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Biomedical subjects

E Schön

Publications and source records attributed to E Schön.

At least 19 recordsLinked to original sources

Dendritic cell vaccination protects mice against lethality caused by genital herpes simplex virus type 2 infection.

We have evaluated the ability of antigen pulsed bone-marrow derived dendritic cells (bmDC), to induce protective immunity against a genital tract infection with herpes simplex virus type 2 (HSV-2) in mice. Intravenous but not vaginal administrations of bmDC pulsed in vitro with UV-inactivated HSV-2, or with purified HSV-2 envelope glycoproteins gave rise to complete protection against disease, as well as death caused by genital herpes infection. Protection was dependent on the antigens being presented by the bmDC as neither the antigens alone, nor the mock-pulsed bmDC prevented disease. Immunity was associated with HSV-2 specific IFN-gamma and antibody production, and was shown to be dependent on CD4(+) cells secreting IFN-gamma. Thus, ex vivo antigen-pulsed bmDC represents a powerful tool for the study of protective immunity to genital herpes infection, and for the identification of protective antigens. These findings might also have an impact on the design of vaccines against other sexually transmitted viral diseases.

Administration, Intravaginal↗

Cholera toxin B subunit as a carrier molecule promotes antigen presentation and increases CD40 and CD86 expression on antigen-presenting cells.

Cholera toxin B subunit (CTB) is an efficient mucosal carrier molecule for the generation of mucosal antibody responses and/or induction of systemic T-cell tolerance to linked antigens. CTB binds with high affinity to GM1 ganglioside cell surface receptors. In this study, we evaluated how conjugation of a peptide or protein antigen to CTB by chemical coupling or genetic fusion influences the T-cell-activating capacity of different antigen-presenting cell (APC) subsets. Using an in vitro system in which antigen-pulsed APCs were incubated with antigen-specific, T-cell receptor-transgenic T cells, we found that the dose of antigen required for T-cell activation could be decreased >10,000-fold using CTB-conjugated compared to free antigen. In contrast, no beneficial effects were observed when CTB was simply admixed with antigen. CTB conjugation enhanced the antigen-presenting capacity not only of dendritic cells and B cells but also of macrophages, which expressed low levels of cell surface major histocompatibility complex (MHC) class II and were normally poor activators of naive T cells. Enhanced antigen-presenting activity by CTB-linked antigen resulted in both increased T-cell proliferation and increased interleukin-12 and gamma interferon secretion and was associated with up-regulation of CD40 and CD86 on the APC surface. These results imply that conjugation to CTB dramatically lowers the threshold concentration of antigen required for immune cell activation and also permits low-MHC II-expressing APCs to prime for a specific immune response.

Animals↗

[Antibiotic prophylaxis in cesarean section].

Childbirth by Caesarean section is associated with 7-10x more complications than spontaneous childbirth [28] whereby the second place is held by infection. One of the possible ways how to prevent these infectious complications is antibiotic prophylaxis. Views on the latter still differ as regards selection of the antibiotic, its effectiveness, onset of administration, dosage, period of administration etc. Prophylaxis should meet the following demands; it should be aimed, of short-term character, bactericide and non-toxic-these demands are met by cephalosporins of the second generation [11]. The objective of the present work was to evaluate the contribution of the prophylactic administration of antibiotics, i.e. a cephalosporin of the second generation-Zinacef (Cefuroxime). The group was formed by 23 women to whom a dose of Zinacef was administered after childbirth by Caesarean section and subsequently twice after 8-hour intervals (1.5-0.75-0.75 i.m.). The control group (23 women) did not have this prophylaxis. In both groups the authors compared the indication of s.c., time of loss of amniotic fluid before s.c., results of cultivations from the cervix, vagina, amniotic fluid, lochiae and sutures. The authors evaluated the postoperative course where they were interested in infectious complications, the temperature curve, period of hospitalization, the necessity to administer another antibiotic or to proceed with the antibiotic therapy after the prophylactic dose. The results are clearly in favour of the prophylactic administration of antibiotics to the risk group of patients delivering by Caesarean section.

