Biomedical subjects

M Heckmann

Publications and source records attributed to M Heckmann.

At least 73 records · Page 4Linked to original sources

PubMed1993

Function and energy metabolism of isolated hearts obtained from hyperthyroid spontaneously hypertensive rats (SHR). A 31P-nuclear magnetic resonance study.

It was the aim of this study to evaluate the effects of hyperthyroidism on heart function and cardiac energy metabolism of spontaneously hypertensive (SHR) rats. Hyperthyroidism was induced by daily injections of T3 (0.2 mg/kg s.c.) for 14 days. The hearts were then isolated and perfused in the Langendorff mode. ATP, phosphocreatine (PCr), and inorganic phosphate (Pi) were measured continuously by means of 31P-nuclear magnetic resonance (NMR) spectroscopy. Work load was altered by varying stepwise the Ca++ concentration in the perfusion fluid from 0.5 to 1.0, 1.5, and 2.0 mM, respectively. At every elevation of the Ca++ concentration, the increase in left ventricular developed pressure (LVDP) was higher in the hyperthyroid SHR than in the untreated SHR hearts. The ATP and PCr concentrations were lower in the hyperthyroid SHR compared to the untreated SHR hearts throughout the perfusion period. PCr decreased at every Ca++ elevation in both the untreated and hyperthyroid SHR hearts. The PCr/ATP ratio was not altered at any Ca++ concentration neither in the untreated SHR nor in the hyperthyroid SHR hearts. The Ca(++)-induced stepwise elevation in LVDP was higher at any given PCr/Pi ratio in the hyperthyroid SHR than in the untreated SHR hearts. Thus, the Ca(++)-inducible contractile reserve was greater in the hyperthyroid SHR heart.

Adenosine Triphosphate↗

PubMed1993

Biphasic effects of interleukin-1 alpha on dermal fibroblasts: enhancement of chemotactic responsiveness at low concentrations and of mRNA expression for collagenase at high concentrations.

Fibrotic reactions in the skin are frequently preceded by infiltration of inflammatory cells and subsequent migration of fibroblastic cells. Interleukin-1 is secreted by inflammatory cells and can regulate proliferation and protein synthesis of fibroblasts. Its role in fibroblast chemotaxis has not been elucidated in any detail. Using the well-established Boyden chamber assay for measurement of chemotaxis in vitro, we studied a wide range of recombinant human interleukin-1 alpha concentrations to assess intrinsic chemotactic activity of interleukin-1 alpha and to determine the capacity of this mediator to modify the chemotactic response of fibroblasts to other chemoattractants. This was compared with the interleukin-1 alpha dose required for enhancement of mRNA expression for collagenase. Although interleukin-1 alpha was not chemoattractive for fibroblasts, it specifically augmented migration toward fibroblast-conditioned medium and toward platelet-derived growth factor but not toward epidermal growth factor, fibronectin, or transforming-growth factor-beta. Interleukin-1 alpha did not measurably alter the expression of mRNA for the platelet-derived growth factor receptor or its platelet-derived growth factor-binding characteristics. Doses required to enhance fibroblast chemotaxis were distinctly lower than those required for stimulation of collagenase mRNA expression.

Cell Division↗

PubMed1993

Alteration of cardiac energy state during development of hypertension in rats of the Lyon strain: a 31P-NMR study on the isolated rat heart.

