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Biomedical subjects

H Runge

Publications and source records attributed to H Runge.

At least 19 recordsLinked to original sources
PubMed2001

All-trans retinoic acid regulates proliferation, migration, differentiation, and extracellular matrix turnover of human arterial smooth muscle cells.

OBJECTIVE: The vitamin-A derivative all-trans retinoic acid (atRA) is a potent regulator of cell growth, differentiation, and matrix formation of various cell types and plays an important role in embryogenesis. However, sparse data are available about its effects on human vessel diseases. Thus, we studied the effects of atRA on human arterial smooth muscle cell (haSMC) and endothelial cell (haEC) proliferation, migration, differentiation and extracellular matrix (ECM) turnover in mono- and transfilter cocultures. METHODS: Effects of atRA on human arterial cells in monocultures were determined using cell counting assays, BrdU-ELISA and MTT-tests. In transfilter cocultures haSMC-growth was studied under the stimulatory effect of proliferating haEC. Using Northern blot analysis, effects of atRA on mRNA expression of ECM-proteins were examined while protein expression and activity of matrix metalloproteinases were determined by Western blotting and zymography. RESULTS: atRA caused a dose dependent inhibition of haSMC-growth in monocultures (IC(50) at 0.022 microM) whereas haEC-growth was inhibited less potently (IC(50) at 97 microM). In addition, proliferation and migration of haSMC through a porous membrane were inhibited dose dependently by micromolar atRA-doses after non-stop and single dose application of atRA on the endothelial side of the complex transfilter coculture system. Immunostainings and Northern blotting demonstrated an enhanced alpha-smooth muscle actin and heavy chain myosin expression in haSMC after atRA-treatment. Whereas mRNA-expression of the glycoproteins thrombospondin-1 and fibronectin were decreased, collagen-1 mRNA expression was even slightly stimulated. Transcription of biglycan and TGF-beta1 were not influenced in a specific manner. Finally, protein expression and activity of the matrix metalloproteinases MMP-2 and MMP-9 were inhibited significantly by atRA. CONCLUSIONS: atRA was found to be a potent inhibitor of both haSMC-proliferation and -migration, even in coculture with haEC releasing growth factors. In addition, redifferentiation, ECM synthesis and ECM degradation were regulated by atRA which also influence haSMC migration and intima formation. Thus, atRA-treatment seems to be a promising strategy for the inhibition of processes involved both in atherosclerosis and restenosis.

Arteries↗
PubMed2000

Effects of cerivastatin on human arterial smooth muscle cell proliferation and migration in transfilter cocultures.

Statins competitively inhibit 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase activity reducing mevalonate synthesis. In this study, antiproliferative and antimigratory effects of the new compound cerivastatin were analyzed and compared with classic statins of the first and second generation using mono- and cocultures of human arterial smooth muscle (haSMC) and endothelial (haEC) cells. Effects on the mitotic index and mitochondrial activity of haEC and haSMC monocultures were tested using BrdU enzyme-linked immunosorbent assay (ELISA) and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) tests, respectively. In lactate dehydrogenase (LDH) assays, cytotoxicity of statins was studied. Transfilter cocultures were performed for 14 days to evaluate haSMC growth under the stimulatory effect of proliferating haEC, which release growth factors [e.g., platelet-derived growth factor (PDGF)]. The hydrophobic statins simvastatin, lovastatin, and atorvastatin significantly inhibited haSMC and haEC growth in monocultures at 0.5-50 microM. However, most potent effects were exerted by cerivastatin in 10- to 30-fold lower doses without any significant cytotoxicity. More important, cerivastatin showed also significant effects on haSMC proliferation and migration in transfilter cocultures at extremely low doses (IC50, 0.04-0.06 microM), even when applied exclusively to the endothelial side and in the presence of low-density lipoprotein (LDL). Addition of mevalonate abolished the effects of cerivastatin completely. Even in the presence of growth-stimulating haEC and LDL, cerivastatin was found to be the most potent inhibitor of haSMC proliferation and migration in doses that also can be reached in human serum after oral drug administration. The results support the concept that statins seems to influence additional cellular mechanisms beyond cholesterol reduction, which might also have a relevance for the prevention of restenosis.

Analysis of Variance↗
PubMed1997

Growth factor expression of human arterial smooth muscle cells and endothelial cells in a transfilter coculture system.