Adult↗

Dipeptidyl peptidase IV in the immune system. Effects of specific enzyme inhibitors on activity of dipeptidyl peptidase IV and proliferation of human lymphocytes.

Dipeptidyl peptidase IV (DP IV) is a membrane peptidase playing a significant role in the process of activation and proliferation of human thymus-derived lymphocytes. This conclusion is drawn from (1) the induction of this enzyme on mitogen-activated T lymphocytes (cf. Schön, E. & Ansorge, S. (1990) Biol. Chem. Hoppe-Seyler 371, 699-705) and (2) the impairment of different functions of activated T cells in the presence of specific inhibitors and antibodies against DP IV (Schön, E. & al. (1987) Eur. J. Immunol 17, 1821-1826). This paper is aimed at testing new active site-specific peptide inhibitors for their efficiency as inhibitors of lymphocyte DP IV and DNA synthesis of mitogen-stimulated lymphocytes. These inhibitors comprise (i) diacylhydroxylamine derivatives of Xaa-Pro or Xaa-Ala peptides, (ii) different oligopeptides with N-terminal Xaa-Pro-sequences, and (iii) amino-acid amides of the pyrrolidide and the thiazolidide type. The thiazolidides of epsilon-(4-nitrobenzyloxycarbonyl)-L-lysine and of L-isoleucine as well as Ala-Pro-nitrobenzoylhydroxylamine are the most effective inhibitors in both test systems, yielding half-maximal inhibitory concentrations in the micromolar range. Cell viability was not impaired in this effective concentration range. Other inhibitors of DP IV are one to two orders of magnitude less efficient in the suppression of lymphocyte proliferation.

Binding Sites↗

Membrane-bound peptidases of lymphocytes: functional implications.

The paper is aimed towards the role of the membrane ecto-enzymes aminopeptidase N (CD13, AP-N) and dipeptidyl peptidase IV (CD26, DP IV) in the immune system. Both peptidases have been identified on T lymphocytes, AP-N also on monocytes and non-T cells. Using enzyme inhibitors and antibodies it has been shown by different groups that DP IV plays a key role in T cell activation and growth. Inhibition studies of our laboratory, using bestatin, actinonin and probestin, also demonstrated an essential role of AP-N in regulation of T cell growth. Moreover, the action of cytokines/lymphokines having DP IV susceptible bonds, as IL-1, IL-2 and IL-6, on lymphocyte proliferation, was found to be suppressed by specific inhibitors of DP IV as well as AP-N. These results are in favour of our hypothesis that DP IV and AP-N, possibly both in a concerted action, are involved in cytokine/lymphokine mediated signalling between immune cells.

Amino Acid Sequence↗

[The treatment of zygomatic fractures. An anatomico-clinical study].

The treatment of malar bone fractures by stable osteosynthesis represents a well established method. The necessity of a second surgery is one of the major disadvantages of using metal implants. Resorbable plates can only be deformed by very difficult methods. We found out that, cause of the anatomical structure of malar bone region, only three types of plates are necessary to treat every kind of malar bone fracture of males and females.

Adolescent↗

[Changes in serotonin-containing EC-cells in the lamina epithelialis mucosae of the small intestine in young children with growth disorders caused by intestinal diseases].

Duodenal jejunal biopsy material from children with growth retardation due to enteric disease was investigated. The disease dependent mucosa types were classified into three groups according to Shmerling (1970). 5-hydroxytryptamine was demonstrated with an impregnation technique and histochemically, as well, in EC-cells in the crypt epithelium. The EC-cell content in specimens with subtotal villus atrophy (type III) was higher significantly compared to normal mucosa (type I). The findings were discussed with regard to the possible role of 5-hydroxytryptamine in the pathogenesis of the growth retardation due to enteric disease in children.

