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Biomedical subjects

S Iki

Publications and source records attributed to S Iki.

At least 19 recordsLinked to original sources
PubMed2001

Tyrosine phosphorylation of proteins in primary human myeloid leukemic cells stimulated by macrophage colony-stimulating factor: analysis by disease type and comparison with normal human hematopoietic cells.

We investigated tyrosine phosphorylation of proteins in primary human leukemic cells stimulated by macrophage colony-stimulating factor (M-CSF) in 60 patients with acute myeloid leukemia (AML) and 5 patients with chronic myelomonocytic leukemia and compared the findings for leukemic cells with those of normal human monocytes and bone marrow immature hematopoietic cells. M-CSF induced tyrosine phosphorylation of p140-200, p110, p60, p44, and p42 frequently, and that of p95 and p55 less frequently, in primary myeloid leukemic cells, whereas M-CSF-induced phosphorylation of proteins was not detected in the normal human hematopoietic cells tested. Of these phosphoproteins, p140-200 was phosphorylated in all patients who responded to M-CSF and was considered to be almost identical to Fms, a product of the c-fms proto-oncogene. M-CSF-induced tyrosine phosphorylation was observed frequently (89%) in AML of French-American-British class M4 and infrequently in all other subtypes of AML, including M5. In chronic myelomonocytic leukemia, M-CSF-induced protein phosphorylation was prominent in blast crisis but was not detected in the chronic phase. Both bone marrow immature cells and mature monocytes showed low responsiveness to M-CSF. These findings for responsiveness to M-CSF were correlated with the amount of Fms in each type of cell. We also identified tyrosine phosphorylation of Vav, Shc, and extracellular signal-regulated kinase by M-CSF in some cases. These findings clarified an M-CSF-specific pattern of protein tyrosine phosphorylation and the responsiveness to M-CSF of primary human myeloid cells. Particularly, enhanced phosphorylation responses to M-CSF and increased amounts of Fms protein were observed in restricted human hematopoietic cells with a premature myelomonocytic character.

Acute Disease↗
PubMed2001

[Successful combined therapy with ATG, cyclosporin and G-CSF for both liver dysfunction and bone marrow failure in hepatitis-associated aplastic anemia].

A 28-year-old man developed cryptogenic hepatitis in January 1999, and treatment with glycyrrhizic acid improved his liver function. From June, however, pancytopenia began to develop gradually. The patient received G-CSF against leukocytopenia (WBC 1,100/microliter, neutrophils 590/microliter) and was transferred to our hospital in August 1999. A diagnosis of hepatitis-associated aplastic anemia was made on the basis of liver dysfunction (AST 156 IU/l, ALT 386 IU/l), hypoplastic bone marrow, and pancytopenia (WBC 4,400/microliter, neutrophils 3,340/microliter under G-CSF administration, Hb 9.8 g/dl, platelets 2.4 x 10(4)/microliter, reticulocytes 4.7 x 10(4)/microliter). Immediately after starting combined therapy with ATG, cyclosporin, and G-CSF, his liver function began to improve and was normalized on day 7. Pancytopenia began to ameliorate on day 9, and blood parameters on day 60 were WBC 4,200/microliter (without G-CSF administration), Hb 12.0 g/dl, platelets 9.0 x 10(4)/microliter, and reticulocytes 4.1 x 10(4)/microliter. Although the prognosis of hepatitis-associated aplastic anemia is generally poor, immunosuppressive therapy was markedly effective for both pancytopenia and hepatic dysfunction in the present case.

Adult↗
PubMed2001

[Successful treatment of idiopathic pure red cell aplasia with antithymocyte globulin].

