N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) resulted in strongly enhanced phagocytosis of polystyrene latex beads by peritoneal macrophages of BALB/c mice after intraperitoneal administration. Binding of C3 cleavage product (C3b) to peritoneal macrophages after intraperitoneal injection of W-7 was also enhanced as shown by fluorescent antibody technique. Antibody against W-7 was not detected in the sera of these mice. Therefore, close association of enhanced phagocytosis of polystyrene latex beads with increased binding of C3 cleavage product to macrophages was demonstrated through induction by a low-molecular weight compound in vivo.

Animals↗
PubMed1983

[Fundamental studies on intravesical instillation of carboquone for treatment of urinary bladder tumors--on the effects of intravesical instillation of carboquone in normal beagle dogs].

The effects of intravesical instillation of Carboquone at the clinically used doses of 5 and 10 mg on the normal mucosa of female beagle dogs was compared with that of 10 mg Mitomycin C used as the control drug. Intravesical instillation for 48 hours of 10 mg carboquone/20 ml phosphate buffer solution (PBS) after bilateral cutaneous uretrostomies produced severe inflammatory changes in all layers of the bladder wall. However, no secondary effects were observed in blood laboratory examinations or histological examinations of the whole organ after autopsy. Phosphate buffer solution produced no remarkable secondary effects in animals. Five milligrams carboquone per 20 ml PBS was instilled intravesically once a week for 3 weeks in normal animals. Cystoscopically , the bladder mucosa recovered normally. Blood laboratory examinations showed no abnormal results, but the bladder epithelium had regenerative epithelial hyperplasia and slightly inflammatory changes in the submucosal layers. Two of the three control animals given instillation of 10 mg of Mitomycin C/20 ml PBS had slight leucopenia at 7 days after the last intravesical instillation, but leucocyte count was normal at the end of the experiment. Cystoscopic and histological examination of the epithelium of the urinary bladder revealed severe inflammatory changes in 2 of the 3 animals.

Administration, Topical↗
PubMed1983

[Clinical study of urothelial tumors of the upper urinary tract. 1: Primary renal pelvic tumors].

Forty primary renal pelvic tumors treated at our University between 1963 and 1981, were reviewed retrospectively. The conclusions of this study are as follows. Sex and age distribution of the patients were 30 males and 10 females (3: 1), and average age was 60.5 years old. The major symptoms were hematuria and flank pain; however, palpable mass was rare. The majority of patients were admitted to our clinic within 6 months from manifestation of symptoms. The major findings of IVP were non-functioning kidney and filling defect. The positive rate of urinary cytology was 46.7%. Total nephroureterectomy with bladder cuff was performed in 20 out of 32 cases. Histologically, 29 cases were transitional cell carcinoma and 4 cases were squamous cell carcinoma with renal calculi. Simultaneous urothelial tumors were seen in 10 cases, 3 in the ureter and 7 in the bladder. A subsequent ureteral tumor was found in one out of 12 cases in which ureters were resected incompletely, and 7 subsequent bladder tumors were found out of 32 cases receiving surgical treatment in the follow-up period. The 5-year survival rate by the actuarial method was 75.9%. Among several factors, grade and stage of the tumor were the most influencing factors for prognosis. An effective method of post-operative treatment could not be established.

Adult↗
PubMed1983

[Clinical study of urothelial tumors of the upper urinary tract. 2: Primary ureteral tumors].

Twenty-five primary ureteral tumors treated at our University between 1963 and 1981, were reviewed retrospectively. The conclusions of this study are as follows. Sex and age distribution of the patients were 18 males and 7 females (2.6: 1), and average age was 63.04 years old. The major symptom was hematuria. The majority of the patients were admitted to our clinic within 6 months from manifestation of symptoms. The major finding of IVP was non-functioning kidney. The positive rate of urinary cytology was 63.2%. Total nephroureterectomy with bladder cuff was performed in 21 out of 23 cases. Histologically, 22 cases were transitional cell carcinoma and one case was squamous cell carcinoma. Simultaneous urothelial tumor was found in 13 cases in the bladder. Most of the ureteral tumors (63.6%) were found in the lower third segment of the ureter. Subsequent urothelial tumors were seen in 3 bladders and one urethra out of 22 cases receiving surgical treatment in the follow-up period. The 5-year survival rate by actuarial method was 39.4%. Among several factors, grade and stage of tumor were the most influencing factors for prognosis. An effective method of post-operative treatment could not be established.

Adult↗
PubMed1982

Differential effects of sulpiride and metoclopramide on brain. Homovanillic acid levels and shuttle box avoidance after systemic and intracerebral administration.