Biopsy↗

[Transfer of resistance to the newer beta-lactam antibiotics in Czechoslovakia].

Transmitted resistance to recent cephalosporin antibiotics of the third generation was first proved in 1983 by the authors. Approximately five years later the authors revealed during systematic monitoring of bacterial strains resistant to cephtazidime, cephtriaxone and cephotaxim also transmitted resistance to these and other more recent beta-lactam antibiotics in Czechoslovakia. The authors advocate rational use of new cephalosporins and other beta-lactams (e. g. aztreonam) as reserve antibiotics.

Anti-Bacterial Agents↗

Prognostic implications of DNA ploidy in squamous cell carcinomas of the tongue assessed by flow cytometry.

A total of 47 primary squamous cell carcinomas of the tongue were analysed by DNA flow cytometry. With respect to their clonal DNA content two distinct tumor groups could be distinguished. In 14 cases the tumors (29.8%) were dipoid, whereas in 33 cases (70.2%) additional cell lines characterized by abnormal DNA content could be detected. A significant increase of aneuploid cases with tumor size as well as with decreasing histological differentiation could be detected. Aneuploid cell lines are lacking in T1 as well as in most G1 carcinomas but predominate in T3 and G3. Furthermore, cervical lymph node involvement was recognized in the majority of aneuploid primary carcinomas (81.8%) but was largely lacking in diploid tumors (21.4%). Hence, the presence of aneuploid cell lines is clearly connected with clinical and histopathological parameters, each of which have turned out to worsen the prognosis in tongue carcinomas.

Carcinoma, Squamous Cell↗

Dipeptidyl peptidase IV in the immune system. Cytofluorometric evidence for induction of the enzyme on activated T lymphocytes.

Dipeptidyl peptidase IV (DP IV) is a membrane peptidase with essential functional significance in thymus derived lymphocytes. This conclusion is drawn from 1) the induction of this enzyme after stimulation of T lymphocytes in vitro and 2) the impairment of T cell functions in presence of active site-specific inhibitors of the enzyme. The first item will be addressed in this paper, whereas the second one will be treated in a forthcoming article. Using flow cytofluorometry we investigated the expression of dipeptidyl peptidase IV on activated lymphocytes and the phenotype of lymphocytes expressing this enzyme. After stimulation by mitogenic lectins the number of epitopes on the cell surface binding polyclonal antibodies against DP IV increases 4 to 6 times. By means of double fluorescence staining the enzyme has been shown to be restricted nearly exclusively to T lymphocytes even after mitogenic stimulation. The highest density of DP IV epitopes has been found in cells coexpressing activation markers like receptors for interleukin 2 or transferrin in a high density.

Dipeptidyl Peptidase 4↗

[Different DNA forms in cell nuclei of the lamina epithelialis mucosa of small intestines of children with growth disturbances due to enteric disease].

From children with growth retardation due to enteric disease, duodenal jejunal biopsy material was investigated. Using a modified Feulgen-reaction--acridine orange staining after acid hydrolysis according to Fukuda et al. (1986)--different DNA forms could be demonstrated in nuclei of cells of the lamina epithelialis mucosae by fluorescence microscopy. These clear cut forms of DNA by different fluorescence colours were only found in altered mucosa. The findings were discussed with regard to the possibility of mitotic disorders and cancerogenesis.

Child, Preschool↗

[Characterization of T lymphocyte defects in patients with Hodgkin's disease using enzyme chemical markers].

