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Biomedical subjects

M Gruschwitz

Publications and source records attributed to M Gruschwitz.

14 recordsLinked to original sources
PubMed2006

Human chorionic gonadotropin (hCG) in the male reproductive tract.

Normal hypothalamic-pituitary testicular and prostatic functions are essential for maintenance of male fertility, whereby glycoprotein hormones (GPH) as well as androgens are major endocrine and local regulators. We have investigated whether the GPH human chorionic gonadotropin (hCG) and the free alpha and beta subunits thereof are produced in the target organs themselves and potentially act as auto/paracrine modulators of fertility. Immunofluorometric assays (IFMAs) based on our panel of highly selective monoclonal antibodies, immunohistochemistry (IHC), confocal laser scanning microscopy (CLSM) and 1- and 2D gel electrophoreses with subsequent western blotting have been utilized for the detection of hCGalpha, hCGbeta and its metabolite hCGbeta core fragment (cf) in human testis, prostate and seminal plasma. Both organs synthesize hCGalpha and hCGbeta, which are subsequently detectable at high concentrations in seminal plasma of healthy probands (n=17): hCGalpha 2630+/-520 ng/mL (mean+/-S.E.M.), hCGbeta 2+/-0.28 ng/mL, hCGbetacf and hCG 0.19+/-0.039 ng/mL. These parameters significantly exceed physiological values, e.g. ten thousand-fold in the case of hCGalpha, in serum of young men (n=20): hCGalpha 0.142+/-0.054 ng/mL (mean+/-S.E.M.), hCGbeta 0.05 ng/mL and hCG 0.004+/-0.003 ng/mL. Levels of these markers were not correlated with sperm counts. Of all body fluids including those of pregnant women seminal plasma is the richest physiological source for genuine free i.e. non-dissociated GPHalpha (M(r,app) 23k) which may even appear as di- or tetramers. Its concentration is similar to that observed in maternal serum (weeks 10-12 of gestation) and in extra-embryonic coelomic fluid. In contrast to those fluids where ratios of free subunits to hCG are in the range of 1:100 highly inverse ratios in the range of 10.000:1.000:1 were observed for hCGalpha:hCGbeta:hCG in seminal plasma. hCGalpha is not derived from heterodimeric GPH suggesting hCG-independent functions of hCGalpha and hCGbeta in male and female fertility.

Blotting, Western↗
PubMed1993

Effects of cytokine application on glucocorticoid secretion in an animal model for systemic scleroderma.

We previously reported on an altered immune-endocrine feedback loop via the hypothalamo-pituitary-adrenal (HPA) axis in Obese strain (OS) chickens afflicted with spontaneous autoimmune thyroiditis. These animals are deficient in plasma corticosterone increase after antigenic challenge or application of cytokine-containing conditioned medium of mitogen-stimulated spleen cells (CM). To investigate whether the impaired ability to respond to cytokines with glucocorticoid-increasing factor (GIF) activity, e.g. interleukin 1 (IL 1), is restricted to OS chickens as a model for an organ-specific autoimmune disease, we extended our experiments to another autoimmune-prone animal strain, the chickens of the University of California at Davis line 200 (UCD-200). These animals develop an inherited inflammatory fibrotic disease that closely resembles human progressive systemic sclerosis (scleroderma). Application of GIF-containing CM to UCD-200 chickens leads to a transient increase in glucocorticoid serum levels within 1-2 hours comparable to that of controls. But, while corticosterone levels in the latter returned to normal baseline levels after 4 hours, they were still elevated in autoimmune chickens. Although the peak of the glucocorticoid hormone serum concentrations was equal to that of controls, UCD-200 had to secrete twice as much adrenocorticotropic hormone to achieve this corticosterone serum level due to an apparent hyporesponsiveness of the adrenal gland to this secretagogue. The altered cytokine-induced glucocorticoid secretion is found in early as well as in chronic, sclerotic stages of the disease. Cellular alterations in the peripheral blood of UCD-200 chickens during the prolonged elevated corticosterone section, i.e. between 2-4 hours after CM application, are characterized by a significant decrease in the percentage of CD4+ and CD8+ cells. Furthermore, a significant increase in B cells up to 24 hours with a maximum after 1 hour was found. The proliferative response to the mitogen concanavalin A of peripheral mononuclear cells was inversely correlated to the serum corticosterone level, showing a permanent decrease of 80-90% after 1-4 hours in autoimmune animals. This functional alteration in UCD-200 was accompanied by an 80% decrease in serum interleukin 2 (sIL 2) activity 4 hours after CM application. Twenty-four hours later an eight-fold increase in sIL 2 rebound activity was found, indicating that the inhibitory effect of corticosterone in UCD-200 chickens is not long-lasting.

