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Biomedical subjects

J Tsukada

Publications and source records attributed to J Tsukada.

At least 55 records · Page 3Linked to original sources
PubMed1994

Transcription factors NF-IL6 and CREB recognize a common essential site in the human prointerleukin 1 beta gene.

A site located between -2782 and -2729 of the human prointerleukin-1 beta (IL1B) gene functions as a strong lipopolysaccharide (LPS)-responsive enhancer independent of the previously identified enhancer located between -2896 and -2846 (F. Shirakawa, K. Saito, C.A. Bonagura, D.L. Galson, M. J. Fenton, A. C. Webb, and P. E. Auron, Mol. Cell. Biol. 13:1332-1344, 1993). Although these two enhancers appear to function cooperatively in the native sequence context, they function independently as LPS-responsive elements upon removal of an interposed silencer sequence. The new enhancer is not induced by dibutyryl cyclic AMP (dbcAMP) alone but is superinduced by costimulation with LPS-dbcAMP. This pattern of induction depends upon the nature of the sequence, a composite NF-IL6-cAMP response element (CRE) binding site. This pseudosymmetrical sequence is shown to contrast with a classical symmetric CRE which responds to dbcAMP but not LPS. DNA binding studies using in vivo nuclear extract, recombinant proteins, and specific antibodies show that LPS induces the formation of two different complexes at the enhancer: (i) an NF-IL6-CREB heterodimer and (ii) a heterodimer consisting of NF-IL6 and a non-CREB, CRE-binding protein. Cotransfection studies using NF-IL6 and CREB expression vectors show that NF-IL6 transactivates the enhancer in the presence of LPS, whereas CREB acts either positively or negatively, depending upon its cAMP-regulated phosphorylation state. Our data demonstrate that the newly identified enhancer is a specialized LPS-responsive sequence which can be modulated by cAMP as a result of the involvement of NF-IL6-CRE-binding protein heterodimers.

Base Sequence↗
PubMed1993

Angiotropic lymphoma of paranasal sinuses with initial symptoms of oculomotor nerve palsy.

A 78-year-old female was found to have angiotropic lymphoma, a rare fatal disease, with initial symptoms of oculomotor nerve palsy. A biopsy of the paranasal sinus mucosa showed that the small vessels were occupied by large mononuclear cells which upon immunohistochemical examination tested positive for pre B-cell markers. She felt a gradually increasing pain in her left thigh. Magnetic resonance imaging suggested the involvement of neoplastic cells in the left femoral bone marrow. Following chemotherapy treatment remission was achieved. Early diagnosis of angiotropic lymphoma appears very significant, as this disorder could be well controlled by systemic chemotherapy.

Aged↗
PubMed1993

Enhancing effects of IL-2 on M-CSF production by human peripheral blood monocytes.

Monocytes have the capacity to produce granulopoietic factors such as M-CSF and G-CSF. Our findings here showed that interleukin-2 (IL-2), at a concentration of more than 0.05 ng/ml, led to a 12-fold increase in the production of M-CSF in the human peripheral blood mononuclear cells after 72 h incubation compared to the control culture. Even in purified monocyte cultures with added IL-2, a 3-fold increase in M-CSF production was observed at an IL-2 concentration of 50 ng/ml. The enhancing effect of IL-2 on M-CSF secretion was also observed when IL-2-stimulated non-phagocytic cell-conditioned medium was added to monocyte cultures. These results indicated that IL-2, both directly and indirectly, activated monocytes to enhance the production of M-CSF. In addition, the expression of IL-2 receptor (CD25) on monocytes was more enhanced in cultures containing IL-2 than in cultures without IL-2. On the other hand, IL-2 did not induce G-CSF production in purified monocytes. These in vitro results suggest that when IL-2 is used clinically, the various biological activities of M-CSF should also be taken into consideration.

Cells, Cultured↗
PubMed1993

[Detection of granulocyte-macrophage colony-stimulating factor activity in the supernatant of the cultured leukemic cells of adult T-cell leukemia with eosinophilia].

