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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Inflammation research 46 (1997), S. 392-397 
    ISSN: 1420-908X
    Keywords: Key words: LPS — Inflammation — Leukocyte traffic — Thalidomide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. Objective and Design: Thalidomide is very effective in the treatment of idiopathic aphthous stomatitis, characterized by recurrent focal intramucosal leukocytic vasculitis. The mode of action of thalidomide in this clinical entity may include inhibition of the extravasation of leukocytes. Therefore, we studied the effect of thalidomide on different steps of leukocyte migration by intravital microscopy.¶Material: Male Syrian golden hamsters were used.¶Treatment: Leukocyte migration in buccal mucosa of the hamster cheek pouch was elicited by the local application of lipopolysaccharide (LPS, 20 μg/ml) or murine tumor necrosis factor-α (muTNF-α, 10 ng/ml). (+)-Thalidomide (20–200 mg/kg i.p.) was administered 60 min before the local application of LPS or muTNF-α. Dexamethasone (2 × 1.0–10 mg/kg i.p.) was administered 18 h and 60 min before topical LPS application.¶Methods: The numbers of rolling, firmly adherent and migrating leukocytes were estimated by intravital microscopy up to 165 min after the topical applications of LPS or muTNF-α and evaluated by an interactive image analysis software.¶Results: Thalidomide (20–200 mg/kg i.p.) dose-dependently inhibited LPS-stimulated perivenular leukocyte migration by up to 87 ± 5% and muTNF-α-induced leukocyte migration by up to 78 ± 4%. Dexamethasone (2 ± 1.0–10 mg/kg i.p.) inhibited LPS-stimulated leukocyte migration by up to 85 ± 13%. (+)-Thalidomide (200 mg/kg i.p.) inhibited LPS-stimulated rolling by 80 ± 5% and reduced the number of firmly adherent leukocytes by about 40%. Dexamethasone (2 × 10 mg/kg i.p.) did not reduce the number of rolling leukocytes but inhibited leukocyte adherence by 72 ± 9%.¶Conclusions: These results show that (+)-thalidomide predominantly inhibits leukocyte rolling and thus differs from the glucocorticoid dexamethasone. The inhibition of LPS- or muTNF-α-induced leukocyte extravasation by thalidomide may account for some of its clinical activities.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1440
    Keywords: Homosexual men ; Lymphadenopathy ; HTLV-III ; Epidemiological factors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The study provides information on the epidemiology of HTLV-III infection and the lymphadenopathy syndrome (LAP) in 374 German homosexual men. Sexual contacts in the USA and rectal enemas before receptive anal intercourse are the main risk factors associated with virus transmission. HTLV-III seropositivity is significantly correlated with LAP. Prominent clinical signs are infreqquent. Immunological and haematological abnormalities are prevalent, and the retrovirus infection is frequently associated with serological markers of other viruses (hepatitis B, herpes group viruses). Lymphadenopathy as a manifestation of HTLV-III infection is discussed within the context of AIDS-related disorders.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    FEMS immunology and medical microbiology 12 (1995), S. 0 
    ISSN: 1574-695X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: Abstract The Shwartzman reaction is an animal model displaying histopathological vasculitis phenomena. Extravasation and swelling due to increased vascular permeability and cellular infiltration, which are hallmarks of the Shwartzman reaction, were evaluated as leakage of i.v.-injected Evans Blue dye and by histological and immunohistological characteristics in rabbits and mice. (±)-Thalidomide, (−)-thalidomide, (+)-thalidomide and dexamethasone inhibited the increase of vascular permeability in the local Shwartzman reaction. Histologically, the intensity of the Shwartzman reaction was reduced. In mice thrombus formation and leukocytoclastic vasculitis was inhibited by (±)-thalidomide and (+)-thalidomide. ICAM-1 expression was markedly reduced after (+)-thalidomide injection. Thalidomide and dexamethasone pretreatment reduced Mac-1 expression on perivascular infiltrated granulocytes. The inhibitory effect of thalidomide on vasculitis of the Shwartzman reaction may thus be related to reduction of adhesion molecule expression.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 34 (1991), S. 0 
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: In chronic infection with Schistosoma mansoni, IL-4 and IFN-γ are co-modulated in opposite directions. This was shown when testing sera and cell culture supernatants from .11 Brazilian patients with schistosomiasis before, and three months after treatment with praziquantel. Thorough examinations were undertaken to account for polyparasitism with intestinal nematode infections involving tissue migrating larval stages that may induce analogous changes. Controls free of S. mansoni included a group (n = 17) matching the schistosomiasis patients’parasitation by intestinal nematodes and a group (n= 16) free of helminths other than T. trichiura. Serum lL-4 was 〉30 pg/ml in 81% of schistosomiasis patients but in only 33 and 25%. respectively, of controls with and without intestinal nematodes. IL-4 data correlated inversely with the mitogen-induced if N-y synthesis. Generation of IL-4 in response to phorbol esters was related to the intensity of infection by schistosomes and intestinal nematodes. The parasitological status three months after therapy with cither praziquantel or mebendazole revealed a dichotomy: whereas the ratio of IFN-7 lo IL-4 generated in vitro was identical in uninfected controls and in patients who cleared the parasites, failure to eliminate the parasites was associated with lower IFN-v/IL-4 ratios generated in vitro.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 31 (1990), S. 0 
