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  • 1
    Electronic Resource
    Electronic Resource
    NSAIDs upregulate β2-integrin expression on human neutrophils through a calcium-dependent pathway (1997)
    Oxford UK : Blackwell Science Ltd.
    Alimentary pharmacology & therapeutics 11 (1997), S. 0 
    Details
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Margination of circulating neutrophils (PMN) into the gastric microcirculation is an early and critical event in the pathogenesis of non-steroidal antinflammatory drug (NSAID)-induced gastropathy. This effect is mediated through the upregulation of β2 integrins on the PMN surface.〈section xml:id="abs1-2"〉〈title type="main"〉Aims:To investigate whether indomethacin modulates: (1) Mac-1 expression; (2) Ca2+ mobilization ([Ca2+]i), protein kinase C and nitric oxide accumulation; and (3) mitogen-associated protein kinase phosphorylation in human PMN.〈section xml:id="abs1-3"〉〈title type="main"〉Methods:Human PMN were isolated by centrifugation through a double Ficoll gradient. [Ca2+]i was measured in PMN loaded with fura-2 and Mac-1 expression by flow cytometry.〈section xml:id="abs1-4"〉〈title type="main"〉Results:Indomethacin caused a concentration- and time-dependent upregulation of CD11b and CD18 expression and PMN adhesion to endothelial cells. Maximal upregulation of Mac-1 expression (40–50%) occurred after a 30-min incubation with 0.1 mM indomethacin. The effect was prevented by removing the Ca2+. Ionomycin and thapsigargin caused a 7–10-fold increase in [Ca2+]i and a 2–4-fold increase in Mac-1 expression. Indomethacin induced a concentration-dependent phosphorylation of a 41-kDa mitogen-associated protein kinase. Tyrosine kinase inhibitors prevented the effect of indomethacin on Mac-1 expression and Ca2+ mobilization. Indomethacin and ionomycin increased superoxide generation, myeloperoxidase secretion and PMN adherence to endothelial cells and stimulated nitric oxide production. Indomethacin-induced Mac-1 upregulation was prevented by a nitric oxide synthase inhibitor.〈section xml:id="abs1-5"〉〈title type="main"〉Conclusions:Indomethacin-induced upregulation of Mac-1 is mediated by changes in [Ca2+]i and nitric oxide. Phosphorylation of the 41-kDa mitogen-associated protein isoform is a previously unreported target of NSAID action. These effects might help to explain the ability of indomethacin to cause gastric neutrophil margination.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2036.1997.00190.x
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  • 2
    Electronic Resource
    Electronic Resource
    T-Cell Response to Phorbol Ester PMA and Calcium Ionophore A23187 in Down's Syndrome (1989)
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 30 (1989), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The proliferative response of purified T cells to anti-CD2 monoclonal anybodies (TII2plus TII3) was found to be markedly reduced in 12 subjects with Down's syndrome (DS). The addition of phorbol ester PMA, which activates Ca2+/phospholipid-dependent enzyme protein kinase C, or calcium ionophore A23187, which increases intracytosolic free Ca2+ concentration, enhanced, but did not normalize, the defective anti-CD2-mediated T-cell mitogenesis. In contrast, the proliferation of resting lymphocytes from trisomic patients was comparable to that of the control cells when PMA and A23187 were used as co-blastogenic reagents. Because PMA and A23187 together bypass the early activation pathways and promote T-cell growth through the direct induction of membrane interleukin 2 (IL-2) receptor expression and IL-2 synthesis and secretion, it could reasonably be hypothesized that the faulty DS T-cell activation induced by antigen or mitogen is due to a deranged transmembrane signal transduction, rather than a defect in the later intracellular events.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-3083.1989.tb02465.x
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  • 3
    Electronic Resource
    Electronic Resource
    CD26 Surface Antigen Expression on Peripheral Blood T Lymphocytes from Children with Down's Syndrome (Trisomy 21) (1994)
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 39 (1994), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: A phenotypical analysis carried out by two-colour flow cytometry showed that the proportion of circulating CD4+ T lymphocytes co-expressing the membrane-associated ectoenzyme dipeptidyl peptidase IV (CD26 antigen), a functional collagen receptor involved in T-cell triggering through its interaction with the CD45 protein tyrosine phosphatase, was significantly lower in 28 children with non-translocated trisomy 21 (Down's syndrome) (DS) than that calculated in the bloodstream of 27 age- and sex-matched healthy controls. Agonist anti-CD26 monoclonal antibodies (MoAbs), such as anti-lF7, not only modulate the surface expression of this molecule, but also enhance the proliferative activity of normal human T cells via the CD3- and CD2-mediated activation pathways. T-lymphocyte proliferation induced by antigen or polyclonal T-cell activators, including anti-CD3 or -CD2 MoAbs, is severely impaired in DS. Although the physiological ligand of CD26 surface structure is unknown, the fact that CD4+ T lymphocytes found in the blood of trisomic subjects are mostly CD26− (anti-lF7−) suggests that their faulty mitogenic response may be due to phenotypical and, perhaps, strictly correlated functional abnormalities.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-3083.1994.tb03424.x
