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Biomedical subjects

S Ohga

Publications and source records attributed to S Ohga.

At least 73 records · Page 4Linked to original sources
PubMed1994

Homologous dinucleotide (GT or TG) deletion in Japanese patients with chronic granulomatous disease with p47-phox deficiency.

The cytosolic 47-kDa protein designated as p47-phox (phagocyte oxidase) is one of the essential components of the superoxide-generating system in phagocytes, and its defect is known to cause chronic granulomatous disease (CGD). Five unrelated CGD patients with p47-phox deficiency were found among 82 CGD patients in Japan. We sequenced the cDNAs and the genomic DNAs corresponding to p47-phox derived from these patients. In all cases examined, the defect was identified to be a GT (or TG) dinucleotide deletion at bases 75/76 (or 74/75, respectively) in the coding sequence for the protein. The same mutation was reported previously for a total of 9 alleles from 5 CGD patients in England and in the United States. It seems, therefore, that the dinucleotide GT deletion is the common mutation in 47-phox deficient CGD due to certain structural issues.

Adolescent↗
PubMed1994

Cellular distribution of CD63 antigen in platelets and in three megakaryocytic cell lines.

CD63 is a 53 kDa lysosomal membrane glycoprotein that has been identified as a platelet activation molecule. We investigated the localization of CD63 antigen in platelets and in three megakaryocytic cell lines (K562, HEL and CMK11-5) using flow cytometry and immunoelectron microscopy. Flow cytometry showed that a monoclonal antibody directed against CD63 bound to 8.1% of unstimulated platelets and 59.2% of thrombin-stimulated platelets. Immunoelectron microscopy demonstrated that CD63 antigen was distributed randomly inside unstimulated platelets, while it was localized in the open canalicular system of washed platelets and on the cell membranes of thrombin-stimulated platelets. Flow cytometry detected CD63 on 16.4% of HEL cells, 31.2% of K562 cells, and 43.2% of CMK11-5 cells. Immunoelectron microscopy demonstrated that CD63 was localized in the granules and on the surface membranes of HEL cells, in the vesicles and on the membranes of K562 cells, and in the granules and vesicles as well as on the membranes of CMK11-5 cells. Thus, the distribution of CD63 differed markedly among these three megakaryocytic cell lines.

Antigens, CD↗
PubMed1994

Liposteroid against refractory pulmonary haemorrhage in idiopathic pulmonary haemosiderosis.

We describe two Japanese children with idiopathic pulmonary haemosiderosis (IPH), whose refractory haemorrhages were treated with an intravenous lipid emulsion containing dexamethasone (liposteroid). A 22-month-old boy and a 14-month-old girl have been observed with similar symptoms; periodic bouts of anaemia, reticulocytosis, diffuse infiltrates on chest X-ray and the finding of siderophages in sputum or gastric lavage fluid. The MRI of the lung was useful for the diagnosis. Methylprednisolone pulse therapy was successful in treating acute massive bleeding. Subsequent oral prednisolone could not prevent chronic recurrent haemorrhages. However, the intermittent administration of liposteroid (0.05 mg/kg/dose IV) led to a cessation of bleeding; the haemoglobin concentration rose to normal levels. This observation emphasizes the usefulness of liposteroid in the management of refractory IPH.

Dexamethasone↗
PubMed1994

Serum erythropoietin levels in term and preterm infants during the first year of life.

