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  • 1
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    AG dinucleotide insertion in a patient with chronic granulomatous disease lacking cytosolic 67-kD protein (1995)
    American Society of Hematology
    Details
    Publication Date: 1995-07-01
    Description: The 67-kD cytosolic protein (p67-phox) is an essential component of the superoxide-generating system in phagocytes, and its defect is known to cause chronic granulomatous disease (CGD). We sequenced p67-phox cDNA from one of seven patients found in Japan and his parents. In the patient's cDNA, homozygous AG dinucleotide insertion at position 399 (or 401) was found together with three other homozygous substitutions in a coding region (A-542 to G, T-895 to C and A-983 to G) compared with the sequence reported for HL-60 cells. In cDNA from his parents, the AG insertion was found to be heterozygous. In contrast, the other three substitutions were found homozygously in his father's specimen and the latter two in his mother's specimen. The substitution of A-542 to G was heterozygous in his mother's cDNA. The AG insertion would induce a frame shift and bring about a stop codon at the position of 433. However, the other three differences would give insignificant changes for the protein function, if any, because the substitutions of A-542 to G and A-983 to G result in the conservative amino acid transitions, ie, Lys-180 to Arg and Lys-327 to Arg, and that of T-895 to C no amino acid change. Neutrophils from the patients completely lacked superoxide generating activity whereas those from his parents generated substantial amounts of superoxide anion upon stimulation. Thus, it is concluded that the AG dinucleotide insertion is responsible for the disease in this patient.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Published by American Society of Hematology
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  • 2
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    An established CD4+ T lymphoma cell line derived from a patient with so- called Lennert's lymphoma: possible roles of cytokines in histopathogenesis (1988)
    American Society of Hematology
    Details
    Publication Date: 1988-01-01
    Description: A T lymphoma cell line, KT-3, was established from the peripheral blood of a patient with so-called Lennert's lymphoma when the patient developed leukemic lymphoma. The KT-3 cells stain positively for alpha- naphthyl acetate esterase, PAS, and acid phosphatase. The surface phenotype is E rosette-positive, CD1-, CD2+, CD3-, CD4+, CD5+, CD8-, CD11-, CD20-, CD25 (anti-Tac)+, OKla-1+, HNK-1-, J-5-, and My9-, and the surface membrane immunoglobulin is negative, which is almost the same phenotype as the leukemic cells studied when the culture was started. Southern blot analysis showed rearrangement in both beta and gamma T cell receptor genes. Although KT-3 cells proliferate spontaneously and form clusters, they cease proliferating when they are cultured at low cell densities. They proliferate vigorously in response to macrophages, macrophage-derived factor, or recombinant interleukin 2 (rIL-2) added to the culture. Furthermore, they secrete interferon- gamma (IFN-gamma) spontaneously, and the secretion is augmented when they are stimulated with macrophage-derived factor. The macrophage- derived factor enhancing KT-3 cell growth is different from IL-1 alpha, IL-1 beta, IL-2, or IFN-gamma. To our knowledge, this is the first tumor cell line established from a patient with Lennert's lymphoma. The results conclusively confirmed that, at the least, Lennert's lymphoma included CD4+ T lymphoma and also suggested that cytokines or factors secreted by T lymphoma cells and epithelioid histiocytes play an important role in the histopathogenesis of Lennert's lymphoma.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Published by American Society of Hematology
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  • 3
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    Hb Toyoake: beta 142 (H20) Ala replaced by Pro. A new unstable hemoglobin with high oxygen affinity (1981)
    American Society of Hematology
    Details
    Publication Date: 1981-04-01
