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Biomedical subjects

R Sasaki

Publications and source records attributed to R Sasaki.

At least 235 records · Page 13Linked to original sources
PubMed1989

Medium pH determines the differentiation of human promyelocytic leukemia cells to basophils or eosinophils by culturing in a protein- and serum-free medium.

Cells containing large basophilic granules in the cytoplasm appeared after culturing human promyelocytic leukemia cells (HL-60) in a protein- and serum-free alkaline medium. These granules were stained with toluidine blue and alcian blue. Cells were morphologically and cytochemically similar to basophils. The existence of histamine in the cell lysates was detected in both uninduced and alkaline medium-induced HL-60 cells. After culturing HL-60 cells in a protein- and serum-free acidic medium, cells containing eosin-stained small granules (eosinophils) appeared. The differentiation of HL-60 cells to basophils or eosinophils may therefore depend on medium pH by culturing in a protein- and serum-free medium.

Basophils↗
PubMed1989

Effects of 12-O-tetradecanoyl phorbol-13-acetate (TPA) on rat thymocytes.

The short-term incubation of rat thymocytes with 12-O-tetradecanoylphorbol-13-acetate (TPA) resulted in a significant increase in sialyltransferase (S-T) activity and a decrease in terminal deoxyribonucleotidyl transferase (TdT) activity. The ratio of peanut agglutinin (PNA)-positive cells and of TdT-positive cells in TPA-treated cells also decreased. However, TPA had no significant effects on the viability, morphology, DNA synthesis, and DNA polymerase alpha activity of the cells. More marked changes were observed by incubating a non-T, non-B human lymphoid leukaemia cell line with TPA. Similar findings were also noted in TPA-treated mouse thymocytes. These changes may represent an aspect of TPA-induced differentiation of murine thymocytes.

Animals↗
PubMed1989

Behenoyl cytosine arabinoside, aclacinomycin A, 6-mercaptopurine, and prednisolone combination therapy for acute non-lymphocytic leukaemia in adults.

38 consecutive, previously untreated adult patients with acute non-lymphocytic leukaemia (ANLL) were treated with BHAC-AMP (N4-behenoyl-1-beta-D-arabinofuranosyl-cytosine, aclacinomycin A, 6-mercaptopurine, and prednisolone) therapy between March 1980 and February 1985. 25 patients (65.8%) achieved complete remission (CR). Median CR duration and median survival of patients who achieved CR were 14, and 24 months, respectively. The Kaplan-Meier analysis revealed a probability for remaining in CR of 18.0% at 5 years. Analysis of failure cases revealed that most of them were due to resistant disease. Major toxicities were infection, diarrhoea, liver dysfunction, nausea and vomiting but these were acceptable. The results indicate that BHAC-AMP therapy is comparable to the regimen with daunorubicin and cytosine arabinoside and a further clinical trial is necessary for previously untreated adult patients with ANNL.

Aclarubicin↗
PubMed1989

Characterization and use of monoclonal antibodies directed against human erythropoietin that recognize different antigenic determinants.

We have established four hybridoma cells that produce monoclonal antibodies (MoAbs) R2, R4, R6, and R12 directed toward recombinant human erythropoietin (rHuEPO). MoAbs R2, R4, and R6 bound to EPO with high affinities (kd = approximately 2, 4, and 1 nmol/L, respectively) but MoAb R12 had a low affinity (240 nmol/L). These antibodies inhibited the biological activity of rHuEPO and EPOs from humans, rats, mice, and rabbits. This inhibition was due to the blocking of EPO binding to the target cells. The fully deglycosylated rHuEPO bound to the MoAbs, indicating that they recognized peptide sequences of the antigen but not the carbohydrates attached to the antigen. An immunosorbent column with the immobilized MoAb R2 was effective for the rapid purification of EPO. MoAb R6 bound to EPO at a site(s) different from those to which other MoAbs bound. Based on this finding, a sensitive and rapid enzyme-linked immunosorbent assay of EPO, in which EPO was sandwiched between two MoAbs (R2 and R6), was developed. The assay measured plasma levels of EPO as low as 5 mU/mL within several hours.

Animals↗
PubMed1989

[Coma, hyperviscosity syndrome, hyperammonemia and myelofibrosis in a patient with IgG, lambda type multiple myeloma].

