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Biomedical subjects

H Michna

Publications and source records attributed to H Michna.

At least 55 records · Page 3Linked to original sources
PubMed1989

Induced locomotion of human and murine macrophages: a comparative analysis by means of the modified Boyden-chamber system and the agarose migration assay.

This study was designed to gain detailed information concerning the kinetic activity of connective tissue-derived macrophages from living human specimens. Their kinetic activity in vitro was estimated using the agarose-migration assay and the modified Boyden-chamber, and compared with that of murine peritoneal macrophages. These assays permit the distinction of chemotactic and chemokinetic patterns as well as spontaneous migration. These kinetic activities were stimulated by and calculated for ultrasound-crushed suspensions of Escherichia coli, zymosan-activated human serum, human serum albumin, casein-activated human serum, tripeptide f-Met-Leu-Phe (N-alpha-formyl-L-methionyl-L-leucyl-L-phenylalanine), phytohemagglutinin, modified Eagle's medium and phosphate buffer. Investigation of the migratory performance (in micron) in the Boyden-chamber and by the agarose migration assay for chemokinetics and chemotaxis by using tripeptides as chemotactically attracting agents revealed a somewhat higher activity in murine than in human macrophages.

Animals↗
PubMed1989

Adaptation of tendon collagen to exercise.

We report an experimental study on the effect of exercise on tendon structure in mice. After one week of physical training an increase in mean diameter, in number, and in cross-sectional area, as well as a change in mean fibril diameter distribution, was demonstrated. In the long-term, there was an increase in fibril number, a fall in mean diameter, but no statistically significant changes in the relative cross-sectional area per unit compared with the control tendons.

Animals↗
PubMed1989

Human macrophage function and physical exercise: phagocytic and histochemical studies.

Macrophages derived from human connective tissue were assayed for their enzyme content and phagocytic activity after physical exercise. A single exhaustive endurance-running test caused increased phagocytic and enzymatic activities of the macrophages. Thus, an exercise challenge activates the functional status of the cells. This effect of physical exercise on macrophages is inconsistent with the practical experience that high performance athletes suffer more frequently from harmless infectious diseases.

Adult↗
PubMed1989

Antitumor activity of the antiprogestins ZK 98.299 and RU 38.486 in hormone dependent rat and mouse mammary tumors: mechanistic studies.

In the transplantable MXT mammary tumor model of the mouse and in the DMBA- and MNU-induced mammary tumor models of the rat, the progesterone antagonists ZK 98.299 and RU 38.468 were shown to have potent antitumor activity. The weight and/or morphology of the ovaries, uterus, and vagina, as well as the effects on serum hormone levels, indicate that the antitumor activity of both antiprogesterones in these models does not depend on a blockade of the ovarian and pituitary functions and does not depend on a non receptor-mediated cytotoxic effect. On the other hand, the morphology of the MXT and the DMBA-induced mammary tumors after treatment with the progesterone antagonists is completely different from that observed after ovariectomy. Treatment with the antiprogesterones seems to trigger differentiation of the mitotically active polygonal tumor cells towards glandular structures and acini with a massive sequestering of secretory products, as well as towards spindle-shaped necrobiotic subpopulations. By contrast, the induction of tumor cell degeneration and cytolysis is the predominant feature of the mammary tumors after ovariectomy. In conclusion, our results indicate that the main mechanism of the antitumor action of antiprogesterones in these models is a direct progesterone receptor-mediated antiproliferation effect at the level of the mammary tumor cells, most probably via the induction of terminal differentiation associated with terminal cell death. This antiproliferative effect seems to be dissociated from the antihormone (antiprogestational) activity of these progesterone antagonists.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1989

Antitumor effect of a specific aromatase inhibitor, 1-methyl-androsta-1,4-diene-3,17-dione (atamestane), in female rats bearing DMBA-induced mammary tumors.