    Description: A new unstable hemoglobin with high oxygen affinity, Hb Toyoake: beta 142 (H20) Ala replaced by Pro, was found in Japanese male with a normal blood hemoglobin level, shortened red cell survival, and increased plasma erythropoietin. Hemoglobin studies showed heat and isopropanol instability, and an increased tendency to heme loss and to subunit dissociation. Electrophoresis of whole hemolysate showed inconstant abnormal bands with reduced mobilities due to progressive heme loss during the in vitro procedure. Isolated Hb Toyoake with normal heme content migrated slightly faster than HbA. Oxygen affinity of red cells was elevated with P50 of 17.0 mm Hg at pH 7.4 and 37 degrees C (normal 25.0 mm Hg). Studies on hemolysate implied that Hb Toyoake had an almost normal Bohr effect, a diminished cooperativity, and a reduced response to inositol hexaphosphate. These multiple abnormalities are associated with a substitution of Pro for beta 142 Ala, resulting in disruption of the H-helix and the adjacent C-terminal portion of beta chain, which contain residues crucial for normal oxygen binding.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Published by American Society of Hematology
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  • 4
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    Unknown
    An established CD4+ T lymphoma cell line derived from a patient with so- called Lennert's lymphoma: possible roles of cytokines in histopathogenesis (1988)
    American Society of Hematology
    Details
    Publication Date: 1988-01-01
    Description: A T lymphoma cell line, KT-3, was established from the peripheral blood of a patient with so-called Lennert's lymphoma when the patient developed leukemic lymphoma. The KT-3 cells stain positively for alpha- naphthyl acetate esterase, PAS, and acid phosphatase. The surface phenotype is E rosette-positive, CD1-, CD2+, CD3-, CD4+, CD5+, CD8-, CD11-, CD20-, CD25 (anti-Tac)+, OKla-1+, HNK-1-, J-5-, and My9-, and the surface membrane immunoglobulin is negative, which is almost the same phenotype as the leukemic cells studied when the culture was started. Southern blot analysis showed rearrangement in both beta and gamma T cell receptor genes. Although KT-3 cells proliferate spontaneously and form clusters, they cease proliferating when they are cultured at low cell densities. They proliferate vigorously in response to macrophages, macrophage-derived factor, or recombinant interleukin 2 (rIL-2) added to the culture. Furthermore, they secrete interferon- gamma (IFN-gamma) spontaneously, and the secretion is augmented when they are stimulated with macrophage-derived factor. The macrophage- derived factor enhancing KT-3 cell growth is different from IL-1 alpha, IL-1 beta, IL-2, or IFN-gamma. To our knowledge, this is the first tumor cell line established from a patient with Lennert's lymphoma. The results conclusively confirmed that, at the least, Lennert's lymphoma included CD4+ T lymphoma and also suggested that cytokines or factors secreted by T lymphoma cells and epithelioid histiocytes play an important role in the histopathogenesis of Lennert's lymphoma.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Published by American Society of Hematology
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  • 5
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    Interleukin-6 (B-cell stimulatory factor 2)-dependent growth of a Lennert's lymphoma-derived T-cell line (KT-3) (1988)
    American Society of Hematology
    Details
    Publication Date: 1988-11-01
    Description: A T lymphoma cell line (KT-3) established from a patient with Lennert's lymphoma showed macrophage-dependent growth. Macrophage-derived factors were able to replace the macrophage functions. Experiments using a variety of cytokines demonstrated that KT-3 proliferated in response to recombinant interleukin-2 (rIL-2), rIL-4, or rIL-6 but did not proliferate in response to rIL-1 alpha, rIL-1 beta, rIL-3, recombinant granulocyte colony-stimulating factor (rG-CSF), rGM-CSF, recombinant interferon-alpha (rIFN-alpha), rIFN-gamma, recombinant tumor necrosis factor (rTNF-alpha), or native IFN-beta. Polyclonal rabbit anti-IL-6 antibody almost completely neutralized the activities of macrophage- derived factors or IL-6 but not IL-2 or IL-4. Scatchard plot analysis demonstrated that KT-3 cells indeed express IL-6 receptors. The results indicate that the macrophage-derived factor that supports the growth of KT-3 is IL-6 and suggest that macrophage-derived IL-6 may play an important role in the histopathogenesis of Lennert's lymphoma.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Published by American Society of Hematology
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  • 6