PURPOSE: To evaluate the kinetics of erythropoietin (EPO) production and address the pathogenesis of anemia of prematurity, we measured EPO levels in infants during the first year of life. PATIENTS AND METHODS: Using a radioimmunoassay, serum EPO levels were measured in 97 infants classified into three groups according to weight: group A, n = 40, < 1,500 g; group B, n = 19, 1,500-2,499 g; and group C, n = 38, > or = 2,500 g. RESULTS: The serum EPO level ranged widely during the early neonatal period from days 0 to 6 (group A, < 5 to 307 mU/ml; group B, 10-340 mU/ml; and group C, 9-108 mU/ml). EPO reached its lowest level (< 20 mU/ml) between days 7 and 50 in all groups. The hemoglobin concentration reached its nadir between days 51 and 150 in all groups, with the lowest concentration observed in low birth weight infants. In contrast, the EPO level during the anemic phase was approximately 20 mU/ml and was independent of birth weight. A negative correlation between serum EPO level and hemoglobin concentration was observed only in group C (r = -0.54, p < 0.05). The negative slope of the regression equation in group C exceeded that of groups A and B (p < 0.05). When the relationship between EPO and Hb was evaluated over periods of 7-50 days, 51-100 days, and > 101 days, respectively, we noted a significant correlation between values on days 7 and 50 in group A (r = -0.53, p < 0.05) and between days 51 and 100 in group B (r = -0.76, p < 0.05). CONCLUSIONS: These data suggest the appreciable EPO production in premature infants, but its insufficient response to the depressed hemoglobin level, implying the need to administer exogenous EPO to infants with anemia of prematurity.

Anemia↗
PubMed1994

Acute promyelocytic leukaemia in a patient treated with etoposide for Langerhans cell histiocytosis.

We report a child with acute promyelocytic leukaemia (APL) who was treated with etoposide (VP16) for Langerhans cell histiocytosis (LCH). A 3-year-old Japanese girl was diagnosed as having LCH. She was treated with combination chemotherapy using VP16 and prednisolone. 56 months after beginning the chemotherapy she developed APL. Her bone marrow was occupied with atypical promyelocytes including giant granules and multiple Auer bodies. A cytogenetic analysis of the leukaemic cells showed 46,XX,11p-,14q+,t(15,17). The cumulative dose of the administered VP16 was 12,120 mg/m2, which suggested that VP16 may be responsible for the development of APL. The risk of developing secondary leukaemia after the administration of VP16 should therefore be considered when managing patients with LCH.

Child↗
PubMed1994

Severe aplastic anemia in a patient with primary immunodeficiency.

This paper reports the case of a 6 year old boy with primary immunodeficiency disease, whose marrow cells showed dyshematopoietic features, that was subsequently transformed to severe aplastic anemia. He was first diagnosed as having congenital immunodeficiency comprising deficiency of immunoglobulin A (IgA), IgG2 and IgG4, depressed mitogen responses, lymphopenia with inverted CD4/CD8 ratio and an increased proportion of T-cell receptor gamma/delta-bearing cells. Cytogenetic study of the peripheral blood showed a normal karyotype of 46,XY, but that of the marked hypoplastic marrow demonstrated one cell with monosomy 7 and another with trisomy 8 in the 20 cells examined.

Anemia, Aplastic↗
PubMed1994

Cerebrospinal fluid concentrations of interleukin-1 beta, tumour necrosis factor-alpha, and interferon gamma in bacterial meningitis.

To investigate the role of the inflammatory cytokines, the cerebrospinal fluid concentrations of interleukin (IL)-1 beta, tumour necrosis factor-alpha (TNF-alpha), and interferon gamma (IFN-gamma) were measured in 11 children with bacterial meningitis and two with mycoplasmic meningoencephalitis and compared with those in 50 children with aseptic meningitis and 15 with non-pleocytotic cerebrospinal fluid. Concentrations of IL-1 beta and TNF-alpha were each significantly higher in the cerebrospinal fluid of patients with bacterial meningitis than in those with aseptic meningitis or those with non-pleocytotic cerebrospinal fluid. IFN-gamma was detected at low concentrations in the cerebrospinal fluid of only 2/11 of those with bacterial meningitis. On the other hand, the IFN-gamma concentration was the highest in the cerebrospinal fluid of patients with aseptic meningitis. These results suggest that the inflammatory cytokines are differently released in the intrathecal space infected with viruses or bacteria.

Adolescent↗
PubMed1994

Molecular basis of beta-thalassemia in Japan: heterogeneity and origins of mutations.