A 63-year-old man was admitted to our hospital with tremor and somnolence, followed soon by coma. Anemia and retinal bleeding were observed. The blood smear exhibited rouleaux formation and leukoerythroblastosis. A bone marrow aspiration resulted in dry tap. The biopsy specimens revealed remarkable infiltration of myeloma cells with fibrosis. The M-component of IgG-lambda type and hyper-ammonemia were detected in the serum. Liver and renal functions, however, were within normal range. His consciousness recovered after plasmapheresis. Two courses of VMCP (vincristine, melphalan, carboquone and prednisolone) did not affect the paraproteinemia. Five courses of VAD (vincristine, adriamycin and dexamethasone) could lower the level of IgG. He died of pneumonia. The plasma of some patients with multiple myeloma may contain unidentified factors which increase the plasma ammonia.

Ammonia↗
PubMed1989

[Germ-line configuration of the immunoglobulin heavy chain gene in a case of B cell precursor acute lymphoblastic leukemia].

A 20-year-old man was admitted to our hospital because of fever and knee joint pain on March 20, 1986. Physical examination revealed generalized lymphadenopathy and hepatomegaly. White blood cell count was 32,800 microliters with 74.4% blast cells. Bone marrow was hypercellular with 93.6% blast cells. Blast cells were weakly positive for acid phosphatase and PAS stainings but were negative for peroxidase, sudan black B and esterase stainings. Cell surface marker analysis of blast cells disclosed that they were positive for anti-HLA-DR, CD19, CD24, CD33 and CD38, but were negative for CD10 and CD20. Cytoplasmic immunoglobulin of blast cells was negative and TdT activity by immunofluorescent method was positive. Chromosomal analysis of bone marrow samples revealed normal karyotype. Therefore, this case was diagnosed as having acute lymphoblastic leukemia (L2) and achieved complete remission with LVP therapy consisting of 1-asparaginase, vincristine and prednisolone. Gene analysis of blast cells disclosed germ-line configuration of both the immunoglobulin heavy chain gene and T cell receptor beta chain gene. We speculated that the phenotype of leukemic cells might precede the genotype in some cases of acute leukemia.

Acute Disease↗
PubMed1989

[Immunohistochemical study of cancer-associated carbohydrate antigens in carcinoma of the biliary tract].

To reveal the cell-biological character of biliary tract cancer, localization and distribution of three cancer-associated carbohydrate antigens (CA19-9, sialyl SSEA-1, NCC-ST-439) and carcinoembryonic antigen (CEA) were studied immunohistochemically in 35 cases of gallbladder carcinoma, 21 of bile duct carcinoma, 16 of chronic cholecystitis, and 3 of normal gallbladder. 1) All carbohydrate antigens and CEA were present in 70-90% of the cases of gallbladder and bile duct carcinoma. In particular, NCC-ST-439 had the highest incidence of positive staining (95.2%) in bile duct carcinoma. 2) The mode of localization was diverse and was not fixed by the kind of antigen. Antigens flowing out to the surrounding stroma were affected by the rate of positive cells. 3) No significant correlation was observed between the histological type or degree of differentiation and tissue positivity. 4) The positivity of tissue CEA was higher in the cases with serous membrane invasion, gamma INF pattern, and neuro-, vascular-, and lymphatic invasion. 5) In chronic cholecystitis, CA19-9, NCC-ST-439, and CEA were stained in mucosal cells and/or metaplastic cells, while sialyl SSEA-1 was stained only in one case in the goblet cells and the cells with pseudopyloric metaplasia. None of the antigens were stained in normal gallbladders. These results suggest that these antigens may be useful in the diagnosis and therapeutic treatments in patients with biliary tract cancer.

Adenoma, Bile Duct↗
PubMed1989

Epidemiological study on sarcoidosis in Japan. Recent trends in incidence and prevalence rates and changes in epidemiological features.

This paper presents the results of an investigation made on the recent trends in the estimated prevalence and incidence rates of sarcoidosis in Japan and the changes in its epidemiological characteristics based on the results of nation-wide surveys conducted in 1972 and 1984. Age-adjusted mortality trends based on vital statistics were also examined. The estimated prevalence rate in males increased from 3.0 per 100,000 population in 1972 to 3.8 in 1984 and in females from 3.3 to 5.6, respectively (p less than 0.01), while the estimated incidence rate remained unchanged (1.2 per 100,000 in males and 1.4 in females). The age-adjusted mortality rate showed a gradually decreasing tendency from 0.2 to 0.1 per million. The estimated age-sex specific prevalence and incidence rates showed a pronounced increase in the middle-aged and elderly age groups particularly in females but a marked decrease in those 19 years and under. The increase in prevalence rate may be attributable to the prolonged duration of the disease. Noteworthy changes in the pattern of the disorder included a marked increase in the proportion of patients with eye lesions (males: from 31.3% to 44.4% and females: 41.6% to 58.7%) indicative of poor prognosis and statistically insignificant increase in pulmonary parenchymal lesions (males: from 38.1% to 43.4% and females: from 33.5% to 36.4%), the majority of which showed pulmonary mottling not accompanied with severe fibrosis often seen in Europe and America. The standardized prevalence ratios were observed in hot, warm and cold areas.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

The effect of immunoadsorption therapy by a protein A column on patients with thrombocytopenia.

