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Biomedical subjects

K Sakurada

Publications and source records attributed to K Sakurada.

At least 145 records · Page 8Linked to original sources
PubMed1986

Protein phosphorylation of lysosomal arylsulfatase B in normal and leukemic leukocytes.

An acidic variant form of arylsulfatase B from normal leukocytes and chronic myelogenous leukemia (CML) leukocytes was found to be phosphorylated at its serine and threonine residues through in vivo phosphorylation with 32Pi. However, the predominant phosphorylation site was serine in normal cells, in contrast to threonine in CML cells. A cyclic AMP-dependent protein kinase was responsible for phosphorylation of the sulfatase of CML cells.

Chondro-4-Sulfatase↗
PubMed1986

The activity of suppressor cells in the spleen of murine bone marrow chimeras.

An intrasplenic injection (i.s.) of BALB/c bone marrow cells induces a higher survival rate than an intravenous injection (i.v.) in irradiated C3H/He recipients. Coculture experiments revealed the presence of alloantigen-specific and nonspecific suppressor cells in the spleens of mice injected i.s. and i.v. Suppressor activity decreased 50-60 days after bone marrow transplantation in i.v. chimeras, while there was no decrease in i.s. chimeras. In vitro suppressor activity was correlated with in vivo activity. Histopathological changes in the liver were examined. A total of 28% of the i.v. chimeras showed severe changes compared with 6% of the i.s. chimeras. The spleen indices of i.v. and i.s. chimeras were compared. Although there was no statistically significant difference between the spleen indices of i.v. chimeras and those of i.s. chimeras, spleen indices of i.v. chimeras tended to be higher than those of i.s. chimeras. These results show that suppressor cells in i.s. chimeras appear to inhibit graft-versus-host reactions more efficiently. Furthermore, an adoptive transfer assay showed that suppressor cells detected in i.s. chimeras were effective in vivo. We therefore suggest that suppressor cells detected in vitro correlate with in vivo activity and may play some role in the induction and maintenance of transplantation tolerance.

Animals↗
PubMed1986

Impaired alpha-interferon production and natural killer activity in blood mononuclear cells in myelodysplastic syndromes.

The producibility of interferon (IFN)-alpha, which indicates one of the functions of large granular lymphocytes (LGL), was impaired at a high frequency in myelodysplastic syndrome (MDS) patients. However, IFN-alpha production in refractory anaemia, which is a subtype of MDS, was almost normal. In contrast, abnormality has not been observed in either proliferative response or the production of IFN-gamma of T-cells by stimulation with PHA. NK activity of peripheral blood mononuclear cells (PBMC) from MDS patients was generally low and was not augmented by IFN-alpha treatment. These results indicate that, in addition to the abnormality at the level of haematopoietic tissues, LGL among PBMC may be impaired in MDS patients.

Adult↗
PubMed1986

[Hematological disorders in malignancy].

We examined hematopoietic disorders in 74 patients with various malignancies. The proportions of patients with anemia in the case of esophageal carcinoma, gastric carcinoma, colorectal carcinoma, hepatoma, and pancreatic carcinoma were 75%, 87.5%, 77%, 64% and 87.5%, respectively. Hypochromic microcytic anemia was mainly observed in showed patients with carcinoma of the gastro-intestinal tract which showed severe bleeding. The major proportion of patients with hepatoma and pancreatic carcinoma showed normochromic normocytic anemia. The WBC count was usually within the normal range except for patients with liver cirrhosis or generalized metastasis who showed decreased WBC counts. The mean lymphocyte count in the peripheral blood, which is thought to be correlated with the prognosis of cancer patients, was less than 1,500/microliter except for patients with gastric carcinoma, whose five-year survival rate was 28.6%. Monocytosis was mainly observed in patients with colorectal carcinoma and pancreatic carcinoma, accounting for 24.5% of the total cases. This finding may suggest some relationship between cancer and monocytes. Thrombocytosis was seen in patients with severe bleeding, but thrombocytopenia was seen in patients with liver cirrhosis. Most cancer patients showed normo-cellular marrow and normal M/E. We also examined the ferrokinetics and ferritin levels in cancer patients.

Anemia↗
PubMed1986

[The development of a convenient enzyme-immunoassay method to detect human serum ferritin].