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  • 4
    Electronic Resource
    Electronic Resource
    Lymphocytes Bearing the γ/δ T-Cell Receptors in Down's Syndrome (1992)
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 35 (1992), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Subjects with Down's syndrome (DS), or trisomy 21, have an increased susceptibility to infections, malignant diseases and autoimmune phenomena. Various arms of the immune system are severely impaired in trisomie patients. We found that the proportion of blood lymphocytes bearing the γ/δ T-cell receptor (TCR) was significantly higher in adults with trisomy 21 than in age- and sex-matched healthy controls. Interestingly, the increase was mainly due to an over-expansion of cells which bear non-covalently bound γ/δ chains on their surface. This contrasts with the normal blood picture, where the great majority of γ/δ T cells express the disulphide-linked form of the TCR. The fact that trisomie γ/δ T cells are both numerically and phenotypically unbalanced provides further evidence that immunological abnormalities are integral features of DS.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-3083.1992.tb02859.x
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  • 5
    Electronic Resource
    Electronic Resource
    T-Cell Response to Anti-CD2 Monoclonal Antibodies in Down's Syndrome (1989)
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 30 (1989), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Peripheral blood mononuclear cells from 10 subjects with cytogenetically documented Down's syndrome (DS) and from 10 age- and sex-matched healthy controls were assayed for their ability to proliferate in response to phytohaemagglutinin, anti-CD3 (OKT3), or anti-CD2 (T112 plus T113) monoclonal antibodies. Interleukin 2 (IL-2) receptor expression and IL-2 production in mitogen-pulsed lymphocyte cultures was also investigated in parallel. DS cells responded poorly to all the blastogenic stimuli used in this study. Under certain experimental conditions (anti-CD3 or anti-CD2 antibody stimulation), the patients' lymphocytes expressed low levels of IL-2 surface receptors and failed to produce normal amounts of this lymphokine. Studies are currently in progress in our laboratories to determine whether these defects are due to an impairment of the early signalling events surrounding the complexing of CD3, CD2, or lectin receptors to their respective ligands.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-3083.1989.tb01186.x
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  • 6
    Electronic Resource
    Electronic Resource
    Multicentric Castleman's disease in a patient with primary Sjögren's syndrome (1992)
    Springer
    Rheumatology international 12 (1992), S. 251-253 
    Details
    ISSN: 1437-160X
    Keywords: Sjögren's syndrome ; Castleman's disease ; Lymphoproliferative disorder ; Monoclonal gammopathy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A 38-year-old woman suffering from primary Sjögren's syndrome for 2 years developed angiofollicular hyperplasia (multicentric Castelman's disease). In Sjögren's syndrome (SS) a number of findings indicate the presence of a B-cell hyperactivity that may evolve to a lymphoproliferative disorder. This report adds another pathological event to the complex spectrum of lymphoproliferative diseases in SS.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00301012
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  • 7
    Electronic Resource
    Electronic Resource
    A fibrillar elastic apparatus around human lymph capillaries (1990)
    Springer
    Anatomy and embryology 181 (1990), S. 281-286 
    Details
    ISSN: 1432-0568
    Keywords: Lymph capillaries ; Oxytalan fibres ; Elaunin fibres ; Elastic fibres
