Biomedical subjects

B Schnyder

Publications and source records attributed to B Schnyder.

46 records · Page 3Linked to original sources

PubMed1995

Role of interferon-gamma in interleukin 12-induced pathology in mice.

Interleukin 12 (IL-12) activates natural killer (NK) and T cells with the secondary synthesis and release of interferon-gamma (IFN-gamma) and other cytokines. IL-12-induced organ alterations are reported for mice and the pathogenetic role of IFN-gamma is investigated by the use of mice deficient in the IFN-gamma receptor (IFN-gamma R-/-). IL-12 caused a rapid infiltration of liver and splenic red pulp with activated macrophages; this and increased NK cells resulted in a fivefold increase of splenic weight in wild-type mice. Splenomegaly was associated with myelosuppression and decreasing peripheral leukocyte counts. IL-12-induced changes in wild-type mice were associated with markedly increased IFN-gamma serum levels and up-regulation of major histocompatibility complex (MHC) class I and II expression in various epithelia. IL-12 induced a qualitatively similar macrophage infiltration in IFN-gamma R-/- mice, less marked splenomegaly (to 2 x normal), and no MHC upregulation. Strikingly increased vascular endothelial intercellular adhesion molecule-1 expression was apparent in both IFN-gamma R-/- and IFN-gamma R+/+ mice. Restricted to mutant mice was a severe, invariably lethal, interstitial, and perivascular pulmonary macrophage infiltration with diffuse pulmonary edema. Extensive quantitative reverse transcriptase polymerase chain reaction analysis revealed an increase of only IL-6 and IL-10 pulmonary gene transcripts in IFN-gamma R-/- mice compared with wild-type mice. IL-12-induced myelosuppression is due to IFN-gamma-release from NK cells and T cells, and is associated with macrophage activation and distinct MHC class I and II antigen upregulation. The pulmonary pathology in IFN-gamma R-/- mice, however, reveals a toxic potential for IL-12 and suggests that endogenous IFN-gamma plays a protective role in preventing fatal pulmonary disease in these mice.

Animals↗

PubMed1994

Growth inhibition of human colorectal-carcinoma cells by interleukin-4 and expression of functional interleukin-4 receptors.

The growth-inhibitory effect of interleukin-4 (IL-4) was investigated in a panel of 7 human colorectal-carcinoma cell lines. In 5 cell lines (HT29, WiDr, LS411N, LS513, LS1034) a dose-dependent reduction of proliferation was documented. At 100 U/ml, IL-4 inhibited thymidine incorporation between 45 and 75% and MTT conversion (26 to 41%). The ability of LS513 and WiDr cells to form colonies after IL-4 treatment was reduced by 85 and 62% respectively. LS513 was the most sensitive cell line, with IL-4 inducing half-maximal inhibition at 5 to 6 U/ml. The inhibitory effect of IL-4 was completely neutralized by anti-IL-4 antibodies. Northern-blot analysis revealed the presence of IL-4-receptor (IL-4R) mRNA in all cell lines. The membrane expression of the 130-kDa IL-4R was assessed by FACS, utilizing an anti-IL-4R monoclonal antibody and was confirmed by biotinylated IL-4 binding. Our results attribute an important role for IL-4 as a negative regulator of colorectal-carcinoma cell growth, thus indicating a possible avenue for intervention in this disease.

Blotting, Northern↗

PubMed1994

Interferon gamma receptor deficient mice are resistant to endotoxic shock.