An 18-year-old woman was admitted to our hospital because of severe anemia on October 16, 1999. Laboratory data included hemoglobin 3.5 g/dl, reticulocytes 2,200/microliter, WBC 3,500/microliter, and Plt 38.5 x 10(4)/microliter. Bone marrow aspiration showed a normocellular marrow with severe erythroid hypoplasia, suggesting a diagnosis of pure red cell aplasia. Methylprednisolone pulse therapy was started on October 20, but there was no response. Administration of cyclosporine A (CyA; 400-450 mg) was begun on November 1, but again there was no response. Antithymocyte globulin (ATG; 800 mg/day for 5 days, 15 mg/kg) was started from December 1 in addition to prednisolone (60 mg/day) and CyA (450 mg/day). On day 7 of ATG therapy, the reticulocyte count began to increase, and reached a peak of 32.6 x 10(4)/microliter on day 20. The patient's hemoglobin level started to increase on day 13, and reached 8.5 g/dl on day 27. A complete response has been maintained up to the time of writing, and the hemoglobin level was 11.9 g/dl on December 14, 2000. This is the first detailed Japanese case report of successful treatment of pure red cell aplasia using ATG.

Adolescent↗
PubMed2000

[An aplastic anemia patient died of severe anemia who refused transfusion].

A 41-year-old woman who had been given a diagnosis of aplastic anemia 14 years before was admitted because of recurrence of the disease. Despite therapy, the anemia progressed gradually. The patient refused blood product transfusions for religious reasons. Angina pectoris-like chest pain without ischemic changes on electrocardiograms appeared at a hemoglobin concentration (Hb) of 1.6 g/dl. The patient died of heart failure at Hb 1.5 g/dl. Autopsy showed enlargement of the heart, fatty changes in the myocardium and liver due to chronic hypoxia, and no changes in coronary arteries.

Adult↗
PubMed2000

[Treatment of adult acute lymphoblastic leukemia by KHALL-93--long-term outcome].

Twelve previously untreated adult patients with acute lymphoblastic leukemia were treated with a KHALL-93 regimen. The mean age was 46.9 years. Four patients (1/3) were over 60 years old, and 5 were Ph1 positive (42%). The complete remission rate was 100%. The 5-year survival was 50% (6/12). The 5-year event-free survival was 50% (6/12) in total, 71% (5/7) in Ph1 negative patients, and 63% (5/8) in patients younger than 60 years old. These results indicate that a KHALL-93 regimen is an effective therapy for adult acute lymphoblastic leukemia.

Adult↗
PubMed2000

[Prevention and treatment of the side effects of cancer chemotherapy].

Management of the side effects of chemotherapy in cancer patients is important because side effects can affect the tolerability and continuation of therapy, in addition to lowering the quality of life of patients. A significant efficacy of serotonin receptor antagonists against nausea and vomiting due to cancer chemotherapy, and granulocyte colony-stimulating factor against neutropenia secondary to chemotherapy, has been recently demonstrated. New chemoprotective drugs have been developed, such as amifostine for cisplatin-induced nephrotoxicity and neurotoxicity, and dexrazoxane for cardiac toxicity due to anthracyclines. Antiviral agents including lamivudine and interferons suppress virus replication, preventing the development of fulminant hepatitis during chemotherapy in cancer patients who have chronic hepatitis B infection. Various supportive therapies have resulted in the advance of cancer chemotherapy.

Antineoplastic Agents↗
PubMed1999

[X-linked sideroblastic anemia].

A 20-year-old man presented with microcytic hypochromic anemia (hemoglobin: 9.3 g/dl, MCV: 82.0 fl, MCHC: 29.5 g/dl) and dimorphism RBCs in circulating blood (RDW: 26.8%). Ringed sideroblasts accounted for 29.5% of bone marrow erythroblasts. Iron overload was also observed. Because the patient had a clear family history of anemia, he was given a diagnosis of X-linked sideroblastic anemia. The activity of delta-aminolevulinic acid synthase (ALAS) in bone marrow erythroblasts was low. However, we did not detect mutation of the gene for ALAS. The patient has responded well to a treatment regimen consisting of oral vitamin B6, Fe-chelation therapy, and phlebotomy.

Adult↗
PubMed1999

[Successful treatment with splenic irradiation for idiopathic thrombocytopenic purpura associated with primary immunodeficiency syndrome].

