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Biomedical subjects

M S Gruschwitz

Publications and source records attributed to M S Gruschwitz.

15 recordsLinked to original sources
PubMed1997

Up-regulation of class II major histocompatibility complex and intercellular adhesion molecule 1 expression on scleroderma fibroblasts and endothelial cells by interferon-gamma and tumor necrosis factor alpha in the early disease stage.

OBJECTIVE: To investigate the expression patterns of interferon-gamma (IFN gamma) and tumor necrosis factor alpha (TNF alpha), both of which are potent inducers of class II major histocompatibility complex (MHC) and intercellular adhesion molecule 1 (ICAM-1) expression, and their codistribution with HLA-DR and ICAM-1 in skin lesions, cultured fibroblasts, and peripheral blood mononuclear cells (PBMC) of systemic sclerosis (SSc) patients in different stages of disease. METHODS: Investigations were carried out using immunohistochemistry studies, reverse transcriptase-polymerase chain reaction, dot-blot hybridization, and cytometric analysis. Serum levels of TNF alpha were determined by enzyme-linked immunosorbent assay. RESULTS: In the early inflammatory stage of SSc, class II MHC and ICAM-1 expression could be detected on most endothelial cells and on fibroblasts located especially in perivascular areas surrounded by infiltrating lymphocytes, which belong to the T helper 1 phenotype expressing IFN gamma and TNF alpha. In this early disease stage, an enhanced expression of TNF alpha on cultured dermal fibroblasts and PBMC, as well as elevated serum titers of soluble TNF alpha, could be found. CONCLUSION: These data suggest that class II MHC antigens and ICAM-1 on fibroblasts and endothelial cells are induced by IFN gamma and TNF alpha in an early stage of SSc after the influx of mononuclear-cells, and may be important in the putative autoimmune response and in the perpetuation of fibrotic processes in SSc.

Adult↗
PubMed1997

In situ expression and serum levels of tumour necrosis factor alpha receptors in patients with lichen planus.

In lichen planus (LP), an inflammatory skin disease of unknown origin, adhesion molecules and their ligands combined with the local and systemic release of various cytokines are fundamental in regulating inflammation. Therefore, we investigated the expression of tumour necrosis factor alpha receptor (TNF-R) I and II in lesional skin of 15 patients suffering from acute eruptive LP by means of immunohistochemistry. In addition, the serum levels of their soluble forms (sTNF-R) were measured by enzyme-linked immunosorbent assay (ELISA), compared with those of healthy volunteers (n = 10) and correlated with the in situ inflammatory response. In contrast to healthy controls, LP patients showed significantly increased serum levels of sTNF-RI as well as sTNF-RII (p < 0.02). These enhanced serum titres were correlated with a prominent expression of TNF-RI on lesional keratinocytes (basal > suprabasal) and of both receptors on skin-infiltrating lymphocytes. Our data suggest an important role of the TNF ligand/receptor interactions in the induction and/or perpetuation of the pathogenetical and apoptotic events in LP.

Antigens, CD↗
PubMed1997

In situ expression and serum levels of tumor necrosis factor-alpha receptors in patients with early stages of systemic sclerosis.

OBJECTIVE: Tumor necrosis factor-alpha (TNF-alpha) is an important cytokine in the early stage of systemic sclerosis (SSc), which is characterized by mononuclear cell infiltration and microvascular alterations. Most effects of TNF-alpha are mediated by its interaction with 2 types of TNF receptors and depend on their surface expression on individual cell subsets. Our purpose was to correlate the serum levels of soluble TNF receptors-TNF-RI(p55) and RII(p75)-with (1) their in situ expression and distribution in lesional skin and on peripheral blood mononuclear cells (PBMC), and (2) the clinical disease progression and inflammatory serum variables in patients with SSc. METHODS: Serum samples of 32 patients with SSc and 36 healthy probands were examined by ELISA. We performed immunohistological stainings and in situ hybridization on cryostat sections of skin lesions, cytometric analysis on PBMC, and reverse transcriptase polymerase chain reactions using RNA from cultured skin fibroblasts in 17 of these 36 patients. RESULTS: In contrast to healthy skin and chronic fibrotic SSc, TNF-RI is expressed on about 30% of mononuclear infiltrating cells in early skin lesions. Neither TNF-RI nor RII was detectable on fibroblasts by immunohistochemistry, but specific mRNA could be found on the transcriptional level. TNF-RII is found on most lymphocytes and on 30-50% of endothelial cells, especially in early SSc. Expression of both receptor types on PBMC in patients and controls was not significantly different. Serum levels of soluble TNF-RI and RII correlated well with their in situ expression and with clinical and laboratory signs of inflammation and disease progression in patients with SSc. CONCLUSION: Our data provide evidence for a central role of the TNF-alpha/TNF-R system in the early pathological events of scleroderma with prominent inflammation and endothelial cell damage. Determination of TNF-R serum levels provides a useful diagnostic tool for characterization of the disease stage and progression, and to guide experimental therapy in patients with SSc.

