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  • 1
    ISSN: 1432-0428
    Keywords: Type 1 diabetes ; suppressor cells ; monoclonal antibodies ; T-lymphocyte subsets ; cell-mediated immunity disorders
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Humoral and cell-mediated disorders in Type 1 (insulin-dependent) diabetes suggest that an imbalance of immunoregulatory T-cell subsets exists. In 23 newly diagnosed (onset 〈 3 months) and 21 long-standing Type 1 diabetic patients, T lymphocyte subsets were analyzed using monoclonal antibodies (OKT3, OKT4, OKT8, OKM1). The newly diagnosed patients showed a reduction with a significant difference from healthy controls in total T cells (OKT3+: 58.1 ±8.5% versus 70.7±8.0%), helper/inducer cells (OKT4+: 33.8 ±7.0% versus 47.1 ±8.3%), suppressor/cytotoxic cells (OKT8+: 18.5±7.3% versus 32 ± 6.8%) and monocytes (OKM1+: 11.5±3.8% versus 19.9±5.2%) (p〈 0.001). The long-standing diabetic patients also revealed a low number of immunoregulatory T cells compared with control subjects, although to a lesser extent (p〈 0.01–0.05). The helper/suppressor ratio (OKT4+/OKT8+) was higher in newly diagnosed patients than in control subjects (2.2±1.3 versus 1.5±0.3; p〈 0.02). When compared with 95% tolerance limits in the control subjects, the reduction of OKT8+ cells in the newly diagnosed diabetic patients appeared more marked: the mean (18.5%) coincided with the lower limit of normal subjects (18.3%). Ten of the newly diagnosed Type 1 diabetic patients had a value below the normal lower limit. Our data point to the occurrence of different immunoregulatory abnormalities in newly diagnosed Type 1 diabetic patients, especially in OKT8+ and OKT4+ cells. The imbalance in T lymphocyte subsets is further proof of the role of cellular autoimmunity in the pathogenesis of the early phases of Type 1 diabetes.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1420-9071
    Keywords: Bovine gamma globulins ; macrophages ; chemiluminescence ; phagocytic activity ; Salmonella typhimurium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Mice treated with bovine gamma globulins showed an increased resistance toSalmonella typhimurium infection. This phenomenon seems to be bound to an increase of peritoneal macrophage phagocytic activity, as shown by the method of chemiluminescence, in experiements performed on peritoneal macrophages from mice traated with bovine gamma globulin.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Inflammation research 18 (1986), S. 544-549 
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Hyaluronate of 120,000 molecular weight has been injected in the peritoneal cavity of mice to study its effect on migration of inflammatory cellsin vivo. After one day a dosedependent granulocyte migration is observed. Three days later the number of granulocytes is greatly reduced and macrophages form about half of the total cell population. Hyaluronateelicited macrophages show a decreased 5′-nucleotidase and an increased acid phosphatase activity as compared to resident macrophages. The production of superoxide anion in response to the phorbol ester tetradecanoyl-phorbolacetate, and the phagocytic activity are also enhanced. Macrophages elicited by hyaluronate secrete growth factor(s) for non-lymphoid mesenchymal cells. It is concluded that hyaluronatein vivo stimulates the migration of inflammatory cells, thus causing the recruitment of a population of stimulating macrophages. These effects may explain previous reports on the acceleration of wound healing by hyaluronate.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0428
    Keywords: Keywords Type I diabetes ; oral insulin ; insulin antibodies ; prevention.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. Induction of tolerance to insulin is achievable in animal models of Type I (insulin-dependent) Diabetes mellitus by oral treatment with this hormone, which can lead to prevention of the disease. In the Diabetes Prevention Trial of Type I diabetes (DPT-1), oral insulin is given with the aim of preventing disease insurgence. We investigated whether if given at diagnosis of Type I diabetes in humans, oral insulin can still act as a tolerogen and therefore preserve residual beta-cell function, which is known to be substantial at diagnosis. Methods. A double-blind trial was carried out in patients (mean age ± SD: 14 ± 8 years) with recent-onset Type I diabetes to whom oral insulin (5 mg daily) or placebo was given for 12 months in addition to intensive subcutaneous insulin therapy. A total of 82 patients with clinical Type I diabetes ( 〈 4 weeks duration) were studied. Basal C peptide and glycated haemoglobin were measured and the insulin requirement monitored every 3 months up to 1 year. Insulin antibodies were also measured in 27 patients treated with oral insulin and in 18 patients receiving placebo at the beginning of the trial and after 3, 6 and 12 months of treatment. Results. The trial was completed by 80 patients. Overall and without distinction between age at diagnosis, at 3, 6, 9 and 12 months baseline mean C-peptide secretion in patients treated with oral insulin did not differ from that of those patients treated with placebo. In patients younger than 15 years a tendency for lower C-peptide values at 9 and 12 months was observed in the oral insulin group. Insulin requirement at 1 year was similar between the two groups as well as the percentage of glycated haemoglobin. Finally, IgG insulin antibodies were similar in the two groups at each time point. Conclusion/interpretation. The results of this study indicate that the addition of 5 mg of oral insulin does not modify the course of the disease in the first year after diagnosis and probably does not statistically affect the humoral immune response against insulin. [Diabetologia (2000) 43: 1000–1004]