A 50-year-old man was admitted to our hospital because of intracranial hemorrhage and thrombocytopenia (platelet count: 3,000/microliter). Low levels of IgG (76 mg/dl) and IgA (30 mg/dl) and a normal pattern of peripheral blood T and B cell subsets yielded a diagnosis of common variable immunodeficiency (CVID). The number of megakaryocytes in bone marrow was within normal limits (64/microliter), and a diagnosis of idiopathic thrombocytopenic purpura was made. Both high-dose intravenous gamma-globulin and prednisolone were ineffective. Because of the coexistence of CVID, splenic irradiation (total 15 Gy) was performed instead of splenectomy. The platelet number began to increase 5 days after the initiation of irradiation, had increased to 8.7 x 10(4)/microliter at the end of irradiation, and was 22.9 x 10(4)/microliter 2 weeks later.

Common Variable Immunodeficiency↗
PubMed1999

[Successful pregnancy and delivery during alpha-interferon therapy for essential thrombocythemia].

Essential thrombocythemia (ET) was diagnosed in a 31-year-old woman who had a miscarriage in the first trimester of her first pregnancy. Because of her wish for child, the patient was given alpha interferon (alpha-IFN) instead of hydroxyurea or aspirin to lower her platelet count to about 80 x 10(4)/microliter. She also had a miscarriage in her second pregnancy. Thereafter, the platelet count was kept at 60-70 x 10(4)/microliter by dose escalation of alpha-IFN. In the 35th week of her third pregnancy, the patient delivered a healthy baby with a normal blood count. Several small infarctions were observed in the placenta. Control of platelet count by alpha-IFN administration was effective in preventing recurrent miscarriage associated with ET, and had no adverse effect on patient fertility or fetal development.

Adult↗
PubMed1998

Chronic neutrophilic leukemia associated with chronic lymphocytic leukemia.

We report on an 83-year-old male with chronic neutrophilic leukemia (CNL) associated initially with IgM monoclonal gammopathy and later with B cell chronic lymphocytic leukemia (CLL), in which the clone differed from that of the preceding monoclonal gammopathy. At initial presentation, the patient had hepatosplenomegaly, leukocytosis (29100 x 10(6)/l) with an increase of mature neutrophils (83%), 20q- chromosomal abnormality, an increased leukocyte alkaline phosphatase score, elevated serum levels of vitamin B12 and uric acid, a low serum level of granulocyte colony-stimulating factor, and high serum IgM (1015 mg/dl: lambda type M protein). Thereafter, lymphocytosis developed gradually. Three years after the initial presentation, the patient had no serum M protein, but showed evidence of leukocytosis (36600 x 10(6)/l) with 20q- chromosomal abnormality and an increase of mature neutrophils (51%) and small lymphocytes (43.5%), CD5+/19+/20+/HLA-DR+ and surface membrane IgM+/D+/kappa+. Gene rearrangements of the immunoglobulin heavy and kappa light chains were also present. To our knowledge, this is the first reported case of CNL associated with CLL.

Aged↗
PubMed1998

Tyrosine phosphorylation of proteins in primary human myeloid leukemia cells stimulated by cytokines: analysis of the frequency of phosphorylation, and partial identification and semi-quantification of signaling molecules.

We investigated tyrosine phosphorylation of proteins in primary human leukemia cells stimulated by granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage CSF (GM-CSF), interleukin-3 (IL-3), tumor necrosis factor (TNF), thrombopoietin (TPO) and phorbol myristate acetate (PMA) in 61 patients with acute myeloid leukemia (AML), nine patients with chronic myeloid leukemia (CML) in blastic crisis and four patients in chronic phase, and compared these data of leukemia with those of normal human immature hematopoietic cells. These cytokines and PMA induced tyrosine phosphorylation of proteins in a manner characteristic for each cytokine or PMA in AML cells. G-CSF, GM-CSF and IL-3 frequently phosphorylated p92, p80, p70, p44 and p42. p95 was frequently phosphorylated by G-CSF, and was phosphorylated in one third of the cases by TPO. On the other hand, TNF selectively induced tyrosine phosphorylation of p42, and PMA selectively induced that of p44 and p42. In marked contrast to AML cells, CML cells responded poorly to cytokines with protein tyrosine phosphorylation, and normal human bone marrow mononuclear cells and CD34-positive cells also showed poor response to cytokines. The results of the immunoprecipitation studies showed tyrosine phosphorylation of signal transducers and activators of transcription (Stat) 5 induced by G-CSF, GM-CSF, IL-3 and/or TPO in six cases, that of extracellular signal-regulated kinase (ERK) by GM-CSF in two cases and that of p38 by TNF in three cases. Intracellular amount of Stat5 was markedly increased in AML cells compared with that in CML cells and normal human bone marrow cells. whereas intracellular amount of ERK and p38 was uniformly abundant in both leukemic and normal cells. These results show cytokine-specific and amplified tyrosine phosphorylation of proteins in AML cells and suggest that amplified response might, at least in part, result from the increased amount of signaling molecules such as Stat5.

