[Radioimmunoassay kit for human prostate acid phosphatase--experimental and clinical evaluation of RIA-Quant P.A.P. Test Kit].
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Biomedical subjects
Publications and source records attributed to K Shida.
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The goal of this study was to achieve clinical application of antiandrogens for the treatment of carcinoma of the prostate. Based on the results obtained from animal experiments and from a pilot clinical trial on prostatic cancer patients using various antiandrogenic compounds, chlormadinone acetate (CMA) was selected for a clinical trial in patients with carcinoma of the prostate. With nine universities and their affiliated hospitals participating, the therapeutic effect of CMA for carcinoma of the prostate was investigated nationwide. Highly satisfactory antitumor effects with CMA were observed in stage A and B patients of the primary treatment group. For stage C patients in the primary treatment group, good antitumor effects were obtained with CMA treatment. For stage D patients, however, results were poor. No serious side effects were observed in spite of the long period (as long as 6.3 years) and relatively large doses (100 mg daily) of CMA. Therefore, it was concluded that CMA can be recommended as a first choice drug for patients with carcinoma of the prostate.
Three commercial radioimmunoassay kits for prostatic acid phosphatase (PAP) were compared on the basis of their ability to measure the enzyme in normal male sera. These kits, issued by Eiken ICL (EIK), Clinical Assays (CLA), and Mallinckrodt (MKT), could measure the serum samples containing PAP above normal levels with precision and reproducibility, and showed excellent linearity on the dilution tests and good correlation with the enzymatic activity. PAP in the serum did not lose immunoreactivity for two weeks if stored below 4 degrees C. However, the sensitivity of CLA and MKT kits should be improved to give reliable values for normal sera with lower PAP contents (less than 1 ng/ml). The upper mean + 2 SD normal limits in ng/ml obtained with these kits were 2.2 (MKT), 2.5 (EIK), and 2.8 (CLA). Some differences in the purity of the standard preparations among these kits were also found. These kits gave different assays values for PAP control sera from CLA and multipurpose QC-RIA sera from Eiken ICL.
To clarify the mechanism of action of Estracyt, we performed experiments using 3H-estramustine of high specific activity. 3H-Radioactivity accumulated selectively in the ventral prostate of castrated male rats after the administration of 3H-estramustine. Estramustine and its metabolites were retained in the ventral prostate for long time periods. The uptake of 3H-radioactivity was almost totally localized in the cytosol fraction, but not in a purified receptor fraction. The apparent equilibrium dissociation constant of the estramustine binding protein was 18.9 nM, and the apparent equilibrium Bmax value was 0.76 nmoles/mg of cytosol protein. In addition, we wish to report in this paper the results of clinical trials of Estracyt studied by a cooperative research group in Japan from 1977 to 1979. It was concluded that Estracyt was effective in 89% of previously untreated prostatic cancer patients and in 38% of reactivated cancer patients.
In three cases of chorea-acanthocytosis (acanthocytosis and neurological disease, or familial degeneration of the basal ganglia with acanthocytosis), biopsies of short peroneal muscles and sural nerves were studied histologically. The muscles showed groups of atrophic fibres with clumping of sarcolemmal nuclei in all cases. It was concluded that neurogenic muscular atrophy should be included as one of the main pathological findings in chorea-acanthocytosis. The sural nerves showed a small number of large myelinated fibres in two cases. This finding remains to be confirmed in other cases.
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Cytoplasmic microtubules of 4 strains of rat ascites hepatoma cells including YS, AH 66F, AH 130 and AH 100B were investigated electron microscopically. Microtubules were clearly demonstrated when the cells were fixed at 20 degrees C or 37 degrees C and stained by tannic acid. Morphology, localization and volume density (AH 130 greater than AH 66F greater than YS greater than AH 100B) of microtubules were examined comparatively in these 4 strains and correlation between microtubules and cell deformability was discussed.
The antiandrogenic properties of a new nonsteroidal antiandrogens, AA560 (N-2-chloromethyl-2-hydroxypropionyl)-3, 4, 5-trichloroaniline) were investigated. The ventral prostate, dorselateral prostate and coagulating gland weights in rats given AA560 at 1-9 mg/head were significantly less than those in the intact rats. The seminal vesicle weights in rats given 3-9 mg/head were significantly less than those of the intact group. In intact animals given daily 3 or 9 mg of AA560 there were significantly increases of serum FSH, LH and testosterone concentrations. In the in vivo experiment, the pretreatment with AA560 decreased the uptake of 3H-androgens in the nuclear fraction of the ventral prostate. On the other hand, a significant increase in the uptake of 3H-radioactivity in the cytosol fraction was observed. It was proved by the in vitro displacement study that AA560 inhibited the binding of 5 alpha-dihydrotestosterone with a receptor protein in the prostatic cytosol.
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Subacut e cardiotoxic effect of aclacinomycin A or adriamycin given by daily intraperitoneal injections for 5 days was studied in rats by electrocardiography (ECG), blood biochemical analysis, light microscopy and electron microscopy. Dose levels of aclacinomycin A and adriamycin were 4 and 8 mg/kg, and 2 and 4 mg/kg, respectively. The two drugs caused severe body weight loss at a dose of 8 mg/kg and 4 mg/kg, respectively. Aclacinomycin A-treated rats at a dose of 4 mg/kg showed slight changes in ECG, whereas adriamycin-treated rats at the same dose showed a heart rate decrease, QRS duration and QT interval prolongation and R and S waves amplitude elevation. Blood biochemical changes caused by both drugs at a dose of 4 mg/kg were increased in lipoperoxide and alpha-hydroxybutyrate dehydrogenase activity. Aclacinomycin A gave slight ultrastructural changes in some cardiac cells such as formation of myelin figure and vacuolization in mitochondria. But adriamycin caused remarkable alterations such as degeneration and destruction of mitochondria, vacuolization of sarcoplasm and disappearance of myofilaments, which were often observed near the capillaries and nuclei. These results suggest that the two antibiotics caused cardiotoxicity by a similar mechanism. However, the damage produced by aclacinomycin A was milder than that of adriamycin.
Human sural nerve fascicles from a patient with Fabry disease were transplanted into nude-mouse sciatic nerves to determine whether transplanted perineurial cells and smooth-muscle cells of an epineurial artery would express the genetic abnormality of the disease. Four months after grafting, both perineurial cells and smooth-muscle cells contained the cytoplasmic lamellated inclusion bodies characteristic of Fabry disease. This provided evidence of human perineurial cells and smooth-muscle cells in the regenerated xenografts.
The binding of 5alpha-dihydrotestosterone to the hypophyseal and hypothalamic cytosol macromolecules prepared from castrated male rats was observed. The effects of antiprostatic agents on 5alpha-dihydrotestosterone binding to both hypophyseal and hypothalamic cytosol macromolecules was examined. Cyproterone acetate and chlormadionone acetate showed the significant inhibiting effects on 5alpha-dihydrotestosterone binding to 7-8 S macromolecules of cytosol from both hypophysis and hypothalamus. SCH 13521 and AA 560 did also affect 5alpha-dihydrotestosterone binding to 7-8 S macromolecules of cytosol from both tissues.
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