Adrenocorticotropic Hormone↗
PubMed1993

Microcirculatory functions in systemic sclerosis: additional parameters for therapeutic concepts?

To study the functional reactivity of the cutaneous microcirculation in progressive systemic sclerosis (PSS), hyperemic responses after arterial occlusion (3 min) and during local heating (42 degrees C) were investigated with simultaneous measurements of red blood cell flux and cutaneous oxygen tension (pcuO2) of the skin in female patients (n = 19) with PSS and in healthy female controls (n = 15). Additionally, serum levels of 6-keto-prostaglandin 1 alpha (PGF1 alpha), a stable metabolite of prostacyclin, were compared to the microcirculatory data, and both were used to evaluate further a standardized therapy with 10-d intravenous calcitonin (100 IU/d) infusion in six PSS patients. In PSS, the initial mean pcuO2 value was significantly reduced and was inversely proportional to flux and to PGF1 alpha levels, whereas the flux and pcuO2 responses to the above hyperemic stimuli showed significant reductions, revealing a pattern of "hyperemic hypoxia" probably due to exhausted functional reserves of cutaneous perfusion. During calcitonin infusion significant rises in pcuO2 and temporarily in PGF1 alpha and flux were found. After 10 d of therapy, increased pcuO2 was associated significantly with decreased flux, indicating a shifting of blood from deeper regulatory vessels to the subepidermal capillaries. Both clinical improvement and the results of microcirculatory measurements demonstrate a beneficial effect of calcitonin on the cutaneous microcirculation in PSS patients, possibly due in part to a short-term increase in release of endogenous prostacyclin from the vascular endothelium during the infusion. The disturbed reactivity of the dermal vessels in PSS is important for the evaluation of therapeutic concepts and stresses, together with the elevated PGF1 alpha plasma levels, vascular factors in the pathogenesis of PSS.

Aged↗
PubMed1992

Investigation of ACTH responses of chickens with autoimmune disease.

An altered immunoendocrine feedback regulation within the hypothalamo-pituitary-adrenal axis may modulate the pathogenesis of an avian autoimmune disease. To date studies have been hampered by a lack of reliable, specific, and sensitive methods for determining adrenocorticotropic hormone (ACTH) in chickens. The present study describes the determination of ACTH in plasma of chickens with a commercial radioimmunoassay, the antibody of which binds to the midregion of human ACTH 1-39. The chickens, kept on a 12-hr day and 12-hr night shift with artificial light, showed changes in plasma ACTH concentrations during the light phase with maximum values 8 hr after the light was turned on. ACTH was not measurable after treatment with dexamethasone. Intravenous administration of supernatants from concanavalin A-stimulated spleen cells increased basal plasma ACTH concentrations more than 20-fold within 1 hr. This increase in plasma ACTH was higher and longer lasting in UCD 200 chickens, an animal model for scleroderma, compared with outbred and inbred normal White Leghorn chickens.

Adrenocorticotropic Hormone↗
PubMed1992

Distribution of adhesion molecules, IgE, and CD23 in a case of angiolymphoid hyperplasia with eosinophilia.