An adult T-cell leukemia (ATL) accompanied with eosinophilia is described. A 75-year-old female was admitted to our hospital because of lymphadenopathy. Her leukocyte count was 73,300/microliters, with 35.5% abnormal lymphocytes and 19% eosinophils. A majority of lymphocytes expressed CD4+CD8-. Acute ATL was diagnosed, since anti-HTLV-1 antibody in her serum and monoclonal integration of HTLV-1 proviral DNA in her peripheral mononuclear cells were detected. She was treated with THP-adriamycin, cyclophosphamide (CPA), and vincristine (VCR). Abnormal lymphocyte and eosinophil counts decreased and there was improvement in the lymphadenopathy. However she then complained of lymphadenopathy again. Her leukocyte count rose to 76,300/microliters, with 89% abnormal lymphocytes. Combination therapy with CPA, VCR, and doxorubicin was started and there was a temporal regression in lymphadenopathy, but her lymphadenopathy recurred and she died. The activity of granulocyte-macrophage colony-stimulating factor (GM-CSF) was detected in the supernatant of the cultured ATL cells, although interleukin-3, interleukin-5, and GM-CSF activities were not detected in her serum. It seems likely that the secretion of GM-CSF by ATL cells are responsible for the eosinophilia.

Aged↗
PubMed1992

Interactions between recombinant human erythropoietin and serum factor(s) on murine megakaryocyte colony formation.

We investigated the interactions between human erythropoietin (hEpo) and serum factor(s) on murine megakaryocyte (MK) colony formation. Serum-free cultures supported the growth of a large number of murine MK colonies in the presence of murine interleukin-3 (mIL-3). The addition of fetal calf serum (FCS) to mIL-3-containing cultures resulted in only a minimal increase in the number of murine MK colonies. In contrast, hEpo alone had no murine MK colony-stimulating activities in serum-free cultures. hEpo required the presence of FCS, murine serum, or human serum in cultures to promote murine MK colony growth and synergized with these sera to stimulate murine MK colony formation. Furthermore, sera from patients with aplastic anemia showed higher synergistic activities with hEpo than sera from hematologically normal persons (normal human serum). When normal human serum was fractionated by gel-filtration chromatography, two peaks with the synergistic activity were observed in the eluent. However, serum did not show any synergistic effects with hEpo on the growth of murine GM colonies or murine colony-forming unit-erythroid-derived colonies. Although human serum synergized with hEpo to stimulate murine MK colony formation, human cytokines such as IL-3, IL-4, IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte-CSF (G-CSF) failed to induce murine MK colony formation in Epo-containing cultures. In cultures containing human IL-1 alpha + human IL-6 + hEpo as well as in cultures containing hEpo, human IL-3 and human GM-CSF failed to show stimulatory effects on murine MK colony formation. Moreover, the synergistic activity of human serum with hEpo could not be neutralized by antibodies such as antihuman IL-1 alpha, antihuman IL-3, antihuman IL-4, antihuman IL-6, antihuman G-CSF, and antihuman GM-CSF. Our data show that serum contains a growth factor(s) that synergizes with Epo to stimulate the proliferation and differentiation of MK precursors, and strongly suggest that this factor(s) is an unique growth factor(s) that is distinct from IL-1 alpha, IL-3, IL-4, IL-6, G-CSF, and GM-CSF.

Anemia, Aplastic↗
PubMed1992

[Adult T cell leukemia with cytomegalovirus retinitis].