Atamestane is a potent competitive inhibitor of estrogen biosynthesis (aromatase) in several species, in vitro and in vivo, and has no endocrine side effects. In this study, the efficacy of atamestane in suppressing tumor growth was evaluated in comparing with that of a non-steroidal aromatase inhibitor (CGS 16949A, Ciba-Geigy) and ovariectomy. Female Sprague-Dawley rats bearing DMBA-tumors were treated s.c. once daily either with 30 or 150 mg/kg atamestane or with 0.1 or 0.5 mg/kg CGS 16949A for 4 weeks. At these biologically equivalent doses both aromatase inhibitors effectively inhibited tumor growth: at the end of treatment they caused a marked reduction in tumor size (up to 70%), while ovariectomy led to a complete remission of tumor growth. The histo-morphological pictures of the mammary tumors from treated animals were qualitatively almost similar to those of the control. In hosts, neither compound exerted any influence on the weight of genital organs (ovary, uterus and vagina), although the peripheral LH levels were significantly elevated by the higher dose of the aromatase inhibitors. This effect on LH levels is probably due to the elimination of the negative feed-back effect of estrogens on gonadotropin secretion (counter regulation). The serum prolactin levels were decreased by the aromatase inhibitors, indicating a diminution of estrogen levels in the treated animals. The present results clearly demonstrate that, in spite of the counter regulation, a pure aromatase inhibitor such as atamestane in sufficiently high doses is able to inhibit the growth of DMBA-induced mammary tumors in intact female rats.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1989

The antitumor mechanism of progesterone antagonists is a receptor mediated antiproliferative effect by induction of terminal cell death.

The antiprogesterones Onapristone, ZK 112.993 (Schering AG), and Mifepristone (Roussel-Uclaf) proved to possess progesterone receptor-mediated antiproliferative effects in experimental mammary carcinomas. In this study, the potency and mechanism of the antitumor action of Onapristone and ZK 112.993 is characterized by ovariectomized, progestagen and/or estradiol substituted mice bearing hormone-dependent MXT(+) mammary tumours. Medroxyprogesterone acetate (MPA, 0.8 mg/mouse, 3 times weekly, s.c.) could only induce a poor stimulation of tumour growth (% T/C = 40; intact control % T/C = 100), which was only marginally inhibited (% T/C = 21) by Onapristone (0.2 mg/mouse, 6 times weekly, s.c.) during a 6-week therapy. Therefore, the antitumor mechanism of antiprogesterones cannot preferably depend on a classical progesterone antagonism. In contrary, the pronounced stimulation of tumor growth (% T/C = 152) by estradiol benzoate (EB, 0.33 microgram/mouse, 3 times weekly, s.c.) was completely inhibited (% T/C = 7) by the antiprogesterones. An even more stimulated tumour growth was achieved by a combination of EB and MPA (% T/C = 365 using 0.17 mg; % T/C = 225 using 0.8 mg MPA). Onapristone dramatically blocked tumor growth (% T/C = 7) at the lower dose of MPA; no inhibition (% T/C = 203), however, was detected at the higher dose of MPA. These data and a morphological analysis indicate that the potent antitumor activity of the progesterone antagonists depends on the binding to a number of available progesterone receptors high enough to trigger an antiproliferative effect via the induction of terminal differentiation associated with terminal cell death.

Animals↗
PubMed1989

Antitumor activity of the progesterone antagonists ZK 98.299 and RU 38.486 in the hormone-dependent MXT mammary tumor model of the mouse and the DMBA- and the MNU-induced mammary tumor models of the rat.

The antitumor activities of the antiprogesterones ZK 98.299 and RU 38.486 (RU 486) were tested in the hormone-dependent MXT(+) mammary tumor model of the mouse and the DMBA- and MNU-induced mammary tumor models of the rat. In the MXT(+)-tumor model, treatment with the two antiprogesterones (1-10 mg/kg daily) starting on day 1 after tumor implantation led to an almost complete inhibition of tumor growth identical to that accomplished with tamoxifen. Treatment of established MXT(+) tumors with ZK 98.299 (1, 10 and 50 mg/mg) resulted in a strong, dose-dependent inhibition of tumor growth. At the 10 and 50 mg doses, the effect of ZK 98.299 was superior to that of tamoxifen (4 mg/kg) and equal to that of ovariectomy and of RU 486, whereas megestrol acetate and medroxyprogesterone acetate had no significant effect. In contrast to the massive induction of cell degeneration and cytolysis in the MXT mammary tumors resulting from ovariectomy, the treatment with the two progesterone antagonists seems rather to trigger differentiation of the mitotically active polygonal tumor cells towards glandular structures and acini with secretory activity as well as towards the development of spindle-shaped necrobiotic cell populations. The weights of the ovaries were increased after therapy with ZK 98.299 and RU 486. Due to this inhibition of the negative feedback and an 'unopposed estrogen effect', uterine weight was also significantly increased. In the DMBA-induced mammary carcinoma, ZK 98.299 (10 mg/kg) caused strong tumor-inhibiting activity almost comparable to that of ovariectomy. The inhibition was very uniform and in this regard superior to RU 486. The MNU-induced mammary carcinoma of the rat was significantly inhibited by ZK 98.299, whereas RU 486 showed only a weak effect. In the light of these results antiprogesterones can be considered to be a very promising new class of mammary tumor inhibitors.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1989

Anatomical anomaly of human digastric muscles.