Acute Disease↗
PubMed1998

[Polyclonal plasmacytosis in peripheral blood and leukocytoclastic vasculitis in Castleman's disease].

A 62 year-old man had fever, splenomegaly, systemic lymphadenopathy and palpable petechiae. Laboratory studies showed leukocytosis (10,200/microliters) with plasma cells (23%) and polyclonal gammopathy. Southern blot analysis of peripheral blood mononuclear cells showed no rearrangement of immunoglobulin genes, indicating polyclonal plasmacytosis in peripheral blood. A diagnosis of Castleman's disease was made by the cervical lymph node biopsy, which showed onion-skin structures in the germinal centers and plasmacytosis in the interfollicular region. A skin biopsy of the purpura lesion disclosed leukocytoclastic vasculitis. This is an unusual case of Castleman's disease presenting plasmacytosis in peripheral blood and leukocytoclastic vasculitis.

Castleman Disease↗
PubMed1998

[Mediastinal germ-cell tumor associated with AML (M7)--the syndrome of mediastinal germ-cell tumors associated with hematologic neoplasia?].

In October 1992, a 36-year-old man was diagnosed as having mediastinum mixed germ cell tumor (stage II), and was treated with surgical operation and combination chemotherapy including VP16 (total VP16 dose; 1,500 mg/m2). After that, remission had been sustained, but leukocytosis (15,700/microliter) with 37% of peroxidase-negative blasts and thrombocytopenia developed in September, 1995. Bone marrow showed remarkable reticulin fibrosis and increase of atypical immature cells that were immunophenotypically factor VIII+/CD42+/CD61+. Thus, we diagnosed acute megakaryoblastic leukemia (M7). Based on no abnormality of chromosome 11q23 and no rearrangements of MLL gene, we diagnosed the syndrome of mediastinal germ-cell tumors associated with hematologic neoplasia. Furthermore, the neuron-specific enolase level was elevated (95.9 ng/ml). Soon after complete remission was reached by combination chemotherapy, the leukemia was relapsed, and the he died 3 months after the onset of leukemia. To our knowledge, this is the third case report of this syndrome in Japan and the first one of leukemia with high level of serum neuron-specific enolase.

Adult↗
PubMed1997

Interstitial pneumonia in patients receiving granulocyte colony-stimulating factor during chemotherapy: survey in Japan 1991-96.

Twenty cases of interstitial pneumonia secondary to treatment with granulocyte colony-stimulating factor (G-CSF) were reviewed. Their interstitial pneumonia had the following features: (a) it occurred predominantly in patients aged 60 years or older; (b) it was prevalent among patients with haematological malignancies, particularly non-Hodgkin's lymphoma; (c) in all patients G-CSF was given after anti-cancer agents with potential to affect the lungs; (d) at the onset, many patients had symptoms such as dyspnoea and fever; and (e) the leucocyte (neutrophil) count as well as lactate dehydrogenase (LDH) and C-reactive protein (CRP) levels were usually higher than normal at the onset. These findings indicate that, when G-CSF is used in combination with pneumotoxic anti-cancer agents, respiratory function should be monitored before and during treatment. If the leucocyte (or neutrophil) count and/or LDH and CRP increase suddenly in association with dyspnoea and fever during administration of G-CSF, interstitial pneumonia should be suspected. Accordingly, a chest radiograph and pulmonary functional tests should be performed promptly. If a diagnosis of interstitial pneumonia is made, steroid pulse therapy should be commenced immediately.

Adult↗
PubMed1997

Influence of thrombopoietin on platelet activation in myeloproliferative disorders.