The effect of different chronic blood pressure levels on cardiac energy metabolism was studied by 31P-NMR spectroscopy in perfused hearts from the Lyon strains of hypertensive (LH), normotensive (LN) and hypotensive (LL) rats at the ages of 12 and 21 weeks. The in vivo assessment of haemodynamic parameters measured at 21 weeks in anaesthetized rats with an ultraminiature catheter pressure transducer confirmed that left ventricular systolic pressure and mean aortic pressure were significantly greater (+25%) in LH rats than in LN and LL rats. In the LL animals, left ventricular systolic pressure was slightly reduced (-10%) and cardiac contractility (estimated by LV dP/dtmax) showed a 24% decreased compared to normotensive animals. The energy state of the cardiomyocytes was characterized at different work levels of isolated rat hearts, by determining the concentration of the free phosphorylated compounds at each work level. Changes in workload were induced by varying the calcium concentration in the perfusion fluid. Increasing extracellular calcium concentration resulted in a similar increase in left ventricular developed pressure (LVDP) in all groups studied. Intracellular pH was not influenced by either the age of the animals or the level of cardiac work, in the three groups of animals. ATP content of the LN and LL rats remained constant during the whole perfusion period while the 12 week-old LH rats showed a decreased ATP content with increasing cardiac work. In the older LH rats, ATP content was decreased at the highest work level (corresponding to 2 mM calcium). In response to the increase in work, phosphocreatine (PCr) content diminished and inorganic phosphate (Pi) content increased in both LN, LH and LL animals. PCr degradation and Pi accumulation were higher in the LH rats and less in LL rats compared to the LN. These changes were more important in the younger than in the older hypertensive animals. The relationship between LVDP and [Pi]/[PCr] indicates that oxidative metabolism is maximally activated in the young hypertensive rats and suggests that this maximal activation represents an adaptive phase to the increase in blood pressure. Since the difference between the metabolic pattern of the 21 week-old LH rats and age-matched LN rats was less pronounced, it is likely that a compensatory stage has been reached at that age.

Animals↗

PubMed1993

Cardiovascular response to triiodothyronine in Sprague-Dawley and spontaneously hypertensive rats.

In this study we have compared the influence of triiodothyronine (T3) on cardiovascular function and heart weight in Sprague-Dawley and spontaneously hypertensive rats. We also investigated whether the effects induced by T3 are reversible. T3 was administered daily (0.2 mg/kg subcutaneously) for 14 days in female Sprague-Dawley and spontaneously hypertensive rats. Treatment was then stopped for 14 days. At the end of the treatment and of the period without T3, hemodynamic measurements were made in the intact, anesthetized animals by catheterization of the left ventricle with a Millar ultraminiature catheter pressure transducer. Cardiac output was measured by thermodilution. The development and regression of myocardial hypertrophy was measured by the ratio of heart to body weight. The systolic pressure in the left ventricle was higher in spontaneously hypertensive rats than in Sprague-Dawley rats matched for body weight. At the end of treatment with T3, the heart rate was increased to exactly the same extent in both groups. Left ventricular systolic pressure was increased by 15% in Sprague-Dawley rats, but was not altered significantly in spontaneously hypertensive rats. T3 induced an increase in left ventricular dp/dtmax by 106% in Sprague-Dawley rats, but by only 32% in spontaneously hypertensive rats. Cardiac output increased by 63% in Sprague-Dawley rats, but by only 31% in spontaneously hypertensive rats (statistically not significant). When T3 treatment was stopped for 14 days, all the functional changes returned to control values.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Effect of transforming growth factor-beta on collagen type VI expression in human dermal fibroblasts.

Steady-state mRNA levels and protein synthesis of collagen type VI were determined after stimulation of human dermal fibroblasts with transforming growth factor-beta (TGF beta). While there was a 227% increase in the alpha 3(VI) subunit mRNA at maximal TGF-beta concentration, alpha 1(VI) and alpha 2(VI) subunit mRNA levels remained unchanged. Concomitantly collagen type VI immuno-reactive material increased up to 172% of controls in cell culture medium and cell layer extracts. Regulation of alpha 3(VI) gene expression is therefore critical for the control of collagen type VI synthesis and determines the deposition of collagen type VI heterotrimeric molecules.

Blotting, Northern↗

PubMed1992

The effect of interferon-gamma on the invasiveness of HT-180 cells.

