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Biomedical subjects

R Hein

Publications and source records attributed to R Hein.

At least 91 records · Page 5Linked to original sources
PubMed1990

Influence of eicosanoids on fibroblast chemotaxis and protein synthesis in vitro.

Metabolism of fibroblasts plays a key role in wound healing, fibrosis, rheumatoid arthritis, and similar physiological and pathological processes. The regulatory influence of eicosanoids, an important class of inflammatory mediators, on fibroblast metabolism, in these processes is, to date, unclear. The aim of this study was to investigate the effect of some eicosanoids on chemotaxis and protein synthesis of fibroblasts in vitro. Of twelve eicosanoids tested, only 5(S)-HETE, LTB4, and 12(S)-HETE were active as chemo-attractants for fibroblasts. 5(S)-HETE was the most potent attractant. It exerted its maximal activity at 10(-10) mol/l. 12(S)-HETE and LTB4 caused similar dose dependent fibroblast chemotaxis with a maximum of activity at 10(-7) M and 5 x 10(-8) M, respectively. Hydroxylation of LTB4 on C20 or methylation of the carboxy group of 12(S)-HETE decreased reactivity of the parent compounds only slightly. Eicosanoid induced chemotaxis could be antagonized by 12(S)-HETE but not by the proteinaceous chemoattractants fibronectin, PDGF, or EGF. Receptors for peptide and eicosanoid mediated chemotaxis are thus different. Inhibition of collagen synthesis was observed in the presence of 5(S)-HETE and 12(S)-HETE while total protein synthesis was unaffected by 12(S)-HETE and augmented by 5(S)-HETE. These data suggest that certain eicosanoids specifically regulate fibroblast activities in wound healing and similar events of connective tissue reorganization.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1990

Tumor necrosis factor alpha induces invasiveness of human skin fibroblasts in vitro.

The chemotactic response of fibroblasts plays an important role during wound healing and fibrosis. Several substances have been found to mediate fibroblast migration in vitro. In the tissue, however, fibroblasts have also the potential to pass through connective tissue barriers following a chemotactic stimulus. Since tumor necrosis factor alpha (TNF alpha) is a cytokine released by mononuclear cells during wound healing, we have been interested in studying its effect on the regulation of fibroblast chemotaxis and invasive migration. TNF alpha did not attract skin fibroblasts nor did it alter their chemotactic response towards other chemoattractants like fibroblast conditioned medium or fibronectin. However, whereas normal skin fibroblasts did not invade a collagen I gel, preincubation of the cells with TNF alpha markedly induced their invasive migration into the gel. This seems to be associated with a specific degradation of type I collagen, because TNF alpha did not promote the invasion of skin fibroblasts through a reconstituted basement membrane (Matrigel).

Adult↗
PubMed1990

Invasive migration of epidemic Kaposi's sarcoma cells in vitro.

Kaposi's sarcoma (KS) is a low grade malignant neoplasm which shows invasive growth and often occurs in immunosuppressed patients with the Acquired Immune Deficiency Syndrome (AIDS; epidemic KS). It is also found in elderly men where it is usually limited to the skin (classic KS). The present study investigated the chemotaxis and invasive migration of epidemic KS cells in vitro and compared them to cells grown from classic KS lesions and to fibroblasts. Epidemic KS cells demonstrated invasive migration through reconstituted basement membrane (Matrigel) as well as through interstitial connective tissue (collagen I) in early passages, whereas fibroblasts did not invade either barrier. Epidemic KS cells in late passages did not show any invasive migration. Following pretreatment with tumour necrosis factor alpha (TNF-alpha) there was no enhanced migration through the Matrigel and collagen I for epidemic KS cells, whereas classic KS cells showed an increased migration through the type I collagen barrier.

Basement Membrane↗
PubMed1990

Melphalan and prednisone (MP) versus vincristine, BCNU, adriamycin, melphalan and dexamethasone (VBAMDex) therapy for multiple myeloma. Early results of a multicenter trial. The German Myeloma Treatment Group.

136 untreated multiple myeloma patients of stage II and III were collected in the study. 37/51 stage II patients had progressive disease and were treated with melphalan and prednisone (MP). 85 patients were of stage III and randomized into MP and vincristine, BCNU, adriamycin, melphalan and dexamethasone (VBAMDex) treatment groups. 55% of MP treated patients responded versus 75% of the VBAMDex group. Since the study has been activated only 16 months ago, no difference in survival could be observed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Cyclosporin in localized and systemic scleroderma--a clinical study.

