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Query: UMLS:C0013080 (Down syndrome)
 14,180 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Trisomy 21 (Down's syndrome, DS) is the most frequent chromosomal aberration. Triplication of a small region of chromosome 21, the fragment 21q22 is sufficient to cause the DS phenotype including immunodeficiency, premature aging, neurodegenerations, mental retardation and an increased risk of leukemia. Chromosomal aberrations caused by X-ray irradiation were observed in DS lymphocytes and DS fibroblasts, but the correlation to cell death or repair deficiency was not clear. We approached this problem and report here on a profound X-ray repair deficiency of DS cells. With a colorimetric viability assay we observed an UV sensitivity of DS fibroblasts at doses beyond 14 Jm-2 but no significant X-ray sensitivity. By the nucleoid sedimentation technique, a deficient restoration of nucleoids in DS cells after X-ray irradiation was demonstrated. The same features apply for cells, which contain an overexpressed Cu/Zn-superoxide dismutase (SOD-1) gene. Radiation sensitivity of DS cells and SOD-1 overexpressing cells resemble those of ataxia telangiectasia (AT) fibroblasts. Additionally, DS and AT cells exert lack of inhibition of DNA synthesis after X-ray irradiation.
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PMID:Radiation sensitivity of Down's syndrome fibroblasts might be due to overexpressed Cu/Zn-superoxide dismutase (EC 1.15.1.1). 252 18

We report a 3 1/2-week-old male infant with Down's syndrome who presented with abdominal distention, ascites, and eosinophilia and was subsequently diagnosed as having an abdominal non-Hodgkin's lymphoma of T-cell type. Because of the unusual association of these two conditions, especially at this early age, the literature was reviewed regarding the possible oncogenic mechanisms in Down's syndrome patients and the various malignancies associated with this condition. Non-Hodgkin's lymphoma is discussed briefly with emphasis on its possible etiologic mechanisms and predisposing conditions, especially the immunodeficiency states. Because this infant presented with non-Hodgkin's lymphoma at an early age, it is considered unlikely that an immunoaberration is responsible. Also, a short discussion of this patient's peripheral and bone marrow eosinophilia is given, implicating a T-cell product (e.g., eosinophil differentiation factor) as the putative pathophysiologic mechanism.
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PMID:Non-Hodgkin's lymphoma in a neonate with Down's syndrome. Case report and literature review. 252 4

Sixty-eight human fibroblast cell strains were assayed for radioresistant DNA synthesis (RDS), which is defined here as the absence of a steep component of inhibition of DNA synthesis in a dose-response curve when rate of DNA synthesis is plotted against radiation doses from 0 to 20 Gy or more. Twenty-seven strains from patients who were previously diagnosed to have ataxia-telangiectasia (AT) were positive for this feature. Among the cell strains that did not show RDS were two from AT obligate heterozygotes (i.e., the parents of AT patients), two from patients with Alzheimer disease, two from patients with Friedreich ataxia, one from a patient with Bloom syndrome, one from a patient with Down syndrome, and six from patients with various immunodeficiencies. Four strains demonstrated RDS that was less pronounced than in most AT cells: one was from a patient with Nijmegen breakage syndrome, one was from a patient without ataxia but with choreiform movement disorder, telangiectasia, and elevated concentrations of alpha-fetoprotein in the blood, and two were from AT patients. RDS therefore is not a necessary trait of human genetic diseases that involve radiosensitivity or immunodeficiency. Although recent reports suggest that some AT patients do not exhibit RDS, we found RDS in all the AT cells we tested.
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PMID:Radioresistant DNA synthesis and human genetic diseases. 272 85

To correlate the histologically observed thymic abnormalities with the cellular immunodeficiency found in Down's syndrome (DS), thymus fragments and thymocyte suspensions from 14 noninstitutionalized DS subjects were studied. Histologic examination and immunohistologic studies using an anticluster of differentiation (CD) 1 monoclonal antibody showed a contracted cortex due to cortical thymocyte depletion. When DS unselected thymocytes were phenotyped, a significant reduction of CD3-, CD1-, CD4-, and CD8-positive cells was found as compared to controls. To evaluate if the deficient expression of these markers was due to the reduction of thymocyte subsets identifiable on the basis of their physical properties, we separated DS unselected thymocytes into 10 fractions by continuous Percoll density gradient centrifugation. DS thymuses were almost completely devoid of high density thymocytes. Since in normal thymus, these cells correspond to small CD1+, CD4+, CD8+, and 50% CD3+ cortical thymocytes, their absence may explain the unrestricted reduction of markers on DS unfractionated thymocytes. Furthermore DS thymuses appeared to be enriched in CD1+ first fraction (Fr1) low density thymocytes of the Percoll gradient. Fr1 CD1+ cells constitute the main spontaneously proliferating pool in normal human thymus. When the spontaneous proliferating activity of DS Fr1 was compared to that of the control, a significant reduction was observed. This reduction associated with the absence of high density thymocytes, with the reduction of cells expressing alpha- and beta-chains of the T cell receptor and in conclusion with the lymphocyte depletion, suggests that in DS thymuses there is a deficient expansion of immature T cells resulting in a reduction of the various thymocyte subpopulations, including the thymocyte pool able to differentiate into functionally mature T cells.
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PMID:Alterations in thymocyte subpopulations in Down's syndrome (trisomy 21). 297 89

