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Biomedical subjects

M Migita

Publications and source records attributed to M Migita.

At least 37 records · Page 2Linked to original sources
PubMed1996

Treatment of anterior vitreous before suturing and intraocular lens to the ciliary sulcus.

PURPOSE: To clarify the relationship between suturing an intraocular lens (IOL) and residual vitreous after vitrectomy and transscleral IOL suturing. SETTING: Toranomon Hospital, Tokyo, Japan. METHODS: Enucleated pigs' eyes were fixed to the observation device. Three methods for removing the crystalline lens and the vitreous were tested; and IOL was then sutured to the ciliary sulcus. Miyake's posterior approach and an endoscope were used to observe the movement of fluorescein-stained residual vitreous during these procedures. RESULTS: Considerable residual vitreous and extensive vitreous entwinement with the IOL were seen when IOL suturing followed anterior vitrectomy through a limbal incision. These were absent when IOL suturing followed careful pars plana vitrectomy and capsulectomy. CONCLUSIONS: Our findings indicate that suturing the IOL to the ciliary sulcus should be followed by the removal of as much anterior vitreous and lens capsule as possible to prevent such postoperative complications as tractional retinal detachment and cystoid macular edema.

Animals↗
PubMed1996

Improvement of bone disease with increased dose of glucocerebrosidase in a Gaucher disease patient who had a bone lesion presenting during low-dose enzyme replacement therapy.

In recent years, enzyme replacement therapy has been shown to be useful for the treatment of Gaucher disease. A 10 year old Japanese boy with Gaucher disease underwent splenectomy at the age of 5 years and received enzyme replacement therapy from the age of 6 years. He had avascular necrosis of the bilateral femoral heads, which was not seen at the beginning of the therapy, without deterioration of hematological variables during maintenance therapy. The enzyme dosage was increased from 20 to 120 IU/kg per month resulting in an improvement of the clinical symptoms and bone lesion. In enzyme replacement therapy, dose increase is considered to be essential for improvement in bone disease; however, it is important to watch for the development of bone lesion.

Child↗
PubMed1995

Selection of transduced CD34+ progenitors and enzymatic correction of cells from Gaucher patients, with bicistronic vectors.

The gene transfer efficiency of human hematopoietic stem cells is still inadequate for efficient gene therapy of most disorders. To overcome this problem, a selectable retroviral vector system for gene therapy has been developed for gene therapy of Gaucher disease. We constructed a bicistronic retroviral vector containing the human glucocerebrosidase (GC) cDNA and the human small cell surface antigen CD24 (243 bp). Expression of both cDNAs was controlled by the long terminal repeat enhancer/promoter of the Molony murine leukemia virus. The CD24 selectable marker was placed downstream of the GC cDNA and its translation was enhanced by inclusion of the long 5' untranslated region of encephalomyocarditis virus internal ribosomal entry site. Virus-producing GP+envAM12 cells were created by multiple supernatant transductions to create vector producer cells. The vector LGEC has a high titer and can drive expression of GC and the cell surface antigen CD24 simultaneously in transduced NIH 3T3 cells and Gaucher skin fibroblasts. These transduced cells have been successfully separated from untransduced cells by fluorescence-activated cell sorting, based on cell surface expression of CD24. Transduced and sorted NIH 3T3 cells showed higher GC enzyme activity than the unsorted population, demonstrating coordinated expression of both genes. Fibroblasts from Gaucher patients were transduced and sorted for CD24 expression, and GC enzyme activity was measured. The transduced sorted Gaucher fibroblasts had a marked increase in enzyme activity (149%) compared with virgin Gaucher fibroblasts (17% of normal GC enzyme activity). Efficient transduction of CD34+ hematopoietic progenitors (20-40%) was accomplished and fluorescence-activated cell sorted CD24(+)-expressing progenitors generated colonies, all of which (100%) were vector positive. The sorted, CD24-expressing progenitors generated erythroid burst-forming units, colony-forming units (CFU)-granulocyte, CFU-macrophage, CFU-granulocyte/macrophage, and CFU-mix hematopoietic colonies, demonstrating their ability to differentiate into these myeloid lineages in vitro. The transduced, sorted progenitors raised the GC enzyme levels in their progeny cells manyfold compared with untransduced CD34+ progenitors. Collectively, this demonstrates the development of high titer, selectable bicistronic vectors that allow isolation of transduced hematopoietic progenitors and cells that have been metabolically corrected.

