Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0013080 (Down syndrome)
 14,180 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A comparison of immune competence in 26 patients with Down syndrome in an institution and 26 matched healthy controls revealed an atypical pattern of T-cell immunodeficiency in the Down-syndrome patients. The patients with Down syndrome had a lymphocytosis in blood with high counts of T (and B) cells, but with impaired effector function of T cells as judged by anergy to dinitrochlorobenzene, low responsiveness to ubiquitous antigens which elicit delayed-type hypersensitivity reactions, and low mitogenic activity of non-stimulated and phytohaemagglutinin-stimulated lymphocytes in culture. Helper-T-cell function measured by the humoral immune response to flagellin was intact, and there were minor abnormalities of the B-cell system. Attempted restoration of T-cell function with levamisole was unsuccessful. This pattern of T-lymphocytosis with impaired effector function could be explained by "stress-deficiency" of the immune system consequent upon a heavy load of infection in early life.
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PMID:Stress deficiency of the T-lymphocyte system exemplified by Down syndrome. 6 97

The reproducibility of a simplified, sensitive and rapid agarose-cell droplet assay for leucocyte migration inhibition factor (LIF) activity was studied. Removal of T cells with anti-T-cell serum eliminated LIF activity, indicating that in humans it is probably the T cell that produces LIF. Cord blood lymphocytes produce LIF, although spontaneous migration of leucocytes is less than in older children. The cause of this apparently does not reside in the PMN leucocytes. Studies of children with immunodeficiency suggest that the T-cell population in humans is heterogenous. B-cell deficiencies such as hypogammaglobulinaemia, have normal PPD and PHA induced LIF production, whilst some patients with ataxia-telangiectasia have defective PPD LIF activity, their PHA LIF activity being only minimally depressed. On the other hand, Down's syndrome patients with reduced blood T cells have remarkably deficient LIF activity to PHA and relatively good activity to PPD. Children receiving steroid therapy lose much of their ability to produce LIF to the specific antigen PPD, but not to the non-specific mitogen PHA.
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PMID:Leucocyte migration inhibition factor (LIF) production by lymphocytes of normal children, newborns, and children with immune deficiency. 13 10

The relationship between the presence of hepatitis B surface antigen (HBsAg) and antibodies to human thyroglobulin (HTgAb) has been studied in 110 subjects with Down's syndrome (DS) from 4 months to 50 years of age and in 122 controls carefully matched for sex, age and socio-environmental conditions. The overall percentage of HBsAg carriers was 22.7 in DS and 6.6 in controls and that of HTgAb-positive subjects was 41.8 in DS and 19.7 in controls. In DS the frequency of HTgAb-positive subjects was very high, even in the youngest age groups in which the percentage of HBsAg carriers was relatively low; the latter thereafter showed a marked increase with age. A positive association between the presence of HBsAg and HTgAb was found only in the oldest age group of DS subjects. It is thus concluded that in DS the high frequency of HTgAb cannot be attributed to chronic hepatitis B virus infection. On the contrary, the presence of HTgAb might well represent an early "marker" of immunodeficiency and increased susceptibility to infection with hepatitis B virus.
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PMID:Immunodeficiency in Down's syndrome: relationship between presence of human thyroglobulin antibodies and HBsAg carrier status. 14 56

The immunopotentiating effect of levamisole was assessed in a double-blind trial in two comparable groups of patients with Down's syndrome, with which the immunodeficiency and susceptibility to infection are known to be associated. One group was given levamisole continuously and at the same dose for 16 weeks, and the other group was given placebo tablets. A checklist was designed to record the type, frequency, and duration of all infections which occurred in the patients, and delayed type hypersensitivity responses to various antigens were measured. There were no differences between the two groups in body weight, number of intercurrent infections, duration of illness, nor was there any change in degree of depression or cutaneous delayed-type hypersensitivity. These findings, taken with claims of success in some patients and failure in others, suggest that levamisole is not a general immunopotentiating agent, although it may have a specific site (or sites) of action on the immune system. If levamisole is to be used more selectively, this action needs to be characterized.
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PMID:Levamisole: lack of immunopotentiation in a controlled trial. 15 Apr 87

