Vesnarinone induced agranulocytosis.
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Aged↗
Biomedical subjects
H Enokihara
Publications and source records attributed to H Enokihara.
GM-CSF and eosinophil chemotactic factors in an acute lymphoblastic leukemia patient with eosinophilia.
We describe a patient with common acute lymphoblastic leukemia associated with blood and cerebrospinal fluid (CSF) eosinophilia. Serum obtained at onset and conditioned medium prepared from T cells obtained at remission stimulated with interleukin-2 contained eosinophil colony stimulating activity (Eo-CSA), which was confirmed to be predominantly GM-CSF. Leukemic cell conditioned medium and serum obtained at remission contained no Eo-CSA. The CSF contained increased eosinophil chemotactic activity, however, this factor was not identified.
Adult↗
Increased serum level of interleukin-5 in a patient with episodic angioedema and eosinophilia syndrome.
A case of episodic angioedema and eosinophilia syndrome is reported. An 18-year-old male suffered from monthly episodes of angioedema, pruritic papules, weight gain, and fever for twelve years. During the episodes, peripheral eosinophils and serum levels of interleukin (IL)-5, an eosinophil proliferating cytokine were elevated. Extensive evaluations disclosed neither visceral involvement nor evidence of parasitic infections, collagen diseases, or neoplastic disorders. Corticosteroid treatment brought about a dramatic clinical improvement concomitant with decrement of eosinophils and serum IL-5 was observed. These observations suggest that IL-5 may be a causative factor for this pathological state.
Adolescent↗
[Biochemistry and biological activities of eosinophil granule proteins].
The biochemistry, the molecular biology and the biological activity of the eosinophil granule proteins, major basic protein (MBP), eosinophil cationic protein (ECP), eosinophil-derived neurotoxin (EDN) and eosinophil peroxidase (EPO) are reviewed. MBP is present in the core of the eosinophil granule and is toxic to parasite and host cells. ECP and EDN are proteins in the matrix of the granule and share sequence similarity and ribonuclease activity. These two proteins can provoke the Gordon phenomenon in rabbits and are toxic to parasites. EPO consists of two polypeptide and is a toxin for parasite and host cells with or without H2O2. The common characteristics of these proteins are their high isoelectric points and cytotoxic activities.
Amino Acid Sequence↗
[Non-Hodgkin's T cell lymphoma associated with marked eosinophilia].
A case of non-Hodgkin's T cell lymphoma (diffuse lymphoma, large cell type) associated with marked eosinophilia and pleurisy in a 57-year-old male is reported. The leukocyte count was 12.5 x 10(3)/microliters and eosinophil count was 53% and the absolute count of 6.6 x 10(3)/microliters. The patient's serum and pleural effusion fluid, containing abundant lymphoma cells, showed eosinophil colony stimulating factor (Eo-CSF) activity. Conditioned medium (CM) prepared from patient's T cells (T-CM) produced Eo-CSF and this was enhanced by interleukin-2 (IL-2) stimulation. We demonstrated that the patient's serum contained a significant amount of interleukin-5 (IL-5) and the patient's T-CM, particularly after IL-2 stimulation contained a significant amount of granulocyte-macrophage colony-stimulating factor (GM-CSF). These findings suggest that Eo-CSF produced by neoplastic T cells or normal T cells activated by tumor antigen stimulated the production of eosinophils in this patient and that both IL-5 and GM-CSF might play a role in Eo-CSF activity.
Eosinophilia↗
High Eo-CSF activity in T-cell non-Hodgkin's lymphoma with eosinophilia.
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Aged↗
[A case of new type scrub typhus (tsutsugamushi disease) presenting with acute respiratory failure and hemophagocytic syndrome].
A 47-year-old male was referred to our hospital with persistent high fever. He had received antibiotics (ASPC) for the diagnosis of acute infectious disease, which failed to respond, and subsequently developed marked lymphocytopenia and thrombocytopenia. During his hospitalization, hypoxic respiratory failure rapidly developed. A bone marrow aspiration revealed marked hemophagocytosis, leading to the tentative diagnosis of opportunistic respiratory infection associated with malignant histiocytosis. Treatment for suspected malignancy and Pneumocystis carinii pneumonia was commenced. However, because of the initial lack of response to ASPC, generalized skin rashes without an ordinary stick wound which had diminished before the hospitalization, and a history of working outdoors in a nearby mountain area, the possibility of new type tsutsugamushi disease was strongly suggested. Intravenous administration of minocycline promptly improved his symptoms and laboratory data. The diagnosis was confirmed by a significant increase in the titer of antibody to Rickettsia tsutsugamushi. The thrombocytopenia was considered to have been caused by co-existent hemophagocytic syndrome.