Immunoadsorption therapy employing protein A columns (PROSORBA columns) was used for the treatment of patients with naturally occurring or transfusion-induced immune thrombocytopenia purpura (ITP). Plasma from one unit of blood was perfused through the columns and returned to each patient. This procedure was performed once or twice weekly. In two cases of acute ITP, platelets markedly increased, and platelet-associated IgG (Pa-IgG) and circulating immune complexes (CIC) were decreased following the treatments. A transient increase in platelets was achieved in one patient with chronic ITP. Some improved response to platelet transfusions was noticed in one patient with aplastic anemia and platelet alloimmunization. Two mechanisms are suggested for the effect of protein A column therapy: one is the stimulation of the production of anti-idiotype antibody that neutralizes platelet auto-antibody and the other is activation of complement that induces solubilization and removal of CIC containing platelet autoantibodies. Immunoadsorption by protein A column is a useful therapy for some ITP cases, especially those that are acute.

Antibodies↗
PubMed1989

Dealing with the proportional hazards assumption when using the proportional hazards model with a single independent variable.

In order to examine the proportional hazards assumption implicit in the proportional hazards model, three types of simulations were carried out on two groups of hypothetical survival data. Simulation 1 assumed that the hazard rate for one group was higher than that for the other group but that they were not proportional. Simulation 2 was an example of hazard rates crossing each other. Simulation 3 demonstrated the effect of the extent to which the hazard rates crossed. The test statistic, Z:PH, used for testing the proportional hazards assumption was calculated, along with the logarithm of the hazard ratio with its standard error. Although the increase in number of subjects was found to favor detections of violations of the proportional hazards assumption, cases such as those in Simulation 1 were considered acceptable for clinical use. Cases such as those in Simulation 2 were not suitable for the proportional hazards model. Simulation 3 suggested that cases with a substantial degree of unproportionality could be detected to violate the proportional hazards assumption, even when groups of 100 subjects each were involved in the analysis.

Computer Simulation↗
PubMed1988

Erythropoietin receptor of a human leukemic cell line with erythroid characteristics.

A new cell line of human erythroleukemia cells differentiates spontaneously so that 30% of the cells are always hemoglobinized. Erythropoietin did not affect the percentage of such cells but stimulated the cell growth, indicating that the cells have functioning receptors. Binding of human recombinant radioiodinated erythropoietin to the receptors was specific. The bound ligand was internalized into cells at 37 degrees C but not at 15 degrees C. Scatchard analysis showed two classes of binding sites. Covalent binding of erythropoietin to its receptors yielded two products detected on sodium dodecyl sulfate-polyacrylamide gels electrophoresed under reducing conditions. Under non-reducing conditions, these species disappeared and larger products appeared.

Cell Differentiation↗
PubMed1988

Comparative structural study of N-linked oligosaccharides of urinary and recombinant erythropoietins.

The structures of the N-linked oligosaccharides of the urinary erythropoietin (u-EPO) purified from urine of aplastic anemic patients were analyzed and compared with those for recombinant erythropoietin (r-EPO) prepared with baby hamster kidney (BHK) cells. Asparagine-linked neutral oligosaccharides were released from each EPO protein by N-oligosaccharide glycopeptidase (almond) digestion. The reducing ends of the oligosaccharide chains thus obtained were aminated with a fluorescent reagent, 2-aminopyridine, and the mixture of pyridylamino derivatives of the oligosaccharides was separated by high-performance liquid chromatography (HPLC) on an ODS silica column. More than 8 and 13 kinds of oligosaccharide fractions for u-EPO and r-EPO (BHK), respectively, were completely separated by the one-step HPLC procedure. The structure of each oligosaccharide thus isolated was analyzed by a combination of sequential exoglycosidase digestion and another kind of HPLC with an amide-silica column. Furthermore, high-resolution proton nuclear magnetic resonance (1H NMR) spectroscopy and methylation analyses were carried out in the case of r-EPO (BHK).(ABSTRACT TRUNCATED AT 250 WORDS)

Carbohydrate Sequence↗
PubMed1988

Intermediate lymphocytic lymphoma of the salivary gland.

