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H Umadome

Publications and source records attributed to H Umadome.

At least 19 recordsLinked to original sources
PubMed1999

[Decrease serum erythropoietin level induced by iron replacement therapy in patients with iron deficiency anemia].

The relationship between serum erythropoietin (EP) and hemoglobin (Hb) concentrations was investigated in patients of iron deficiency anemia (IDA) in the course of iron replacement therapy to elucidate how the therapy induced changes in that relationship. At first Hb-dependent EP levels were determined in 123 IDA patients prior to the treatment by the third-degree logarithmic regression of EP on the Hb deficit (d-Hb). Following the start of iron supply, the deviation of observed EP values from the predicted level (EPc), i.e., delta-EP, was most obvious at the next phase of the onset of reticulocyte crisis; however, this deviation reduced with the alleviation of IDA. The value in maximum phase (delta-EPmx), as individually defined for each of 95 patients, correlated significantly with the severity of the pretreatment ID state (r = 0.502, p < 0.01). Partial correlation analysis revealed that about 80% of this gap was attributable to the ID state. Also, it was assumed that EP upregulation was twice that attributable to the Hb-deficit factor alone. The phase sequence of the delta-EP versus d-Hb relationship in 21 relapsed patients demonstrated a different rout from that observed in their improvement phase. The ID state-induced upregulation of EP, i.e., EPc, was followed by a therapy-induced overshooting drop that was attributable to acute uptake of EP by shifted erythroid precursors. From the viewpoint of erythropoietic regulation, the subsequent down-regulation of EP in the mid to late phases was considered appropriate for the prevention of Hb over production.

Adolescent↗
PubMed1998

[Increased erythron transferrin uptake associated with ineffective erythropoiesis in iron deficiency state--the common factors to iron deficiency anemia and portal hypertensions].

We calibrated the erythron transferrin uptake (ETU) and efficiency ratio (R-Ef) in erythropoiesis on the basis of ferroerythrokinetic data in 90 patients with iron deficiency anemia (IDA) and 64 patients with noncirrhotic and cirrhotic portal hypertension with splenomegaly (PH). Then we analyzed the data to elucidate how iron deficiency (ID) status effects variation of these values. ETU was significantly higher and R-Ef was lower in IDA subgroup before treatment (n = 71) than those with any recent treatment (n = 19), and in PH with anemia of ID type (PH-ID n = 39) than those without ID state (n = 34). A remarkable inverse correlation was obtained between ETU and R-Ef in both IDA and PH-ID and iron replacement therapy effected synchronous improvement of these values. We deduced the quantitative parameter of ID status (ID-x) on blood chemistry data in IDA by multiple regression of ETU and of R-Ef respectively. These calibration formulae were extrapolated to the data in PH-ID. Thus we delineate the factor which represents ID status in common to these two diseases to increase ETU and decrease R-Ef, although the contribution of ID-x was greater in IDA than PH-ID. Additional factors to enhance or modify these values were shortened survival of erythrocytes, splenomegaly and hepatic dysfunction.

Anemia, Iron-Deficiency↗
PubMed1997

Successful thromboendarterectomy for chronic pulmonary embolism in a patient with systemic lupus erythematosus and antiphospholipid syndrome.

Chronic pulmonary thromboembolism is known to be associated with poor prognosis with conservative medical treatment. Pulmonary thromboendarterectomy for chronic pulmonary thromboembolic disease is a potentially lifesaving procedure that prevents right-sided cardiac failure as a result of secondary pulmonary hypertension caused by pulmonary thromboembolism. We report a rare case of systemic lupus erythematosus with antiphospholipid syndrome in a patient who presented with pulmonary hypertension secondary to chronic proximal multiple pulmonary thromboembolism. To our knowledge, this is the first case report of chronic pulmonary thromboembolism complicated by systemic lupus erythematosus with antiphospholipid syndrome. Thromboendarterectomy was performed with satisfactory results.

Adult↗
PubMed1997

[Heterogeneity of ineffective erythropoiesis in myelodysplastic syndromes evaluated by application of newly devised parameters based on ferroerythrokinetic data].