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    Unknown
    Two-exon skipping due to a point mutation in p67-phox--deficient chronic granulomatous disease (1996)
    American Society of Hematology
    Details
    Publication Date: 1996-09-01
    Description: The cytosolic 67-kD protein in phagocytes (p67-phox) and B lymphocytes is one of essential components of the superoxide-generating system in these cells, and its defect causes an autosomal recessive type of chronic granulomatous disease (CGD). We performed mutation analysis of p67-phox mRNA from a CGD patient who lacks the protein and found an in- frame deletion from nucleotide 694 to 879, which corresponds to the entire sequence of exons 8 and 9. This sequence encodes one of two Src homology 3 domains and a part of proline-rich domain in p67-phox and lack of these domains seem to have influenced stability of this protein. To know causative reason for the deletion, we analyzed genomic DNA for p67-phox using two sets of primers that covered exons 8 and 9 with adjacent introns. The DNA fragments from the patient were shown to be same in length as those from control. However, the single-strand conformation-polymorphism analysis of the fragments showed that a patient's specimen that included the splice junction of exon 9 exhibited different mobility from the control. By sequencing of the fragment, a homozygous G to A replacement at position +1 of intron 9 was found to be a sole mutation, which reduced the matching score of the splicing sequence to the consensus calculated according to the formula proposed by Shapiro and Senapathy (Nucleic Acids Res 15:7155, 1987). The reduced matching score at the splice doner site (5′ splice site) of intron 9 and the original low matching score at the acceptor site (3' splice site) of intron 7 may explain the skipping of exon 8 and 9, and another predicted mechanism is discussed on the basis of Shapiro and Senapathy's hypothesis.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Published by American Society of Hematology
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  • 7
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    Unknown
    Interleukin-6 (B-cell stimulatory factor 2)-dependent growth of a Lennert's lymphoma-derived T-cell line (KT-3) (1988)
    American Society of Hematology
    Details
    Publication Date: 1988-11-01
    Description: A T lymphoma cell line (KT-3) established from a patient with Lennert's lymphoma showed macrophage-dependent growth. Macrophage-derived factors were able to replace the macrophage functions. Experiments using a variety of cytokines demonstrated that KT-3 proliferated in response to recombinant interleukin-2 (rIL-2), rIL-4, or rIL-6 but did not proliferate in response to rIL-1 alpha, rIL-1 beta, rIL-3, recombinant granulocyte colony-stimulating factor (rG-CSF), rGM-CSF, recombinant interferon-alpha (rIFN-alpha), rIFN-gamma, recombinant tumor necrosis factor (rTNF-alpha), or native IFN-beta. Polyclonal rabbit anti-IL-6 antibody almost completely neutralized the activities of macrophage- derived factors or IL-6 but not IL-2 or IL-4. Scatchard plot analysis demonstrated that KT-3 cells indeed express IL-6 receptors. The results indicate that the macrophage-derived factor that supports the growth of KT-3 is IL-6 and suggest that macrophage-derived IL-6 may play an important role in the histopathogenesis of Lennert's lymphoma.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Published by American Society of Hematology
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  • 8
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    Unknown
    Hb Toyoake: beta 142 (H20) Ala replaced by Pro. A new unstable hemoglobin with high oxygen affinity (1981)
    American Society of Hematology
    Details
    Publication Date: 1981-04-01
    Description: A new unstable hemoglobin with high oxygen affinity, Hb Toyoake: beta 142 (H20) Ala replaced by Pro, was found in Japanese male with a normal blood hemoglobin level, shortened red cell survival, and increased plasma erythropoietin. Hemoglobin studies showed heat and isopropanol instability, and an increased tendency to heme loss and to subunit dissociation. Electrophoresis of whole hemolysate showed inconstant abnormal bands with reduced mobilities due to progressive heme loss during the in vitro procedure. Isolated Hb Toyoake with normal heme content migrated slightly faster than HbA. Oxygen affinity of red cells was elevated with P50 of 17.0 mm Hg at pH 7.4 and 37 degrees C (normal 25.0 mm Hg). Studies on hemolysate implied that Hb Toyoake had an almost normal Bohr effect, a diminished cooperativity, and a reduced response to inositol hexaphosphate. These multiple abnormalities are associated with a substitution of Pro for beta 142 Ala, resulting in disruption of the H-helix and the adjacent C-terminal portion of beta chain, which contain residues crucial for normal oxygen binding.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Published by American Society of Hematology