We have developed an enzyme-immunoassay (EIA) method which is easily and conveniently handled to detect human serum ferritin instead of using the radioisotopes. Rabbit anti human liver ferritin antiserum was adsorbed to a 96 well microplate. Then, sera from patients were put into each well following the addition of peroxidase-labelled rabbit anti human liver ferritin antiserum. Therefore, this is composed of so-called "sandwich" method. One of the beneficial characteristics in this method is to be able to examine many samples at once and easily. Based on this principle, this is clinically useful for screening the abnormal level of serum ferritin from various patients.

Ferritins↗
PubMed1985

Inhibition by gossypol of phospholipid-sensitive Ca2+-dependent protein kinase from pig testis.

Gossypol, a polyphenolic binaphthalene-dialdehyde extracted from cotton plants which possesses male antifertility action in mammals, is a potent inhibitor of phospholipid-sensitive Ca2+-dependent protein kinase from pig testis. Gossypol inhibited Ca2+-dependent activity of the enzyme without affecting its basal activity. The IC50 value (concentration causing 50% inhibition) was 31 microM when lysine-rich histone was used as substrate. Kinetic analysis indicated that the compound inhibited the enzyme non-competitively with respect to ATP (Ki = 31 microM) or lysine-rich histone (Ki = 30 microM), and competitively with respect to phosphatidylserine (Ki = 2.1 microM). With Ca2+, irrespective of the presence or absence of 1,3-diolein, the compound lowered Vmax and increased the apparent Ka for Ca2+. The compound also inhibited phosphorylation by the enzyme of high-mobility-group 1 protein (one of the endogenous substrates in the testis for the enzyme located in nucleosome), with an IC50 value of 88 microM. These results suggested that a phospholipid-sensitive Ca2+-dependent protein phosphorylation system in the testis is involved in the regulation of spermatogenesis.

Animals↗
PubMed1985

Phosphorylation of high mobility group 1 protein by phospholipid-sensitive Ca2+-dependent protein kinase from pig testis.

Phospholipid-sensitive Ca2+-dependent protein kinase was partially purified from total particulate fraction of pig testis. The enzyme phosphorylated high mobility group 1 protein (HMG 1), one of the major chromatin-associated non-histone proteins. Other HMG proteins (HMG 2, 14 and 17) were not phosphorylated by the enzyme. Exhaustive phosphorylation of HMG 1 revealed that 1 mol of phosphate was incorporated/mol of HMG 1. The apparent Km value for HMG 1 was 3.66 microM. 1,3-Diolein stimulated the phosphorylation at 10 microM-Ca2+ in the presence of phosphatidylserine. The phosphorylation of HMG 1 was inhibited by adriamycin, an inhibitor of spermatogenesis.

Animals↗
PubMed1985

Peculiar cytoplasmic inclusions in acute lymphoblastic leukemia: cytochemical and electron microscopic observations.

In acute lymphoblastic leukemia (ALL) of a 19-year-old woman, blast cells in the blood and bone marrow contained peculiar large cytoplasmic inclusions. The inclusions, measuring 0.5-3.5 micron in diameter, were stained with methylene blue, toluidin blue, pyronin, and periodic acid-Schiff. Activities for acid phosphatase and alpha naphthyl butyrate esterase were not detected in the inclusions. The cytochemical findings indicated that the inclusions contained basophilic material and polysaccharides and that they were not lysosomal in nature. In electron microscopy, the inclusions were membrane bound and contained densely packed microvesicles, measuring 40-70 nm in diameter; amorphous electron-dense material; and whorled membranous figures. The microvesicles often had a nucleoid-like core and resembled viruses in size and structure.

Adult↗
PubMed1985

Effects of heparin and polyamines on the phosphorylation of high mobility group proteins by cyclic nucleotide-independent phosvitin kinase from pig testis.

In order to study the physiological role played by cyclic nucleotide-independent phosvitin kinase in pig testis, effects of heparin (an inhibitor of RNA synthesis) and polyamines (stimulators of the synthesis) on the enzyme, distribution in nuclei of the enzyme, and identification of endogenous substrates for the enzyme were examined. The enzyme was shown to be inhibited by heparin, nd the inhibition was removed by the addition of polyamines, when phosvitin (the best exogenous substrate for the enzyme) was used as substrate. The inhibition by heparin and inhibition removal by polyamines was dependent on Mg2+ concentration. The enzyme was found to be present in pig testis nuclei as well as in the cytosol. The enzyme phosphorylated chromatin-associated non-histone proteins in the testis nuclei. Of the non-histone proteins, high mobility group (HMG) 14 and 17 were identified as substrates for the enzyme. Phosphorylation of HMG 14 and 17 was also inhibited by heparin and inhibition of HMG 14 phosphorylation was removed by the addition of polyamines, although the effect was less dependent on Mg2+ concentration. These results suggested that phosvitin kinase was involved in the regulation of RNA synthesis int he testis.