Ineffective erythropoiesis was evaluated in 100 studies in 87 patients with myelodysplastic syndromes (MDS) applying newly devised parameters based on ferroerythrokinetic (FEK) data including erythron transferrin uptake (ETU). The efficiency ratio (R-Ef) was calibrated with V-2, the second canonical discriminant variate which underwent axis rotation. Based on discriminated FEK patterns, as previously reported, the patients were classified into five types i.e. I-z, ineffective, H-z, hemolytic hyperplastic, O-z, hypoplastic, I-H-z and I-O-z, combination of these, groups. The proportion of I-z group was 48% and that of I-H-z and I-O-z groups was 30%. Significant correlations were obtained in I-z group between R-Ef and ETU (r = -0.628), unclear abnormality scores (R = 0.664) or ringed sideroblast scores (R = 0.742), scored by dummy variables regression. In the other groups, significant deviation from these correlations was observed, indicating that there is an obvious heterogeneity in MDS patients concerning association or dissociation of morphological abnormality, in addition to hyperplasia of erythroblasts, with or from ineffective erythropoiesis.

Erythrocytes↗
PubMed1997

[Ferrokinetics].

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Anemia↗
PubMed1995

[A quantitative parameter of ineffective erythropoiesis deduced by canonical discrimination and axis rotation on the basis of ferroerythrokinetic data].

Ferroerythrokinetic data including erythron transferrin uptake (ETU) calibration of 134 cases of control, hemolytic anemia, hypoplastic anemia and ineffective erythropoiesis (IEP) were subjected to canonical discrimination analysis. Axis rotation was then performed for the second variate so as to be parallel to the long axis of distribution ellipsoid of IEP group. The process yielded three variates. The first one, V-1, was assumed to represent the amount of effective erythropoiesis, the second one, V'-2, its efficiency ratio and the third one, V'-3, the rate of peripheral hemolysis. A definite correlation (r = -0.872) was obtained in IEP group between V'-2 and ETU, i.e. reduction in efficiency and compensatory hyperplasia in erythropoiesis. On the plane with concised parameters of V-1 and V'-2, an ellipse of 95 percent confidence of IEP group and three discrimination lines delineated five areas representing five patterns of ferroerythrokinetics, i.e. IEP, hemolytic, hypoplastic, IEP combined with hemolytic or with hypoplastic ones. This method is considered to be useful for application to those erythropoietic disorders having partial or complicated factors described above, where routine ferroerythrokinetic parameters may, be indecisive.

Calibration↗
PubMed1989

Expression of cytokine mRNA in leukemic cells from adult T cell leukemia patients.

HTLV-I infection of peripheral mature T cells appears to induce the expression of cellular genes including those of some cytokines and their receptors. We examined the expression of interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-2, IL-3, IL-4 and granulocyte/macrophage colony-stimulating factor (GM-CSF) at the mRNA level in fresh leukemic cells from 20 adult T cell leukemia patients to see whether there is any association between cytokine expression and HTLV-I expression and between their expression and clinical manifestations such as hypercalcemia or neutrophilia. IL-1 alpha, IL-1 beta and IL-3 expression was observed in 3, 7 and 1 of 20 cases examined, respectively. However, there seemed to be no association between IL-1 expression and clinical manifestations. IL-2, IL-4 and GM-CSF mRNA expression was not detected. HTLV-I viral RNA expression was detected only in one case in which IL-3 mRNA was expressed in both peripheral blood and lymph node cells and a relatively high proportion of leukemic cells expressed IL-2 receptor (p55, Tac). Thus, in the present study we could not find any correlation between cytokine expression and HTLV-I expression in peripheral blood fresh leukemic cells except in one unusual case.

Adult↗
PubMed1988

Characteristics of the IL-2 receptor expressed on large granular lymphocytes from patients with abnormally expanded large granular lymphocytes. Implication of a non-Tac IL-2-binding peptide.

