Search PubMed⌕ Search

Biomedical subjects

T Kitagawa

Publications and source records attributed to T Kitagawa.

At least 595 records · Page 33Linked to original sources

Follow-up study of a nation-wide neonatal metabolic screening program in Japan. A collaborative study group of neonatal screening for inborn errors of metabolism in Japan.

A nationwide neonatal screening program for phenylketonuria (PKU), maple syrup urine disease (MSUD), homocystinuria, histidinemia and galactosemia was started in Japan in 1977. The total number of infants screened had reached 6,311,754 by March, 1982. A follow-up study revealed the incidence of the disease in Japan: 1/108,823 for PKU; 1/450,840 for hyperphenylalaninemia (HPA); 1/1,577,939 for biopterin deficiency; 1/525,980 for MSUD; 1/1,051,959 for homocystinuria; 1/8,371 for histidinemia, and 1/788,969 for galactosemia type 1. The incidences of PKU, HPA, homocystinuria, and galactosemia (type 1) were found to be markedly low in Japan as compared with those in Caucasian countries. There was no great difference in the incidence of MSUD between both. On the other hand, the incidence of histidinemia was higher in Japan. It was found that most of the patients with PKU, HPA, MSUD, homocystinuria, or galactosemia are developing normally due to the early initiation of dietary treatment. These results clearly indicate that the neonatal mass screening program plays a great role in preventing the occurrence of handicapped children.

Biopterins↗

Dose-response studies on promoting and anticarcinogenic effects of phenobarbital and DDT in the rat hepatocarcinogenesis.

Possible discrepancy between the dose level required for promoting action, when given after initiation process, and that needed to exert an anticarcinogenic effect when given simultaneously with a carcinogen, of hepatic promoters were investigated in an attempt to obtain a 'practical' threshold dose of promoters. Phenobarbital (PB) and dichlorophenyltrichloroethane (DDT) were used as promoters and 3'-methyl-4-(dimethylamino)-azobenzene (3'-Me-DAB) was used as the carcinogen. Male weanling rats were treated with 600 p.p.m. 3'-Me-DAB for 3 weeks followed by a diet containing a promoter at various dose levels (5-500 p.p.m.), or the animals were treated with a low dose (100 p.p.m.) of 3'-Me-DAB plus a promoter at various dose levels (20-500 p.p.m.). The effects of promoters were measured by scoring size and number of enzyme-altered islands at weeks 12 and 24 of rat age. The promoting effect of PB and DDT was demonstrated in dose-dependent fashion, in the dose range of 10-500 p.p.m. and 20-500 p.p.m., respectively. On the other hand, promoters given simultaneously with a low dose of carcinogen enhanced the carcinogenesis at all the dose levels tested, quite in contrast with their inhibitory effect on carcinogenesis when given together with relatively high doses of carcinogens.

Animals↗

A successful trial of enzyme replacement therapy in a case of argininemia.

A 5-year-old boy with severe mental retardation and spastic quadriplegia accompanied by tonic seizures and hyperammonemia was diagnosed as having argininemia due to an arginase deficiency in his erythrocytes. His motor and mental abilities began to deteriorate at the age of 3 years. Thereafter, he lost his ability to stand alone, to sit and even to crawl by himself. After he was diagnosed as argininemia , a protein restricted diet was given as therapy, which was accompanied with a supplement of essential amino acids. However, his clinical condition had not improved very much. The erythrocytes in a normal person was found to have the ability to decrease the patient's elevated plasma arginine level to normal when they are mixed in vitro. First we tried replacing his red cells by a blood transfusion. Then we replaced them with the aid of an IBM 2997 blood cell separator. Following this his clinical and biochemical condition improved, and as a result so did his sitting and crawling abilities. It appears that the replacement of red blood cells improves not only the clinical and biochemical conditions, but the general condition of the patient as well.

Amino Acid Metabolism, Inborn Errors↗

Development and application of a sensitive enzyme immunoassay for 7-N-(p-hydroxyphenyl)mitomycin C.

An antibody specific for 7-N-(p-hydroxyphenyl)mitomycin C (M-83) was developed and used in a simple and sensitive enzyme immunoassay for detection of this anticancer drug in serum. The imino group of M-83 was covalently coupled to mercaptosuccinyl groups introduced into bovine serum albumin with a cross-linker, N-maleoylaminobutyric acid. The resulting conjugate was then used for the production of a specific antibody to M-83 in rabbits. Enzyme labeling of M-83 was performed using beta-D-galactosidase (EC 3.2.1.23) via m-maleoylbenzoic acid. Antibody production was of sufficiently high titer in rabbits to allow the development of a highly sensitive enzyme immunoassay for the free drug which accurately measures 15 pg of M-83 per assay tube. This assay was monospecific to M-83 and showed almost no cross-reactivity with a variety of other mitomycin analogues (mitomycin A, B, and C; porfiromycin; and acetylmitomycin C). Using this assay, preliminary pharmacokinetic study was undertaken using serial serum samples obtained from a patient who received the drug i.v., revealing a biphasic fashion of the kinetics, with an alpha-serum half-life of 9.7 min and a beta-serum half life of 80 min. An i.v. injection of M-83 into rats and assay of serum concentration revealed a similar biphasic response with an alpha-serum half-life of 8.3 min and a beta-serum half-life of 62 min.