It has been shown that tumour necrosis factor-alpha (TNF-alpha) induces the gene expression of collagenase and enhances the invasiveness of many cell types. However, we have previously demonstrated that interferon-gamma (IFN-gamma) induces the chemotactic response of cells and we have studied the in vitro effects of both cytokines on invasive migration using a human fibrosarcoma cell line (HT-1080). Invasive migration occurred with HT-1800 cells through a basement membrane equivalent (matrigel) and collagen type I gel. Pre-incubation of cells with increasing concentrations of IFN-gamma resulted in a dose-dependent reduction of this invasive migration. TNF-alpha considerably enhanced the invasiveness of HT-1080 cells and of fibroblasts. This effect could be significantly diminished by the pre-incubation of cells with IFN-gamma. Inhibition of invasiveness did not appear to be due to an altered binding to the barriers or altered collagenolytic activity of these cells, as shown by attachment and collagenase assays. These data support the concept that IFN-gamma can reduce the invasiveness of transformed cells which contributes to its in vivo anti-neoplastic effect.

Cell Adhesion↗

PubMed1992

[Erosive pustular dermatosis of the scalp after zoster ophthalmicus and trauma].

Erosive pustular dermatosis of the scalp (EPDS), first described in 1979, is a rare, chronic, pustular condition with scarring alopecia, and nonspecific histological findings. While the initial responded to steroids is good, it can be treated successfully by oral administration of zinc sulphate. Local trauma has recently been suggested to play a role in the pathogenesis of EPDS. The differential diagnosis of EPDS includes folliculitis decalvans, sterile eosinophilic pustulosis Ofuji, pustular psoriasis vulgaris, trichophytosis, Perifolliculitis capitis abscedens et suffodiens, pemphigus vulgaris and cicatricial pemphigoid. We present the cases of a 74-year-old woman suffering from EPDS following herpes zoster ophthalmicus and of a 54-year-old man in whom EPDS followed a head injury.

Aged↗

PubMed1991

Steady-state mRNA levels of collagens I, III, fibronectin, and collagenase in skin biopsies of systemic sclerosis patients.

Total RNA was extracted from skin biopsies of nine patients suffering from systemic sclerosis (SSc). Steady-state mRNA levels of collagen alpha 1(I) and alpha 1(III), collagenase, fibronectin, and beta-actin were studied using specific cDNA probes and compared to those of 12 sex- and age-matched healthy individuals. There was a more than three-fold elevation of collagen I mRNA levels in SSc skin compared to controls. No difference was found, however, for collagen III, collagenase, and fibronectin mRNA levels in SSc and control biopsies. The selective increase of collagen alpha 1(I) mRNA levels indicates a specific alteration of fibroblast metabolism in scleroderma. Analysis of mRNA levels in skin biopsies might not only offer a direct approach to the understanding of the pathophysiology of SSc, but also facilitate the monitoring of fibrotic activity in SSc patients during therapeutic trials.

Adult↗

PubMed1991

[Recent findings in physiology and pathology of endothelial cells of the skin].

Perivascular cell infiltrates with concomitant changes of the endothelium represent a histological hallmark of numerous inflammatory dermatoses. Therefore, the pathophysiology of dermal endothelial cells is of particular importance for the understanding of inflammatory processes within the skin. In recent years, the development and refinement of endothelial cell culture techniques have facilitated investigations in cell biology and molecular biology, which complement histological observations, so leading to sounder knowledge of endothelial cell pathophysiology. The following review will discuss characteristic features of endothelial cells as well as in-vitro culture techniques. Focussing on endothelial cell interactions with leukocytes and with the extracellular matrix, recent developments in this area of research will be presented.

Cell Adhesion Molecules↗

PubMed1990

Palliative chemo-radiotherapy with ifosfamide and epirubicin as first-line treatment for high-risk metastatic breast cancer. Results of a prospective multicenter trial.

From June 1986 to December 1988, 107 patients (median age, 49 years; median performance score, 1) with haematogeneous metastases from breast carcinoma were treated with concomitant radiation and chemotherapy. Overall, 97% of the patients had been pretreated with surgery; 65%, with radiation; and 56%, with hormones. In all, 38% had received adjuvant chemotherapy. Patients with prior palliative chemotherapy were excluded from the study. All patients fulfilled at least two high-risk criteria. Chemotherapy was given according to the EI protocol (4-epirubicin and ifosfamide), and all patients simultaneously received radiation to the main tumour sites. Gastro-intestinal toxicity was moderate (11.1%, WHO grade 4), and bone marrow depression was marked in all cases. After three treatment courses, the overall response rate was 67% [21% complete response (CR), 46% partial response (PR)]. In all, 28% had stable disease (NC) and the rate of progressive disease (PD) was 5%. The median duration of tumour response was 8 months, with 12 months for CRs, 9 months for PRs and 6 months for NCs. The median survival was 13.5 months.