Large granular lymphocytes (LGL) from four patients with abnormally expanded LGL in the peripheral blood were studied regarding their receptor for IL-2. LGL from none of the cases examined expressed Tac Ag, an Il-2R glycoprotein recognized by anti-Tac mAb. However, 125I-labeled IL-2 binding experiments demonstrated that 1400 to 2800/cell IL-2 binding sites with a single affinity (K: 0.46-1.4 nM) were expressed on LGL from the four patients. The affinity was not high but about 10-fold higher than that of the low affinity IL-2R expressed on activated normal T lymphocytes. Furthermore, LGL from the four patients proliferated in response to higher concentrations of IL-2 and these responses were not inhibited by an excess amount of anti-Tac antibody. 125I-Labeled IL-2 cross-linking studies performed in two cases revealed the predominant expression of an IL-2 binding molecule with an estimated Mr of 70,000 to 75,000. After the culture with IL-2 for 48 h, expression of a small amount of Tac Ag (p55) was induced on LGL in at least three cases. These data strongly suggested that the IL-2R expressed on LGL is functional and identical to the p70, a novel IL-2 binding peptide that has been recently identified and speculated to form the high affinity IL-2R in association with the p55.

Adult↗
PubMed1988

Increase in cytoplasmic free calcium concentration initiated by T3 antigen stimulation is imparied in adult T-cell leukemia cells.

We studied the change in cytoplasmic free calcium ion concentration ([Ca2+]i) in the peripheral blood leukemic cells from adult T-cell leukemia (ATL) patients stimulated by anti-T3 (CD3) or anti-T11 (CD2) antibodies in order to see whether there is an abnormal response in the early activation processes following T3 or T11 antigen stimulation. Peripheral blood mononuclear cells (PBMC) from four T-cell chronic lymphocytic leukemia (T-CLL) patients showed a rapid and clear increase in [Ca2+]i (from 165 +/- 26 nM to more than 299 nM) when stimulated by OKT3 antibody and anti-mouse IgG antibody. This response was comparable to that of PBMC from 10 normal individuals (from 151 +/- 20 nM to 252 +/- 34 nM). In contrast, PBMC from 10 ATL patients showed only a slight increase in [Ca2+]i (from 137 +/- 21 nM to 176 +/- 32 nM) following T3 stimulation. The experiments with higher concentrations of OKT3 antibody suggested that this attenuated increase in [Ca2+]i in ATL cells was not exclusively due to impaired expression of T3 antigen. The [Ca2+]i increase in ATL cells induced by the stimulation with two anti-T11 antibodies recognizing different epitopes of the T11 antigen, however, was comparable to that of normal PBMC. The abnormal response of [Ca2+]i to the T-cell receptor/T3 antigen stimulation in ATL may be related to dysfunction or leukemogenesis of HTLV-I-infected cells.

Adult↗
PubMed1988

Close association between interleukin 2 receptor mRNA expression and human T cell leukemia/lymphoma virus type I viral RNA expression in short-term cultured leukemic cells from adult T cell leukemia patients.

Human T cell leukemia/lymphoma (T-lymphotropic) virus type I (HTLV-I) infection has been considered to be closely associated with the leukemogenesis of adult T cell leukemia (ATL), in which interleukin 2 (IL-2) receptors are abnormally expressed. In this study, however, Southern blot analysis revealed no gross rearrangement or obvious amplification of the IL-2 receptor gene in ATL leukemic cells, indicating that abnormal IL-2 receptor expression in ATL is not due to the structural change of its gene. Hence, we studied the expression of the IL-2 receptor and HTLV-I at the RNA level during short-term cultures of leukemic cells from 9 ATL patients. Cytoplasmic dot hybridization and Northern hybridization revealed that fresh leukemic cells from seven of nine patients expressed a small amount of IL-2 receptor mRNA but HTLV-I RNA was undetectable in all cases. After cultures for up to 7 d, both IL-2 receptor mRNA and HTLV-I RNA (including pX message) expression concomitantly increased, whereas the amounts of other cellular genes, except for beta-actin, did not. The increases in their RNA expression were inhibited by early addition (within 12 h after the beginning of the culture) of cycloheximide, indicating that these increases are mediated by newly synthesized protein(s). These results strongly suggested that IL-2 receptor expression is closely associated with HTLV-I expression in leukemic cells from ATL patients.

Adult↗
PubMed1988

Leukemic cells from a chronic T-lymphocytic leukemia patient proliferated in response to both interleukin-2 and interleukin-4 without prior stimulation and produced interleukin-2 mRNA with stimulation.

