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Biomedical subjects

H Takebe

Publications and source records attributed to H Takebe.

At least 109 records · Page 6Linked to original sources
PubMed1986

A case of xeroderma pigmentosum with clinical appearance of dyschromatosis symmetrica hereditaria.

A 9-year-old boy complained of increased freckling on the extremities since very early infancy. Examination showed mottled pigmentation with areas of depigmentation on the backs of the hands and tops of the feet, and less strikingly on the arms and legs. Scattered, small, pigmented freckles on the face were also noticed. The condition was clinically diagnosed as dyschromatosis symmetrica hereditaria (DSH) at first. Unscheduled DNA synthesis was reduced to 66% of the normal value, however, and an ultraviolet sensitivity test by colony formation on fibroblasts revealed moderate sensitivity. Therefore this case was finally diagnosed as xeroderma pigmentosum. It is necessary to study cellular repair capacity to make a precise diagnosis when the distinction is so difficult.

Child↗
PubMed1986

[Genetic factors in carcinogenesis].

A genetically high risk group for cancer may consist of persons with the following characteristics. Deficient or reduced capacity for repair of DNA damage, mostly occurring in patients with cancer-prone hereditary diseases, and possibly heterozygotes with the autosomal recessive genes of these diseases. The presence of chromosomal diseases with high incidence of cancer (e. g. Down's syndrome). The presence of autosomal dominantly inherited cancer-prone diseases. Efficient capacities for metabolic activation of potential carcinogens or reduced capacities for decomposition of carcinogens. Although the number of persons with a hereditary high risk may be small, heterozygotes of cancer-prone hereditary disease genes may account for a few percent of the general population. Relative risk, however, may be much lower in these heterozygotes than in patients, judging from the epidemiological data for ataxia telangiectasia and xeroderma pigmentosum. Correlation between cancer-proneness in these genetically high-risk groups for cancer and mutability in the cells originating from these persons has not been clearly demonstrated. Family studies and twin studies may provide further aspects for consideration of genetic factors.

DNA Repair↗
PubMed1985

High sensitivity of murine teratocarcinoma cells to UV radiation and the effect of post-irradiation treatment with caffeine.

The radiosensitivity of murine teratocarcinoma cells was investigated. Our findings are as follows: (1) the undifferentiated teratocarcinoma cells are 3 times more sensitive to UV than their differentiated counterpart and BALB/3T3 cells; (2) X-ray sensitivity of the undifferentiated cells is comparable to that of BALB/3T3 cells; (3) post-irradiation treatment with caffeine strongly sensitizes a fraction of the undifferentiated cells to UV and X-rays resulting in biphasic survival curves of the cells; (4) high UV sensitivity and hyper-sensitization by caffeine is lost upon differentiation of the cells. Possible mechanisms for the unusually high sensitivity of undifferentiated teratocarcinoma cells to radiation and post-irradiation treatment with caffeine will be discussed.

Animals↗
PubMed1985

[Genetically high risk group for cancer associated with DNA repair deficiency].

Since the discovery of a DNA repair defect in xeroderma pigmentosum, which had been known as a hereditary cancer-prone disease, the presence of a genetically high risk group for cancer has been clearly recognized. Clinical and cellular investigations on xeroderma pigmentosum patients in Japan in comparison with those carried out in the United States and Europe have revealed that the characteristics of Japanese patients are considerably different from those in other countries. Similar differences have been noted in other related diseases like Bloom's syndrome. These results suggested that each ethnic group might have unique features with regard to the genetic background of carcinogenesis. Our research over the last 10 years has always been in good collaboration with colleagues in the USA, Europe and Korea thanks to support from the Japan Society for the Promotion of Sciences and the US-Japan Cooperative Medical Science Program, which has enabled us to perform comparative experimental work in foreign countries and to standardize methods and evaluation criteria.

Ataxia Telangiectasia↗
PubMed1985

DNA repair and its possible involvement in the origin of multiple cancer.