Characterization of beta-thalassemia mutations was attempted for 13 unrelated Japanese patients heterozygous for beta-thalassemia. We have systematically analyzed beta-thalassemia genes using polymerase-chain-reaction-related techniques; dot blot hybridization with oligonucleotide probes complementary to known mutations, restriction endonuclease assay and direct sequencing of amplified genomic DNA. Seven different mutations were detected. Six of them are an amber mutation in codon 90 (GAG to TAG), a four-base-pair deletion in codons 41 and 42 causing premature termination due to frameshift, a C-T substitution at position 654 of IVS-2, a G-A substitution at position 1 of IVS-2 and a C-G substitution at position 848 of IVS-2, leading to splicing defects, and an ocher mutation (GAA-TAA) in codon 121 causing a thalassemia intermedia phenotype with inclusion body formation in erythrocytes. A silent mutation (CTG-TTG) was also detected in codon 91 of the allele with the IVS-2 position 1 mutation. These mutations have been reported previously in the Japanese population. The other mutation is a novel one in the Japanese, an amber mutation (TGG-TAG) in codon 15, causing a beta zero-thalassemia phenotype by premature termination of the beta-globin chain synthesis. We analyzed haplotypes of chromosomes bearing each beta-thalassemia mutation. Origins and a spectrum of mutations in comparison with those detected in malaria-endemic regions are discussed.

Adolescent↗
PubMed1993

Deregulated production of interleukin-4 (IL4) in autoimmune thyroid disease assayed with a new radioimmunoassay.

A sensitive, reproducible and specific radioimmunoassay for human interleukin-4 (IL4) has been developed. Using 125I-labeled IL4 and polyclonal rabbit antisera raised against recombinant human IL4, a competitive inhibition assay was developed which could detect 5 pg/ml of human IL4. Other interleukins, growth factors, hormones, peptides and lectins did not affect the assay. IL4 was measured in supernatants of culture media of stimulated human peripheral blood mononuclear cells (PBMC). Kinetics of IL4 production in PHA-stimulated PBMC from seven normal subjects revealed that the peak levels of IL4 were seen at 24 h and then declined. Peak IL4 levels in PHA stimulation of PBMC from untreated patients with autoimmune thyroid diseases (Graves' disease and chronic thyroiditis) were significantly higher than normal controls. However, after treatment, IL4 production decreased to normal. The present study demonstrates the usefulness of quantitating human IL4 produced by PBMC and that there exists a deregulated production of IL4 in autoimmune thyroid diseases.

Antibody Specificity↗
PubMed1993

Serum interleukin-6 and fever at diagnosis in children with acute leukemia.

PATIENTS AND METHODS: We examined serum interleukin (IL)-6 and tumor necrosis factor (TNF) alpha levels at initial diagnosis in acute leukemic children in order to clarify the roles of these cytokines on the febrile and hematological responses in the disease. RESULTS: IL-6 levels were significantly higher in 34 leukemic children than in 18 healthy controls and 15 patients with various malignant diseases in long remission (p < 0.0001). Three patients with apparent bacterial infections showed especially high IL-6 levels of > 100 pg/ml. In all the leukemic children, the high IL-6 levels at initial diagnosis had decreased to a low range at the time of complete remission, regardless of the use of antibiotics. In 10 of 14 leukemic children, TNF levels were high at diagnosis and then decreased to undetectable levels at remission. The relationship between IL-6/TNF levels and clinical/laboratory findings in leukemic children at diagnosis was also examined. Serum IL-6 significantly correlated with elevated body temperature (BT) (p < 0.001) and C-reactive protein (CRP) levels (p < 0.001), but not with other parameters such as leukocyte and platelet counts, hemoglobin levels, lactate dehydrogenase, and serum immunoglobulin. On the other hand, serum TNF did not show any statistical linkage with these parameters. CONCLUSION: These data provide evidence for the role of IL-6 in the pathogenesis of tumor-related fever and other acute phase responses in acute leukemia.