Adult↗

PubMed1990

Type III collagen aminopropeptide and laminin P1 levels in serum of patients with silicosis-associated and idiopathic systemic scleroderma.

A group of 191 patients with systemic scleroderma and 12 patients with silicosis-associated scleroderma were investigated for connective tissue turnover. The serum levels of type III collagen aminopropeptide (P-III-P), the laminin PI (Lam PI) fragment and the acid lysosomal beta-galactosidase (beta-Gal) were determined by specific radioimmunoassays and spectrofluorometry, respectively. Increased levels of type III collagen aminopropeptide strongly correlated with enhanced activity of beta-galactosidase. Both parameters correlated with the clinical course in idiopathic systemic scleroderma and in silicosis-associated scleroderma. Serum levels of Lam PI were also found to be elevated in both groups, although there was no correlation with the severity of the disease. Autoantibodies directed against the DNA topoisomerase Scl-70 and against centromeric proteins were found in a similar range in patients with idiopathic systemic and silicosis-associated scleroderma. These results suggest that P-III-P, Lam PI and beta-Gal are useful serological markers of fibrotic activity and demonstrate similarities between idiopathic systemic scleroderma and scleroderma associated with silica-dust exposure.

Aged↗

PubMed1990

[Effect of various technical parameters on potential danger of an electric injury in the bathtub].

In contrast to common beliefs there is not strict necessity for lethal danger during electric shock in a bathtub. Measurements of the electric field demonstrates the ground conditions and water temperature are of vital importance as are a variety of other parameters. With an electronic amplifier especially designed for this problem measurement of the electric parameters in the water was made possible.

Baths↗

PubMed1990

[Heart current density as the most important biological parameter of electrocution in the bathtub].

The most important factor during electrocution in a bathtub is the amount of current flowing through a body, not the amount of voltage. A method of measurement is introduced which--under simulation of various electrical situations--provides the possibility to measure the current flowing through the heart and to determine it's direction and density in the tissue. Hereby a ranking of the different factors influencing electrocution can be set up.

Baths↗

PubMed1989

Down-regulation of alpha 3(VI) chain expression by gamma-interferon decreases synthesis and deposition of collagen type VI.

Treatment of cultured human skin fibroblasts with increasing doses of gamma-interferon produces a distinct reduction of steady-state levels of the alpha 3 chain of collagen VI mRNA by about 60% but not of the alpha 1 and alpha 2 chain mRNAs. A similar decrease was also observed for collagen I and III mRNA while fibronectin mRNA remained at the same level. The decrease in alpha 3(VI) mRNA is accompanied by a reduced synthesis of collagen VI and by a reduced deposition of both collagen VI and fibronectin in urea-insoluble form in the cell matrix. No other gamma-interferon effects were observed for fibronectin biosynthesis. Immunoprecipitation of metabolically labeled collagen VI demonstrated a strongly reduced synthesis (by 65-80%) of intracellular alpha 3(VI) chains with no decrease found for alpha 1(VI) and alpha 2(VI) chains. All three chains were, however, found to be reduced in the culture medium. Pepsin treatment of immunoprecipitated collagen VI showed similar chain ratios for material in the culture medium obtained in the absence or presence of gamma-interferon. It indicates that correctly assembled heterotrimers of the composition [alpha 1(VI) alpha 2(VI) alpha 3(VI)] are formed and secreted also in the absence of an equivalent alpha 3(VI) chain synthesis but at a reduced rate. The data support previous predictions from sequence analyses [Chu et al. (1988) J. Biol. Chem. 263, 18,601-18,606] that collagen VI molecules composed of all three constituent chains are more stable than other assembly alternatives.

Actins↗

PubMed1989

Synergistic effect of tumor necrosis factor-alpha and interferon-gamma on collagen synthesis of human skin fibroblasts in vitro.