By releasing growth factors, vascular cells can modulate proliferation and migration of neighboring cells in the arterial wall. Previous histological studies in transfilter cocultures, a culture model aimed to simulate vessel wall architecture, indicated that human arterial endothelial cells (haEC) can influence human arterial smooth muscle cell (haSMC) growth significantly. The aim of this study was to investigate the expression and secretion of various growth factors in order to better define the functional interactions between haEC and haSMC. Protein levels of platelet-derived-growth factor-AB (PDGF-AB), transforming-growth factor-beta1 (TGF-beta1), and tumor-necrosis factor-alpha (TNF-alpha) in mono- and cocultures were determined by ELISA 6, 12, 24, 48, 72 h after serum reduction. Highest PDGF-AB levels were found in monocultures with proliferative haEC, showing a peak after 24 h. In cocultures of haEC and haSMC, PDGF-AB levels were significantly lower. In contrast, neither proliferative, nor confluent haSMC released PDGF-AB significantly. Highest TGF-beta1 concentrations were detected in cocultures, followed by monocultures of haSMC and monocultures of haEC. In all cultures, TGF-beta1 levels increased in parallel with cultivation time and cell numbers, showing a maximum after 72 h. TNF-alpha could not be detected in any culture. Northern blots demonstrated a strong expression of PDGF-B chain-mRNA in haEC, but not in haSMC. PDGF-A chain and TGF-beta1-mRNA were expressed by haSMC and haEC. Addition of PDGF-AB to haSMC resulted in a potent growth stimulation, whereas TGF-beta1 and TNF-alpha exerted only moderate, divergent effects on haSMC. Histological observations in transfilter cocultures demonstrated that proliferative haEC induce the formation of fibromuscular plaques. These results suggest that proliferative haEC act as potent growth stimulators for haSMC, predominantly by PDGF-AB or -BB release.

Cell Division↗
PubMed1990

[The difference between the mineral content and the width of the radius on each side and its significance for handedness determination of skeletal material].

The objective of our work was to investigate whether the side-different use of the upper extremities due to handedness produces detectable differences in bone-mineral content (BMC) and bone width (BW). For this purpose 251 recent individuals whose handedness was established, were examined by means of the 125I-photon-absorption technique. Highly significant right-left differences in BMC and BW were found on the midshaft and distal radius. Discrimination functions based on BMC and BW were carried out, allowing for the classification into the appropriate handedness categories. Applying the same method we tried to diagnose the handedness of the skeletal material of 40 medieval and 27 neolithic individuals.

Absorptiometry, Photon↗
PubMed1988

Correlations between endogenous prostaglandin E formation in the bone and spongiosa density.

The formation of prostaglandin (PG) E in the femoral head and the lumbar vertebral body of rats under ex vivo conditions after a linoleic acid (LA) rich diet (13.3 J%) has been compared to that of rats after an LA poor diet (0.5 J%). LA rich diet increased the formation of PGE in the lumbar vertebral body. In the femoral head were a similar, but statistically insignificant effect. The spongiosa density in the femoral head and the lumbar vertebral body increased after LA rich diet in contrast to LA poor fed rats. We conclude that the spongiosa density could be modulated by the LA content of the diet possible via alterations of endogenous PG biosynthesis.

Animals↗
PubMed1981

Cerebral potentials during skilled slow positioning movements.

Movement-related potentials recorded from the scalp of man were investigated in two skilled positioning tasks, requiring flexions at different joints of the upper extremities. The average response time was approximately 1 sec. Subjects paced their movements themselves and performed without visual control or other external cues. After each trial a delayed visual feedback was given. It was found that the negative potential shift prior to the EMG onset, the 'Bereitschaftpotential', is followed by a persisting negativity during the execution of the action until the target position is reached. Approximately at this point a positive-going deflection appears. This 'goal-directed movement potential' is composed of at least two components: (a) a widely distributed, centrally dominant negativity, and (b) a smaller negative wave over the sensorimotor cortex contralateral to the responding limb. Small variations in response force do not influence the amplitude of the potentials. A negative shift in anticipation of the visual feedback has a topography different from the movement-related potentials, being predominant over the right hemisphere independent of the hand used

Adult↗
PubMed1980

[Bone mineral content determination by the photon absorption technic in chronic non-occupational fluoride exposure].

Bone mineral content and bone width of radius were examined by use of bone mineral analyser in persons with long-term nonoccupational fluoride exposition. Investigations took place in 275 female and 194 male without professional fluoride influence. Comparison with normal values showed no significant differences after fluoride exposition. The meaning of these findings is discussed.

Adolescent↗
PubMed1980

[Evaluation of the mineral content of peripheral bones (radius) by photon-absorption technique in normals as well as in patients with various types of bone diseases (author's transl)].

The evaluation of the mineral content of peripheral bones by measuring the photon absorption of the radius has proven to be a valuable method for routine clinical work: for diagnosis, follow-up and control of therapy. While there was a significant difference in the findings of normal persons compared with those of patients suffering from osteoporosis, renal osteodystrophy, osteogenesis imperfecta and skeletal fluorosis, there was no difference between normals and these patients suffering from Bechterew, Scheuermann, coxarthrosis, spondylosis, skoliosis and rheumatoid arthritis. Normal values for the mineral content and width or the radius at the junction of the middle and lower third--based on 8000 examinations--are mentioned.

Adolescent↗
PubMed1979

[Bone changes in hemoblastoses and malignant lymphomas].

In haematological systemic diseases such as acute and chronic leukoses, malignant lymphomas, lymphogranulomatoses, osteomyelofibroses, polycythaemias and aplastic anaemias with a different proportion changes of the bones in form of osteoporoses, osteolytic processes and deformations of the vertebral bodies are to be found. The proof may be performed radiologically and histologically. In 461 patients with different haematological diseases absorption measurings of monoenergetic rays of a J-125-source were performed at the distal third of radius and ulna. It was shown that the bone mineral content of patients with proved bone destructions did not significantly differ from the normal group. The too peripherally located place of the measuring and also the late inclusion of the compacta into the changes is regarded as cause for the negative result.

Bone Diseases↗