Angiolymphoid hyperplasia with eosinophilia developed in a 13-year-old boy. The immune phenotype of infiltrating cells and the distribution of adhesion molecules of the integrin, immunoglobulin, and selectin families were analyzed with monoclonal antibodies. The infiltrate consisted mainly of helper lymphocytes, monocytes, eosinophils, CD1+ dendritic cells, and mast cells. A CD23/Fc epsilon receptor was present on 40% of these cells, and surface bound IgE was present on 30% of these cells. The latter was found on all cell types. A cellular adhesion molecule analysis revealed that the proliferating endothelial cells were expressing constitutive ICAM-1, LFA-3, VLA-1, VLA-3, VLA-5, alpha 6, and beta 3-integrin chain as well as activation-dependent VLA-2, VCAM-1, and human lymphocyte antigen-DR. The infiltrating cells expressed LFA-1 and CD2, the correlating ligands for ICAM-1 and LFA-3. Our studies support previous observations of an unusual IgE-mediated immune reaction, and suggest an additional pathogenic role for adhesion events in the development of the pathognomonic cellular composition in angiolymphoid hyperplasia with eosinophilia.

Adolescent↗
PubMed1992

Expression of adhesion proteins involved in cell-cell and cell-matrix interactions in the skin of patients with progressive systemic sclerosis.

BACKGROUND: Lymphocytic infiltration and activation of connective tissue metabolism in the early phase of progressive systemic sclerosis (PSS, scleroderma) may be critically influenced by cellular adhesion molecules (CAMs), which mediate cell-cell and cell-extracellular matrix interactions. OBJECTIVE: The tissue distribution might demonstrate a pathogenetic role of these adhesion molecules in early edematous and chronic fibrotic scleroderma. METHODS: We investigated by immunohistochemical techniques the in situ expression and distribution of beta 1 and beta 2 integrins, selectins, and CAMs of the immunoglobulin superfamily in patients with scleroderma. RESULTS: In the early disease stage a moderate percentage of perivascular CD3+/CD4+/TCR alpha/beta + lymphocytes showed expression of the alpha 3, alpha 5, and beta 1 chains and, to a lesser degree, of the alpha 1, alpha 2, alpha 4 and alpha 6 subunits. In contrast to chronic PSS, LFA-1 alpha, LFA-1 beta and ICAM-1 expression on mononuclear infiltrating cells was seen more frequently in acute scleroderma. Different percentages of fibroblasts expressed alpha 1-, alpha 3-, alpha 5- and beta 1-integrin chains. In acute PSS ICAM-1 was expressed especially by fibroblasts located around perivascular inflammatory infiltrates as well as by endothelial cells (ECs). A few ECs expressed alpha 2 beta 1 integrins. CONCLUSION: Our observations suggest that CAMs are intimately involved in early pathogenetic events in scleroderma, mediating cellular interactions between lymphocytes, ECs, and fibroblasts, as well as homing and tissue targeting of mononuclear infiltrating cells.

Acute Disease↗
PubMed1991

Expression of class II-MHC antigens in the dermis of patients with progressive systemic sclerosis.

Expression of class II major histocompatibility complex (MHC) antigens on normally negative cell types may convert them into effective antigen-presenting cells. It was therefore of special interest to elucidate whether the main cell populations involved in progressive systemic sclerosis (PSS) express class II antigens on their surfaces and participate in the initiation and/or perpetuation of a cellular immune response in the connective tissue. Immunofluorescence studies on frozen skin sections of scleroderma patients using double-staining techniques revealed a pronounced dermal mononuclear cellular infiltrate with signs of activation manifested by expression of MHC class II antigens in the acute phase of the disease. Most endothelial cells of the papillary and deeper dermal vessels were class II-positive as seen in other inflammatory dermatoses. Moreover, class II antigen-positive fibroblasts were found, especially in the deeper dermis within infiltrated areas around blood vessels. MHC class II molecules were also detected in higher density and on increased numbers of perivascular dermal dendrocytes. On all cell types, HLA-DP was much less frequently expressed than HLA-DR, but more frequent than HLA-DQ. However, in the chronic phase of the disease, with reduced inflammation and increasing sclerosis, MHC class II antigen expression on dermal fibroblasts was again diminished or even absent, as seen in normal and non-PSS inflammatory control biopsies and clinically unaffected skin of scleroderma patients in the acute inflammatory disease stage. Our data speak against a primary expression of class II molecules on PSS-fibroblasts. It seems more likely that Ia-antigens on fibroblasts and an increase of MHC class II positive dermal dendrocytes are induced in an early stage of the disease, i.e., after the influx of the mononuclear infiltrate, most probably by mediators released from these cells. Since an enhanced transcription rate of collagen genes in fibroblasts surrounded by infiltrating cells has been described, this early expression of class II MHC antigens does not seem to play a central role in the induction phase, but rather, may be important in the perpetuation of fibrotic processes in scleroderma.