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0428
    Keywords: Bcl-2 ; apoptosis ; T cells ; flow cytometry ; cell-mediated immunity in insulin-dependent diabetes mellitus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The bcl-2 gene product has been shown to regulate apoptotic cell death, and its dysregulation has been shown to induce several abnormalities in the immune system. No data exist regarding bcl-2 expression in autoimmune diseases, such as human insulin-dependent diabetes mellitus (IDDM). We investigated bcl-2 protein expression by testing T lymphocytes from 15 newly-diagnosed (〈3 weeks) IDDM patients in comparison to 10 age-matched control subjects. The expression of bcl-2 on CD3+ lymphocyte subsets was investigated after membrane permeabilization by two- or three-colour immunofluorescence. When the percentage and mean fluorescence intensity (MFI) of bcl-2+/CD3+ cells from normal individuals and patients were compared, we found that bcl-2 expression within the CD3+ and CD4+ CD45R0+ T-cell populations was reduced significantly in IDDM patients (46.8±15.4 vs 79.6±11.7; 25.7±3.8 vs 47.15±5.7, respectively; p〈0.001). To establish whether low bcl-2 expression in T cells from newly-diagnosed patients reflects their susceptibility to death by an apoptotic process, we also evaluated DNA staining with propidium iodide in CD3+ lymphocyte suspension after a (24–72 h) culture period (spontaneous apoptosis). We found that IDDM patients have higher levels of spontaneous apoptosis (mean±SEM: 24 h=4.6±0.8; 48 h=9.9±1; 72 h=12.8±1.1) than control subjects (24 h=1.8±0.4; 48 h=4.6±0.4; 72 h=5.7±0.3; p〈0.02–0.001). Our study suggests that recent onset IDDM is characterised by reduced bcl-2 expression, which in turn may be associated with the increased spontaneous apoptosis we observed.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0428
    Keywords: CD95 ; Fas/APO1 ; insulin-dependent diabetes mellitus ; cellular immunity, apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Triggering of CD95 (Fas/APO-1) cell surface receptors regulates the elimination of autoreactive T and B lymphocytes through a mechanism of cell suicide called apoptosis. Three different mutations involving CD95 or its ligand are responsible for induction of autoimmunity in susceptible mouse strains. To determine whether a defect involving the CD95 receptor is associated with human insulin-dependent diabetes mellitus (IDDM), we have studied the expression of CD95 on peripheral blood mononuclear cells from IDDM patients at different stages of the disease. Three-colour flow cytometry and mean fluorescence analysis showed that T and B lymphocytes from newly diagnosed IDDM and patients with long-standing disease, and subjects at high risk of developing the disease were highly defective in CD95 expression (p〈0.001), whereas monocytes from all the groups studied expressed normal amounts of CD95 molecules on their cell surface. T-cell subset analysis showed that the impairment of CD95 expression in IDDM patients and high-risk subjects involved both CD3+ CD4+ (p〈0.001) and CD3+ CD8+ cells (p range: 〈0.01–0.001), suggesting that this alteration concerns both helper and cytotoxic T cells. Moreover, after activation in vitro with anti-CD3 monoclonal antibody, T cells from newly diagnosed IDDM patients maintained a reduced CD95 expression during the entire cell culture period (24–72 h) in comparison to the control population (p〈0.001). In conclusion, we found a reduced expression of the apoptosis-inducing CD95 receptor on T and B lymphocytes of individuals with clinical and preclinical IDDM. We hypothesize that this defective expression may impair the capacity of autoreactive lymphocytes to undergo CD95-mediated apoptosis, contributing to the lack of control on beta-cell specific B- and T-cell clones.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0428