Although thrombopoietin itself does not influence platelet aggregation, it enhances platelet activation in response to certain agonists. We evaluated the effects of thrombopoietin on platelet activation using platelet-rich plasma from 16 patients with myeloproliferative disorders (MPD group) and 16 healthy volunteers (control group). Preincubation with thrombopoietin significantly enhanced platelet aggregation stimulated by ADP, collagen, or epinephrine in the MPD group as well as the control group. However, aggregation induced by 3 micro ADP or 16 microM epinephrine showed significantly less augmentation by thrombopoietin in the MPD group than in the control group. Thrombopoietin significantly shortened the lag time between the addition of 3 microM ADP or 16 microM epinephrine and initiation of secondary aggregation and the lag time between addition of 2 microg/ml collagen and initiation of aggregation in both groups. When platelet-rich plasma was used without adjustment of the platelet count, thrombopoietin itself induced aggregation in two patients. Hypoaggregation after addition of 0.5 microg/ml collagen was observed in seven out of nine patients with normal thrombopoietin levels and only one of six patients with high levels (P = 0.04). Enhancement of 0.5 microg/ml collagen-induced aggregation by thrombopoietin was seen in five out of nine patients with normal thrombopoietin levels and none of the six patients with elevated levels (P = 0.04). These results indicate that platelet activation by certain agonists is enhanced by thrombopoietin in patients with these diseases as well as in normal controls and that the serum thrombopoietin level may regulate the function of circulating platelets in vivo.

Enzyme-Linked Immunosorbent Assay↗
PubMed1997

Increased neutrophil respiratory burst in myeloproliferative disorders: selective enhancement of superoxide release triggered by receptor-mediated agonists and low responsiveness to in vitro cytokine stimulation.

The neutrophil superoxide (O2-)-producing capacity in 57 patients with chronic myeloproliferative disorders (MPDs) and eight patients with chronic myelomonocytic leukemia (CMML) was investigated. O2- release in neutrophils stimulated by chemotactic peptide was markedly increased in all types of chronic MPD, including chronic myelogenous leukemia in both chronic phase and blastic crisis, polycythemia vera, and essential thrombocythemia, but was normal in CMML, which is thought to be a myelodysplastic disorder rather than MPD. Increase in O2(-)-producing capacity in MPD was also observed when other receptor-mediated agonists such as interleukin-8 and concanavalin A were used, but not when phorbol ester, a direct activator of protein kinase C, was used as the triggering agonist of O2- release. Priming effects of granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage CSF (GM-CSF), and tumor necrosis factor (TNF) on chemotactic peptide-induced O2- release was observed in all patients with MPD and CMML, though fold enhancement of priming effects was much less in MPD compared with normal subjects. In addition, the priming effects of TNF were less than those of GM-CSF in 10 cases, whereas the priming effects of TNF were consistently and markedly greater than those of GM-CSF in normal subjects. Tyrosine phosphorylation of 42-kDa protein stimulated by G-CSF, GM-CSF, and TNF was observed in CML neutrophils to be identical to that in normal neutrophils. Present results indicate specific potentiation of the receptor-mediated route of signaling that is linked to the respiratory burst and downregulated responsiveness to cytokines in neutrophils in patients with all types of chronic MPD, suggesting in vivo priming of patient neutrophils via certain mechanism by cytokines or related stimuli in these hematological disorders.

Concanavalin A↗
PubMed1997

[False positive FDP test associated with malignant lymphoma].

We present a man with non-Hodgkin's lymphoma who had false positive FDP test results and who had monoclonal IgM and IgG. At admission, laboratory examinations showed elevated FDP levels and prolonged PT and APTT, which did not improve by anti-coagulation therapy. Although coagulation system data returned to normal levels after steroid pulse therapy, the FDP level increased. Positive pregnancy test and results of dilution analyses on FDP assay yielded a diagnosis of false positive FDP test results due to serum latex agglutinin. The addition of anti-immunoglobulin antibody inhibited latex agglutination by serum. FDP levels positively correlated with serum IgM concentrations. These data suggest that the false positive FDP test in this case was due to latex agglutination by monoclonal IgM.

Connectin↗