[A study on the hematopoietic recovery in patients with aplastic anemia successfully treated with immunosuppressive therapy].
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to H Yamamura.
Explore the source record for details and available documents.
The effect of ad libitum feeding of a defined diet in liquid form on the incidence of gastric adenocarcinomas induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was investigated in Wistar rats. Fresh defined diet was supplied once every 24 h from 2 weeks before oral administration of MNNG to the end of the experiment in week 52. Oral administration of the defined diet resulted in significant decrease in the incidence of gastric cancers in experimental week 52. It also caused a significant increase in the incidence of atypical glandular hyperplasia, which is a precursor of gastric cancer. Furthermore, administration of the defined diet for 30 and 52 weeks also resulted in significant decrease in the serum gastrin level and the marked gastric mucosal hypoplasia. These findings indicate that the defined diet in liquid form inhibited the development of gastric cancers and that this effect may have been related to its effect in decreasing proliferation of cells in the antral mucosa.
Since an experiment in monkeys showed that tizanidine (DS 103-282), a centrally-acting muscle relaxant, has a certain amount of reinforcing property, a double-blind comparative study using questionnaires was carried out in 12 healthy volunteers to investigate the subjective effects of the drug as a measure of its psychic dependence potential using diazepam and a placebo. The dosages of tizanidine were 3 mg and 6 mg and that of diazepam was 10 mg. Neither the maximal clinical dosage of tizanidine (3 mg) nor twice that dosage (6 mg) induced any marked somatic or psychic symptoms compared with the placebo. On the other hand, diazepam 10 mg induced symptoms at a significantly higher incidence than the placebo and tizanidine; i.e., many of those given diazepam mentioned experiencing such symptoms of central nervous system depression as drowsiness and absent-mindedness. With diazepam the volunteers gave positive answers to some items which are regarded as direct parameters of psychic dependence; e.g., one noted that the drug effects were "desirable", two indicated a "euphoric feeling", and five noted a "drunken feeling". Influence on tapping, blood pressure, etc., were observed in the tizanidine 6 mg group in the same extent as in the diazepam group. The blood concentration of tizanidine 6 mg was about four times as high as tizanidine 3 mg. These results indicate that tizanidine is very unlikely to have psychic-dependence potential because of a lack of observable subjective effects and thus, it was concluded that there is little possibility of the drug being abused.
Ca2+/phospholipid-dependent protein kinase (protein kinase C) and trypsin-activated protein kinase C (protein kinase M) phosphorylated the synthetic peptide R1-A13 (Arg-Arg-Leu-Ser-Ser-Leu-Arg-Ala-Ser-Thr-Ser-Lys-Ala) which contains both cAMP- and insulin-regulated phosphorylation sites in rat liver ribosomal protein S6 [Wettenhall, R. E. H. & Morgan, F. J. (1984) J. Biol. Chem. 259, 2084-2091]. Both enzymes showed essentially the same kinetic properties; V and apparent Km were determined to be 0.16 mumol min-1 mg-1 and 30 microM, respectively. At first, tryptic phosphopeptides were prepared at the early stage of phosphorylation and purified by high-performance liquid chromatography (HPLC). Through these analyses, four radioactive peptides were isolated. When protein kinase C was employed, phosphorylation was observed on all four peptides in a Ca2+/phospholipid-dependent manner. Irrespective of the protein kinase employed, phosphate incorporation into these peptides increased linearly with time; the peptide concentration did not affect the ratio of phosphate distribution into these four peptides. Analysis of amino acid composition and phosphoamino acid of radioactive peptides obtained after extensive phosphorylation showed that phosphates were incorporated into Ser-4, Ser-5, Ser-9 and Ser-11. The latter three serine residues were major phosphorylated sites. When rat liver 40-S ribosomal subunits were employed as substrate for protein kinases C and M, a radioactive protein with Mr,app = 31,000, which corresponded to S6 protein, was detected on an autoradiogram of a sodium dodecyl sulfate/polyacrylamide slab gel. The rate of phosphorylation with protein kinase M was twice as fast as that with protein kinase C. The elution profile of radioactive tryptic peptides in HPLC suggest that phosphorylation occurred on the sites in S6 protein corresponding to Ser-5, Ser-9 and Ser-11 as major sites and Ser-4 as the minor one. These results indicate that protein kinase C has an ability to recognize at least four sites derived from hormone-dependent phosphorylation sites in ribosomal protein S6 irrespective of the mode of activation of this enzyme.