We analysed the expression of lymphocyte function-associated antigen LFA-1 on the cell surface of peripheral blood lymphocytes, monocytes and granulocytes from 20 children with Down's syndrome. No differences in LFA-1 expression was found within monocytes or granulocytes from either normal or Down's syndrome children; however, a clear-cut difference was observed on lymphoid cells. Both normal and Down's syndrome lymphocytes displayed a bimodal pattern of LFA-1 staining by flow cytometry, with a predominance of cells with low expression in normal population, and an increased proportion of lymphocytes with high level of LFA-1 expression in Down's syndrome children. This difference correlates well with the abnormal proportion of T cell subsets and inversion of CD4/CD8 observed in a majority of our cases, and therefore, it could merely reflect the increase of certain T cell subsets normally expressing higher number of LFA-1 molecules. Taken together, our results do not support an abnormally increased expression of leucocytes integrins in trisomy 21 cells, and raise some doubt about the suggested role of the abnormal cellular expression of LFA-1 in the pathogensis of secondary immunodeficiency associated to Down's syndrome.
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PMID:Differential expression of lymphocyte function-associated antigen (LFA-1) on peripheral blood leucocytes from individuals with Down's syndrome. 134 67

We have isolated a lymphoid cell line, MDS, from the pleural exudate of a patient with chronic myelomonocytic leukemia. The cells are biphenotypic, containing various T-cell and myeloid markers, and are surface negative for CD4 and CD8 but have low CD4 mRNA. The cells grow in suspension with a doubling time of 15 hr, have been karyotyped as trisomy 21, are negative for human immunodeficiency virus type 1 (HIV-1), and are tumorigenic in the nude mouse. We have isolated two stable HIV-1-producing cell lines, MDS-T, by transfecting MDS cells with pHXBc2, and MDS-I, by infecting MDS cells with HIV-1IIIB. In 24 hr, 1 x 10(5) MDS-T or MDS-I cells produce 46 ng of p24 per ml and reverse transcriptase that is capable of incorporating 0.2 pmol of [32P]TTP into oligo(dT).poly(A). Ultrastructural studies showed numerous mature viral particles in MDS-T and MDS-I cells that are capable of infecting T cells. HIV-1 infection could be inhibited by 25% in the MDS cells with the anti-CD4 antibody Leu 3a. For over a year MDS-T and MDS-I cells have been producing high concentrations of HIV-1 in culture. A subclone derived from the MDS cells behaves like the parent cells when transfected or infected with HIV-1. In contrast to other T-cell lines, neither phorbol 12-myristate 13-acetate nor tumor necrosis factor alpha stimulated the replication of HIV-1, whereas bromoadenosine 3',5'-cyclic monophosphate or interferon alpha caused 50% and 80% inhibition of reverse transcriptase production, respectively. These chronically infected T-cell lines are a useful model system to study the effect of anti-HIV agents and cellular factors required for HIV-1 replication.
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PMID:Productive nonlytic human immunodeficiency virus type 1 replication in a newly established human leukemia cell line. 143 50

This is a presentation of the hypothesis of a pathogenetic mechanism common to the dementia seen in Alzheimer's disease (AD), Down's Syndrome (DS) and the acquired immunodeficiency syndrome (AIDS). As there is experimental evidence of defective DNA repair capacity in AD and DS, unrepaired damage to DNA occurs in these diseases and may lead to complete breakdown of cellular function and ultimate cell death. Cobalamin and folate are coordinated in a vulnerable key position in the synthesis of DNA and S-adenosylmethionine (SAM). Cobalamin/folate deficiency, a significant feature in senile dementia of Alzheimer type and in AIDS-related dementia complex, will result in concomitant slowed synthesis of DNA and SAM. The enzyme cystathionine-beta-synthetase (CBS) has been localized to the chromosome band 21q22.3. Owing to gene dosage, CBS activity is increased in trisomy 21. As a consequence, cobalamin/folate metabolism is inhibited, which leads to slowing of DNA and SAM synthesis in DS patients. Amyloidosis is a hallmark of AD and DS brain neuropathology and recent experimental findings support the view that amyloid or amyloid precursors stimulate DNA synthesis, which is in agreement with the hypothesis presented in this paper. In summary, demented patients with cobalamin/folate deficiency, trisomy 21 and human immunodeficiency virus (HIV) infection display a simultaneous downregulation of DNA and SAM synthesis, which may indicate a pathway common to the dementia seen in AD, DS and AIDS.
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PMID:Slowed synthesis of DNA and methionine is a pathogenetic mechanism common to dementia in Down's syndrome, AIDS and Alzheimer's disease? 1629 95