Animals↗
PubMed1985

Expression of arylsulfatase B variant from leukocytes in chronic myelogenous leukemia related to chemotherapy.

Lysosomal arylsulfatase B of human leukocytes consisted of two forms; a basic form (B) and a variant form (B1) which is phosphorylated at the carbohydrate chains of the B form (Uehara, Y., Gasa, S., Makita, A., Sakurada, K., and Miyazaki, T. (1983) Cancer Res. 43, 5618-5622). The amounts of the variant form relative to the basic form were considerably increased in leukocytes of chronic myelogenous leukemia (CML). The present communication demonstrates that, upon chemotherapy of the patients with CML, degree of phosphorylation as well as the relative amounts of the phosphorylated variant form of CML leukocytes are markedly decreased concomitantly with an increase of the basic, less phosphorylated form. This effect of chemotherapy on the variant form preceded to clinical improvement of the CML patients, suggesting that the relative amount of the phosphorylated enzyme will be a potential prognostic indicator for the therapeutic effect of CML.

Adult↗
PubMed1985

[A case of triple neoplasm with acute myelogenous leukemia, squamous cell carcinoma of the lung and adenocarcinoma of the stomach].

A 70-year-old man had undergone middle and lower lobectomy of the right lung for pulmonary squamous cell carcinoma in January 1979. He was treated with anticancer drugs including alkylating agents. In February 1983, he was diagnosed as AML (FAB, M2). Although cytoreduction effect was observed, he died of prolonged pneumonia on the 30th admission day. Autopsy revealed a well-differentiated tubular adenocarcinoma of the stomach (Borrman II type) and a poorly differentiated epidermoid carcinoma of the right hilar lymph node.

Adenocarcinoma, Mucinous↗
PubMed1985

Translocation of phospholipid-sensitive Ca2+-dependent protein kinase and its substrate, Mr 38,000 protein, in chronic myelocytic and acute myelocytic leukemias.

Phospholipid-sensitive Ca2+-dependent protein kinase (PL-Ca-PK) and its substrates were investigated in neutrophils from normal subjects and in chronic myelocytic and acute myelocytic leukemic cells from patients with or without treatment for leukemia. PL-Ca-PK and its substrates were found in total particulate fraction of normal neutrophils, but less in cytosol. In leukemic cells from chronic myelocytic leukemia patients without treatment, PL-Ca-PK and its substrate, Mr 38,000 protein, increased in cytosol but decreased in total particulate fraction as compared with normal neutrophils. In leukemic cells obtained from chronic myelocytic leukemia patients after treatment mainly with busulfan, PL-Ca-PK and Mr 38,000 protein were increased in total particulate fraction but decreased in cytosol. Using leukemic cells from acute myelocytic leukemia patients with or without treatment, similar results were obtained. The change of localization of PL-Ca-PK and Mr 38,000 protein in leukemic cells appeared to be correlated to the increase or decrease of the number of leukemic cells. These results suggested that PL-Ca-PK together with the substrate, Mr 38,000 protein, might be translocated from total particulate fraction to cytosol with the onset of leukemia, and from cytosol to total particulate fraction accompanying treatment for leukemia.

Cell Division↗
PubMed1985

[Phase II study with methyl 6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy-alpha-D-glucopyranoside (MCNU) in hematological malignancies].

Forty-two cases of hematological malignancy (18 cases of CML, three cases of polycythemia vera, 10 cases of malignant lymphoma and 11 cases of multiple myeloma) were treated with MCNU. The results obtained were as follows. MCNU was markedly effective on CML cases, being especially useful during the chronic phase, and a partial remission was observed in one of three patients with CML blastic crisis. A good response was observed in all cases with polycythemia vera. In some cases of malignant lymphoma, a fair response was observed. No response was observed in any of the cases of multiple myeloma. Myelosuppression was a major side effect of MCNU, but other side effects other than melena were not severe.

Adult↗