The effect of tumor necrosis factor-alpha (TNF alpha) and interferon-gamma (IFN gamma) on collagen metabolism by human diploid fibroblasts in confluent monolayer culture was examined. Recombinant TNF alpha reduced collagen mRNA levels 2-fold and stimulated collagenase mRNA levels 5-fold, while recombinant IFN gamma affected only collagen mRNA levels. The combination of TNF alpha (10 ng/ml) and IFN gamma (100 ng/ml) resulted in a much stronger (about 30-fold) reduction of collagen mRNA levels indicating that the two cytokines act synergistically. In contrast no such synergism was observed with respect to collagenase mRNA levels. The effect of TNF alpha and IFN gamma on collagen metabolism reported here indicates a complex interaction of different cytokines in the control of tissue remodeling that occurs during inflammation, repair, or atrophy.

Adult↗

PubMed1989

Biological and pharmacological modulations of fibroblast functions.

During recent years, considerable progress in the field of connective-tissue research has brought about detailed information on the behaviour of fibroblastic cells under culture conditions and in in vivo situations. Well-characterized biological functions of fibroblasts include cell migration, cell attachment, cell proliferation and biosynthesis as well as degradation of multiple connective-tissue components. An exact control of these functions is essential in physiological processes of tissue development and repair, while, on the other hand, fibrotic diseases or poor wound healing are associated with functional deviances of fibroblasts. Therefore, the modulation of fibroblast functions has become the focus of ongoing research aiming to expand the pathophysiological understanding and therapeutic options in connective-tissue diseases. Discussing scientific approaches to investigate various fibroblast functions, this review surveys biological and pharmacological factors which affect the behaviour of fibroblasts.

Animals↗

PubMed1989

Regulatory mechanisms of fibroblast activity.

Fibroblasts are mesenchymal cells present in most organs which play a crucial role in repair processes but are also involved in the development of fibrosis. Although fibroblasts have been grown in culture for many years, their multiple functions including migration, chemotaxis, protein synthesis and others have only recently been investigated in detail. These studies demonstrated that cellular responses of fibroblasts can be elicited by matrix-mediated signals as well as by cytokines released from inflammatory or other differentiated cells. The aim of the present paper is to review the influence of such signals and to discuss their role in disease processes, particularly in fibrosis, keloids or scleroderma.

Cell Movement↗

PubMedDate not supplied

Effects of triiodothyronine in spontaneously hypertensive rats. Studies on cardiac metabolism, function, and heart weight.

We have studied the effects of triiodothyronine (T3) on heart function, on the myocardial oxidative pentose phosphate pathway, and on heart weight in spontaneously hypertensive (SHR) rats. Another aim was to examine whether these T3-effects may be reversible. T3 was administered daily (0.2 mg/kg s.c.) for 14 days. Compared to the untreated SHR controls, T3 induced an increase in heart rate (beats/min) from 357 +/- 10 (n = 17) to 553 +/- 10 (n = 17), in the pressure-rate-product (mm Hg/min) from 78 400 +/- 4500 (n = 15) to 113 700 +/- 4800 (n = 15), and in the heart weight/body weight ratio (mg/g) from 4.2 +/- 0.2 (n = 20) to 5.8 +/- 0.2 (n = 19). The activity of myocardial glucose-6-phosphate dehydrogenase, the first and rate-limiting enzyme of the oxidative pentose phosphate pathway (units/g protein), was elevated from 4.2 +/- 0.2 (n = 9) to 7.0 +/- 0.6 (n = 9) after 14 days of T3-treatment, while the activity of 6-phosphogluconate dehydrogenase, one of the following enzymes in the pathway, was not altered appreciably. These changes returned to the respective control values when T3-treatment was discontinued for 14 days. Our results demonstrate that T3 had a positive chronotropic effect and induced an additional heart enlargement in an animal model with already established cardiac hyperfunction and hypertrophy. The effects on heart function and weight, which were fully reversible, were not as pronounced as in normal Sprague-Dawley rats.

Animals↗