Acute Disease↗
[Regulation of eosinophilopoiesis].
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Asthma↗
Myeloid progenitor cell growth characteristics and effect of G-CSF in a patient with congenital cyclic neutropenia.
A 17-year-old male with congenital cyclic neutropenia was treated with recombinant human granulocyte colony stimulating factor (G-CSF) administered subcutaneously at 1 to 2 micrograms/kg per day. The peak and nadir counts of neutrophils and the peak counts of monocytes were significantly elevated, and the period of cycling decreased from 3 to 2 weeks. Bone marrow culture studies revealed the following abnormalities in granulocytic progenitor cells (CFU-G): a decrease in the concentrations of G-cluster forming cells, stimulated by a maximal dose of G-CSF, and a tendency of abnormally low responsive growth of the CFU-G to lower concentrations of G-CSF and GM-CSF. Our findings suggest that administration of G-CSF at relatively low doses overcomes or compensates for these abnormalities, though not completely, as fluctuation in the neutrophil counts persisted.
Bone Marrow↗
Interleukin 5 activity in sera from patients with eosinophilia.
Sera from 10 patients with eosinophilia contained eosinophil colony stimulating factor (Eo-CSF) activity. Using anti murine (m) interleukin-5 (IL-5) antibody, we demonstrated that this activity was mainly derived from IL-5. Administration of prednisolone to patients decreased both Eo-CSF activity in sera and the number of eosinophils in blood. These results extend our recent study demonstrating that T cells from eosinophilic patients produce IL-5 with IL-2 stimulation and may support the speculation that IL-5 is an important factor which induces eosinophilia.
Blood Cell Count↗
Interaction of monocytes and T cells in the regulation of normal human megakaryocytopoiesis in vitro: role of IL-1 and IL-2.
Autologous or allogeneic peripheral blood T cells can stimulate the human megakaryocyte progenitor cell (CFU-Meg)-derived colony formation in a dose-dependent fashion in agar cultures of nonadherent (NA), T cell-depleted (NT) bone marrow (BM) cells. Low concentrations of monocytes and T cells can collaborate in the stimulation of CFU-Meg colony formation or in the production of megakaryocyte colony stimulating factor (Meg-CSF) by T cells in the presence of mitogens or IL-2. Monocytes alone can produce only negligible Meg-CSF under any conditions. When monocyte conditioned medium (CM) was added to T cell-stimulated NA, NT BM cell cultures, CFU-Meg colony growth was appreciably increased compared with that stimulated by T cells alone. Dose-dependent increase in CFU-Meg colony growth was noted when varying concentrations of IL-1 were added to T cell-stimulated NA, NT cell cultures, although IL-1 itself could support no CFU-Meg colony growth in the absence of T cells. These data suggest that a synergistic interaction between T cells and monocytes during the production of Meg-CSF by T cells could be partly mediated by IL-1. IL-2 was found to stimulate Meg-CSF production by T cells in the presence or absence of mitogens. IL-2-stimulated Meg-CSF production by T cells was augmented by the addition of monocytes. Although IL-2 itself had no stimulatory effect on CFU-Meg colony growth, dramatic augmentation in the CFU-Meg colony number was noted when IL-2 was added to T cell-stimulated NA, NT cell cultures. High concentrations of monocytes and prostaglandin E (PGE) inhibited the CFU-Meg colony formation. These results suggest that IL-1 and IL-2 may play a stimulatory role on the normal human in vitro megakaryocytopoiesis, and may be involved in the development of reactive thrombocytosis and bone marrow megakaryocytic hyperplasia in various inflammatory diseases.
Cell Communication↗
Interleukin-2 treatment-associated eosinophilia is mediated by interleukin-5 production.