Adult↗
PubMed1996

Endothelial cell apoptosis is a primary pathogenetic event underlying skin lesions in avian and human scleroderma.

The mechanism that may cause degenerative fibrotic skin lesions was studied in situ using skin biopsies from patients with systemic sclerosis (SSc), localized scleroderma, or keloids, and at the initial disease stage in the University of California at Davis (UCD) lines 200/206 chickens, which develop a hereditary systemic connective tissue disease resembling human SSc and permit study of disease stages not accessible in humans. Frozen skin sections were analyzed simultaneously for apoptosis by terminal deoxynucleotidyl transferase-mediated FITC-dUTP nick end labeling and indirect immunofluorescence staining of cell markers with tetramethylrhodamine isothiocyanate conjugates. The results showed that endothelial cells are clearly the first cells to undergo apoptosis in the skin of UCD-200/206 chickens, a process that seems to be induced by anti-endothelial cell antibodies. In human fibrotic skin diseases, apoptotic endothelial cells could only be detected in early inflammatory disease stages of SSc and localized scleroderma.

Adolescent↗
PubMed1995

Correlation of soluble adhesion molecules in the peripheral blood of scleroderma patients with their in situ expression and with disease activity.

OBJECTIVE: To correlate serum levels of the soluble adhesion molecules intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), E-selectin, and P-selectin with (a) clinical disease activity and progression and (b) the in situ expression and distribution of these adhesion molecules in lesional skin, in patients with systemic sclerosis (SSc). METHODS: Serum samples from 12 SSc patients and 36 healthy controls were examined by enzyme-linked immunosorbent assay. Immunohistologic staining was carried out on cryostat sections of lesional skin. RESULTS: Patients whose SSc was in the early inflammatory stage or who had prominent disease progression showed elevated serum levels of soluble adhesion molecules. Serum levels correlated positively with the expression of these molecules on endothelial cells and fibroblasts in lesional skin. CONCLUSION: Serum levels of soluble ICAM-1, VCAM-1, P-selectin, and, to a lesser degree, E-selectin correlate well with their in situ activity and with clinical disease activity. These parameters therefore provide a useful tool for the characterization of disease stage, progression, and prognosis in SSc.

Adult↗
PubMed1994

[Snake bite by a poisonous snake. Report of an unusual case].

We report on a 31-year-old white woman, who was bitten in her right calf by a "spitting cobra" (Neia nigricollis) during a safari in Tansania. Minor initial systemic symptoms such as nausea and vomiting were followed by severe oedematous swelling of the extremity after 2-3 h and demarcation of a 2.75 x 2.75 in. area of necrotic skin. The patient returned to her home country, where 8 days after the snake-bite necrosectomy was performed. Antibiotics, anti-inflammatory agents and local therapy with hydrocolloidal wound dressings were administered. With this therapy the lesion healed completely with minor scarring within 5 months. A new Salmonella strain was isolated from the ground of the ulcer.

Adult↗
PubMed1994

[Initial visceral involvement with diffuse systemic scleroderma].

