Reduced Number of Peripheral Blood Granulocytic Progenitor Cells in Patients with Down's Syndrome

Standen, Graham R.; Philip, Mark A.; Fletcher, J.

doi:10.1111/j.1365-2141.1979.tb01150.x

Cited by 17 publications

(6 citation statements)

References 20 publications

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“…A marked decrease in the number of haematopoietic colony-forming cells has been observed in peripheral blood of DS patients (Standen et al, 1979) and fetal liver of trisomy 16 mouse embryos (Herbst et al, 1982;Epstein et al, 1985). The data presented here show that genedosage of CuZnSOD alone can cause a decrease in haematopoietic colony-forming cells in the bone marrow from adult mice, especially under stress conditions.…”

Section: Discussionmentioning

confidence: 98%

“…DS patients suffer from a wide range of symptoms including mental retardation and abnormal external features (Benda, 1969;Epstein, 1986). They also show high susceptibility to infections and have abnormalities in their thymus and bone marrow (Benda, 1969; Levine et al, 1979;Standen et al, 1979;Tolksdorf and Wiedemann, 1981;Ugazio, 1981;Epstein, 1986Epstein, , 1989. Mouse fetuses with trisomy 16, a mouse model for human trisomy 21 (Epstein et al, 1990), also exhibit abnormalities similar to those found in DS; a hypoplastic thymus and a decreased number of haematopoietic progenitor cells in their liver (Epstein et al, 1985(Epstein et al, , 1990).…”

Section: Introductionmentioning

confidence: 99%

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Thymic abnormalities and enhanced apoptosis of thymocytes and bone marrow cells in transgenic mice overexpressing Cu/Zn-superoxide dismutase: implications for Down syndrome.

et al. 1995

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The copper‐zinc superoxide dismutase (CuZnSOD) gene resides on chromosome 21 and is overexpressed in Down syndrome (DS) patients. Transgenic CuZnSOD mice with elevated levels of CuZnSOD were used to determine whether, as in DS, overexpression of CuZnSOD was also associated with thymus and bone marrow abnormalities. Three independently derived transgenic CuZnSOD strains had abnormal thymi showing diminution of the cortex and loss of corticomedullary demarcation, resembling thymic defects in children with DS. Transgenic CuZnSOD mice were also more sensitive than control mice to in vivo injection of lipopolysaccharide (LPS), reflected by an earlier onset and enhanced apoptotic cell death in the thymus. This higher susceptibility to LPS‐induced apoptosis was associated with an increased production of hydrogen peroxide and a higher degree of lipid peroxidation. When cultured under suboptimal concentrations of interleukin 3 or in the presence of tumour necrosis factor, bone marrow cells from transgenic CuZnSOD mice produced 2‐ to 3‐fold less granulocyte and macrophage colonies than control. The results indicate that transgenic CuZnSOD mice have certain thymus and bone marrow abnormalities which are similar to those found in DS patients, and that the defects are presumably due to an increased oxidative damage resulting in enhanced cell death by apoptosis.

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Thymic abnormalities and enhanced apoptosis of thymocytes and bone marrow cells in transgenic mice overexpressing Cu/Zn-superoxide dismutase: implications for Down syndrome.

et al. 1995

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“…It is thought to be provoked by stress or by a misdiagnosed viral infection, but the magnitude of the response is such that acute leukemia is diagnosed and the diagnosis is not rectified until the affected child recovers. Other abnormalities include thrombocytopenia, neonatal polycythemia, a reduced number of granulocytic progenitor cells, and abnormalities in the lobe counts of polymorphonuclear leucocytes (Mittwoch 1958, Weinberger and Oleinick 1970, Sigler and Zinkham 1972, Standen et al 1979. The existence of the reversible leukemoid reaction, together with the other abnormalities, suggests that a stemcell defect is associated with the syndrome.…”

Section: Leukemia and Other Cancersmentioning

confidence: 99%

Leukemia and other Cancers, Anomalies and Infections as Causes of Death in Down's Syndrome in the United States during 1976