Four patients with systemic scleroderma and 1 patient with localized scleroderma were treated with ciclosporin (CS), given in daily doses between 2.2 and 5.6 mg/kg body weight for 3-26 months. Under this medication clinical improvement was observed in 4 patients with partial regression of cutaneous sclerosis and inflammation, healing of fingertip ulcerations or leg ulcers and improvement of articular mobility. However, in 1 patient with rapidly advancing systemic scleroderma a short-term therapy with CS in low doses (2-3 mg/kg body weight) resulted in arterial hypertension and renal dysfunction. Therefore careful selection of patients and close-meshed controls are indicated when CS is considered as anti-inflammatory treatment in scleroderma.

Acute Kidney Injury↗
PubMed1990

Chemotactic migration of normal dermal fibroblasts towards epidermal growth factor and its modulation by platelet-derived growth factor and transforming growth factor-beta.

During the repair phase of wound healing, fibroblasts migrate to the site of injury where they proliferate and synthesize constituents of the extracellular matrix of connective tissue. Their activity is regulated by mediators originating from cells of the blood clotting and inflammatory stage such as platelet-derived growth factor, epidermal growth factor, transforming growth factor-beta and other cytokines. This communication shows that chemotactic migration of normal dermal fibroblasts is elicited by epidermal growth factor in vitro and that platelet-derived growth factor and transforming growth factor-beta can down-regulate this activity. This suggests that in vivo these growth factors are part of an intricate network which connects and coordinates proliferation, protein synthesis and chemotactic migration of fibroblasts.

Cell Movement↗
PubMed1990

[Granulomatous inflammation with combined immunodeficiency].

Pulmonary infection with mycobacterium tuberculosis and clonal B-cell expansion is described in a 26-year-old woman with granulomatous disease of lung, liver, and bone marrow as well as a late onset common variable immunodeficiency syndrome (CVID).

Adult↗
PubMed1989

Assessment of occupational benzene exposure in petrol filling stations at Rangoon.

An occupational health survey was conducted on workers, who inhale petrol fumes which contain low concentrations of benzene, at petrol filling stations in the city of Rangoon, Burma. To evaluate the exposure to benzene, urinary phenol (which is a principal metabolite of absorbed benzene) was measured in workers at petrol filling stations and in a control group of healthy male adults. The survey revealed that the urinary phenol content of workers exposed to petrol fumes was significantly higher than that of workers who were not exposed.

Adult↗
PubMed1988

Influence of corticosteroids on chemotactic response and collagen metabolism of human skin fibroblasts.

Following chronic administration of corticosteroids in vivo, a number of complications occur, which mainly involve the metabolism of connective tissue cells. Therefore, several attempts have been made to develop corticosteroids, which show less pronounced side effects. Fibroblasts were kept in monolayer cultures and were exposed to corticosteroids demonstrating similar anti-inflammatory activity (prednicarbate, desoximetasone). Chemotaxis of fibroblasts was studied over 4 hr, protein and collagen synthesis were estimated using proteinchemical methods and also by dot blot hybridization. Corticosteroids used in a high dosage (10 microM) affected all biosynthetic capacities of the investigated fibroblasts. Protein synthesis and production of collagen types I and III were reduced and a similar decrease of mRNA levels for collagen type I could be found indicating an influence on the pretranslational control. In the same concentrations desoximetasone was much more active than prednicarbate. Fibroblast migration was dosage dependently inhibited from 10(-9) M to 10(-5) M for desoximetasone, while incubation with prednicarbate did not cause a reduction of the chemotactic response at concentrations lower than 10(-7) M. These data suggest that modifications of corticosteroids might result in a dissociation of some of their biological activities and can specifically influence their effects on biosynthetic capacities of fibroblasts.

Adrenal Cortex Hormones↗
PubMed1988

[Local recurrent centroblastic lymphoma of the skin].

A 57-year-old patient suffered from a cutaneous centroblastic polymorphic non-Hodgkin lymphoma. This tumour first occurred 6 years ago and showed local relapses after two surgical excisions without any internal manifestations. The tumour had unusual morphological features with a sarcomatous growth pattern and numerous multilobated nuclei, which first led to the diagnosis of a malignant fibrous histiocytoma. Additional immunohistological studies of both the primary tumour and the lesions demonstrated the presence of lymphocytic marker proteins and allowed the definitive classifications as a high-grade malignant non-Hodgkin lymphoma of the B-cell type.

Biomarkers, Tumor↗
PubMed1988

[Pathophysiology of fibroses. Progressive systemic scleroderma as a model disease].