Multiple skin cancers and other cancers in patients with xeroderma pigmentosum (XP) were investigated in relation to DNA repair defects in the cells of the patients. Multiple skin cancers of the same or different histopathological types were found in many patients and six patients had cancers, one each, in organs other than the skin. The frequency of basal cell carcinoma was higher than that of squamous cell carcinoma in XP patients, while the two types were reported to be approximately equal in frequency in all skin cancers in Japanese. Defect in the excision-resynthesis type of repair presumably enhances the error-prone type of repair of DNA damage in XP patients and may lead to the development of cancer. Although a similar DNA repair defect of damage caused by ionizing radiation has been suspected in ataxia telangiectasia (AT), induction of mutation by gamma-rays in AT cells was lower than that in normal cells at the same survival levels. The high incidence of malignancy in AT patients could be due to factors not associated with DNA repair.

Adolescent↗
PubMed1984

[DNA repair and carcinogenesis].

Recent research support the idea that DNA damage is the initial event in the process of carcinogenesis. Involvement of DNA repair in the fixation of DNA damage leading to cancer has been suggested by the presence of several cancer-prone hereditary diseases associated with DNA repair deficiency. Among them, xeroderma pigmentosum has been most extensively investigated and the "SOS response" hypothesis, originally implied to the mechanism of mutagenesis in bacteria, appears to be an attractive hypothesis for the understanding of the cancer-proneness in xeroderma pigmentosum. The DNA repair of ionizing radiation damage, however, has not been clearly demonstrated in association with the process of radiation carcinogenesis, and further studies will be needed to understand the mechanisms of radiation carcinogenesis and the involvement of DNA repair in it.

Cell Survival↗
PubMed1984

Gamma-irradiation induces mutation in ataxia-telangiectasia lymphoblastoid cells.

Ataxia-telangiectasia (AT) cells are hypersensitive to the lethal effect of gamma-rays, whereas little or no gamma-ray induced mutation has been observed. In this work, exposure to gamma-rays of an Epstein-Barr virus-transformed AT lymphoblastoid cell line, GM2783, resulted in a clear dose-dependent increase of mutation for 6-thioguanine resistance.

Ataxia Telangiectasia↗
PubMed1983

[Effects of cianidanol (KB-53) on experimental liver injury in mice--histopathological, histochemical and enzyme-histochemical studies].

Protective effects of KB-53 on acute liver injury induced by carbon tetrachloride (CCl4) and 1-naphtylisothiocyanate (ANIT) in mice was investigated by means of histopathological, histochemical and enzymehistochemical examinations. Diffuse centrilobular necrosis, ballooning degeneration of hepatocytes and hemorrhage were markedly observed in the livers of the mice one to three days after a subcutaneous injection of CCl4. On the other hand, in the livers of KB-53 pretreated mice, forcal necrosis was observed and inflammatory cells had already infiltrated one day after CCl4-intoxication. Three days later, remarkable development of absorbent granulation tissues with syncytium and hepatocytic mitosis was observed. Furthermore, a number of PAS positive materials such as mucopolysaccharides and mucoproteins were detected in the livers of KB-53 pretreated mice. KB-53 inhibited the disappearance of glucose-6-phosphatase (G-6-Pase) in the liver after CCl4-intoxication and the rise of alkaline phosphatase (Al-Pase) in the liver after ANIT-intoxication. In addition, KB-53 inhibited the rise of Al-Pase and total bilirubin in the serum of mice after CCl4 and ANIT-intoxication. All these findings suggest that KB-53 protects liver against the morphological and functional changes, and it potentiates the proliferative and regenerative activity of the liver impaired with CCl4 and ANIT.

1-Naphthylisothiocyanate↗
PubMed1983

[Effects of cianidanol on chronic liver injury induced by carbon tetrachloride and on liver regeneration after partial hepatectomy in rats].