Progressive systemic sclerosis (PSS) is characterized in most patients by initially unspecific symptoms like acrocyanosis. Raynaud's phenomenon, general malaise or acral paresthesia. Clinical manifestations appear with an edematous-inflammatory stage of disease leading to a chronic-progressive phase with increasing fibrosclerosis of the skin and internal organs. Dermal involvement and the demonstration of immunopathological abnormalities in the peripheral blood precede visceral fibrosis in most cases. We report on an unusual case of diffuse PSS with preceding involvement of internal organs. Early visceral fibrosis is demonstrated by histomorphological results and is correlated with laboratory findings. Serum antinuclear antibodies could not be obtained until 4 months ante finem and the liver was also involved in the fibrotic process.

Antibodies, Antinuclear↗
PubMed1993

Antinuclear antibody profile in UCD line 200 chickens: a model for progressive systemic sclerosis.

The fully blown disease of human progressive systemic sclerosis (PSS, scleroderma) is serologically associated with the emergence of several types of autoantibodies, some of them regarded as more specific for scleroderma (e.g. Scl-70, anti-centromere) and some common also to other connective tissue diseases (e.g. anti-ssDNA). Since most patients suffering from PSS are not under medical control until clinical manifestations are fully established, only scarce data are available on the dynamics and clinical significance of autoantibodies in the very early stages of this systemic fibrotic disease. The University of California at Davis line 200 (UCD 200) of chickens spontaneously develop a PSS-like disorder with an acute inflammatory stage around 60 days after hatching, leading to fibrosis with fast progression. In order to address a possible correlation between the occurrence and titer of autoantibodies and the initial disease activity, we have chronologically investigated the presence and titer of autoantibodies directed against several human nuclear antigens in this animal strain. In UCD-200 chickens, we found a progressive increase in autoantibodies to histones, to ssDNA and--to a lesser degree--dsDNA with peaks at the age of 60 and 120 days, to poly(I) and poly(G) with a peak at 120 days and an elevation in anti-cardiolipin antibodies. Total immunoglobulin concentrations, anti-Ro, anti-La and anti-Sm showed no significant differences as compared to negative results in healthy normal controls. Our data reveal parallels in the antinuclear antibody (ANA) spectrum between UCD-200 chickens and human autoimmune collagen diseases, but do not reflect the typical ANA spectrum found in the foudroyant form of diffuse scleroderma.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1993

Effects of interferon-alpha-2b on the clinical course, inflammatory skin infiltrates and peripheral blood lymphocytes in patients with severe atopic eczema.

Increased serum IgE and enhanced susceptibility to viral infections, decreased levels of interferons, lymphocytic skin infiltrates and IgE-bearing epidermal Langerhans cells are striking features in patients with atopic eczema (AE). Since the hyper-IgE syndrome is known to improve under alpha-interferon (alpha-IFN) therapy, we treated 7 patients with severe AE and high serum IgE exclusively with 3 x 10(6) units IFN alpha 2b thrice weekly for 3 months. Before treatment the skin infiltrates mainly consisted of CD3+/CD4+/TcR alpha/beta + lymphocytes, whereas the CD3+/CD8+ phenotype was limited to about 10% of cells. After 6 weeks of therapy, epidermal inflammation with CD4+ and CD8+ cells was reduced but dense infiltrates remained in papillary perivascular areas. Expression of TcR gamma/delta, HLA-DR and CD25 showed no significant changes. Initially high serum IgE and soluble CD23 as well as cell-bound IgE dropped under therapy, whereas a short-term elevation in serum IL-2 receptor was observed. On peripheral blood lymphocytes slightly reduced expression of HLA-DR, LFA-1, CD23 and ICAM-1 was seen after 100 days. LFA-3 expression became reduced in 4 patients, the CD4/CD8 ratio decreased in all cases. After an initial therapeutic response of all patients, significant longer-lasting improvement of the skin lesions could only be observed in 2 of 7 patients. The data of our long-term study suggest that systemic IFN alpha 2b treatment leads to a remarkable reduction in epidermal inflammation but does not significantly influence cutaneous cell subsets. Immunomodulatory effects became obvious by reduced peripheral cell subsets expressing TcR alpha/beta, MHC class II and adhesion molecules.