Antibodies↗

Clinical experience with the 22-MeV microtron at the National Cancer Center Hospital.

Experience with the 22-MeV microtron is presented. The maintenance and ease of operability of the system are satisfactory. The physical characteristics showed many clinical advantages. Fundamental measurement of dose distribution and depth dose curves were performed and clinically applied. The two-gantry system is very satisfactory and effective for irradiation by photons and electrons to treat many patients per day. The facility for intraoperative radiotherapy and the physical conditions for total body irradiation are also sufficient because of the well-designed building layout and the systematized facility with the microtron system.

Humans↗

[Extra-abdominal desmoid tumor--report of a case].

A case of an extra-abdominal desmoid tumor in a 17-year-old female is reported. At the time of the first examination, the tumor was found to already involve the floor of the mouth, the submandibular region, both sides of the neck, the anterior chest wall and the mediastinum and hence was considered inoperable. The patient was treated by external irradiation and interstitial irradiation (Ir and Au). The therapeutic response was very slow, becoming noticeable 4 months after completion of the therapy and lasting for more than a year. Experience in this case indicates that in order for radiotherapy to prove successful in the treatment of desmoid tumor, it must be administered in relatively high doses. Since desmoid tumors reportedly have the potential for sarcomatous transformation, a long-term follow-up seems to be necessary in the management of patients with this neoplasm. It is considered that inoperable extra-abdominal desmoid tumors are a good indication for radiation therapy.

Adolescent↗

A mouse model for Niemann-Pick disease: phospholipid class and fatty acid composition of various tissues.

Recently, a strain of mice bearing an autosomal recessive gene, spm, has been described. On the basis of clinical and pathological findings these mice have been suggested as a useful model of human Niemann-Pick disease. Phospholipids and their fatty acid compositions were analyzed for liver, spleen, whole brain, erythrocytes, and blood plasma from "Niemann-Pick"animals (spm/spm) and heterozygous controls (spm/+). Sphingomyelin and bis(monoacylglycero)phosphate accumulated in the liver and spleen of the affected mice, whereas no significant proportional change of phospholipids was observed in the whole brain. The phospholipid composition in erythrocytes and blood plasma of the homozygous mice was not different from that of the heterozygous controls. The fatty acyl chain profile of accumulated bis(monoacylglycero)phosphate was characterized by the high content (more than 80%) of unsaturated fatty acids; the main components were oleic acid, linoleic acid, and docosahexaenoic acid. A high unsaturation index of the fatty acyl chain was found in sphingomyelin accumulated in organs and in almost all phospholipids of brain, erythrocytes, and blood plasma of "Niemann-Pick" mice. It is conceivable that desaturation of fatty acids is enhanced in the "Niemann-Pick" mice.

Animals↗

[Cervical adenocarcinoma: histologic staging and pelvic lymph node metastasis].

The relationship between histologic staging of cervical adenocarcinoma and pelvic lymph node metastasis was analyzed in 138 patients who had undergone hysterectomy. In AIS, the cervical glands were replaced by cancer. When glandular or solid cancer budding into the stroma was identified in AIS, it was designated Stage Ia adenocarcinoma. Pelvic lymph node metastases were found in cases with Stage Ib-III adenocarcinoma, but not in Stage Ia adenocarcinoma. This suggests that Stage Ia adenocarcinoma might be treated the same as AIS.

Adenocarcinoma↗

Lack of promotion effect of phenobarbital on pulmonary tumorigenesis in ddy mice initiated by transplacental exposure to 1-ethyl-1-nitrosourea.

The promoting effect of phenobarbital (PB) on lung tumorigenesis in mice was examined. Pregnant ddy female mice were injected ip with a single dose of 50 mg/kg 1-ethyl-1-nitrosourea at the 16th day of gestation. Offspring, 160 in total, were divided into two groups: one group of animals was fed a diet containing 0.05% PB continuously and the other was kept on the basal diet. All the animals were killed at 6 months of age and the number, size and histology of pulmonary tumors were examined. There were over 10 pulmonary tumors per animal on average, measuring from 0.5 to 10.2 mm in size, and the histology varied from grade I to III in atypism. A comparative study revealed no difference between PB-treated and control mice in any aspect of the tumorigenesis. It was concluded that PB does not have promoting effect on pulmonary tumorigenesis in this system.

Animals↗

[Previous abortions exert favourable effects on the prognosis of breast cancer patients].

The effect of previous abortions, both induced and spontaneous, on the prognosis of breast cancer patients was analysed, applying the hazard regression model of 1190 radically mastectomized Japanese women. The 10-year disease-free survival rate of 800 patients without abortion, 312 with one or two abortions and 78 with 3 or more abortions was 64.8%, 69.8% and 77.3%, respectively. Previous abortions had a significantly favourable effect on the prognosis when the effects of 8 other co-variants were taken into account (p = 0.008). Histologic findings on resected materials showed that patients with previous abortions had a higher incidence of well-differentiated breast cancer (25%) than those without abortions (19%) (p = 0.026). The former group had significantly less metastasis to visceral organs (11.8%) than the latter (17.5%) (p = 0.011) when the first recurrence site was investigated.

Abortion, Induced↗