[Citrullinemia].
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to H Ichiki.
Explore the source record for details and available documents.
We have developed a sensitive enzyme immunoassay (EIA) for the quantification of argininosuccinate synthetase (ASS) in the range of 0.05-1 ng/tube using a Fab'-peroxidase conjugate prepared with maleimide compound devised by Ishikawa et al. Amounts of hepatic ASS in control subjects were determined by this method with the purified enzyme as a standard and their specific activities were calculated to be 1.3-1.4 mumol product/min (U)/mg of ASS, which was quite similar to that of the purified enzyme. Amounts of ASS in the liver of patients with three types of citrullinemia, type I, II and III according to our arbitrary classification, were determined by the EIA method. The following results were obtained: hepatic ASS from a patient diagnosed as type I citrullinemia because of its abnormally large Km values for citrulline and aspartate was calculated to have a specific activity of 0.18 U/mg of ASS, indicating that the enzyme is a variant; specific activities of ASS in the hepatic extract of type II citrullinemic patients were 1.2-1.3 U/mg of ASS, confirming the finding obtained by single radial immunodiffusion method that the decrease of the activity in type II is caused by a decrease in the total amount of ASS protein; a very small amount of immune cross-reactive material was detected in the liver of a patient diagnosed as type III citrullinemia based on findings of undetectable ASS activity in the liver and cultured skin fibroblast.
The structural abnormality of mRNA for argininosuccinate synthetase (ASS) and the structure of immune cross-reactive material for ASS (ASS-CRM) in the liver of a patient with type III citrullinemia were analyzed using dot and Northern blot hybridization, S1 nuclease analysis, and a sensitive enzyme-linked immunosorbent assay. The patient's liver contained no detectable ASS activity, the ASS-CRM content was about 0.5% of that in the control and the ASS mRNA content was almost normal. The ASS mRNA of the case was found to have an apparent structural abnormality; approximately 1.57 kb in length caused by a defect of about 0.1 kb near the 3' end of the coding region. Furthermore, gel filtration analysis revealed that the ASS-CRM had a molecular weight indistinguishable from the control ASS. These results indicate that the abnormal mRNA of the patient was translated in vivo to an immune-cross-reactive protein that was able to form a quaternary structure.
This paper deals with enzymological, immunochemical and molecular genetic analyses of citrullinemia and argininosuccinic aciduria. Citrullinemia has been classified by Saheki et al. [J. inher. Metab. Dis. 8: 155-156, 1985] into three types from the properties of the deficient argininosuccinate synthetase (ASS) of the patients. Analysis of hepatic mRNA coding for ASS revealed certain characteristics in type II and III citrullinemic patients whose hepatic ASS protein was low. A newly developed enzyme-linked immunosorbent assay (ELISA) of argininosuccinate lyase (ASL) protein showed that 8 out of ten cases of argininosuccinic aciduria had no detectable ASL protein in the liver, erythrocytes, cultured skin fibroblasts or cultured amniocytes.
Explore the source record for details and available documents.
Therapeutic effects and dynamics of UFT were studied using beagles with ENNG-induced gastric cancers. Nine canine subjects confirmed to have gastric cancers by punch biopsy under gastrofiberscopy were divided into 3 group given 5 mg/kg/day of UFT for 101 days, 7.5 mg/kg/day for 67 days and 12 mg/kg/day for 45 days, respectively. Although the extent of macroscopic change revealed by gastrofiberscopy was minor, one of the dogs in the third group did show a Grade II b effect according to the criteria of Histopathological Effects on Cancer Tissues by Chemotherapy proposed by Oboshi and Shimozato. Animals were sacrificed by bleeding 4 hours after the last administration of anticancer agent and concentration of 5-FU and tegafur in the serum and each organ were determined. It was recognized that the concentration of anticancer agent in gastric cancer tissue was higher than that in neighboring normal gastric tissue.
We treated terminal malignant tumor cases with the immunopotentiator OK-432 and determined the absolute numbers of neutrocytes, lymphocytes, and lymphocyte subpopulations, carrying out the SU-PS and PPD skin tests. After the start of therapy, SU-PS test changed to positive in one-third of the patients. The SU-PS -responder patients showed an increase in lymphocytes and Leu 11A-positive cells, and an elevation of the OK T4/T8 ratio two weeks later. In the SU-PS-nonresponder group, OKT4-positive cells declined, while OKT8-positive cells increased with time. That is, the OKT4/T8 ratio remained low throughout the test period. In the SU-PS-responder group, OK-432 therapy was found to prolong the survival period.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Treatment with 5.0 mg/kg of hydrocortisone twice a week for 12 months led to the significant decreased levels of serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D. A histomorphometric evaluation of iliac cortical and trabecular bones was carried out using tetracycline double labelling method and tetrachrome staining. The excessive hydrocortisone treatment produced poor or no fluorescent labelling in the iliac cortex, indicating the absence of any newly established bone. Our present data demonstrate that excessive glucocorticoid may induce bone disorder in dogs by indirectly causing the decrease of serum 1,25-dihydroxyvitamin D3 levels or by directly inhibiting mineral apposition of bone.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The distribution of Adriamycin (ADM), Mitomycin C (MMC) and 7-N-(p-Hydroxyphenyl)-Mitomycin C (KW 2083) in various organs inclusiding plasma level after intraarterial or intravenous infusion was determined in mongrel dogs and experimental dogs. Similar plasma time-course of ADM was obtained with both routes, showing the maximum level at 5 minutes after infusion. The maximum level with intravenous infusion was twice as highs as that with intraarterial administration. High levels of ADM were encountered in the liver, gallbladder and kidney after proper hepatic arterial infusion, in the angular region of the stomach after left gastric arterial infusion and in the gastric antrum after right gastroepiploic arterial infusion (0.8 mg/kg). There was no significant difference in plasma levels of MMC (0.2 mg/kg) and KW 2083 (1.0 mg/kg) between intraarterial and intravenous infusion. It was of interest that MMC was hardly measurable in the liver after proper hepatic arterial infusion of 0.4 mg/kg. On the other hand, rather high level of KW 2083 was observed in the liver, gallbladder and pancreas after proper hepatic arterial infusion of 1.0 mg/kg. Hepatic necrosis around the central hepatic vein noted at the histological examination seems to be due to infusion of above-mentioned anticancer agents. It is worth mentioning that the concentration of KW 2083 in tumor tissue of the stomach of experimental dog after right gastroepiploic arterial infusion was twice as high as that in intact gastric wall. Grade IIA histological alterations of tumor cells by Oboshi and Shimosato's Classification such as vacuolation of cytoplasm and pyknosis of nuclei were noted after KW 2083 infusion.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.