To correlate the intrinsic cellular immunodeficiency, which is a major cause of increased susceptibility to polytopic infections in Down syndrome (DS) patients, with the histologic abnormalities observed in the thymus of these patients, we have studied thymus fragments and thymocyte cell suspensions from 15 non-institutionalized DS subjects. Comparing to the control age-matched samples, a reduced thymic cortex and a distinct depletion of CD1-positive (+) cells was observed by immuno-histologic examination. The phenotypic analysis of unselected thymocytes showed a significant reduction of CD3+, CD1+, CD4+, and CD8+ cells. When the total thymocyte population was separated into 10 fractions, using a continuous Percoll density gradient, a difference in cell distribution was observed. DS thymuses are almost devoid of high-density thymocytes (fractions 6-9) while more than 75% of the cells were recovered in the lightest 3 fractions (Frs). In addition, these thymuses were characterized by a marked depletion of CD1+ cells and by a conspicuous reduction of CD3+ cells normally present in the high-density Frs. On the other hand, the lightest 3 Frs of DS subjects were enriched in low-density CD1+ cells. Although enriched in these cells, normally characterized by a high mitotic activity, Fr1 DS thymocytes showed a reduced spontaneous proliferative capacity. When the expression of T cell receptor alpha- and beta-subunits was studied, the percentages of cells stained with anti-alpha and anti-beta antisera were found to be reduced in DS unfractionated thymocytes. The reduced number of high-density CD1+ thymocytes associated with a reduced spontaneous proliferative activity of low-density CD1+ thymocytes 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 which differentiates into functionally mature T cells expressing the alpha-beta T cell receptor.
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PMID:Intrathymic deficient expansion of T cell precursors in Down syndrome. 214 51

Children affected with Down syndrome (DS) show deficient growth, immunodeficiency--especially concerning the T-cell population--and low plasma zinc levels. New growth charts have been recently proposed, and zinc supplementation to the diet has been reported to improve transiently the efficiency of the immune system. The aim of this study was to evaluate if in DS children zinc sulphate therapy could improve the growth rate and affect some endocrine parameters. We studied 22 patients (16 males and 6 females) who received zinc sulphate for 6 to 9 months. Fifteen of 22 patients studied reached a higher centile in their growth rate, whereas the remaining seven showed no change, at least to date. The average height velocity changed from 23.84 +/- 7.98 mm/6 months to 40.80 +/- 7.68 mm/6 months. Growth hormone serum level was 5.94 +/- 4.89 ng/ml compared with 7.49 +/- 6.75 ng/ml before and after therapy, respectively. Somatomedin serum level was 160.27 +/- 68.88 mU/ml and 205 +/- 124.07 mU/ml before and after therapy, respectively. In conclusion, zinc sulphate therapy of patients with DS affects not only the immune system, as previously reported, but can also accelerate growth.
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PMID:Growth delay in Down syndrome and zinc sulphate supplementation. 214 76

To evaluate the possible role of lentiviruses in Alzheimer's disease we searched for cross-reactive antibodies to human immunodeficiency virus type 1, caprine arthritis encephalitis virus, and equine infectious anemia virus in Alzheimer's disease, Down's syndrome, and related dementing illnesses in serum samples and cerebrospinal fluid samples and in healthy age-matched control subjects. No cross-reactive antibodies were detected.
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PMID:The viral hypothesis of Alzheimer's disease. Absence of antibodies to lentiviruses. 230 89


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