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Biomedical subjects

K Nakase

Publications and source records attributed to K Nakase.

17 recordsLinked to original sources

Phenotypical characteristics of acute myelocytic leukemia associated with the t(8;21)(q22;q22) chromosomal abnormality: frequent expression of immature B-cell antigen CD19 together with stem cell antigen CD34.

Twenty-three acute myelocytic leukemia (AML) patients with t(8;21) chromosomal abnormality, all classified as M2 (French-American-British [FAB] classification), were investigated. Blastic cells from all patients were positive for the stem cell-associated antigens, CD34 and HLA-DR, and the immature myeloid antigens, CD13 and CD33. The nonblastic leukemic cells expressed the more mature myeloid antigens, CD11b and CD15, with loss of the immature phenotype. The incidence of positivities for the stem cell-associated antigens, CD34 and HLA-DR, in t(8;21) AML cells was significantly higher in comparison with those in other AML showing granulocytic differentiation (M2 or M3). AML cells with t(8;21) also showed some phenotypic abnormalities. Frequent expression of CD19 was found in the blastic population of t(8;21) AML (18 of 23 cases) without other B-cell antigens and Ig gene rearrangements. CD19 expression was confirmed by immunocytochemistry and Northern blotting. The CD19+ blastic cells coexpressed both CD34 and HLA-DR. In addition, CD33+ cells among the blastic fraction in t(8;21) AML cells were fewer in number than in those of M2 or M3 AML without t(8;21). Our findings indicate that leukemic blasts of t(8;21) AML commonly express CD19 while preserving the stem cell-associated antigens, and differentiate into the granulocytic pathway with discordant maturation such as low CD33 expression.

Adult

Diagnostic and clinical importance of interleukin-2 receptor alpha chain expression on non-T-cell acute leukaemia cells.

The expression of interleukin-2 receptors (IL-2R) was examined in 328 adult patients with non-T-cell (non-T) acute leukaemia and blast crisis of chronic myelocytic leukaemia (CML.BC) using two monoclonal antibodies, anti-Tac for IL-2R alpha chain (IL-2R alpha) and Mik beta 1 for IL-2R beta chain (IL-2R beta). Leukaemic cells in the following cases were positive for anti-Tac; 28/192 of acute myelocytic leukaemia (AML), 24/44 CML-BC, 4/28 CD19(+)CD10(-) acute lymphoblastic leukaemia (ALL), and 20/64 common ALL (c-ALL). IL-2R beta was not detected on leukaemic cells of any case examined. Eleven of IL-2R alpha(+) AML were derived from myelodysplastic syndrome. None of the IL-2R alpha positive leukaemic cells responded to exogenous recombinant human IL-2 (rhIL-2) in culture. In addition, IL-2R alpha expression on non-T leukaemic cells was closely correlated with coexpressing different lineage markers and the presence of the Philadelphia abnormality. Marked increase of serum soluble IL-2R alpha was demonstrated in the IL-2R alpha(+) patients examined. Clinically, the IL-2R alpha(+) patients showed significantly lower response to chemotherapy and poorer prognosis than IL-2R alpha(-) patients. Our results clearly indicate the diagnostic importance of IL-2R alpha expression in non-T acute leukaemia with a close relation to the particular cellular characteristics and the prognosis.

Acute Disease

c-kit gene expression in CD7-positive acute lymphoblastic leukemia: close correlation with expression of myeloid-associated antigen CD13.

Expression of human c-kit proto-oncogene and interleukin-7 receptor (IL-7R) in acute lymphoblastic leukemia (ALL) cells expressing CD7 was examined by Northern-blot analysis and reversed transcription polymerase chain reaction (RT-PCR) assay in relation to the phenotypes. Leukemic cells from four out of 12 CD7+ ALL patients, all of which fulfilled the criteria of ALL in the FAB classification, expressed c-kit genes. Surface CD3 (sCD3) was absent in all of these cases, while cytoplasmic CD3 (cCD3) was found in the two sCD3- cases. CD3 epsilon transcripts were detected in one of the sCD3- cCD3- cases. IL-7R genes were transcribed in the three cases with c-kit gene expression. In addition, there was a good correlation between c-kit gene expression and myeloid associated antigen CD13 positivity of the leukemic cells. None of the patients with c-kit gene expression had mediastinal tumor. Our results show that leukemic cells in a proportion of CD7+ ALL express receptors for cytokines that are secreted by bone marrow stromal cells. Ligands for c-kit genes and IL-7 could play an important role for the regulation of proliferation and differentiation of T-cell progenitors in bone marrow.

Antigens, CD

Pathogenesis of fever of unknown origin in patients with acute leukemia and granulocytopenia.

Interleukin-1 (IL-1) is an endogenous pyrogen produced by blood monocytes or tissue macrophages in response to infection. Since hepatic macrophages (Kupffer cells) make up more than 90% of tissue macrophages and have a possibility of remaining intact after cytotoxic chemotherapy, they may be the major producers of IL-1 in infection during prolonged periods of severe monocytopenia in leukemic patients having modern chemotherapy treatment. Hence, the majority of febrile episodes probably due to infection in patients with acute leukemia and granulocytopenia may be caused by an inflammatory response mediated by IL-1 derived from the Kupffer cells in the liver sinuses.

Agranulocytosis

Effects of pollen-extract components, diamines and derivatives of feruloylputrescine on isolated bladder and urethral smooth muscles of mice.