During a trial using recombinant human interleukin-2 (rhIL-2) immunotherapy for acute myeloblastic leukaemia (AML) in remission, eosinophilia was observed in all patients. We used in-vitro clonogenic assays to investigate the mechanism of the eosinophilia in five patients. The mean eosinophil count increased from 0.05 x 10(9)/l before rhIL-2 to 0.98 x 10(9)/l within 48 h of stopping the infusion, and an exponential correlation between the pretreatment lymphocyte CD4:CD8 ratio and the maximum eosinophil count was observed. RhIL-2 did not stimulate eosinophil colony formation by normal bone marrow. However, serum collected from patients during rhIL-2 infusion was a potent stimulator of eosinophil colony forming units (CFU-Eo), but had no significant stimulatory effect on granulocyte-macrophage colony forming units (CFU-GM). The CFU-Eo stimulation by pre-treatment serum was 2.8-fold higher than control serum. Serum collected during treatment stimulated CFU-Eo 12 times more than control serum (P less than 0.05). By pre-incubating patient serum, collected during rhIL-2 treatment, with monoclonal antibodies to murine IL-5, or human granulocyte-macrophage colony stimulating factor (GM-CSF), a reduction of 80% and 38% respectively in eosinophil and GM colony production was found. The CFU-Eo stimulating effect of patient serum was in the range of the CFU-Eo stimulating effect of normal serum, after the addition of 5 u/ml of recombinant murine IL-5. The results suggest that eosinophilia was caused by IL-5 and GM-CSF production by rhIL-2 stimulated CD4 positive lymphocytes. The location on chromosomes 5 of the genes for IL-5, GM-CSF and IL-3 may be associated with regulation of expression, by a common mechanism, of all the factors known to be involved in eosinophil production. This mechanism may be activated by IL-2 stimulation. The separate location on chromosome 17 of the G-CSF gene may explain the ability of IL-2 to produce a distinct stimulus to eosinophil but not neutrophil production.
Adult↗
[Amylase-producing extramedullary plasmacytoma with multiple cutaneous metastasis following a solitary plasmacytoma of bone].
A 65-year-old woman was admitted because of multiple cutaneous tumors in the left lumbar area in March 1983. In 1979, she had been diagnosed as solitary plasmacytoma (IgG, kappa) of the left femur and amputation of the left leg had been performed. In 1981, the tumor relapsed in the left ilium in association with an increased level of serum IgG with M-component and normal activity of serum amylase. The serum M-protein had been disappeared after resection of the tumor. On admission laboratory examinations showed a slightly high level of serum IgG and elevated activities of serum and urine amylase. Amylase isoenzyme analysis revealed a predominance of the S-isozyme. Bone marrow aspiration revealed no atypical plasma cells. The supernate of cultured plasma cells obtained from the cutaneous tumor contained high amylase activity consisting exclusively of S-type. Thereafter serum amylase activities changed approximately in parallel with serum M-protein levels and total tumor volumes after chemotherapy or radiotherapy. At the terminal phase in 1986, however, serum amylase activities became extraordinarily high compared with serum M-protein levels, suggesting a clonal change of the plasmacytoma cells.
Aged↗
T cells from eosinophilic patients produce interleukin-5 with interleukin-2 stimulation.
Anti-murine (m) interleukin-5 (IL-5) antibody was found to inhibit eosinophil (Eo) colony formation stimulated by recombinant human (rh) IL-5, but did not inhibit the production of Eo stimulated by rh IL-3 or granulocyte-macrophage colony-stimulating factor (GM-CSF). Conditioned medium (CM) prepared from eosinophilic patients' T cells with interleukin-2 (IL-2) stimulation (T-IL-2-CM), was found to contain CFU-Eo growth-stimulating factor. Using anti-mIL-5 antibody, we demonstrated that T-IL-2-CM from patients with eosinophilia contained a significant amount of IL-5. We also detected IL-5 mRNA in T cells from eosinophilic patients with IL-2 stimulation. These results suggest that IL-5 plays an important role in the induction of selective eosinophilia in humans and that IL-5 is produced from T cells with IL-2 stimulation.
Adult↗
Effect of human recombinant interleukin 4 on in vitro granulopoiesis of human bone marrow cells.