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Chronic schistosomiasis mansoni is associated with impaired cell-mediated immune responsiveness (CMI). To assess co-stimulatory factors essential in the induction phase of CMI, interleukin 1 (IL-1) concentration was determined in the sera and cell culture supernatants of Schistosoma mansoni-infected patients, and circulating monocytes were phenotyped, labelling membrane IL-1 and HLA-DP. In addition, adherent cell oxidative-burst capacity was investigated. Since involvement of IL-1β in the pathogenesis of severe granulomatous lesions could not be ruled out, 17 patients with intestinal schistosomiasis and 17 patients with hepatosplenic schistosomiasis were matched for intensity of infection and monitored 3–6 months after praziquantel therapy. Seventeen age- and sex-matched uninfected residents ofthe study area in Alagoas, Brazil, acted as controls. Whereas schistosomiasis patients and controls did not differ in the expression of monoeyte surface antigens and the capacity of adherent cells to generate H2O2, IL-1β release by monocytes in vitro was significantly reduced in both intestinal and hepatosplenic patients. Low concentrations of circulating IL-1β were detected in comparable frequencies in untreated patients and controls. Three months after therapy, IL-Iβ was detectable in serum in an increased proportion of intestinal schistosomiasis patients. IL-1 release in vitro gradually increased in all patients and reached control values 6 months after therapy.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 31 (1990), S. 0 
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Periportal fibroplasia is the dominating feature of hepatosplenic schistosomiasis. Since monokines play an Important role in the regulation of fibroplasia, tumour necrosis factor (TNF) and interleukin 1β (IL-1β) were assessed in sera and cell culture supernatants from patients with intestinal and hepatosplenic schistosomiasis before and 3-6 months after treatment with praziquantel. Uninfected controls were from the study area in Alagoas, Brazil. TNF was measured using an L-M mouse fibroblast bioassay and radioimmunoassays specific for TNF-α. Whereas TNF-α was elevated three fold in the patients' sera, three-to five-fold reductions of TNF were observed by radioimmunoassay and bioassay, respectively, in cell culture supernatants of hepatosplenic schistosomiasis patients. Significant deviations, in opposite directions, from TNF levels in control sera and supernatants are most plausible in the event of a sequestration of TNFα-producing cells from the circulation. This process may be disease stage-specific since a dichotomy between incipient and advanced cases of hepatosplenic schistosomiasis became apparent in the amplitude and kinetics of changes during the follow-up after treatment.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Interleukin 2(IL-2) and gamma interferon (IFN-γ) were determined in supernatantsof mitogen and antigen-driven cell cultures from patients with hepatosplenic or intestinal schistosomiasis. Skin reactivity was tested using a panel of eight recall antigens. Results were compared with those of uninfected local controls. In both schistosomiasis groups, IL-2 activity was reduced before treatment. In less than one third of the patients, schistosomal antigens elicited detectable IL-2 activity. IFN-γ production was reduced more severely in hapatosplenic cases, in particular after stimulation by anti-CD3 monoclonal antibodies. After anti-schistosomal therapy with praziquantel, mitogen-induced IL-2 and IFN-γ activities became normal within 3 months in intestinal schistosomiasis, and within 6 months in the hepatosplenic patient group. Results of in vivo delayed-type hypersensitivity tests paralleled those of in vitro lymphokine production. In conclusion, evidence is presented for severe, antigen-unspecific suppression of lymphokine production and skin reactivity against recall antigens. Anti-parasitic chemotherapy is shown to reverse the impairment of cell-mediated immune responses at the cytokine level.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-1955
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Individuals in an advanced phase of infection bySchistosoma intercalatum in whom viable ova are still present in the rectal mucosa but not excreted in detectable quantity, can be distinguished clinically from a younger group of individuals excretingS. intercalatum ova in their faeces. This clear-cut distinction is underlined by findings in parameters of humoral response. The ratio of anticercarial to anti-adult worm antibodies was higher in the group excreting eggs with probably more recent infection. Levels of total serum immunoglobulin were higher in this group, with the exception of serum IgA, which was lower as long as eggs were being excreted. In a later stage of the disease, relatively more IgG seems to be bound in circulating immune complexes. It is postulated that these stage specific patterns of humoral immune response represent the evolution of the hostparasite relationship during the infection.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-1955
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract In 20 patients with hepatic or hepatosplenic schistosomiasis and 82 individuals infected with S. mansoni, but without liver enlargement, serum parameters reflecting the fibrotic process and hemodynamic alterations as well as immunomodulation were examined. Included as controls were 35 age- and sex-matched healthy individuals from the study region in Northeast Brazil. Peripheral blood cholylglycine levels in patients with hepatomegaly, reflecting the spillover of portal blood into the systemic circulation, were elevated 12-fold over values of patients without liver involvement. Procollagen-III-peptide, a cleavage product of collagen synthesis, was elevated in patients with hepatomegaly (P〈0.001) but normal in uncomplicated cases. Immunomodulation was assessed by in vivo delayed hypersensitivity to recall antigens and by serum Β 2-microglobulin and neopterin, substances released in the context of lymphocyte activation. Neopterin, predominantly a macrophage product, was elevated most strikingly in hepatomegalic cases (P〈 0.001). The possible interrelation between altered immune responses and excess fibrogenesis is discussed.
    Type of Medium: Electronic Resource
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