2',5'-Oligoadenylate Synthetase↗
PubMed1990

Immunology of atherosclerosis: cellular composition and major histocompatibility complex class II antigen expression in aortic intima, fatty streaks, and atherosclerotic plaques in young and aged human specimens.

There is evidence that fatty streaks in arteries can transform into atherosclerotic plaques. Mononuclear cells, including both monocytes and lymphocytes, are among the first cells participating in the development of atherosclerosis of experimental animals. To investigate the roles of different cell types in human atherosclerosis, we enumerated and compared the cellular compositions of normal intima, the transition zone (the area between the normal intima and the core of fatty streaks), fatty streaks, and plaques in young (age 16-30 years) and aged (over 60 years) human specimens using double-staining immunofluorescence with a series of monoclonal and polyclonal antibodies. T lymphocytes, both T helper/inducer (70% of T cells) and T suppressor/cytotoxic (30%) phenotypes, were found in every stage of atherosclerosis, constituting 30 to 40% of total cells in fatty streaks and transition zones of young subjects, and occasionally even in normal intima. Seventy percent of these T cells were HLA-DR positive, which indicated that most of them were activated. Macrophages were most frequent in fatty streaks and around the necrotic core of plaques. Smooth muscle cells, increasing from 5 to 30% with lesion progression, were HLA-DR positive where activated T helper cells occurred in the vicinity. The intracellular presence of the invariant gamma chain confirmed that HLA-DR was actually synthesized by these smooth muscle cells. Endothelial cells were HLA-DR positive above those regions of the lesions where HLA-DR-positive cells had accumulated, but not in normal intima, again suggesting induction of HLA-DR expression by T-cell-derived gamma-interferon. Furthermore, most HLA-DR-positive cells were also identified as HLA-DP and HLA-DQ positive. This aberrant major histocompatibility complex class II antigen expression in smooth muscle and endothelial cells may participate in the perpetuation of the atherogenetic autoimmune reaction.

Adolescent↗
PubMed1990

Transcription and expression of transforming growth factor type beta in the skin of progressive systemic sclerosis: a mediator of fibrosis?

Progressive systemic sclerosis is characterized by extensive generalized fibrotic destruction associated with increased accumulation of collagen and other extracellular macromolecules in the skin and other involved organs. It has been suggested that mediators released from mononuclear or endothelial cells play a critical role in the initial activation of connective tissue metabolism. Transforming growth factors beta(TGF-beta 1, TGF-beta 2) mediate the inhibition of epithelial cell proliferation and the induction of fibronectin and collagen gene expression. Therefore, we investigated the distribution of both TGF-beta 1 and TGF-beta 2 mRNA and the final proteins in PSS skin in comparison with other inflammatory dermatoses and healthy controls by means of in situ hybridization and immunohistochemistry. Our studies revealed TGF-beta 1 and -beta 2 mRNA in dermal and subcutaneous infiltrating cells in both acute and chronic PSS, but also in the other inflammatory skin disorders. In the vicinity of this infiltrate single TGF-beta positive fibroblasts could be found in acute PSS. The cytoplasm of epithelial cells of all skin adnexa showed TGF-beta transcripts and no apparent differences were seen in the distribution and number of autoradiographic grains between diseased and healthy skin samples. Especially, we could demonstrate abundant expression of TGF-beta 1/2 in epithelial hair follicle cells of the outer root sheath. Generally, the expression of TGF-beta 2 was less abundant than TGF-beta 1. Immunohistochemical studies revealed the same distribution pattern of the final proteins. Our data indicate that TGF-beta expression in infiltrating cells is not a specific feature of fibrotic disease, but seems to be associated with highly proliferating cells in general, perhaps functioning as common mediator in regulation of cellular physiology with special importance for negative control of cell growth.