3T3 Cells↗
PubMed1995

Perirenal mass of Langerhans cell histiocytosis.

A 15-month-old girl with Langerhans cell histiocytosis (LCH), Letterer-Siwe disease, was referred to our hospital in 1984. Whilst on treatment with cytotoxic drugs, a perirenal mass was detected and hydronephrosis became evident when she was 29 months old. Percutaneous nephrostomy tubes were placed in the pelvis, bilaterally and replaced every 6 months. The mass was not completely controlled and chronic pyelonephritis continued. Biopsy of the mass convoluted kidney hilus revealed histiocytic invasion. Although multiple organ systems are involved in LCH and abdominal malignant tumours may be accompanied by hydronephrosis, to our knowledge, this is the first case report of abdominal LCH and the ensuing hydronephrosis. Percutaneous nephrostomy tubes proved useful, but more convenient, less painful and infection-limited approaches need to be designed.

Abdominal Neoplasms↗
PubMed1995

Fatal cytomegalovirus myocarditis in a seronegative ALL patient.

Fatal cytomegalovirus (CMV) myocarditis occurred in a 2 year old boy with acute lymphoblastic leukemia (ALL) in remission. The patient showed mild hepatic dysfunction and a rapid progress of pancytopenia after complete remission had been achieved. At the fifth week of complete remission, he presented signs of heart failure such as tachycardia, S4 gallop on auscultation and decreased ejection fraction on echocardiography. However, no significant electrocardiographic changes were recognized. In addition to the cardiac dysfunction, the patient presented a marked tachypnea and dyspnea associated with hypoxemia. These were dramatically improved by methylprednisolone pulse therapy (30 mg/kg per day, for 3 days) and CMV high titer immunoglobulin (400 mg/kg per day, for 3 days). On the sixth day after signs of respiratory failure were improved, the patient suddenly presented a paroxysmal atrial tachycardia followed by a fatal ventricular fibrillation. Although we could detect neither a specific IgM antibody, a significant increase of IgG antibody, nor CMV genome by DNA hybridization techniques during the course of the illness, microscopic examination of necropsy specimens of the heart showed a marked disruption and disintegration of muscle bands associated with cytomegalic inclusion bodies. Polymerase chain reaction (PCR) yielded a 305 bp amplification product in the heart and lung tissues, supporting the view that myocarditis was caused by CMV.

Antibodies, Viral↗
PubMed1995

A late-appearing Philadelphia chromosome in acute lymphoblastic leukemia confirmed by expression of BCR-ABL mRNA.

We report two cases of acute lymphoblastic leukemia (ALL) with a late-appearing Philadelphia chromosome (Ph1), confirmed by the expression of BCR-ABL mRNA, using the reverse transcriptase/polymerase chain reaction (RT/PCR) technique. The first patient was a 10-year-old boy with precursor B cell type ALL-L1 (FAB classification). At diagnosis, no metaphase cells were found by chromosome analysis and BCR-ABL mRNA was not observed. At the beginning of relapse, which occurred after 7 months of complete remission, a normal karyotype was observed. At the terminal stage, leukemic cells with Ph1 and BCR-ABL mRNA for the P190 variety were observed. The second patient was a 12-year-old boy with immature T cell type ALL-L1. The metaphase cells showed a 9p- chromosome at diagnosis and Ph1 appeared in addition to 9p- at relapse. Hybrid mRNA for the P210 variety was detected only when Ph1 had developed. The blast cells with Ph1 were derived from the original leukemic clone through clonal evolution, since the same clonal rearrangements of IGH or TCRB were detected in leukemic cells obtained both at diagnosis and relapse in both patients. Thus, in both cases, Ph1 was detected only in the course of ALL along with expression of BCR-ABL mRNA. This observation also confirmed that, as in de novo Ph1-positive ALL, both the P190 and P210 varieties of BCR-ABL mRNA are observed in ALL with late-appearing Ph1.

Base Sequence↗
PubMed1995

Extraordinarily high eosinophilia and elevated serum interleukin-5 level observed in a patient infected with Paragonimus westermani.