In the submandibular region an anatomical anomaly of muscle arrangement was found. Between the left and right digastric muscles, asymmetric accessory digastric muscles were detected, which all arose from the mandible and were attached to the hyoid bone. Furthermore, the right anterior digastric muscle had an accessory belly. These anomalies of digastric muscles may be anatomical manifestations of a functional support of the mylohyoid muscle.

Facial Muscles↗
PubMed1989

Ultrastructural features of skeletal muscle in mice after physical exercise: its relation to the pathogenesis of leucocyte invasion.

This study was designed to elucidate which factor(s) trigger off the enhanced macrophage activity after strenuous physical exercise. For an understanding of the cause of this phenomenon we extended the study of the ultrastructural features of skeletal muscle after physical exercise to its possible relation to the pathogenesis of leucocyte invasion. Ultrastructural investigations revealed muscle damage after a strenuous physical exercise. The pathogenesis of the detected autolytic alterations could be related to a local accumulation of lactate, to the ischemic compression syndrome, to an insufficient oxygen supply or to anatomical peculiarities. The greatest functional claim was that fibrillolytic degeneration was capable of being triggered off in the skeletal muscular structure, thereby initiating the release of filament fragments, whose peptides were capable of being depicted as chemotactic signals for leucocytes. The appearance of leucocytes in the muscular tissue suggests that the basic humoral immunity reactions control the cellular cooperation in the muscular tissue.

Animals↗
PubMed1989

Collagen fibril dynamics in the anulus fibrosus induced by an anabolic steroid hormone.

This study was designed to elucidate the collagen fibril architecture in the murine anulus fibrosus and to reveal the collagen fibril dynamics induced by hormones which are known to influence protein synthesis, the anabolic steroid hormones. These aims were entered in an ultrastructural morphometric analysis. The diameter distributions, mean diameter, cross-sectional area and volume density of the collagen fibrils in the anulus fibrosus indicate no correlation with age, which is in contrast to the anatomy of the collagenous functional structures in tendon. After treatment with the anabolic steroid hormone, an activation of the collagen synthesis as well as an enhanced density and cross-sectional area were detected. Therefore, the data promise an effective use of anabolic steroid hormones in the therapy of such disorders of connective tissue, which could be treated with a stimulation of the synthesis and hypertrophy of collagen fibrils.

Aging↗
PubMed1989

Intra- and extracellular lysosomes in tendon tissue of the mouse after treatment with an anabolic steroid hormone. Ultrastructural and cytochemical study.

Ultrastructural observations of fibroblasts from 6-week-old mouse tendons were carried out at different times after treatment with an anabolic steroid. The characteristic response of the fibroblasts involves the appearance of great numbers of intracellular lysosomes and the emergence of matrix vesicles, some of which could be identified ultrastructurally by their positive reaction for acid phosphatase as extracellular lysosomes. It is suggested that this fine structural gradient after treatment with the anabolic steroid results from, and may be directly the cause of, an increased level of cyclic AMP. The experimental design and the discussion of the findings consider, on the one hand, the use of anabolic steroid hormones in clinical practice and, on the other hand, the appearance of a collagen dysplasia in competitive sports.

Animals↗
PubMed1988

The influence of physical exercise on peritoneal macrophage functions: histochemical and phagocytic studies.

Peritoneal murine macrophages were assayed for their enzyme content and phagocytic activity after physical exercise. An endurance training as well as a single exhaustive exercise bout caused increased enzyme and phagocytic activities. However, a homogeneous activation could not be observed. The exhaustively exercised animals delivered macrophages with the highest levels of activation. Therefore, physical exercise has to be listed among the stimuli with macrophage-activating function. The inconsistency between an activating effect of physical exercise on macrophages and the observation that high-performance athletes suffer more frequently from harmless infectious diseases is discussed.

Animals↗
PubMed1988

Appearance and ultrastructure of intranuclear crystalloids in tendon fibroblasts induced by an anabolic steroid hormone in the mouse.