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A fibrillar elastic apparatus around the wall of human lymph capillaries is demonstrated by means of histochemical and ultrastructural techniques. This apparatus consists of three interlinked components listed here in order of increasing distance from the capillary wall: 1) oxytalan fibres connected to the abluminal surface of the endothelial cells, known also as “anchoring filaments” and consisting of bundles of microfibrils; 2) elaunin fibres consisting of microfibrils and a small amount of elastin; and 3) typical elastic fibres consisting of microfibrils and abundant elastin. The microfibrillar constituent has similar ultrastructural features in the three components of the elastic apparatus. Microfibrils have a diameter of 12–14 nm, an electrontransparent core and a wall with 3–5 electron-dense subunits and oblique cross striations with a period of 15–17 nm. Microfibrils are the common element of the three components of the elastic apparatus and they link them to one another and to the elastic network of the perivascular connective tissue. An elastic apparatus was not found around blood capillaries and it can thus provide a histological marker to identify lymph capillaries. The possible role of the lymphatic elastic apparatus in the physiological activity of the lymphatic absorbing network is discussed and it is proposed that its disconnection from the elastic network of the tissue may promote pathological conditions such as lymphoedema or diseases related to impaired immune responses.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00174621
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  • 8
    Electronic Resource
    Electronic Resource
    Giant axonal neuropathy. Endocrinological and histological studies (1985)
    Springer
    European journal of pediatrics 144 (1985), S. 274-280 
    Details
    ISSN: 1432-1076
    Keywords: Grant axonal neuropathy ; Endocrinological study ; Ultramicro-scopic hair, sural nerve, conjunctiva, skin findings ; Vitamin B12 and prednisone therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A case of giant axonal neuropathy (GAN) in a boy of 4 years and 6 months, is reported. Nerve conduction velocity (NCV), EEG and CT scan indicated both peripheral and central nervous system involvement. Intestinal absorption tests did not reveal vitamin B12 malabsorption; the endocrine situation was found to be substantially normal. The clinical picture was not modified by 18 months cyanocobalamine administration followed by 2 months therapy with prednisone. Electron microscopic (EM) examination revealed longitudinal and opposing grooves (pili canaliculi) in the hair and bundles of neuro-filaments in the myelinated and unmyelinated nerve fibre axons in sural nerve. EM of conjunctiva and skin revealed masses of intermediate-sized filaments within mastcells, fibroblasts, melanocytes, endothelial and Schwann cells. These findings confirm the hypothesis that GAN is a generalised abnormality of cytoplasmic microfilament formation, probably linked to an unknown disorder of protein metabolism.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00451961
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  • 9
    Electronic Resource
    Electronic Resource
    Free sialic acid storage disease (1987)
    Springer
    European journal of pediatrics 146 (1987), S. 195-198 
    Details
    ISSN: 1432-1076
    Keywords: Free sialic acid storage disease ; Salla disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Increased amounts of free sialic acid were found in cultured fibroblasts and urine of a 4-year-7-month-old Italian boy with mental retardation, hypotonia, failure to thrive, coarse facial features, convergent strabismus, pale skin and fair hair. Ultramicroscopic examination of conjunctival and skin tissues showed a number of membrane-bound vacuoles containing low-density granular material in the cytoplasm of the fibroblasts. The clinical, biochemical and ultrastructural findings are similar to those described in Salla disease. Neuraminidase activity is normal. The molecular basis of the sialic acid storage disease is not known. Evidence for defective transport of sialic acid across the lysosomal membrane has been demonstrated in the patient's fibroblasts. It is possible that this might represent the metabolic abnormality.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02343235
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  • 10
    Electronic Resource
    Electronic Resource
    Phenotypic and functional abnormalities of T lymphocytes in pathological hyperprolactinemia (1987)
    Springer
    Journal of clinical immunology 7 (1987), S. 463-470 
    Details
    ISSN: 1573-2592
    Keywords: Pathological hyperprolactinemia ; T lymphocytes ; prolactin ; neuroendocrine system
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The phenotype and function of T cells circulating in patients with pathological hyperprolactinemia were analyzed and compared to those in sex- and age-matched control subjects. Two-color immunofluorescence study revealed an increased number of CD4+ TQ1+ cells and the presence of phenotypically immature CD1+ T cells, also exhibiting transferrin surface receptor, in peripheral blood of the hyperprolactinemic patients. After chronic treatment with the dopamine agonist bromocriptine, T-cell abnormalities disappeared. In addition, some untreated patients showed enhanced T-cell suppressor activity in anin vitro pokeweed mitogen-driven B-cell transformation assay. These immunological findings confirm a link between neuroendocrine and immune systems in humans.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00915056
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