Fibrosis is characterized by excessive deposition of connective tissue in the involved organs. Although the prime event in the pathogenesis is still poorly understood, several mechanisms are discussed, which finally result in the activation of fibroblasts. Recent studies have demonstrated that immunocompetent cells play a crucial role during the initial phases of the development of fibrosis. Therefore, several mediators have been characterized, which are secreted by platelets, lymphocytes and macrophages and which can attract fibroblasts, induce proliferation and collagen synthesis in mesenchymal cells. These include PDGF, EGF, TGF--beta and many others. In addition, gamma-interferon has been shown to inhibit chemotaxis of fibroblasts and to reduce collagen mRNA levels. A controlled interaction of all the different mediators is required to guarantee a normal functioning of connective tissue. Alterations in these regulation steps can result in excessive deposition of connective tissue and the development of fibrotic processes.

Collagen↗
PubMed1988

Hemodynamic and pathologic evaluation of a unileaflet pericardial bioprosthetic valve.

This study investigated the in vivo hemodynamics and pathologic changes of a unileaflet pericardial bioprosthetic valve 3 to 5 months after implantation in juvenile sheep. Group 1 had 10 sheep with tricuspid valve replacement. Group 2 had nine sheep with mitral valve replacement. Group 3 served as a control with 10 sheep that had tricuspid valve replacement with a trileaflet porcine bioprosthesis. Hemodynamic performance was satisfactory in all three groups despite prominent pathologic changes, particularly in unileaflet valves. Intrinsic cuspal calcification was present in 66% of the unileaflet tricuspid, 88% unileaflet mitral, and 25% porcine tricuspid valves. Neither cuspal tearing nor perforations were found. However, cuspal stretching and redundancy of the mobile cusp was present in six tricuspid, seven mitral unileaflet valves, and no porcine valves. Gross pericardial redundancy correlated with the microscopic appearance of distorted and separated collagen bundles. These findings suggest that multiple modes of primary tissue failure may limit the durability of this unileaflet pericardial valve.

Animals↗
PubMed1987

Inhibition of fibroblast chemotaxis by recombinant human interferon gamma and interferon alpha.

Interferons have recently been recognized as potent mediators in inflammatory processes, exerting profound effects on fibroblasts. The influence of interferons gamma and alpha on the chemotactic movement of fibroblasts toward various attractants was, therefore, investigated. Normal human adult and embryonal dermal fibroblasts, fibrosarcoma-derived fibroblasts and SV40-transformed fibroblasts were tested against conditioned medium from fibroblasts, the chemotactic peptide C-140 of fibronectin, platelet-derived growth factor, and leukotriene B4 as attractants in the presence or absence of the interferons. Interferons gamma and alpha inhibited chemotaxis in a dose-dependent manner and at concentrations at least as low as 10(-2) ng/ml. Inhibition was noticeable when the cells were exposed to interferon for as short a period as 60 minutes, and the effect was not readily reversible. Inhibition occurred when the cells came from sparse or dense cultures, but when platelet-derived growth factor was the attractant and the cells had been grown at low density there was no inhibition. It is concluded that this is a specific effect, not to be wholly explained by overall increase in membrane rigidity. Inhibition of fibroblast chemotaxis by interferons may be an important regulatory mechanism during wound healing or fibrosis and metastatic spread of tumor cells.

Adult↗
PubMed1987

Inhibition of fibroblast chemotaxis by superoxide dismutase.

Superoxide radicals are known to be important mediators in chronic inflammatory and fibrotic processes, in which accumulation of fibroblasts is thought to play a major role in the pathogenetic events. The enzyme superoxide dismutase removes these radicals by a catalytic reaction. Chemotactic response of human fibroblasts and fibrosarcoma-derived cells (HT-1080) to fibroblast conditioned medium, fibronectin and platelet-derived growth factor was inhibited in a dose-dependent manner in the presence of superoxide dismutase, while random migration, cell proliferation, cell viability and synthesis of collagen and non-collagenous proteins was not altered. In contrast, phorbol myristate acetate, an inducer of superoxide generation, stimulated the chemotactic movement of fibroblasts to the attractants. Evidence for the formation of superoxide is provided by the reduction of tetrazolium salt by activated fibroblasts which could be inhibited by superoxide dismutase. Thus, it is concluded that superoxide in small amounts is involved in the mechanism of fibroblast chemotaxis. Superoxide dismutase may, therefore, reduce fibroblast migration into sites of injury or inflammation.

Catalase↗