The appearance of intranuclear crystalloid formations in tendon fibroblasts is described during enhanced protein synthesis. The enhanced protein synthesis was induced by an anabolic steroid hormone. One type of these crystalloids consists of closely packed bundles of filaments, 8-10 mm in diameter arranged in parallel. The other type of intranuclear crystalloids possesses an architecture similar to honeycomb pattern. Both of these paracrystalloid nuclear inclusions seem to be an indicator for an extremely enhanced protein synthesis in these cells after the administration of anabolic steroid hormones. Their numerous descriptions in the literature on hypertrophic or precancerously modified tissues and their increased occurrence under pathological influences both point to this explanation. In this way we now possess for the first time a model for experimental on intranuclear crystalloids of tendon fibroblasts.

Animals↗
PubMed1988

Intracellular collagen fibrils: evidence of an intracellular source from experiments with tendon fibroblasts and fibroblastic tumour cells.

This study was designed to substantiate one or both of the two hypotheses for the explanation of intracellular collagen fibrils in collagen-producing cells. The more obvious is the phagocytosis of extracellular collagen fibrils by the cell and the other is a form of autophagocytosis of newly synthesised collagenous products. Information was collected on fibroblasts from murine tendons after exercise and simultaneously stimulating collagen synthesis by treatment with an anabolic steroid hormone. Moreover, in vivo and in vitro fibroblastic tumour cells which demonstrate enhanced protein synthesis were also treated with the anabolic steroid. The findings of intracellular collagen fibrils in tendon fibroblasts and the sarcoma cells after experimentally stimulating collagen synthesis are discussed in the light of the hypothesis that the findings may represent steps of autophagocytosis of newly synthesised collagenous products in the absence of a control mechanism to remove collagenous products which cannot be secreted.

Animals↗
PubMed1988

Hypertrophy, androgens, and tendon karyometry: functional and experimental investigations.

The aim of the present experimental study is to investigate the functional behaviour of cell nuclei in tendon tissue. For this purpose semithin sections of tendons excised from mice subjected to treadmill exercise are analysed quantitatively to establish the number of cell nuclei of tendinoblasts. The number of nuclei per volume unit of tendon tissue, nuclear size, and the behaviour of these parameters in relation to tendon calibre are determined functionally. Particular attention is given to the question--interesting both from the clinical point of view and with regard to sportsmedicine--whether the use of a synthetic androgen has any harmful effect on tendon tissue: According to the findings of the present study, a dramatic decrease in nuclear density is likely to be of pathogenetic relevance to the occurrence of collagen dysplasia.

Androgens↗
PubMed1988

The human macrophage system: activity and functional morphology.

Macrophages of humans could be extracted in large numbers from the connective tissue using a newly developed, not particularly difficult method. These macrophages were compared with the peritoneal macrophages of mice using light-, scanning and transmission electron-microscopic methods. The sterility of the cell suspension and the high yield of macrophages has allowed the first in vitro study of histiocytes to take place, in contrast to the classic 'microexudate-coated surface method'. The activity of the human in comparison with peritoneal murine macrophages has been evaluated using numerous histochemical and immunological techniques. These methods prove a modulation of the macrophage activity of healthy humans and mice under exemplary conditions of extremely strenuous physical exercising, in accordance with earlier experimental findings on animals alone. The degenerative changes which occur under these experimental conditions in the skeletal muscular system show an invasion of cells of the immune system, which are integrated into an explanation of the increased activity of macrophages. These results find their place in a new theoretical concept supporting the general validity of the co-operation of macrophages and other cells of the immune system in pathological degeneration and regeneration processes in the skeletal muscular system. It has been shown that the increased activity of human and murine macrophages brought about by extreme strenuous physical exercising, insofar as one is able to order them into a progressive scheme of stress happenings, fit very well into the concepts of the 'alarm reaction' phase. The activity of macrophages proves to be sensitive to the mediators of tumours of mesenchymal origin, with respect to the initial stage of phagocytosis, to the further biochemical deterioration, to the cytotoxicity and to the amount of cells; this, however, is not able to halt the rapid growth of sarcoma in a long term experiment. The proof of a weakened migration of macrophages in sarcoma-bearing animals raises the interest in those substances which are able to positively modulate the migration activity. On the one hand the migratory performance of macrophages in sarcoma-bearing animals in a short-term experiment was increased by the introduction of an anabolic steroid hormone. On the other hand, however, a different degree of success was registered for the further parameters of macrophage activity during short- and long-term experimental investigations.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