A 49-year old female in the course of chemotherapy for adult T-cell leukemia (ATL) noticed blurred vision and visual field defect in her right eye on February 26, 1991. Ophthalmoscopic findings showed exudative necrotizing retinitis with white exudative patches and scattered retinal hemorrhages in both eyes. CMV was isolated from the urine by the shell vial cell culture assay. Anti-viral therapy was commenced using ganciclovir and gamma-globulin, which are rich in anti-CMV antibodies. The exudative lesions were absorbed gradually. The ocular signs and symptoms agreed with the patient's systemic immunosuppressed T cell function state. CMV retinitis should be considered in the differential diagnosis of retinitis in immunocompromised patients. CMV retinitis will certainly be found more frequently in accordance with the increasing number of immunocompromised hosts who have received immunosuppressive therapy or transplantation.

Cytomegalovirus↗
PubMed1992

[Adult T-cell leukemia with cervical bone tumor showing immunophenotypic change].

A 60-year-old man born in Miyazaki prefecture was admitted to our hospital complaining of skin rash in December 1989. On hematological examinations, leukocyte count was 14,200/microliters with 49% of abnormal lymphocytes showing lobulated nuclei. The surface marker study revealed their phenotype as CD4+8-. Anti human T cell leukemia virus type I (HTLV-I) antibody and monoclonal integration of proviral DNA were positive. From the above results, he was diagnosed as adult T-cell leukemia (ATL). Abnormal lymphocytes gradually decreased without treatment after the first admission. In January, 1990, he began to complain of neck pain. Two months later he was readmitted because of paresis of extremities and disturbance of urination. Vertebral bone mass and a compressed spinal cord in the 4th cervic level were confirmed by MR imaging. He received a resection of tumor and an anterior fusion of vertebrae. The bone tumor was histologically diagnosed as malignant lymphoma, diffuse medium-size cell type and the infiltrating cells had their phenotype as CD4+8+. He was postoperatively treated with combination chemotherapies, but neurological abnormalities did not improve. He died of pneumonia on 35 days after the operation. A postmortem examination revealed extradural tumor formation with ATL cells. This case is considered to be rare in respect of both the disappearance of most peripheral abnormal lymphocytes without any treatments and the cervical bone tumor showing immunophenotypic change.

CD4 Antigens↗
PubMed1992

[Lymphokine-activated killer (LAK) cells and interleukin-2 (IL-2) therapy that improved lymphadenopathy in a patient with B cell non-Hodgkin's lymphoma].

A 70-year-old man was admitted to our hospital on March 9, 1989 because of fever, superficial generalized lymphadenopathy, upper abdominal mass and right pleural effusion. The diagnosis of non-Hodgkin's lymphoma (follicular medium sized cell type, B cell) was made by a biopsy of the neck lymph node. Peripheral blood mononuclear cells were obtained from the patient by cytopheresis. The cells were cultured for 8 days with interleukin-2 (IL-2) to generate Lymphokine-activated killer (LAK) cells. The patient received a total of 7.7 x 10(9) LAK cells intravenously over a period of 3 weeks. He also received continuous intravenous infusion of IL-2 for 17 days, starting 2 days before the first infusion of LAK cells. After this therapy, although his superficial generalized lymphadenopathy disappeared or decreased in size, the size of the upper abdominal mass did not decrease. Therefore, it is suggested that adoptive immunotherapy is a beneficial treatments for B cell lymphoma. However, LAK cells should be generated in much larger quantities for a more successful therapeutic result.

Aged↗
PubMed1991

[Remarkable improvement of anemia by administration of recombinant human erythropoietin in a patient with aplastic anemia].

A 69-year-old female was admitted for pancytopenia. The hematological examination showed leukocytes 1,800/microliters, hemoglobin 5.3 g/dl and platelets 9.6 x 10(4)/microliters. A bone marrow aspiration revealed hypoplasia, but no abnormal cells. Serum erythropoietin titer was 5,100 mU/ml. Diagnosis of aplastic anemia was made. She received 400 ml of blood transfusion twice, and was then treated with recombinant human erythropoietin (rHuEPO) (12,000 U/day) three times a week for eight weeks. Hemoglobin level gradually increased to the level of 12.0 g/dl. This case suggests that there are some cases of aplastic anemia which can respond to treatment with rHuEPO.