Scholl¹,

Stein²,

Hansen³

1982

Develop Med Child Neuro

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SUMMARY All 995 persons with Down's syndrome who died in the United States during 1976 and whose death certificates listed Down's syndrome as the underlying or a contributing cause of death were identified. This allowed the underlying causes of death of 793 affected persons to be analysed and compared to deaths in the whole US population for that year. Mortality ratios provided evidence that the excess risk of leukemia mortality continues into adulthood and that deaths from other hematopoietic malignancies also occur excessively among Down's syndrome adults. Congenital anomalies of all kinds in infancy and congenital defects of the heart in infancy and later were also excessive. Respiratory tract infections and pneumonia showed persistently high ratios. Diabetes was raised only at ages 24 to 34 years. Ischemic heart disease, non‐hematopoietic cancers, accidents, suicides and violence were under‐represented among the causes of death. Methodological limitations of proportional mortality analysis are discussed. RÉSUMÉ Tous les 995 sujets porteurs de mongolisme, morts aux Etats‐Unis en 1976 et dont le certificat de décès mentionnait le mongolisme comme cause de décès sous‐jacente ou contributive ont été identifiés. Cela a permis d'analyser les causes de décès chez 793 sujets et une comparaison avec les causes de décès de la population générale aux Etats‐Unis pour la même année. Les taux de mortalité démontrent que le risque élevé de mortalité par leucémie persiste à l'âge adulte et que la mort par d'autre hémopathies malignes survien également avec un taux excessif chez les mongoliens adultes. Les anomalies congénitales de toutes sortes durant la première enfance, les affections cardiaques congénitales de l'enfance ou de survenue plus tardive étaient également d'un taux excessif. Les infections du tractus respiratoire et la pneumonie présentaient également des taux constamment élevés. Le diabète ne s'élevait que pour les âges de 24–34 ans. L'ischémie myocardique, les cancers non hémopathiques, les accidents, les suicides et les faits de violence étaient sous‐représentés parmi les causes de décès. La limitation méthodologique d'une analyse proportionnelle des causes de mortalité est discutée. ZUSAMMENFASSUNG Es wurde alle 995 Personen mit Down Syndrom erfaßt, die 1976 in den Vereinigten Staaten gestorben sind und auf deren Totenschein als primüre oder sekundäre Todesursache Down Syndrom angegeben war. Anhand der Daten konnten die primären Todesursachen von 793 Personen analysiert werden und mit den Todesfällen in der Gesamtpopulation der Vereinigten Staaten in diesem Jahr verglichen werden. Die Mortalitätszahlen weisen darauf hin, daß das sehr hohe Risiko der Leukämiesterblichkeit bis ins Erwachsenenalter fortbesteht und daß auch andere hämatopoetische Erkrankungen sehr häufig bei erwachsenen Patienten mit Down Syndrome zum Tode führen. Excessiv hoch waren die kongenitalen Mißbildungen verschiedener Art im Kindesalter und angeborene Herzfehler im Kindesalter und später. Der Anteil der respiratorischen Infekte und Pneu...

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“…Bone marrow was obtained from ribs removed routinely from patients undergoing thoracotomy. Peripheral blood samples from healthy volunteers were separated to produce a mononuclear cell fraction enriched for CFUc (Standen, Philip & Fletcher, 1979). This cell fraction or the bone marrow was used as a source of CFUc (target cells).…”

Section: A T E R I a L S A N D M E T H O D Smentioning

confidence: 99%

The Proliferative State of Granulocytic Progenitor Cells in Human Blood and Marrow

1980

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A double layer agar technique was used to investigate the proliferative state of granulocytic progenitor cells (Colony Forming Units in Culture; CFUc) in human peripheral blood and bone marrow. The sensitivity of the progenitor cells to the S‐phase specific agent, hydroxyurea, was used as an index of the proportion of cells engaged in DNA synthesis. In the presence of low concentrations of colony stimulating factor (CSF) the CFUc were found to be virtually insensitive to the drug. However, when cultured in the presence of increasing concentrations of CSF the proportion of CFUc apparently killed by hydroxyurea increased to a maximum of 23% for those cells in the blood and 39% for those in the marrow. The results indicate that CFUc which are slowly proliferating are sensitive to low concentrations of CSF. In contrast, those CFUc which are proliferating more rapidly require high concentrations of CSF before they will form colonies in culture. A model has been devised which suggests that as CFUc mature, their cell cycle time shortens and their sensitivity to CSF decreases.

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Reduced Number of Peripheral Blood Granulocytic Progenitor Cells in Patients with Down's Syndrome

Cited by 17 publications

References 20 publications

Thymic abnormalities and enhanced apoptosis of thymocytes and bone marrow cells in transgenic mice overexpressing Cu/Zn-superoxide dismutase: implications for Down syndrome.

Thymic abnormalities and enhanced apoptosis of thymocytes and bone marrow cells in transgenic mice overexpressing Cu/Zn-superoxide dismutase: implications for Down syndrome.

Leukemia and other Cancers, Anomalies and Infections as Causes of Death in Down's Syndrome in the United States during 1976

The Proliferative State of Granulocytic Progenitor Cells in Human Blood and Marrow

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