Antibody neutralization studies have established interferon gamma (IFN-gamma) as a critical mediator of endotoxic shock. The advent of IFN-gamma receptor negative (IFN gamma R-/-) mutant mice has enabled a more direct assessment of the role of IFN-gamma in endotoxin (lipopolysaccharide [LPS]-induced shock. We report that IFN gamma R-/- mice have an increased resistance to LPS-induced toxicity, this resistance manifesting well before the synthesis and release of LPS-induced IFN-gamma. LPS-induced lymphopenia, thrombocytopenia, and weight loss seen in wild-type mice were attenuated in IFN gamma R-/- mice. IFN gamma R-/- mice tolerated 100-1,000 times more LPS than the minimum lethal dose for wild-type mice in a D-galactosamine (D-GalN)/LPS model. Serum tumor necrosis factor (TNF) levels were 10-fold reduced in mutant mice given LPS or LPS/D-GalN. Bone marrow and splenic macrophages from IFN gamma R-/- mice had a four- to sixfold decreased LPS-binding capacity which correlated with similar reduction in CD14. Serum from mutant mice reduced macrophage LPS binding by a further 50%, although LPS binding protein was only 10% reduced. The expression of TNF receptor I (p55) and II (p75) was identical between wild-type and mutant mice. Thus, depressed TNF synthesis, diminished expression of CD14, and low plasma LPS-binding capacity, in addition to blocked IFN-gamma signaling in the mutant mice, likely to combine to manifest in the resistant phenotype of IFN gamma R-/- mice to endotoxin.

Animals↗

PubMed1990

Structural organization of the human CaMIII calmodulin gene.

The complete structural organization of the human calmodulin III gene has been determined. This gene specifies the mRNA represented by the previously reported cDNA ht6. The gene contains six exons spread over a total of approx. 10 kb of DNA. Its exon-intron organization is identical to that of the only known chicken calmodulin gene and to that of two of the three characterized rat calmodulin genes. As in many other genes encoding Ca2+ binding proteins, intron 1 separates the ATG initiation codon from the remainder of the coding region. The major and two minor sites of transcription initiation have been determined by primer extension and ribonuclease protection assays. The DNA sequence in the promoter and 5' untranslated region is extremely GC-rich. No typical TATA and CAAT boxes are present upstream of the major transcriptional start site; however, a consensus CAAT box sequence is found further upstream and may play a role in transcriptional initiation from the minor start sites. Six sequence elements with high similarity to monkey SV40-like Sp1-binding regions are present in the putative promoter region, two of which contain perfect GGGCGG core sequences. The structure of the human calmodulin III gene promoter indicates that this gene belongs to a class of 'house-keeping' genes but that its level of expression may also be specifically regulated.

Amino Acid Sequence↗

PubMed1986

[Occurrence of fibrosis in subacute de Quervain thyroiditis].

Subacute thyroiditis of de Quervain is histologically characterized by an inflammatory reaction with histiocytes and giant cells around residues of colloid, producing a tubercle-like granulomatous picture. A variable degree of fibrosis occurs, but recovery is generally almost complete. Investigation of a series of thyroid glands with de Quervain's thyroiditis gave the impression of rather extensive and increasing fibrosis in most of these glands. To substantiate this impression we reviewed the histological slides of all our cases of de Quervain's thyroiditis diagnosed at the Department of Pathology of the University of Zurich between 1940-1950 and 1974-1984. In the majority of the glands of both periods we found rather extensive fibrosis involving more than 50% of the surface. In young patients the fibrosis seemed to be more extensive than in older subjects. There was no sex difference. A certain degree of fibrosis appears to be characteristic of de Quervain's thyroiditis. Differences of frequency and degree of fibrosis between the two periods could not be demonstrated.

Adult↗

PubMed1986

On the role of astrocytes in polyclonal T cell activation.

Murine astrocytes have been identified to possess accessory cell functions, which are thought to be regulated by the inducible expression of surface Ia molecules. The accessory cell functions include the induction of syngeneic and allogeneic T lymphocyte responses, the cytotoxic T cell activation towards haptens and the antigen-induced stimulation of helper T cell lines. In this report, astrocytes initially being Ia antigen-negative cells were found to restore the phytohaemagglutinin (PHA) response of mouse lymph node cells depleted of accessory cells by treatment with leucin methyl ester (Leu ME). Antisera against Ia determinants did not inhibit the PHA response or the release of interleukin-1 (IL-1) by activated astrocytes. Thus, the presence of Ia antigens is not required for mitogen-induced polyclonal T cell activation. In addition to IL-1 release, astrocytes may favour cell-cell contacts necessary for mitogen-induced polyclonal T cell response.

Animals↗

PubMed1979

[Discontinuation of antipsychotic drugs in chronic schizophrenic patients. II. Psychological and psychopathological test differences between patients with and without relapse].