Aged↗
PubMed1991

[Non-Hodgkin's lymphoma with marked infiltration in calf muscle].

A 64-year-old male developed pain and marked swelling of his left calf muscle in September, 1989. Deep-vein thrombophlebitis was suspected, and therapy with warfarin sodium followed by urokinase was instituted. Because of unsatisfactory effect of the therapy, the patient was referred to another hospital on January 3rd 1990. A CT scan of the left leg showed a soft-tissue mass adjacent to the fibula. A biopsy of the mass revealed non-Hodgkin's lymphoma of diffuse medium-sized cell type. Immunohistologic examination confirmed B cell type. He was admitted to our hospital on January 31st 1990. A chest roentgenogram showed right pleural effusion. A CT scan of the abdomen revealed a space-occupying lesion in the liver. A Gallium scintigraphy showed markedly increased isotope uptake in the left calf and liver. He was classed as a Stage IV B. He responded well to combination chemotherapy with cyclophosphamide, THP-adriamycin, VP-16, and prednisolone and achieved a complete remission. Although prominent infiltration of lymphoma cells in skeletal muscles is rarely reported, it is important to perform the biopsy promptly when the mass is found in a muscle. In this case report, we describe a rare case of non-Hodgkin's lymphoma with muscle invasion presented as marked calf muscle swelling.

Humans↗
PubMed1991

[Modified CHOP therapy in patients with non-Hodgkin's lymphoma].

From July 1983 to December 1989, 31 previously untreated patients with non-Hodgkin's lymphoma were treated with modified CHOP regimen (cyclophosphamide 300 mg/m2 on day 1, aclacinomycin 40 mg/m2 on day 1, vincristine 0.7 mg/m2 on day 1 and prednisolone 40 mg/m2 on days 1-5). The therapy was repeated at 2-week intervals. The complete response rate was 66.7% for clinical stage (CS) II according to the Ann Arbor criteria, 60.0% for CS III and 33.3% for CS IV, respectively. The 5-year survival rate was 100% for CS II, 36.6% for CS III and 34.6% for CS IV, respectively. Clinical effects of modified CHOP regimen were almost the same as those of other therapies including adriamycin from the standpoint of 5-year survival rate. On the other hand, the myelosuppression accompanying modified CHOP therapy was not severe. Only one patient had a white blood count below 1,000/microliters during 6 courses of the therapy. It is thought that this regimen is useful to enhance the quality of life of patients because of no severe complications such as myelosuppression.

Aclarubicin↗
PubMed1990

Effect of interleukin-4 on the growth of granulocyte-macrophage progenitor cells stimulated by hematopoietic growth factors.

The effects of recombinant murine interleukin-4 (rmIL-4) on murine granulocyte-macrophage progenitor cells (CFU-GM) were investigated in the presence or absence of recombinant human granulocyte colony stimulating factor (rhG-CSF), recombinant murine granulocyte-macrophage colony stimulating factor (rmGM-CSF) or recombinant murine interleukin-3 (rmIL-3) both in serum-free and serum-containing cultures. IL-4 alone could not support any CFU-GM colony formation in both culture systems. In serum-free cultures, IL-4 inhibited CFU-GM colony formation stimulated by G-CSF, GM-CSF or IL-3 from whole bone marrow cells (whole BM cells), nonadherent, nonphagocytic and T cell-depleted BM cells (fractionated BM cells) or whole BM cells of 5-Fluorouracil (5-FU) treated mice. On the other hand, in serum-containing cultures, IL-4 inhibited CFU-GM colony formation stimulated by GM-CSF or IL-3, but IL-4 dose-dependently enhanced G-CSF-stimulated colony formation from both whole and fractionated BM cells. Morphological examinations revealed that IL-4 predominantly inhibited granulocyte-lineage colony formation stimulated by GM-CSF or IL-3 in both culture systems. When combined with G-CSF, IL-4 predominantly inhibited granulocyte-lineage colony formation and relatively increased macrophage-lineage colonies, but in serum-containing culture, IL-4 significantly increased macrophage-lineage colony formation. The results of the present study suggest that IL-4 has an inhibitory effect on the factors (G-CSF, GM-CSF, IL-3)-dependent CFU-GM colony formation in serum-free condition and enhances only G-CSF-stimulated CFU-GM colony formation in serum-containing condition.