Recently, interleukin-4 (IL-4) has been clarified as having T-cell growth factor activity; therefore, it becomes of interest whether IL-4, as well as interleukin-2 (IL-2), affects the proliferation of leukemic cells derived from mature T cells. In the present study, we describe a case of chronic T-lymphocytic leukemia (T-CLL) with monoclonal proliferation of human T-lymphotropic retrovirus (HTLV)-I or HTLV-II negative CD3(+)4(+)8(-) T cell expressing IL-2 receptors without stimulation. Radiolabeled IL-2 binding assay revealed 750 high-affinity and 6,750 low-affinity binding sites per cell. In accordance with the expression of high-affinity IL-2 receptors, the leukemic cells proliferated in response to exogenous IL-2 without prior stimulation. In addition, exogenous IL-4 also induced their proliferation. Moreover, IL-2 and IL-4 exerted a synergistic effect on the leukemic cell proliferation. Although the expression of IL-2 or IL-4 mRNA was not detected in fresh leukemic cells, the expression of IL-2 mRNA, but not IL-4 mRNA, was induced by phytohemagglutinin stimulation, and the leukemic cells proliferated. These findings suggest that not only IL-2, but also IL-4 are involved in the proliferation of leukemic cells of T-CLL.

Humans↗
PubMed1987

Establishment of an interleukin 2-dependent human T cell line from a patient with T cell chronic lymphocytic leukemia who is not infected with human T cell leukemia/lymphoma virus.

We established an interleukin 2 (IL-2)-dependent human T cell line, Kit 225, from a patient with T cell chronic lymphocytic leukemia (T-CLL) with OKT3+, -T4+, -T8- phenotype. Southern blot analysis showed that Kit 225 is not infected with human T cell leukemia/lymphoma virus (HTLV) type I or II, and is probably derived from the major clone in the fresh leukemic cells. Kit 225 cells express a large amount of IL 2 receptors constitutively and their growth is absolutely dependent on IL 2. No other stimuli, such as lectins or antigens, are required for maintaining the responsiveness to IL 2. As abnormal IL 2 receptor expression was also seen originally in the fresh leukemic cells, the establishment of this cell line with IL 2 suggests that IL 2-mediated T cell proliferation is involved in the leukemogenesis of some cases of HTLV-negative T-CLL.

Antigens, Surface↗
PubMed1986

Dissociation of interleukin-2-mediated cell proliferation and interleukin-2 receptor upregulation in adult T-cell leukemia cells.

We studied cell proliferation and interleukin-2 (IL-2) receptor upregulation mediated by exogenous IL-2 in leukemic cells from adult T-cell leukemia (ATL) patients to characterize some aspects of abnormal IL-2 receptor expression in ATL. Leukemic cells from 7 ATL patients examined showed no or very poor proliferative response to IL-2 though they expressed IL-2 receptors without any stimulation. In contrast, ATL leukemic cells cultured with IL-2 for 2 days expressed about twice as many IL-2 receptors as those of cells cultured without IL-2. Thus, in ATL leukemic cells, there seems to be a dissociation between the signal(s) for two different effects mediated by IL-2, cell proliferation and IL-2 receptor upregulation.

Adult↗
PubMed1986

Expression of interleukin-2 receptor on T cell chronic lymphocytic leukemia cells and their response to interleukin-2.

We analyzed peripheral blood leukemic cells from six patients with T cell chronic lymphocytic leukemia (T-CLL) with monoclonal antibodies including the anti-Tac antibody, which recognizes the receptor for interleukin 2 (IL 2). The patients were divided into two groups according to the reactivity of the monoclonal antibodies. Leukemic cells from three patients with T-CLL reacted with OKT3 and T4 but not T8, whereas those from the remaining three patients reacted with OKT3 and T8 but not T4. IL 2 receptor, which is expressed on activated T cells but not on resting T cells, was preferentially expressed on T4+ T-CLL cells. The IL 2 receptor on T4+ T-CLL cells was indistinguishable from that on normal activated T cells with respect to molecular weight and downregulation by the anti-Tac antibody. Moreover, fresh T4+ T-CLL cells, but not T8+ T-CLL cells, proliferated in response to exogenous IL 2 without prior activation, and this proliferation was inhibited by the anti-Tac antibody. These results suggest that malignant growth of T4+ T-CLL cells can be regulated by IL 2 not only in vitro but also in vivo.

Adult↗