Utilizing in vitro colony assay, we investigated the effect of human recombinant interleukin 4 (hIL-4) on granulopoiesis of normal human bone marrow cells. Though hIL-4 itself did not possess any colony-stimulating activity, the number of neutrophil (N) colonies, particularly the number of small colonies, supported by human recombinant G-CSF (hG-CSF) was significantly increased when hIL-4 was used as a costimulant. In contrast, the number of eosinophil (Eo) colonies supported by hIL-5 was decreased when hIL-4 was used as a costimulant. Also, the numbers of N and Eo colonies supported by hIL-3 or hGM-CSF were both significantly decreased when hIL-4 was added. These data suggest that hIL-4 has diverse positive and negative regulatory effects on human neutro- and eosinophilopoiesis as a cofactor of various CSFs.
Adult↗
[CD8+ agranular lymphocyte proliferative disorder with T-cell receptor beta-chain gene rearrangement associated with thymoma and neutropenia].
A 58-year-old male with a 10-years history of thymoma was admitted to our hospital because of the respiratory infection. Hepatosplenomegaly and systemic lymphadenopathy were revealed on physical examination. Chest roentgenogram showed a large anterior mediastinal tumor and a right pleural effusion. Blood examination showed Hb 11.5 g/dl, leucocyte count 1,600/microliters (1% neutrophils, 34% monocytes, 65% lymphocytes) and platelet count 11.2 x 10(4)/microliters. The lymphocytes in the peripheral blood and pleural fluid were mostly small agranular mature lymphocytes and CD2+ 3+ 4- 8+. A monoclonal rearrangement of TCR beta chain gene was found using Southern blot analysis of the lymphocytes in the peripheral blood and pleural fluid. The CFU-GM colony formation by bone marrow cells was normal, and not suppressed by the patient's serum or peripheral blood lymphocytes. Neutrophil-associated IgG was increased with a direct immunofluorescence test. Serum IgG level was slightly decreased. Radiation therapy for thymoma exerted no effect. Treatment with prednisolone 60 mg daily resulted in complete disappearance of the pleural effusion and partial improvement of hepatosplenomegaly, thymoma and neutropenia. Histological examination of the thymoma revealed predominantly spindle cell type. He is still in good condition 21 months after diagnosis. This case seems to represent neoplastic proliferation of mature CD8+ T cells associated with thymoma.
Agranulocytosis↗
[Spontaneous differentiation from myeloperoxidase-negative acute nonlymphocytic leukemia to acute myelomonocytic leukemia].
We reported a 68-year-old woman with acute nonlymphocytic leukemia, in whom the leukemia transformed from poorly differentiated myeloperoxidase (MPO)-negative type into myelomonocytic type during the observation without chemotherapy. Hematological findings on admission revealed a leukocyte count of 3,500/microliters with 48% blasts and a platelet count of 9.2 x 10(4)/microliters. Bone marrow aspiration showed 68.2% infiltration of blasts negative for MPO. Sudan black B and esterase stains. By electron microscopy MPO was detected in the endoplasmic reticulum and nucleoenvelope of the blasts. Large vacuole-like granules were MPO-negative. She was observed without administration of any antileukemic agent or an immunopotentiator. The leukocyte count rose gradually, in association with increases in the relative and absolute counts of mature neutrophils and monocytic cells, and the platelet count. Twenty-six months after the initial diagnosis, a blood examination showed a leukocyte count of 74,300/microliters with 20.5% mature neutrophils and 15.5% monocytic and a platelet count of 31.4 x 10(4)/microliters. Cytological, cytochemical, ultrastructural and immunological studies of the bone marrow cells showed features compatible with acute myelomonocytic leukemia (FAB M4). This case is unusual in respect that poorly differentiated ANLL transformed spontaneously into moderately differentiated ANLL.
Aged↗
[Neutrophil-associated IgG and neutrophil-binding IgG in autoimmune neutropenia].
Neutrophil-associated IgG (NAIgG) and neutrophil-binding IgG in sara (NBIgG) of 77 patients with neutropenia suspected to be caused by autoimmune mechanisms (group A) and 31 patients with aplastic anemia or myelodysplastic syndrome (group B) were assayed by flow cytometry. Auto-NBIgG was elevated in 32% of the patients in group A, particularly in about 70% of those with collagen diseases or ITP, but the level was normal in group B. Elevated NAIgG with normal auto-NBIgG levels was found in 27% of the patients in group A and in 64% of the patients in group B. The assay of auto-NBIgG was useful for detection of anti-neutrophil autoantibodies and for the diagnosis of autoimmune neutropenia. In addition, the level of NAIgG may be non-specifically elevated in non-immune neutropenia.
Agranulocytosis↗