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  • 9
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    Functional properties of murine macrophages promoted by nerve growth factor (1996)
    American Society of Hematology
    Details
    Publication Date: 1996-12-15
    Description: The stimulating effect of nerve growth factor (NGF) on phagocytosis, parasite killing, and interleukin-1beta (IL-1beta) production of murine peritoneal macrophages was assessed. In the presence of various doses of NGF, macrophages showed the increased phagocytosis of both nonspecific hydrophilic microspheres and sheep red blood cells (SRBC) opsonized with anti-SRBC antibodies (Ab) or complement in a dose-dependent manner. NGF also enhanced killing of Leishmania donovani promastigotes by macrophages, and its ability was comparable with that of an optimal dose of recombinant granulocyte-macrophage colony-stimulating factor or recombinant interferon-gamma. The addition of NGF to peritoneal macrophages and monocyte-macrophage J774A.1 cells led to a significant release of IL-1beta in a dose-dependent manner and expression of IL-1beta mRNA. Because pretreatment of peritoneal macrophages and J774A.1 cells with K-252a, a tyrosine kinase inhibitor, completely suppressed these NGF-mediated stimulating effects and p140trk phosphorylation and because flow cytometric analysis with specific Ab against two distinct NGF receptors showed the expression of p140trk, unlike p75LNGFR, on the surface of macrophages, the stimulating activity of NGF to murine macrophages may be mediated through p140trk. Thus, NGF may act as an activator for murine macrophages in the process of inflammatory and immune actions.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Published by American Society of Hematology
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  • 10
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    Unknown
    Two-exon skipping due to a point mutation in p67-phox--deficient chronic granulomatous disease (1996)
    American Society of Hematology
    Details
    Publication Date: 1996-09-01
    Description: The cytosolic 67-kD protein in phagocytes (p67-phox) and B lymphocytes is one of essential components of the superoxide-generating system in these cells, and its defect causes an autosomal recessive type of chronic granulomatous disease (CGD). We performed mutation analysis of p67-phox mRNA from a CGD patient who lacks the protein and found an in- frame deletion from nucleotide 694 to 879, which corresponds to the entire sequence of exons 8 and 9. This sequence encodes one of two Src homology 3 domains and a part of proline-rich domain in p67-phox and lack of these domains seem to have influenced stability of this protein. To know causative reason for the deletion, we analyzed genomic DNA for p67-phox using two sets of primers that covered exons 8 and 9 with adjacent introns. The DNA fragments from the patient were shown to be same in length as those from control. However, the single-strand conformation-polymorphism analysis of the fragments showed that a patient's specimen that included the splice junction of exon 9 exhibited different mobility from the control. By sequencing of the fragment, a homozygous G to A replacement at position +1 of intron 9 was found to be a sole mutation, which reduced the matching score of the splicing sequence to the consensus calculated according to the formula proposed by Shapiro and Senapathy (Nucleic Acids Res 15:7155, 1987). The reduced matching score at the splice doner site (5′ splice site) of intron 9 and the original low matching score at the acceptor site (3' splice site) of intron 7 may explain the skipping of exon 8 and 9, and another predicted mechanism is discussed on the basis of Shapiro and Senapathy's hypothesis.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Published by American Society of Hematology
    Location Call Number Expected Availability
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