Adolescent↗
PubMed1993

Disseminated intravascular coagulation in a patient with haemophilia B during factor IX replacement therapy.

We report a case of haemophilia B, who developed disseminated intravascular coagulation (DIC) with massive bleeding following an administration of factor IX complex concentrates. A 22-year-old male with severe haemophilia B had a bone fracture of the fibula and haemorrhage in the ankle joint because of a traffic accident. Factor IX complex concentrates were given to keep the plasma factor IX level more than 80% for surgery. 60 h after the infusion he showed epistaxis, haematuria and swelling of the injured ankle with evidence of DIC. A small dose of monoclonal antibody (mAb)-purified factor IX concentrates with heparin and gabexate relieved the haemorrhage. A high dose of the mAb-purified product attained more than 90% levels of plasma factor IX without coagulopathy. This observation emphasizes that currently available factor IX concentrates have thrombogenicity to induce DIC. Highly purified factor IX concentrates are needed for the high-dose replacement in haemophilia B.

Adult↗
PubMed1993

Peripheral expansion of gamma delta T cell receptor-positive cells in a patient with Crohn's disease.

A 13 year old boy with Crohn's disease had a prominent expansion (over 40%) of gamma delta T cell receptor-positive cells (gamma delta T cells) in the peripheral blood. The gamma delta T cells were gradually decreased from 48 to 22% in 18 months. Anti-gamma delta T cell receptor-triggered cytotoxicity was evident at onset and after 1 year. The significance of peripheral expansion of gamma delta T cells in a patient with Crohn's disease is discussed.

Adolescent↗
PubMed1993

Expression of platelet alpha-granule proteins in a human megakaryocytic leukemia cell line (CMK 11-5).

We investigated the expression of three platelet alpha-granule proteins, thrombospondin (TSP), von Willebrand factor (vWF), and fibrinogen (Fbg), in a human megakaryocytic cell line (CMK 11-5) by immunocytochemical staining, using the alkaline phosphatase anti-alkaline phosphatase (APAAP) complex method and immunoelectron microscopy of ultrathin-frozen sections. CMK 11-5, established from a Down's syndrome patient with acute megakaryoblastic leukemia, has characteristics closely resembling those of normal megakaryocytes. Under basal conditions, TSP expression was observed in the alpha-granules, whereas the other two proteins were not detected. When the cells were cultured with 12-o-tetradecanoylphorbol-13-acetate (TPA), the expression of TSP was enhanced and vWF was also detected, but not Fbg. Cells cultured in the presence of plasma for 24 h took up Fbg and stored it in their alpha-granules. These findings suggest that TSP and vWF are synthesized by CMK 11-5 cells, with the former being produced more rapidly than the latter, whereas Fbg is endocytosed from the plasma.

Cytoplasmic Granules↗
PubMed1993

Ultrastructural localization of myeloperoxidase activity in acute monoblastic leukemia.

In five patients with acute monoblastic leukemia (AMoL), the ultrastructural localization of myeloperoxidase (MPO) activity was investigated by two methods, one generally used for the detection of MPO and the other for the detection of platelet peroxidase. The MPO-positive rate achieved was lower with the former method than with the later, indicating that MPO is degraded during the fixation of AMoL cells for electron microscopy. If the ultrastructural MPO positivity of leukemic cells varies when different detection methods are used, the possibility of monocytic leukemia should be considered.

Adult↗
PubMed1993

Inflammatory cytokines in virus-associated hemophagocytic syndrome. Interferon-gamma as a sensitive indicator of disease activity.