The contracting or inhibitory effects of pollen-extract components, diamines and derivatives of feruloylputrescine (FP) were investigated on the isolated bladder or urethral smooth muscles of mice. Among the nine diamines (NH2.(CH2)n.NH2, n = 2-10) tested, five of them with shorter carbon chains (n = 2-6) (0.1-30.0 mM) only slightly contracted the bladder strips and to some extent inhibited the noradrenaline (NA, 1.77 microM)-induced contraction of urethral strips. 1,5-Diaminopentane (C5), a component of the pollen-extract, inhibited most effectively the NA-induced contraction of urethral strips with an IC50 value of 2.3 mM (95% confidence limit: 2.0-2.6 mM). FP, also a component of the pollen-extract, inhibited the NA-induced contraction of urethral strips in a non-competitive manner, producing 32.5 +/- 5.5% (N = 5) inhibition at 378 microM. Among the derivatives of FP, feruloylcadaverine inhibited urethral contraction most potently, producing 46.3 +/- 7.1% (N = 5) inhibition at 359 microM. These derivatives had no effect on bladder contraction. In contrast, four diamines with longer carbon chains (n = 7-10) contracted the bladder strips (3-30 mM) and potentiated the NA-induced contraction of urethral strips (10 microM-3 mM). Thus, the components of the pollen-extract, FP and C5, potently inhibited urethral contraction, which may facilitate the discharge of urine in vivo.

Animals

[Cimetidine-induced aplastic anemia complicated with nonbacterial thrombotic endocarditis and cerebral infarction].

A 72-year-old woman had been given cimetidine 400mg/day for her gastritis since June 17, 1987. On August 8, she developed oral bleeding. Peripheral blood showed pancytopenia (WBC 1,900/microliters, RBC 208 x 10(4)/microliters, Plt 0.8 x 10(4)/microliters) and bone marrow studies revealed markedly depressed hematopoiesis. Bolus methylprednisolone and high dose gamma globulin were administered, but not effective. On December 11, 1987, she lapsed into coma and died three days later. Autopsy disclosed nonbacterial thrombotic endocarditis and cerebral infarction.

Aged

The endothelium-derived vasoconstrictor peptide endothelin inhibits renin release in vitro.

The effect of endothelin, a newly identified endothelium-derived vasoconstrictor peptide, on renin release from rat kidney cortical slices was examined. Endothelin produced a concentration-dependent inhibition of renin release and this inhibitory effect was dependent on extracellular calcium. The dihydropyridine calcium channel blockers nifedipine and nicardipine did not antagonize the inhibitory effect induced by endothelin. On the other hand, nifedipine completely antagonized the extracellular high potassium- or Bay K 8644-induced inhibition of renin release. The endothelin-induced inhibition of the release was markedly blocked by the addition of Co2+. Similar blocking effects of Co2+ were also observed with extracellular high potassium or Bay K 8644. Thus, endothelin exerts an inhibitory action on renin release in vitro, in a calcium-dependent manner. This inhibition may be mediated by the increased calcium influx through dihydropyridine-insensitive calcium channels.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy

Mechanism of anti-ulcer effect of calf blood extract.

The mechanism of anti-ulcer effect of Solcoseryl, an extract from calf blood, was studied. Solcoseryl (10 ml/kg, i. v.) increased basal and chemically reduced potential difference of the gastric mucosa in rats. Solcoseryl (1-10 ml/kg, i.v.) also increased gastric mucosal blood flow and gastroduodenal HCO3- secretion. These results indicate that Solcoseryl has a mucosal protective effect which may contribute to the mechanism of its anti-ulcer effect.

Actihaemyl

[Inhibitory effect and synergism of cernitin pollen extract on the urethral smooth muscle and diaphragm of the rat].

Inhibitory effects of cernitin pollen extract (CN-009), consisting of T-60 (a water-soluble extract) and GBX (an acetone-soluble extract) at a ratio of 20:1, were investigated in rat urethral smooth muscle and diaphragm. In the urethral smooth muscle, CN-009 (3.0 x 10(-4) approximately 3.0 x 10(-3) g/ml), T-60 and GBX (corresponding to CN-009) concentration-dependently inhibited the noradrenaline (NA, 10(-5) g/ml)-induced contraction. According to Bürgi's calculation, the inhibition by T-60 and GBX was synergistic. On the other hand, GBX inhibited the NA-contraction non-competitively and also inhibited the K+-contraction. In contrast, T-60 tended to inhibit competitively, but did not affect the K+-contraction. In the diaphragm, CN-009 (5.25 x 10(-3) approximately 2.1 x 10(-2) g/ml) concentration-dependently inhibited the nerve stimulation-induced twitch response. T-60 (corresponding to CN-009) showed no effect, while GBX slightly inhibited the twitch response. The effects of T-60 and GBX were synergistic. The inhibitory effects of CN-009 (2.1 x 10(-2) g/ml) and GBX (1.0 x 10(-2) g/ml) were specific against the nerve stimulation and were not antagonized by neostigmine (1.0 x 10(-5) g/ml). These results suggested that these effects were neither musculotropic nor competitive against ACh. In conclusion, CN-009 concentration-dependently inhibited the urethral contraction and the skeletal muscular twitch response. It was suggested that T-60 and GBX had different mechanisms and inhibited the response synergistically.

Animals