Usefulness of an etiologic questionnaire was examined in an interview study of 503 children with cancer. The medical records of the children were abstracted, and their parents responded to a questionnaire-interview to identify genetic and environmental causes of cancer. Among 1,123 siblings of the index patients, 10 developed cancer as compared with 2 expected on the basis of cancer rates for the general population. Cancer risk factors were identified in individual patients with predisposing genetic and congenital disorders: neurofibromatosis (brain tumor), hereditary immunodeficiency (lymphoma), Down's syndrome (leukemia), XY gonadal dysgenesis (germ cell tumor), giant nevus (melanoma), and meningocele (sacral teratocarcinoma). Environmental causes of childhood cancer were difficult to discern because prior exposures were numerous, diverse, and usually ill defined. The questionnaire yielded more data than the medical record on gestational and family history and helped identify patients with exceptionally high cancer risk for additional investigation. Although the findings provide anecdotal confirmation of several associations, few original etiologic hypotheses were generated for formal testing with conventional epidemiologic techniques.
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PMID:Questionnaire study of cancer etiology in 503 children. 307 44

The heuristic concept of "inborn errors of metabolism" was introduced more then 70 years ago and by analogy has prompted the more recent introduction of the term "inborn errors of immunity". It is now well recognized that many inborn errors of immunity can be considered inborn errors of metabolism. Typically, many forms of severe combined immunodeficiency result from adenosine deaminase deficiency, i.e., an inborn error of purine metabolism. On the other hand, errors of immunity are often associated with "errors of morphogenesis", resulting from an intrinsically abnormal developmental process (malformation), a secondary or extrinsic interference with originally normal development (disruption), or an abnormal organization of cells into tissues (dysplasia). Twenty years after the original description, the DiGeorge anomaly should be considered an inborn error of morphogenesis and immunity due either to disruption or less frequently to malformation. In other immunodeficiencies, such as ataxia telangiectasia, the morphologic and immunologic errors result from a dyshistogenesis, i.e., dysplasia. Also, true malformation syndromes, such as Down's syndrome, are consistently associated with immunodeficiency.
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PMID:Errors of morphogenesis and inborn errors of immunity 20 years after the discovery of DiGeorge anomaly. 401 10

The high susceptibility to infections, malignancies, and autoimmune disorders of subjects with Down's syndrome (DS) is associated with laboratory and pathological evidence of immunodeficiency. The percentage of circulating T-lymphocytes is indeed low from birth, and lymphocyte proliferative response to mitogens, normal during the 1st decade of life, declines rapidly thereafter. There is indirect evidence that T-lymphocyte maturation is impaired in DS; furthermore, the thymus is morphologically deranged and there is recent direct evidence that serum levels of thymic hormones are low. It is suggested that the immunodeficiency of DS results from a defect limited primarily to the epithelial cells of the thymus which fail to synthesize or secrete one or more hormones necessary for the differentiation of T-lymphocytes.
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PMID:Down's syndrome: problems of immunodeficiency. 621 39

To get more information on the mechanism of cell-mediated immunodeficiency associated with Down's syndrome, 18 patients were studied for PHA-induced lymphocyte transformation and interleukin-2 (IL-2) production. A normal amount of IL-2 was produced although half of the patients showed decreased blast transformation. T cell subpopulations were studied in some patients with decreased and with normal blast transformation. All studied patients with decreased blast transformation had inverted helper/suppressor T cell ratio.
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PMID:Cell-mediated immunodeficiency in Down's syndrome: normal IL-2 production but inverted ratio of T cell subsets. 623 Jan 81

The activities of CDP reductase and thymidine kinase in 10(6) to 5 X 10(6) phytohemagglutinin (PHA)-stimulated lymphocytes isolated from 2 to 5 ml of peripheral blood of individual subjects were measured. The activities of CDP reductase (pmol/h/10(7) cells) and thymidine kinase (nmol/h/10(7) cells) were high in infants, 698 +/- 307 and 64.2 +/- 20.2, constant in subjects of 1-40 years old, 401 +/- 181 and 38.1 +/- 15.3, and low in persons of more than 80 years old, 121 +/- 113 and 22.3 +/- 17.8, respectively. The ratio of thymidine kinase to CDP reductase activity increased with age, indicating that dependency on the salvage pathway of DNA synthesis in lymphocytes increased with age. The activities of CDP reductase and thymidine kinase were reduced in patients with the hyperimmunoglobulin E syndrome, congenital cytomegalovirus infection, anhidrotic ectodermal dysplasia with hyperimmunoglobulin A, Bloom's syndrome, immunodeficiency with hyperimmunoglobulinemia, and Down's syndrome. The clinical symptoms of these diseases seem to be due to impaired DNA synthesis of PHA-stimulated lymphocytes, but the degrees of reduction of enzyme activities were generally greater than that of thymidine incorporation in these patients.
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PMID:Cytidine 5'-diphosphate reductase and thymidine kinase activities in phytohemagglutinin-stimulated lymphocytes of normal subjects of various ages and patients with immunodeficiency. 638 37

Fifty children with IgA deficiency were folllowed for 1 to 4 years from 1975 to 1978. Thirty-five had complete deficiency of serum IgA (less than 2.5 IU/ml) and 15 partial deficiency (serum IgA below the 10th centile for age). Patients with another associated immunodeficiency, such as ataxia-telangiectasia, were not included. Most children with complete deficiency of IgA had recurrent respiratory and/or gastrointestinal infections, about half with onset in the first year of life, while partial deficiency of IgA has probably little if any importance for anti-infectious immunity but is important in the pathogenesis of atopy. Atopic diseases were frequent in both groups. Chromosomal abnormalities were found in 2 patients: trisomy 21 in one and in the other a ring chromosome 18. No important defects in cellular immunity were detected but some isolated, borderline abnormalities were often present.
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PMID:Selective IgA deficiency: clinical and immunological evaluation of 50 pediatric patients. 644 75


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