OBJECTIVE: Although eosinophilia is one of the typical clinical features of some helminth infections, the degree of eosinophilia in helminthiasis is usually 10% to 30% with a total white blood cell count of 10,000 to 20,000/mm3. Here we report a case of extraordinarily high eosinophilia (91%; absolute eosinophil count, 84,000/mm3) caused by Paragonimus westermani infection. To determine the mechanisms of eosinophilia, the levels of several eosinophilopoietic cytokines in the patient's sera were measured during the course of treatment. METHODS: Serum levels of three cytokines, granulocyte-macrophage colony-stimulating factor, interleukin-3 (IL-3), and IL-5 were measured by enzyme-linked immunosorbent assay using commercial kits or our own assay system for IL-5. RESULTS: Although the kinetic changes of IL-5 correlated well with eosinophilia, the serum IL-3 level remained below the detection level throughout the period examined. Although the granulocyte-macrophage colony-stimulating factor level was twofold to threefold higher than the normal level, its kinetics did not parallel the degree of eosinophilia. CONCLUSIONS: These results show that Paragonimus westermani infection can induce an extraordinarily high level of eosinophilia with an associated increase in IL-5 production. Immunoserologic diagnosis for parasitic diseases should be included in the differential diagnosis of eosinophilia.

Animals↗
PubMed1995

[Neutropenia in patient with X-linked hyper-IgM syndrome].

The X-linked form of hyper-IgM syndrome (HIGM1) is a rare disorder characterized by the inability of B cells to undergo isotype switch by a deficiency of CD40 ligand (CD40L) on activated T lymphocytes. The patients suffer from recurrent infections not only due to a lack of B lymphocyte activation but also due to defect of T lymphocyte functions. In addition, neutropenia is frequently accompanied by these symptoms. A patient with HIGM1, we experienced, suffered from recurrent infections and neutropenia. But he had a normal number of hematopoietic stem cell by the in vitro colony forming assay. CD34+ myeloid stem cell has been known to express CD40. We speculated by these facts that myeloid cell numbers are regulated by CD40-CD40L interaction.

Adolescent↗
PubMed1994

Biochemical and functional characterization of soluble form of IL-5 receptor alpha (sIL-5R alpha). Development of ELISA system for detection of sIL-5R alpha.

Interleukin-5 (IL-5) mediates pleiotropic functions in various types of cells through its specific receptor (IL-5R) which is composed of two distinct subunits, alpha and beta. In mice, the alpha subunit (IL-5R alpha) specifically binds IL-5 with low affinity. The beta subunit (IL-5R beta) does not bind IL-5 by itself, but constructs the high affinity receptor with IL-5R alpha. We have isolated cDNA encoding the soluble form of IL-5R alpha (sIL-5R alpha). To elucidate the biochemical and functional properties of sIL-5R alpha, we developed an expression system for sIL-5R alpha cDNA in insect cell line Sf21 using baculovirus expression vector and obtained conditioned medium containing large quantities of mouse sIL-5R alpha. Mouse sIL-5R alpha was purified from the conditioned medium by using anti-IL-5R alpha mAb-coupled beads. Immunoaffinity-purified sIL-5R alpha with an approximate molecular mass of 42 kDa inhibited the binding of 125I-labeled IL-5 to IL-5R. By using purified sIL-5R alpha, we prepared rabbit anti-sIL-5R alpha antibody and developed a sandwich ELISA for detection of sIL-5R alpha. Significant amounts of sIL-5R alpha were detected in sera and ascitic fluids of mice bearing tumors (BCL1 and MOPC104E) that responded to IL-5 for DNA synthesis, but not in sera of normal mice. Interestingly, elevated levels of serum sIL-5R alpha were observed in NZB and NZW mice. The sIL-5R alpha may, therefore, have an immunoregulatory role in vivo.

Animals↗
PubMed1994

Progression of bone disease without deterioration of hematological parameters in a child with Gaucher disease during low-dose glucocerebrosidase therapy.

Gaucher disease is the most prevalent lysosomal storage disease. Although the efficacy of the macrophage-targeted human placental glucocerebrosidase is well known, it is still difficult to develop definitive guidelines regarding the appropriate therapy schedule. We describe an 8-year-old Japanese boy with Gaucher disease who had avascular necrosis of the right femoral head without deterioration of hematological variables during low-dose enzyme replacement therapy (12-13 IU/kg). This case demonstrates that continuous normal hematological findings may not preclude progression of other aspects of Gaucher disease in some patients during enzyme replacement therapy.