Adult↗
PubMed1989

[Comparative histology and immunohistochemistry of tests of immediate allergic reaction and type I contact dermatitis].

Contrary to type IV contact dermatitis, histochemical studies of immunological mechanisms in type I contact dermatitis are rare. To analyse the immunohistochemical kinetics of immediate type I reactions we followed up prick-test reactions to individual specific allergens in 5 atopics with respiratory allergy (group I) and in 4 patients with proven type I contact dermatitis (group II). Punch biopsies (diameter 6 mm) were taken 20 minutes, 6, 24 and 72 h after prick testing. Histological investigations were performed on paraffin-embedded tissue; immunohistochemical studies were done one frozen tissue with a panel of monoclonal antibodies applying the alkaline-phosphatase-anti-alkaline-phosphatase-complex method. In type I contact dermatitis a moderate lympho-monocytic dermal infiltrate appeared, which increased until 72 hrs after testing. In contrast, the immediate allergic reactions of group I revealed only mild lympho-monocytic infiltration in all proven sequential biopsies. No quantitative differences concerning the immunohistochemical pattern of OKM-1, OKM-5, Leu-2a and Leu-3a were observed between the two groups. Group II showed an increase in HLA DR, OKT6, anti-IgE- and anti-IL-2-receptor immunoreactivity whereas group I exhibited only moderate or no immunoreactivity. A dendritic anti-IgE-staining pattern, most probably on Langerhans cells, was only observed in the epidermis of group II patients. A pathogenetic concept of IgE-mediated type I contact dermatitis is presented and possible relationships with atopic dermatitis are discussed.

Adolescent↗
PubMed1988

Immunohistochemical study of palatal salivary glands of denture wearing patients.

The binding pattern of antibodies against different cytokeratin (CK) polypeptides, tissue polypeptide antigen (TPA), carcinoembryonic antigen (CEA), lactoferrin (Lf), lysozyme (Ly) and secretory component (SC) in palatal glands (PSG) of long-term denture wearing patients has been studied to investigate immunohistochemically the localization of these marker proteins in normal PSG and in denture-induced sialadenitis of PSG. The study included palatal gland biopsies from 28 patients (15 f, 13 m; mean age 59 years), 17 of them with normal PSGs, 8 with focal obstructive sialadenitis, and 3 with diffuse sialadenitis. Presence of CK and TPA was found in all intra- and extraglandular salivary ducts, in the basophilic portions of acini, in some mucous acini, and in all atrophic acini. Increased expression of CEA and Lf was observed in inflammed areas of PSG which, on the other site, were devoid of Ly and SC. In the mucous acini of healthy PSG considerable basal Ly immunoreactivity was seen. SC was localized in almost all ductal cells and in some acinar cells. Appearance of Lf in the ductal cells of PSG indicates an early sign of palatal sialadenitis. Some distinctions in the expression pattern of the marker proteins between the mucous acini of major salivary glands and PSG point to differences in the functional activities of either group of salivary glands.

Denture, Complete, Upper↗
PubMed1987

[Comparative immunofluorescence study of actinic keratosis and chronic discoid lupus erythematosus].

Regarding systemic (SLE) and chronic discoid lupus erythematosus (CDLE), the diagnostic value of the lupus band test ist generally accepted. In the literature, however, there are but few obligatory criteria concerning the definition of a positive lupus band. In order to illustrate the influence of sunlight on the evolution of junctional deposits of immunoglobulins, we examplarily studied actinic keratosis (AK) as a chronic light-dependent dermatosis. The junctional deposits in AK were qualitatively and quantitatively compared with the lupus band typical for CDLE. In CDLE we mostly found more distinct band-like junctional deposits of immunoglobulins and complements. Light-dependent, non-specific junctional patterns of immunofluorescence similar to LE, therefore, require clear morphological criteria of immunohistology.

Aged↗