After the discontinuation of the neuroleptic treatment (open design), 10 out of 30 hospitalized chronic schizophrenic patients showed before the end of 4 weeks a significant increase of their symptomatology. This deterioration made the application of neuroleptics necessary. Before the discontinuation of the neuroleptic treatment the group of patients with later relapse and the group without relapse showed only slight differences concerning psychopathological symptoms but significant differences concerning test performance. After 2 weeks without medication a pronounced impairment of performance was found in patients with later relapse. At this time the two groups showed no more significant differences in the psychological tests. At the same time significant differences concerning the psychopathological symptoms had developed.

Adult↗

PubMed1979

[Examination of the retest reliability of the findings of the first psychopathological examination (AMP system)].

80 inpatients were interviewed two times by the same rate during 24 h. Using Kappa, the retest reliability of the following parts of the psychopathological findings was determined: (1) aspects of the interview (median 0.54); (2) AMP symptoms (median 0.72); (3) AMP syndromes (median 0.79); (4) clinical syndromes (median 0.77), and (5) nosologic diagnoses (median 0.93). Based on structured rating of the psychopathological symptoms, a good retest reliability was found.

Adolescent↗

PubMedDate not supplied

High IL-5 production by human drug-specific T cell clones.

To analyze whether and how T cells are involved in drug allergies, we analyzed the drug-induced activation of T cell subsets, T cell receptor V-beta usage and cytokine secretion of T cells from the peripheral blood of drug-allergic individuals. The specificity of the T cells was demonstrated by specific restimulation of drug specific clones. We found that drugs which do not need to be metabolized to become immunogenic (haptens like penicillin G) can stimulate CD4+ and CD8+ T cells in vitro. The T cell response to penicillin can be oligoclonal (use of a certain T cell receptor Vbeta only) or polyclonal. Only polyclonal T cell lines were cross-reactive with other beta-lactam antibiotics. Sulfamethoxazole and lidocaine are thought to gain their ability to bind to proteins by intracellular drug metabolism. They were found to stimulate CD4+ and CD8+ T cells in vitro, and some reactive T cell lines were oligoclonal. The majority of lidocaine-specific clones secreted rather high amounts of IL-5 and IL-4 after PMA/ionomycin stimulations (Th2-like), but some CD4+ and all CD8+ clones had a Th1-like phenotype (high INF-gamma and TNF-alpha). The data clearly demonstrate the existence of drug-specific alphabeta+ T cells in the circulation of drug-allergic individuals and reveal a great heterogeneity of T-cell-mediated responses. Further studies are needed to correlate the type of T cell response to the clinical picture, which can be quite heterogeneous.

Clone Cells↗

PubMedDate not supplied

Characterization of interleukin-13 receptor in carcinoma cell lines and human blood cells and comparison with the interleukin-4 receptor.

The interleukin-13 receptor is characterized by ligand-binding and crosslinking studies and compared with the interleukin-4 receptor. Crosslinking of radio-labeled hIL-4 and hIL-13 to the receptors on human carcinoma and mast cell lines demonstrated a predominant subunit at 130 kDa with two other minor bands of lower molecular mass (75 kDa and 65 kDa) in autoradiography. All binding of 125I-IL-13 was specifically blocked when the carcinoma cell suspensions were incubated with an excess of unlabeled hIL-4. However, unlabeled hIL-13 was unable to completely displace 125I-hIL-4 from the 130 kDa protein. In addition, 125I-hIL-13 showed no binding to mouse fibroblast cells transfected with human 130 kDa hIL-4 receptor c-DNA. Using weighted nonlinear computer modeling of the data from several equilibrium binding studies with human mast cells, a model of two binding sites for IL-4 (Kd = 50 and 190 pmol/L) and one site for IL-13 (Kd = 100 pmol/L) fitted better than a one site model with a very high level of significance (F = 10.66, P < 0.0001). It can be concluded that human IL-4R and hIL-13R are similar but distinct. This conclusion is supported here for the first time by a strong statistical criterion.

Antigens, CD↗