Blood Cell Count↗
PubMed1994

Development of Graves' ophthalmopathy and uveitis after radioiodine therapy for Graves' disease in a patient with HTLV-I associated myelopathy (HAM).

HTLV-I carriers or patients with HTLV-I associated myelopathy (HAM) are prone to immune-mediated inflammatory disorders. We present a 44-year-old female with HAM who developed Graves' disease. She developed severe Graves' ophthalmopathy shortly after 131I therapy, concurrently with a remarkable increase in TSH-receptor antibody titer. Ophthalmopathy was aggravated in spite of prednisolone therapy and euthyroidism being maintained by thyroxine replacement. Uveitis also developed after 131I therapy and iridocyclitis finally required trabeculotomy. This case suggests that HAM patients may have a higher risk of immune-mediated Graves' ophthalmopathy after 131I therapy.

Adult↗
PubMed1993

Acute myeloblastic leukemia (ANLL-M2) with t(8;21)(q22;q22) variant expressing lymphoid but not myeloid surface antigens with a high number of G-CSF receptors.

Leukemic cells from an 8-year-old girl with ANLL-M2 expressed precursor B-cell antigen CD19, but none of the myeloid antigens CD11b, CD13, CD14 and CD33. After culture, the cells expressed CD11b and CD13. The cells carried a high number of granulocyte colony-stimulating factor (G-CSF) receptors. In chromosome analysis, metaphase cells were obtained only in the case of culture with G-CSF. The karyotype was a variant of t(8;21)(q22;q22). Southern blot analysis revealed rearrangement of the AMLI gene located on chromosome 21. These observations may suggest that even without myeloid surface antigens and with precursor B-cell antigen, ANLL-M2 with t(8;21)(q22;q22) has apparent myeloid characteristics.

Antigens, Neoplasm↗
PubMed1993

Irradiated fetal thymus transplantation in a patient with combined immunodeficiency with predominant T cell defect.

A 6 month old boy was diagnosed as a case of combined immunodeficiency (with predominant T cell defect by previous classification). His T cell count was decreased, his B cell count in peripheral blood was increased, his serum IgG level was decreased, his serum IgM level was normal and the thymus was not evident on CT scans and magnetic resonance imaging. Administration of the thymus hormone, thymosin, led to a partial recovery of T cell function without normalization of the T cell count. At age 26 months the patient received an irradiated thymus transplantation from a 16 week old female fetus. After the transplantation, the T cell count (mainly CD4+ cells) increased by 50-70%. A mild graft-versus-host reaction (GVHR) occurred and several immunosuppressants were prescribed. Chromosome analysis showed that the T cells have both 46 XY and 46 XX karyotypes while the B cells have the 46 XY karyotype alone. His cellular immunity (skin tests, DNA synthesis, mixed lymphocyte reaction, cytotoxic activity and natural killer cell function) and his serum IgG level remained low. However, being on regular r-globulin therapy and oral anti-fungal drugs, he is now living normally with almost no trouble at age 6 years and 3 months. This case showed that irradiated thymus transplantation might be a useful method when an adequate donor for bone marrow transplantation is not available. The unexpected observation that the increased T cells were mainly CD4 may be related to the mild GVHR and the clinical improvement.

Female↗
PubMed1993

[The measurement of zinc protoporphyrin for iron deficiency anemia by hematofluorometer in children].

Zinc protoporphyrin (ZPP) is generated in the erythrocytes of patients with lead toxication and iron deficiency anemia by the incorporation of zinc instead of ferrous iron into protoporphyrin. Although the measurement of ZPP has been thought to be a potential screening test for evaluating iron deficiency, no simple and reliable ZPP assay method has been available until recently. A newly developed hematofluorometer allows us to quickly determine the level of ZPP in a drop of unprocessed whole blood. In this study, we measured the concentration of ZPP in 732 children including 22 patients with iron deficiency anemia using this hematofluorometer. The cut off value of whole blood ZPP in children was determined to be 38.2 micrograms ZPP/dl whole blood. The level of ZPP showed a good negative correlation with the concentration of hemoglobin. The specificity and the sensitivity of this assay were 97.2% and 81.8%, respectively. These results indicate that this ZPP assay using the newly-developed hematofluorometer is a practical way to screen for iron deficiency anemia.

Adolescent↗
PubMed1992

Molecular cloning and expression of the human interleukin 5 receptor.