S6 kinase activity was increased in the regenerating liver 5 h after partial hepatectomy compared with sham-operated liver. The protein kinase activity was eluted from DE-52 column at approximately 250 mM NaCl and was not affected by known regulators of protein kinases. The S6 kinase was further purified by chromatography on peptide R1A13-Sepharose 4B and Sephadex G-150. The molecular weight of the enzyme was estimated to be 4.5 X 10(4) by gel filtration. The enzyme catalyzes the phosphorylation of whole histone, mainly H2B histone, at 75 mM Mg2+. These properties are similar to those of a proteolytically modified Ca2+/phospholipid-independent form of protein kinase C.
The 27 kDa protein, a major component of rat liver gap junctions, was shown to be phosphorylated in vitro by protein kinase C. The stoichiometry of the phosphorylation indicated that approx. 0.33 mol phosphate was incorporated per mol 27 kDa protein. Phosphorylation was entirely dependent on the presence of calcium and was virtually specific for serine residues. For comparison, the gap junction protein was also examined for its phosphorylation by cAMP-dependent protein kinase, the extent of phosphorylation being one-tenth that exerted by protein kinase C.
The effects of combined administration of propranolol and tetragastrin on gastric acid secretion and the incidence and histological types of gastric adenocarcinomas induced by N-methyl-N'-nitro-N-nitrosoguanidine were investigated in inbred Wistar rats. Prolonged administration of tetragastrin, 1 but not 0.2 mg/kg body weight in depot form after treatment with N-methyl-N'-nitro-N-nitrosoguanidine significantly reduced the incidence of adenocarcinoma of the glandular stomach. The adenocarcinomas that did develop in rats treated with the higher dose of tetragastrin had high mucin-producing activity and showed little or no typical glandular structure. A combination of propranolol (2 mg/kg) and tetragastrin (1 mg/kg) did not influence the inhibitory effect of gastrin on gastric carcinogenesis. However, concomitant administration of propranolol (2 mg/kg) and tetragastrin (0.2 mg/kg) caused a significant increase in gastric acid secretion and a reduction in the incidence of gastric carcinomas. With this treatment, the incidence of adenocarcinoma was similar to that of treatment with tetragastrin (1 mg/kg). Histological examinations showed that like the cancers in control rats, the adenocarcinomas induced in these rats were all highly differentiated.
The critical period of Purkinje cell degeneration and cerebellar hypoplasia due to bilirubin was examined in rats with transient hyperbilirubinemia induced by a serial subcutaneous injection of novobiocin from 1 to 3, 5 to 7, 10 to 13, or 16 to 20 days after birth. Animals showing total plasma bilirubin levels of 5 to 7 mg/100 ml 6 h after the final injection were used for this study. In nearly midsagittal sections of the culmen, the percentage of the affected Purkinje cells was 0.9%, 17.1%, 0% and 0% at days 3, 7, 13 and 20, respectively. Thus, the Purkinje cells were most vulnerable to bilirubin between days 5 and 7. Cerebella from the rats which showed transient hyperbilirubinemia at day 3, 7, 13 or 20 were weighed at day 30. The cerebellar weight was significantly low only in rats showing hyperbilirubinemia at day 7. Thus, the critical period of the cerebellar hypoplasia due to bilirubin coincided with the period when the Purkinje cells were most sensitive to bilirubin. These results suggest that the Purkinje cell damage leads to the cerebellar hypoplasia in hyperbilirubinemia.
Two patients with aplastic anaemia were treated with immunosuppressive agents and peripheral blood T cells were cryopreserved serially. Inhibitory activity of T cells to autologous CFU-E, gamma-IFN production by T cells and T cell subpopulations were assayed after remission. Inhibitory activity to autologous CFU-E was not correlated with the numbers or ratios of T cell subpopulations. gamma-IFN production by T cells were within the normal range when inhibitory activity was found. In addition, gamma-IFN production increased after haematopoietic recovery. These findings suggest that gamma-IFN is not a soluble mediator of T cell-mediated haematopoietic inhibition in aplastic anaemia.
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.
Explore the source record for details and available documents.
The effect of cetraxate hydrochloride (Neuer) on the induction of intestinal metaplasia by intragastric instillation of 5% NaOH solution was investigated in Wistar rats. Oral administration of cetraxate, beginning 2 days after NaOH treatment, resulted in a significant increase in antral mucosal blood flow and a significant reduction in the incidence and amount of intestinal metaplasia in experimental week 25, but no significant changes in basal acid secretion or antral mucosal pH. On histological examination, goblet cell metaplasia were frequently seen. These results show that the increased gastric blood flow produced by cetraxate hydrochloride may be associated with the suppression of induction of intestinal metaplasias.
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.