PURPOSE: We assayed serum interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) levels in children with virus-associated hemophagocytic syndrome (VAHS) to evaluate the relationship of these cytokines to other laboratory parameters. We also studied the role of IFN-gamma as a macrophage activator in hemophagocytic syndrome (HPS). PATIENTS AND METHODS: Interleukin-1 beta, TNF-alpha, and IFN-gamma were measured in 42 serial sera from six children with VAHS using a sensitive radioimmunoassay. RESULTS: The cytokine IFN-gamma or TNF was detected in 19/19 (100%) or 11/19 (69%) samples, respectively, during the active febrile phase, at much higher levels than during the remission phase of the disease (IFN: p < 0.00001; TNF: p < 0.01). In contrast, IL-1 could be detected in only two sera obtained from a patient during severe relapse. Serial cytokine examination revealed that the elevated TNF and IFN-gamma levels decreased rapidly to an undetectable level in concert with clinical improvement after an effective treatment, and that IFN-gamma, but not TNF, was detected just before a relapse marked by spiking fever. In the active phase, the CD4/8 ratio was depressed, and the total number of CD3+ HLA-DR+ cells was increased. Of the activated T cells, CD8+ cells outnumbered CD4+ T cells. By the Spearman's rank sum test, the IFN-gamma level correlated positively with the peripheral leukocyte count [Correlation coefficient (CC): 0.585, p < 0.05] and serum lactate dehydrogenase level (CC: 0.538, p < 0.05) and negatively with the CD4/8 ratio (CC: -0.618, p < 0.05), but not with any other parameter including ferritin and C-reactive protein. Although TNF and IL-1 were not statistically linked to these parameters, TNF levels were related to IFN-gamma levels (product moment CC: 0.546, p < 0.05). CONCLUSIONS: These results suggest that circulating IFN-gamma is one of the most sensitive indicators of disease activity; it may act as a potent macrophage activator during the hypercytokinemic state of childhood VAHS.

Adolescent↗
PubMed1992

Effects of injected antibody against the platelet glycoprotein IIb/IIIa complex on monkey platelet fibrinogen.

Four monkeys were injected for a 10-day period with the Fab fragment of a murine monoclonal antibody (NNKY 1-32) which inhibits the binding of fibrinogen to the platelet glycoprotein (GP) IIb/IIIa complex. Platelet fibrinogen levels were assessed quantitatively by electroimmunoassay and qualitatively by immunoelectron microscopy. The platelet fibrinogen level fell to 9.0 +/- 2.8% of the control level after antibody administration. Immunoelectron microscopy showed that the injected antibody was localized on the inner surface of the platelet alpha-granule membrane. Our findings suggest that the GP IIb/IIIa complex can be internalized by alpha-granules and that it may mediate the endocytosis of plasma fibrinogen by platelets.

Animals↗
PubMed1992

A protective role of gamma/delta T cells in primary infection with Listeria monocytogenes in mice.

We have previously reported that T cells bearing T cell receptors (TCRs) of gamma/delta type appear at a relatively early stage of primary infection with Listeria monocytogenes in mice. To characterize the early-appearing gamma/delta T cells during listeriosis, we analyzed the specificity and cytokine production of the gamma/delta T cells in the peritoneal cavity in mice inoculated intraperitoneally with a sublethal dose of L. monocytogenes. The early-appearing gamma/delta T cells, most of which were of CD4-CD8- phenotype, proliferated and secreted IFN-gamma and macrophage chemotactic factor in response to purified protein derivative from Mycobacterium tuberculosis, or recombinant 65-kD heat-shock protein derived from M. bovis but not to heat-killed Listeria. To further elucidate the potential role of the gamma/delta T cells in the host-defense mechanism against primary infection with Listeria, we examined the effects of in vivo administration of monoclonal antibodies (mAbs) against TCR-gamma/delta or TCR-alpha/beta on the bacterial eradication in mice infected with Listeria. Most of alpha/beta T cells or gamma/delta T cells were depleted in the peripheral lymphoid organs at least for 12 d after an intraperitoneal injection of 200 micrograms TCR-alpha/beta mAb or 200 micrograms TCR-gamma/delta mAb, respectively. An exaggerated bacterial multiplication was evident at the early stage of listerial infection in the gamma/delta T cells-depleted mice, whereas the alpha/beta T cell-depleted mice exhibited much the same resistance level as the control mice at this stage although the resistance was severely impaired at the late stage after listerial infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