Human interleukin 5 (IL-5) plays an important role in proliferation and differentiation of human eosinophils. We report the isolation of cDNA clones from cDNA libraries of human eosinophils by using murine IL-5 receptor alpha chain cDNA as a probe. Analysis of the predicted amino acid sequence indicated that the human IL-5 receptor has approximately 70% amino acid sequence homology with the murine IL-5 receptor and retains features common to the cytokine receptor superfamily. One cDNA clone encodes a glycoprotein of 420 amino acids (Mr 47,670) with an NH2-terminal hydrophobic region (20 amino acids), a glycosylated extracellular domain (324 amino acids), a transmembrane domain (21 amino acids), and a cytoplasmic domain (55 amino acids). Another cDNA encodes only the extracellular domain of this receptor molecule. Other cDNA clones encode molecules having diversified cytoplasmic domains. COS7 cells transfected with the cDNA expressed a approximately 60-kD protein and bound IL-5 with a single class of affinity (Kd = 250-590 pM). The Kd values were similar to that observed in normal human eosinophils. In contrast to the murine 60-kD alpha chain, which binds IL-5 with low affinity (Kd = approximately 10 nM), the human alpha chain homologue can bind IL-5 with much higher affinity by itself. RNA blot analysis of human cells demonstrated two transcripts (approximately 5.3 and 1.4 kb). Both of them were expressed in normal human eosinophils and in erythroleukemic cell line TF-1, which responds to IL-5. The human IL-5 receptor characterized in this paper is essential for signal transduction, because expression of this molecule in murine IL-3-dependent cell line FDC-P1 allowed these cells to proliferate in response to IL-5.

Amino Acid Sequence↗
PubMed1991

Characterization of the human IL-5 receptors on eosinophils.

Interleukin 5 (IL-5) receptors on the cell surface of human eosinophils and other hematopoietic cells were characterized using radiolabeled recombinant IL-5. The binding of 35S-labeled murine IL-5 to eosinophils from normal human peripheral blood was rapid and saturable within a 30-min incubation at both 4 and 37 degrees C. The binding of 35S-labeled murine IL-5 to eosinophils was inhibited by an excess of unlabeled murine and human IL-5 or by an anti-murine IL-5 monoclonal antibody (NC17) but not by other human cytokines. Scatchard plot analysis revealed that human eosinophils have a single class of high affinity receptor (Kd 170-330 pM; number of binding sites: 260-380/cell). IL-5 receptors on eosinophils from four patients with eosinophilia displayed similar characteristics. Affinity cross-linking experiments resulted in the identification of human IL-5 receptor on eosinophils with a molecular mass of 55-60 kDa. Among the various cells besides eosinophils and cell lines that we could test, a subline of HL-60 (YY-1 cells) was found to display a significant number of IL-5 receptor. These results suggest that IL-5 may act on limited types of cells in the human system.

Aged↗
PubMed1991

Transgenic mice expressing a B cell growth and differentiation factor gene (interleukin 5) develop eosinophilia and autoantibody production.

Interleukin 5 (IL-5) has been suggested to be involved in the growth and differentiation of B cells and eosinophils. Especially, Ly-1+ B cells, which have been considered to produce autoantibodies, are selectively developed by this lymphokine in long-term bone marrow culture. To envisage the possible engagement of IL-5 in the development of these cells in vivo, transgenic mice carrying the mouse IL-5 gene ligated with a metallothionein promoter were generated. Transgenic mice carrying the IL-5 gene exhibited elevated levels of IL-5 in the serum and an increase in the levels of serum IgM and IgA. A massive eosinophilia in peripheral blood, bone marrow, and spleen, and an infiltration of muscle and liver with eosinophils, were observed. When cadmium-containing saline was injected intraperitoneally into transgenic mice, IL-5 production was augmented about five times within 24 h, and a distinctive Ly-1+ B cell population became apparent in the spleen after 5 d. IL-5 receptors were detected on those cells by monoclonal antibodies against IL-5 receptors. Another interesting finding in these transgenic mice was an increase in polyreactive anti-DNA antibodies of IgM class. It is suggested, therefore, that aberrant expression of the IL-5 gene may induce accumulation of Ly-1+ B cells and eosinophils. Furthermore, this IL-5 transgenic mouse can be a model mouse for eosinophilia, and we can determine the role of IL-5 in the differentiation of Ly-1+ B cells and eosinophils by using this mouse.

Animals↗