Effects of cianidanol on chronic liver injury induced by prolonged administration of carbon tetrachloride (CCl4) and on liver regeneration after partial hepatectomy of normal liver and CCl4 chronically injured liver were investigated by the measurement of plasma and liver biochemical parameters. Cianidanol increased the total plasma protein and 14C-Leu incorporation into plasma protein, while it reduced the contents of liver cholesterol and triglycerides. In rats with chronically injured liver or regenerating liver after partial hepatectomy of chronically injured liver, cianidanol improved the retention rate of BSP and the content of liver sugar. In rats with chronically injured liver, plasma GPT and GOT activities were reduced with the administration of cianidanol. Cianidanol had no effect on the regeneration rate after partial hepatectomy of normal liver, but it increased the regeneration rate after partial hepatectomy of chronically injured liver. These results suggest that cianidanol has the effect of improving the function of liver cells damaged by CCl4 treatment and of promoting the recovery of cell function to a normal level.

Alanine Transaminase↗
PubMed1983

[Effects of cianidanol (KB-53) on liver cirrhosis induced by CCl4 in rats: a pathological investigation].

The therapeutic effects of cianidanol on the rat liver cirrhosis induced by CCl4 were investigated by means of pathological examination. Rats were administered with CCl4 subcutaneously twice a week for a consecutive 10 weeks. From a macroscopical viewpoint, pailing grayish discoloration, granular hyperplastic nodules and the disappearance of luster on the surface of the liver, and the formation of pseudolobule on the cut surface were observed in the control group. In the histopathological findings, degenerative fatty change and ballooning degeneration of parenchymal liver cells, a formation of pseudolobule caused by septal fibrosis proliferation, an acinar arrangement caused by pericellular fibrosis, and a cholangiollar proliferation were observed. All these abnormalities were diminished by the oral administration of 200 and 400 mg/kg of cianidanol for 7 days. The therapeutic effects of cianidanol were dose-dependent on the liver cirrhosis rats. Consequently, it is suggested that cianidanol has therapeutic effects on liver cirrhosis induced by CCl4 by relieving hepatocytes disorder, improving regeneration of hepatocytes and the absorption of proliferated fibrotic tissues.

Animals↗
PubMed1982

Acute toxicity study of KB-944, a new calcium antagonist.

The acute toxicity of diethyl 4-(benzothiazol-2-yl)benzylphosphonate (KB-944) was studied in mice, rats and dogs: In mice and rats, toxic symptoms such as deceleration of spontaneous movement, ataxic gait, disappearance of righting reflex, reduction in body temperature and suppression of breathing appeared following administration of a single dose of KB-944. The symptoms developed in dogs were depression, bradycardia and labored breathing. The LD50 values determined in male and female rats were 1622 and 1555 mg/kg, respectively, for oral administration, 2216 and 2820 mg/kg for subcutaneous injection, and 762 and 479 mg/kg for intraperitoneal injection. The LD50 values determined in male and female mice were 2807 and 3856 mg/kg, respectively, for oral administration, greater than 4000 mg/kg for subcutaneous injection, and 815 and 777 mg/kg for intraperitoneal injection. As shown above, there was no evident difference in LD50 between sexes in either species of animals. Since many of the dogs given an oral dose larger than 1000 mg/kg vomited the drug, oral LD50 value could not be determined.

Animals↗
PubMed1982

1-month subacute oral toxicity study of KB-944, a new calcium antagonist, in rats.

Diethyl 4-(benzothiazol-2-yl)benzylphosphonate (KB-944), a new Ca-antagonist, in the dose range of 25--200 mg/kg/day, was orally administered to Jcl:SD rats for five consecutive weeks and the following results were obtained. Neither death nor inhibition of body weight gain nor any toxic symptoms of the drug were noted in rats but an increase in water intake was found in the rats treated with over 100 mg/kg/day of KB-944. In plasma there was a decrease in alkaline phosphatase activity, creatinine level and cholinesterase activity and an increase in GPT activity and total cholesterol level in rats given a higher dosage of the drug. Weight gain of the liver, kidneys, heart, adrenals and ovaries, and degeneration in the epithelium of the renal proximal tubule were observed. However, none of these changes were serious and the maximum non-toxic dose of KB-944 was 25 mg/kg/day.

Animals↗