Patients suffering from lymphogranulomatosis were studied with respect to cellular immune deficiencies. For this purpose, mononuclear cells from venous blood were separated and subjected to analysis of lymphocyte markers. T-lymphocytes were enumerated by means of the sheep erythrocyte (SE) rosette test. T cell subpopulations were determined using enzyme cytochemical staining for dipeptidyl peptidase IV (DP IV) and unspecific acid alphanaphthylacetate esterase (ANAE). In 18 patients with M. Hodgkin a significant reduction in the T lymphocyte count in peripheral blood was found. This T cell defect is due to a selective decrease in the TM-subpopulation as identified by enzyme cytochemical markers DP IV and ANAE (focal reaction). From these results it is concluded that patients with lymphogranulomatosis have characteristic abnormalities in the immune system in the sense of a disturbed equilibrium of immune regulatory cells.

Adult↗

[Aminopeptidase activity in populations of human blood mononuclear cells].

The aminopeptidase N (AP N, EC 3.4.11.2) is an ectoenzyme of the plasma membrane, playing presumably an important role in the regulation of immunological processes. The specific activities of Ala-pNA and Leu-pNA cleavage (per cell) are distributed in monocytes T- and non-T-lymphocytes in a proportion of 1:0.2:0.25 and 1:0.17:0.18, respectively. The capacities of Ala-pNA and Leu-pNA hydrolysis in the total fraction T- and non-T-cells are distributed as 1:0.8 and 1:0.7, respectively. The main part of Ala-pNA cleavage was shown to be caused by AP N on the basis of the KM-value (0.5 mmol/l), the activation by CO2+ ions and the pH optimum (7.0-7.5). The Leu-pNA cleavage is dependent on CO2+ and DTT and distinct from the classical cytosolic leucyl aminopeptidase.

Aminopeptidases↗

[Hormonal contraception and levels of selected serum proteins].

The authors investigated 116 women who took hormonal contraceptives. All women were subjected to detailed clinical and biochemical examinations. In the serum a number of biochemical and immunological tests was made. Special attention was paid to the estimation of prealbumin, alpha-1-antitrypsin, alpha-2-macroglobulin, orosomucoid and ceruloplasmin. In prealbumin 23 values above normal (from a total of 83 women) were found, in alpha-1-antitrypsin 55 values below normal and 13 values above normal (from 114 women) in alpha-2-macroglobulin 18 values below normal and 3 values above normal (from 67 women) and in orosomucoid 26 values below normal and 2 values above normal (from 116 women) and in the case of ceruloplasmin 2 values below normal and 51 values above normal (from 116 women). The authors discuss the influence of hormonal contraception on the levels of the investigated proteins and on possible subsequent metabolic changes and pathological conditions.

Adult↗

Dipeptidyl peptidase IV in human T lymphocytes. Impaired induction of interleukin 2 and gamma interferon due to specific inhibition of dipeptidyl peptidase IV.

Specific inhibitors of the membrane-bound dipeptidyl peptidase IV (DP IV) and polyclonal antibodies against this enzyme were used to investigate the relationships between DP IV activity and the production and action of T cell-derived lymphokines. Production of interleukin 2 (IL-2) and gamma interferon by mitogen plus phorbol ester-stimulated mononuclear cells from human blood was found to be reduced in the presence of N-Ala-Pro-O-(nitrobenzoyl-)-hydroxylamine, epsilon-(4'-nitro) benzoxycarbonyl-Lys-Pro, and anti-(DP IV) immunoglobulin in a dose-dependent manner. Moreover, the proliferative response of mitogen-stimulated mononuclear cells to IL-2 is impaired in the presence of DP IV inhibitors. Therefore it is suggested that the membrane peptidase DP IV is involved in the induction and activation of cytokines controlling lymphocyte proliferation.

Cells, Cultured↗

[Determination of cellular and humoral parameters of fatty liver].

Cellular and humoral immunological parameters were examined in mononuclear cells from peripheral blood of patients with alcoholic and nonalcoholic steatosis hepatis. The ratio of T4 and T8 positive lymphocytes and the number of monocytes of these patients were in the normal range. The percentage of NK-cells, B-lymphocytes and DR-antigen-positive cells was increased.

Antigens, Differentiation↗