Three patients had a painless mass in the parotid (two patients) or submandibular regions (one patient). These patients were 70, 66, and 65 years of age, respectively. One patient was male and the other two were female. No symptoms suggesting the presence of autoimmune sialadenitis had been noticed, although one patient suffered from rheumatoid arthritis. Histologic study showed that small atypical lymphoid cells with slightly irregular and indented nuclear contours proliferated diffusely and secondary lymph follicles were distributed at random among them. These findings are similar to those that we recently reported for intermediate lymphocytic lymphoma (ILL) of the thyroid gland arising in patients with autoimmune thyroiditis. A high frequency of ILL among our series of salivary lymphomas (three of nine cases) is discussed.

Aged↗
PubMed1988

Amino acid sequence of guinea pig liver transglutaminase from its cDNA sequence.

Transglutaminases (EC 2.3.2.13) catalyze the formation of epsilon-(gamma-glutamyl)lysine cross-links and the substitution of a variety of primary amines for the gamma-carboxamide groups of protein-bound glutaminyl residues. These enzymes are involved in many biological phenomena. In this paper, the complete amino acid sequence of guinea pig liver transglutaminase, a typical tissue-type nonzymogenic transglutaminase, was predicted by the cloning and sequence analysis of DNA complementary to its mRNA. The cDNA clones carrying the sequences for the 5'- and 3'-end regions of mRNA were obtained by use of the sequence of the partial-length cDNA of guinea pig liver transglutaminase [Ikura, K., Nasu, T., Yokota, H., Sasaki, R., & Chiba, H. (1987) Agric. Biol. Chem. 51, 957-961]. A total of 3695 bases were identified from sequence data of four overlapping cDNA clones. Northern blot analysis of guinea pig liver poly(A+) RNA showed a single species of mRNA with 3.7-3.8 kilobases, indicating that almost all of the mRNA sequence was analyzed. The composite cDNA sequence contained 68 bases of a 5'-untranslated region, 2073 bases of an open reading frame that encoded 691 amino acids, a stop codon (TAA), 1544 bases of a 3'-noncoding region, and a part of a poly(A) tail (7 bases). The molecular weight of guinea pig liver transglutaminase was calculated to be 76,620 from the amino acid sequence deduced, excluding the initiator Met. This enzyme contained no carbohydrate [Folk, J. E., & Chung, S. I. (1973) Adv. Enzymol. Relat. Areas Mol. Biol. 38, 109-191], but six potential Asn-linked glycosylation sites were found in the sequence deduced.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1988

Simultaneous expression of lymphoid and myeloid phenotypes in acute leukemia arising from myelodysplastic syndrome.

A 57-year-old female developed myelodysplastic syndrome (MDS) that terminated as a biphenotypic leukemia after exposure to chemoradiotherapy. Double staining of blast cells, using monoclonal antibodies specific for myeloid and lymphoid lineage, demonstrated that one-third of the leukemic cells simultaneously expressed the E rosette-associated antigen (OKT11) and myeloid-associated antigen (MY7). This finding suggests the possibility that some cases of MDS are clonal disorders that arise in a pluripotent stem cell that can also differentiate to T cell lineage.

Acute Disease↗
PubMed1988

Stromal cell-dependent growth of leukemic cells from murine erythroblastic leukemia.

Transplantable erythroblastic leukemia was induced by 300-rad irradiation of C3H mice. Conditions for in vitro growth of the leukemic cells were studied. None of interleukin-3, granulocyte/macrophage colony-stimulating factor and erythropoietin could support the growth of the cells in vitro. In contrast, the leukemic cells grew into a stroma-dependent cell line, ELM-D, in close contact with the stromal cell layer of 900-rad-irradiated long-term bone marrow culture. A stroma-independent cell line, termed ELM-I-1, was further established from the non-adherent population in the co-culture of the leukemic cells, ELM-D, with stromal cells. Reverse transcriptase activity was not detectable in ELM-D or ELM-I-1 cells. Studies on binding and cross-linking of 125I-erythropoietin showed that ELM-I-1 cells had erythropoietin receptors, and two major radiolabeled protein products with molecular weights of 120 kDa and 140 kDa were detected on sodium dodecyl sulfate/polyacrylamide gel electrophoresis under reducing conditions.

Animals↗