Adult↗
PubMed1992

Expression of transforming growth factor type beta on human epidermal dendritic cells.

Our study demonstrates that epidermal Langerhans cells (LC) of healthy human skin produce Transforming growth factor-beta (TGF-beta). This multipotent mediator might keep the immunocompetent LC in an "immature" stage, in which they are able to capture and process antigen. Development to potent antigen-presenting cells would become possible after migration from the epidermal network to the draining lymph node to stimulate (auto-)reactive T-cell clones.

Dendritic Cells↗
PubMed1991

Phenotypic analysis of skin infiltrates in comparison with peripheral blood lymphocytes, spleen cells and thymocytes in early avian scleroderma.

University of California at Davis line 200 (UCD-200) chickens develop a hereditary connective tissue disease characterized by severe lymphocytic infiltration, vascular occlusion and fibrosis of skin and internal organs. To identify cellular immunological abnormalities in the acute inflammatory disease stage of this animal model for progressive systemic sclerosis (PSS) we investigated the phenotypic characteristics and function of peripheral blood lymphocytes (PBL), spleen cells and thymocytes in comparison with skin infiltrating cells. Immunofluorescence and immunohistochemical analysis using monoclonal antibodies revealed the overwhelming majority of skin infiltrating mononuclear cells in the deeper dermis and subcutaneous tissue to be T cell receptor alpha/beta (TcR2)+/CD3+/CD4+/class II+ cells, a small portion (5-10%) of which were interleukin 2 (IL-2) receptor positive. In contrast, the inflammatory infiltrate in perivascular areas of the papillary dermis was constituted of mainly TcR gamma/delta (TcR1)+/class II- lymphocytes. Only few B cells (T/B cell ratio greater than 5) were detected. These diseased chickens showed significantly reduced percentages and numbers of circulating peripheral T cells exhibiting TcR1, TcR2, CD3, CD4 or IL-2-receptor, probably owing to an increased influx into lymphoid organs and affected tissues. In contrast to healthy chickens, the thymi of UCD-200 animals revealed fewer cells expressing TcR1, TcR2 and class II antigen, suggesting an altered intrathymic maturation of the T cell lineage. Functional in vitro studies showed a significantly decreased T cell mitogen-induced proliferation rate associated with a decreased capacity to produce IL-2 and to express IL-2 receptors. In contrast to the deficient in vitro IL-2 production the sera of UCD-200 chickens contained significant levels of IL-2 bioactivity. The alteration of T lymphocyte physiology in UCD-200 chickens adds, at least in part, to the parallels between this animal model and its human counterpart. These data confirm our hypothesis that the PSS-like disease of UCD-200 chickens includes a numeric and/or functional alteration of peripheral T cell subsets, especially of TcR1 positive cells, in contrast to the pronounced accumulation in the afflicted tissues.

Animals↗
PubMedDate not supplied

Cytokine levels in the seminal plasma of infertile males.

Cytokines released by various cell subsets in the male urogenital tract are capable of markedly influencing sperm function and fertility. We determined the cytokine content in the seminal plasma of patients with unexplained infertility and correlated the results with urogenital infections and sperm parameters. Routine sperm parameters, bacterial culture of seminal plasma and blood follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone were obtained from 14 infertile males and 8 healthy control subjects. Interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF alpha) levels in the seminal plasma were measured by enzyme-linked immunosorbent assay (ELISA). IL-1 beta, IL-6, and TNF alpha levels in the seminal plasma were negatively correlated with the number of progressively motile sperm, but there was no correlation with total sperm counts, viability, pH, morphological alterations, type of abnormality, and hormone parameters. Cytokine levels were significantly elevated in seminal plasma exhibiting bacterial or mycoplasmal infections of the urogenital tract. Urogenital infections lead to an release of inflammatory cytokines, most probably by immunocompetent cells of the lymphocyte/macrophage origin. Cytokines such as IL-1, IL-6, and/or TNF alpha might influence sperm motility via direct or indirect effects, resulting in reduced mucosa penetration properties. Therefore, our data suggest that cytokines may be involved in reduced male fertility.

Adult↗