Sulpiride (SUL) is more efficacious in antipsychotic activity than metoclopramide (MET), although both appear to possess almost equal affinities for dopamine (DA) receptors. We studied the effects of SUL and MET on the brain homovanillic acid (HVA) level and shuttle box avoidance to clarify their differential modes of action on the blockade of DA receptors. SUL was several times less potent than MET, which was about 50 times less potent than the control drug haloperidol (HAL), for increasing HVA at 4 h after s.c. administration. However, SUL was about 50 times more potent than MET and about equipotent to HAL, at 2 h after drug administration into the lateral ventricle. The potency of SUL by intraventricular administration was 20-fold or more than that by intracisternal administration. HAL and MET did not show such a discrepancy. The HVA level reached the maximum 1 h after intraventricular administration of MET or HAL, while s.c., intracisternal or intraventricular administration of SUL caused a gradual increase in the HVA level with the maximum being reached after 6-8 h. In shuttle box avoidance, MET was about 25 times more potent than SUL by intraperitoneal administration but about 200 times less potent than SUL, which was about 10 times more potent than HAL, by intraventricular administration. These results suggest that SUL causes a potent, long-lasting blockade of DA receptors, while MET has only a weak, short-lasting action. These findings may be related to the differences in their clinical efficacy.

Animals↗
PubMed1982

Isolation of UV-sensitive mutants of mouse L5178Y cells by a cell suspension spotting method.

We have isolated 56 UV-sensitive mutant clones from a mouse L51 T/t line of L5178Y cells by a cell suspension spotting method. Five mutants have also been isolated from L51 T/t and L5178Y cells by the method reported by Thompson and coworkers (22). We divided the mutants into two groups, "highly sensitive" and "moderately sensitive" mutants, according to their sensitivity to UV irradiation. Fifty-eight mutants were highly sensitive and three were moderately sensitive to UV. The reconstruction experiments indicate that more than 90% of highly sensitive mutants were recovered by the cell suspension spotting method. Frequencies of recovered mutants highly sensitive to UV increased with increasing dose of mutagens. Recovered mutant frequency reached 10(-2) after treatment with 1.5 micrograms/ml of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) (survival 0.2%). Eight UV-sensitive mutants were divided into four complementation groups. These mutants were 2-6 times more sensitive to UV than parental L51 T/t cells in terms of D37 (dose required to reduce survival to 37%). Four representative UV-sensitive mutants which are classified into different complementation groups were examined for their sensitivity to killing by UV, 4-nitroquinoline-1-oxide (4NQO), mitomycin C (MMC), X-rays, and MNNG. All four classes of mutants were found to be cross-sensitive to UV, 4NQO, and MMC, but not sensitive to X-rays and MNNG.

Animals↗
PubMed1982

Characteristics of gamma-ray-induced chromosomal aberrations in mutagen-sensitive mutants of L5178Y cells.

We have examined the chromosomal radiosensitivities of an ionizing-radiation-and MMS-sensitive mutant (M10), and a UV- and 4NQO-sensitive mutant (Q31), isolated from mouse lymphoma L5178Y cells, with regard to killing effects. In the first mitoses after 100 R gamma-irradiations, it was found that M10 cells were highly radiosensitive in terms of chromosomal aberrations accompanying longer mitotic delay (3 h); the frequencies of both chromatid-type and chromosome-type aberrations were, respectively, about 7 and 4 times higher than that of wild-type L5178Y cells. Furthermore, chromatid exchanges, particularly triradials, isochromatid breaks with sister union, and chromatid gaps and breaks were markedly enhanced at G1 phase of M10 cells. In contrast, the chromosomal radiosensitivity of Q31 cells after 100 R irradiation was similar to that of L5178Y cells. On the other hand, spontaneous aberration frequencies (overall breaks per cell) of M10 and Q31 cells were, respectively, 5.1 and 2.2 times higher than that of wild-type L5178Y cells. The chromosomal hypersensitivity to gamma-rays in M10 cells is discussed in the light of knowledge obtained from ataxia telangiectasia cells.

Animals↗
PubMed1982

Studies on three mutagen-sensitive mutants of mouse L5178Y cells. I. Characterization of the hybrids between L5178Y and mutagen-sensitive mutants.

Three mutagen-sensitive mutants, MS-1, M10 and Q31, have been isolated from mouse L5178Y cells. MS-1 cells are sensitive to methyl methanesulfonate (MMS), M10 cells are cross-sensitive to X-rays, MMS and 4-nitroquinoline 1-oxide (4NQO), and Q31 cells are cross-sensitive to UV and 4NQO. Lines resistant to 6-thioguanine (TGr) and 5-bromo-2'-deoxyuridine (BUr) were isolated from L5178Y and these three mutagen -sensitive mutants. All the TGr lines were sensitive to 5-bromo-2'-deoxyuridine and HAT medium and all the BUr lines were sensitive to 6-thioguanine and HAT medium. The hybrids homozygous for the mutagen-sensitive markers showed nearly the same sensitivity to UV, 4NQO, X-rays and MMS as their parental TGr and BUr lines. The hybrids constructed by fusing L5178Y BUr and TGr lines from each of MS-1, M10 and Q31 displayed the normal UV, X-ray and MMS resistancy of L5178Y cells. Thus the UV-, X-ray- and MMS-sensitive markers in MS-1, M10 and Q31 were recessive in somatic cell hybrids. The 4NQO-sensitive phenotype, however, behaved codominantly in somatic cell hybrids.