    Keywords: Key words Bcl-2 ; apoptosis ; T cells ; flow cytometry ; cell-mediated immunity in insulin-dependent diabetes mellitus.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The bcl-2 gene product has been shown to regulate apoptotic cell death, and its dysregulation has been shown to induce several abnormalities in the immune system. No data exist regarding bcl-2 expression in autoimmune diseases, such as human insulin-dependent diabetes mellitus (IDDM). We investigated bcl-2 protein expression by testing T lymphocytes from 15 newly-diagnosed ( 〈 3 weeks) IDDM patients in comparison to 10 age-matched control subjects. The expression of bcl-2 on CD3 + lymphocyte subsets was investigated after membrane permeabilization by two- or three-colour immunofluorescence. When the percentage and mean fluorescence intensity (MFI) of bcl-2 + /CD3 + cells from normal individuals and patients were compared, we found that bcl-2 expression within the CD3 + and CD4 + CD45R0 + T-cell populations was reduced significantly in IDDM patients (46.8 ± 15.4 vs 79.6 ± 11.7; 25.7 ± 3.8 vs 47.15 ± 5.7, respectively; p 〈 0.001). To establish whether low bcl-2 expression in T cells from newly-diagnosed patients reflects their susceptibility to death by an apoptotic process, we also evaluated DNA staining with propidium iodide in CD3 + lymphocyte suspension after a (24–72 h) culture period (spontaneous apoptosis). We found that IDDM patients have higher levels of spontaneous apoptosis (mean ± SEM: 24 h = 4.6 ± 0.8; 48 h = 9.9 ± 1; 72 h = 12.8 ± 1.1) than control subjects (24 h = 1.8 ± 0.4; 48 h = 4.6 ± 0.4; 72 h = 5.7 ± 0.3; p 〈 0.02–0.001). Our study suggests that recent onset IDDM is characterised by reduced bcl-2 expression, which in turn may be associated with the increased spontaneous apoptosis we observed. [Diabetologia (1995) 38: 953–958]
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-1017
    Keywords: Key wordsγ-Ray footprinting ; Fluorescence polarization anisotropy ; DNA damage ; Oxidative lesion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Physics
    Notes: Abstract The influence of the oxidative lesion 2′-deoxy-7-hydro-8-oxoguanosine (8-oxodG) on some conformational properties of DNA has been studied. Four 30-mer duplexes of the form [5′-GATCCTCTAGAGTC[G* or G]ACCTGCAGGCATGCA-3′]:[3′-CTAGGAGATCTCAG[C or A]TGGACGTCCGTACGT-5′], in which G* is the 8-oxodG lesion, were synthesized in order to compare the effect of the GA mismatch and of the damaged G*C and G*A forms with the normal GC. Spectroscopic measurements performed by means of UV denaturation and circular dichroism experiments do not show gross changes of stability and overall structure in the damaged and mismatched samples. The control DNA and the samples containing GA mismatch show very similar γ-rays cutting patterns, indicating that the introduction of the GA mismatch does not perturb the phosphate backbone geometry. In the samples containing the 8-oxodG there are some variations of the cleavage pattern near G* which are extended for almost one helical turn. Some differences are observed between G*C and G*A duplexes. In particular, in the G*C sample the reduced accessibility to OH radicals at the G15 site, observed in the control, spreads on the intrastrand adjacent bases and in the G*A sample a shift of the minimum is observed. The hydrodynamic radius R h derived by fluorescence polarization anisotropy decay exhibits a constant value of 11.4 ± 0.2 Å between 5 and 40 °C, in all the samples. The torsional constant α of each oligomer decreases when the temperature is raised and the α values of the damaged samples are higher than those of the normal ones.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    s.l. ; Stafa-Zurich, Switzerland
    Advanced materials research Vol. 47-50 (June 2008), p. 1434-1437 
    ISSN: 1662-8985
    Source: Scientific.Net: Materials Science & Technology / Trans Tech Publications Archiv 1984-2008
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Surface treated titanium implants are increasingly being used in dental and orthopaedicapplications. This study examined the biological response of primary human alveolar osteoblast(aHOB) cells to a novel silicon based anodic spark deposition treated titanium surfaces. Threedifferent titanium surfaces were investigated: anodic spark deposition (ASD) with silicon based(ASDSi), BioSpark™ (BS), and chemically etched (BioRough™, BR). Commercially pure titanium(cpTi) was the non-treated control surface. Physiological and biological evaluations were conductedon all test and control surfaces. Surface scanning (SEM, EDS, and AFM) confirmed anano-topography, which was textured for all surfaces; and similar surface chemical composition (Caand P), of significant was the Si peak on the ASDSi surface. Cell morphological study (SEM) showedgood adhere and spreading over the surface, with metabolically active cells having extendedfilopodia. Biological response was observed with cell proliferation on all test surfaces for the periodstudied. Proliferation rate was seen to increase with time. This initial favourable cell response will beof benefit in the long term osseointegration of the implant surfaces
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of the European Academy of Dermatology and Venereology 4 (1995), S. 0 
    ISSN: 1468-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: We describe a mild form of drug-induced pemphigus in a woman with essential arterial hypertension treated with captopril. Complete recovery was observed three weeks after the therapy had been discontinued.
    Type of Medium: Electronic Resource
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