Animals↗
PubMed1990

Usefulness of neutral red uptake method for investigation of the effects of recombinant hemopoietic growth factors on leukemic blasts proliferation.

By a colorimetric assay with dye (neutral red), the effects of recombinant human hemopoietic growth factors (rhG-CSF, rhGM-CSF, rhIL-3 and rhEPO) on the proliferation of leukemic blasts in vitro were investigated. Leukemic blasts were obtained from eight patients with acute myeloid leukemia (AML) (M1: two cases, M3: two cases, M4: four cases) and from four patients with acute lymphoid leukemia (ALL) (L2: four cases). It was shown that rhG-CSF, rhGM-CSF and rhIL-3 stimulated the blast proliferation in most cases of AML, although the degree and pattern of responses showed a striking variability in different patients. Moreover, rhGM-CSF and rhIL-3 also stimulated the leukemic blasts from some cases of ALL. No clear morphological modification providing evidence for terminal differentiation was observed when assessed by Wright stain. On the other hand, rhEPO did not have any stimulating effects on leukemic blasts in all cases. These results indicate the necessity of investigating the responses of leukemic blasts to hemopoietic growth factors in each patient prior to clinical use of such factors. For this assay, neutral red uptake method is useful because of its simplicity, rapidity, precision and convenience for handling a large volume of materials.

Adult↗
PubMed1990

The effect of high doses of recombinant human erythropoietin on megakaryocytopoiesis and platelet production in splenectomized mice.

The effects of recombinant human erythropoietin (rHuEpo) on megakaryocytopoiesis and platelet production were investigated in splenectomized, sham-operated and intact mice. When splenectomized mice were injected with 50 U of rHuEpo daily for 4 d, peripheral platelet counts, megakaryocyte (MK) size and the percentage of mature MK (stage IV MK) increased from 1 to 4 d after the initial rHuEpo injection. The total number of marrow MK colony forming units (CFU-MK) increased from 2 to 4 d after the initial injection. Furthermore, from days 6 to 8, the total number of marrow MK also increased. In addition, when the dose of rHuEpo was increased to 20-200 U per mouse, clear dose responses were detected in platelet counts and MK numbers. When sham-operated and intact mice were injected with rHuEpo, no significant change in platelet numbers was detected. The number of MK, MK size and the number of CFU-MK increased only in spleen, not in bone marrow. Our data indicate that Epo has stimulatory effects on platelet production in vivo, if used in sufficient quantities.

Animals↗
PubMed1990

[A case of sarcoidosis presenting with high fever and acute respiratory failure].

A 55-year-old man was admitted with complaints of remittent fever (39 degrees C) and dyspnea on exertion which began ten days previously. His family and past histories were non-contributory for diagnosis except his occupation as a stone mason for 26 years. The chest X-ray film taken on admission showed diffuse small nodular shadows associated with small amounts of pleural effusion and bilateral hilar adenopathy. Arterihl blood gas analysis showed severe hypoxemia and hypocapnea (Pao2 32.2 Torr, Paco2 31.6 Torr). The serum level of LDH was 985 IU/L and ACE was 49.0 IU/L, lysozyme was 28.8 micrograms/ml. Biopsied materials of the lung obtained by TBLB, liver and bone marrow showed non-caseating epithelioid granuloma without caseating necrosis. T-lymphocyte ratio increased in BALF. The patient was diagnosed to have sarcoidosis. The administration of prednisolone was initiated, which resulted in a marked improvement of clinical data including chest X-ray films, BGA, LDH, ACE and lysozyme.

Acute Disease↗