4-Nitroquinoline-1-oxide↗
PubMed1982

Studies on three mutagen-sensitive mutants of mouse L5178Y cells. II. Complementation analyses between two methyl methanesulfonate-sensitive mutants and between two 4-nitroquinoline-1-oxide-sensitive mutants.

Three mutagen-sensitive mutants, MS-1, M10 and Q31, were isolated from mouse L5178Y cells. MS-1 cells are sensitive to methyl methanesulfonate (MMS), M10 cells are cross-sensitive to X-rays, MMS and 4-nitroquinoline-1-oxide (4NQO); and Q31 cells are cross-sensitive to UV and 4NQO. MMS-, X-ray- and UV-sensitive markers in these mutants behaved recessively in hybrids between pairs of these mutants as in hybrids between L5178Y and these mutants as reported before (Shiomi et al., 1982b). Complementation analyses were carried out by forming hybrids between two MMS-sensitive mutants (MS-1 and M10) and between two 4NQO-sensitive mutants (M10 and Q31). MMS and 4NQO survivals were measured in these hybrid cells. MS-1 and M10 were found to belong to different complementation groups for MMS-sensitive phenotypes. The hybrid clones between M10 and Q31 were as sensitive to 4NQO as each of the mutants, indicating codominance of 4NQO sensitivity in these mutants. The hybrids constructed with L5178Y and three mutants were stable as to their chromosome constitution for 100 days of cultivation without selective pressure. From the segregation studies on these hybrids, it is concluded that neither the X-ray-sensitive mutation in M10 nor the UV-sensitive mutation in Q31 is located on the X chromosome.

4-Nitroquinoline-1-oxide↗
PubMed1982

A novel mutant of mouse lymphoma cells sensitive to alkylating agents and caffeine.

Two-methyl-methanesulfonate-sensitive strains have been isolated, one of which, M10, was cross-sensitive to X-rays as reported before. Sensitivities of parental L5178Y, M10, and newly isolated MS-1 cells to various mutagens were examined. Mutagens tested were UV, X-rays, 4-nitroquinoline 1-oxide (4NQO), caffeine and alkylating agents; methyl methanesulfonate (MMS), ethyl methanesulfonate (EMS) and mitomycin C (MMC). In terms of D37 values, M10 cells were 2.5-7 times more sensitive to EMS, MMC and 4NQO as well as to MMS and X-rays than were parental L5178Y cells, while the new mutant MS-1 was about 3 times more sensitive to MMS, EMS, MMC and caffeine than were parental cells. The characteristics in sensitivities of M10 cells to X-rays, alkylating agents and 4NQO resemble resemble some ataxia telangiectasia cells; and MS-1 cells to alkylating agents and caffeine are novel among mammalian cell mutants so far reported. Sensitivity of M10 cells to mutagens has so far been stable for one year, and that of MS-1 cells was stable for 6 months in continuous culture.

Alkylating Agents↗
PubMed1981

A mouse-cell mutant sensitive to ionizing radiation is hypermutable by low doses of gamma-radiation.

The mutant mouse lymphoma cell M10, which is sensitive to methyl methanesulfonate and ionizing radiation, was compared with the parental L5178Y cells for mutation induction after gamma-irradiation. The rate of induced mutations to 6-thioguanine resistance in L5178Y cells was 2-3 X 10(-7) per R, as determined after exposures ranging from 25 to 500 R. The induced mutation frequency per unit dose per locus in M10 cells was about 4 times higher than that in L5178Y cells at the lower doses of exposure (25-75 R), but it declined sharply at the higher doses of gamma-rays (100-150 R). The rate of induced mutation per unit cell killing in M10 cells was nearly the same as that in L5178Y cells when they were compared at the levels of lower cell killing.

Animals↗
PubMed1981

Pharmacology of 2-o-chlororbenzoyl-4-chloro-N-methyl-N alpha-glycylglycinanilide hydrate (45-0088-S), a compound with benzodiazepine-like properties.

2-o-Chlorobenzoyl-4-chloro-N-methyl-N alpha-glycylglycinanilide hydrate (45-0088-S), a dipeptido-aminobenzophenone compound, inhibited pentetrazole-induced convulsion and suppressed electroshock-induced fighting behavior in mice, reduced conflict behavior in rats and monkeys, and induced muscle relaxation in cats at lower doses than did diazepam. This pharmacological profile suggests that 45-0088-S can be an active, water-soluble antianxiety agent in man.

Aggression↗