Biomedical subjects

K Müller

Publications and source records attributed to K Müller.

At least 163 records · Page 9Linked to original sources

PubMed1997

Gait analysis by measuring ground reaction forces in children: changes to an adaptive gait pattern between the ages of one and five years.

The aim of this study was to look at the maturational profile of gait parameters by measuring ground reaction forces during independent walking in children. Fifty-four normal children aged 1 to 5 years were examined. The children walked with eight force transducers under each sole. Gait velocity and step length increased with age, whereas step frequency remained relatively constant. Phases of double ground contact expressed as percentages of the total gait cycle decreased significantly from age 1 to 5 with the steepest decrease occurring in the first year of independent walking. No asymmetry between left and right could be detected for any of these parameters. The pattern of ground reaction forces with a significant heel strike and obvious enrollment process resembling that in adults was achieved between the age of 2 and 3 years. Measuring ground reaction forces is a fast and easily manageable method of analysing gait pattern in children and is also a promising tool for detection of gait abnormalities in children with neurological disease.

Adaptation, Physiological↗

PubMed1997

Transbilayer motion of spin-labelled phospholipids in the plasma membrane of epididymal and ejaculated ram spermatozoa.

The transbilayer movement and distribution of spin-labelled phospholipid analogues were studied in the plasma membrane of ram sperm cells isolated from functionally different regions of the epididymis (caput, cauda) and from the ejaculate. As already shown for ejaculated cells, (i) a rapid movement of aminophospholipid analogues phosphatidylserine and phosphatidylethanolamine from the exoplasmic to the cytoplasmic leaflet, and (ii) a slow transbilayer movement of phosphatidylcholine were observed in the plasma membrane of maturating ram sperm cells. This suggests an asymmetric steady state transbilayer distribution of phospholipids, with a preferential enrichment of aminophospholipids on the cytoplasmic leaflet of those cells. The fast inward redistribution of the aminophospholipid analogues is consistent with the presence of an aminophospholipid translocase activity in all three sperm cell preparations. The translocase activity was enhanced slightly during the epididymal transit of spermatozoa. However, compared with epididymal sperm cells, a marked increase in the aminophospholipid translocase activity and a more pronounced phospholipid asymmetry for phosphatidylethanolamine was established for ejaculated spermatozoa. The physiological relevance of the rapid removal of aminophospholipids from the exoplasmic leaflet of the plasma membrane of ram sperm cells is discussed. The quality of sperm cell fractions was characterized by the cell morphology, membrane integrity and the cellular ATP concentration.

Adenosine Triphosphate↗

PubMed1997

[Investigations on the concentration and emission of ammonia and nitrous oxide in various deep litter keeping systems for fattening pigs and in slatted floor keeping].

Concentration of ammonia and nitrous oxide was measured in an air conditioned pig site with two chambers during six rounds (app. 650 measuring days) with different deep litter and a slatted floor keeping system for fattening pigs. Emissions and gaseous nitrogen losses were calculated. With exception of a system with mixing twice a week deep litter keeping leads to decrease of NH3 concentration (up to 26%), partly also of NH3 emission, but to higher N2O emissions compared to liquid manure system. With exception of ENVIROZYME deep litter keeping all other deep litter systems cause higher gaseous nitrogen losses compared to slatted floor keeping.

Ammonia↗

PubMed1997

Renal and hormonal responses to exercise in man at 46 and 37 atmospheres absolute pressure.

BACKGROUND: Exercise increases plasma arginine-vasopressin (PAVP), plasma atrial natriuretic peptide (PANP), plasma renin activity (PRA), and plasma aldosterone (PALDO) in an intensity-dependent manner. With acute exercise, urine osmolality (UOSM) is often decreased despite increased PAVP. The hyperbaric environment lowers PAVP and UOSM, and increases urine flow. HYPOTHESIS: If work produced similar renal effects at hyperbaria, greater than normal dehydration could result from larger free water losses. METHODS: To test this hypothesis, hormonal and renal responses were assessed during exercise at 80% of maximum heart rate at 46 atmospheres absolute (atm abs) in 3 males, and during maximum exercise at 37 atm abs in 4 males. RESULTS: This maximum exercise was performed at the highest pressure thus far reported and revealed no loss in peak power output. Maximum O2 consumption and heart rate were only slightly reduced, 9.5% and 7% respectively, despite a 41% reduction in maximum minute ventilation. Basal levels and the changes resulting from maximum exercise in PRA and PALDO were unaffected by pressure, but basal and exercise-stimulated levels of PANP and PAVP were reduced compared with 1.5 atm abs control values. UOSM was not significantly affected during maximal exercise at sea level, but during maximum exercise at 37 atm abs and submaximum exercise at 46 atm abs UOSM increased over 300 mosm.kg-1 and 180 mosm.kg-1, respectively. CONCLUSION: Contrary to the hypothesis, UOSM was increased by about 200 mosm.kg-1 by both exercise protocols during hyperbaric exposure and free water was conserved.

Adult↗

PubMed1996

[Prospective study of diagnosis, therapy and follow-up of acute gastrointestinal hemorrhage in 397 patients].

The mortality of acute GI hemorrhage in the literature varies considerably, depending on the study design and quality of the data evaluated. We therefore conducted a prospective study over 2.5 years of 397 patients with suspected acute GI hemorrhage at the University hospital of Erlangen for internal quality control. In 99% of cases diagnostic endoscopy identified one or more bleeding sources. 46% of the patients bled from duodenal or gastric ulcers, 21% from esophageal or gastric varices and 33% from other sources. 228 of the 397 patients (57%) were initially treated endoscopically, 76 patients (19%) experienced a recurrence of bleeding. Patients older than 60 years of age with a hemoglobin below 8 g/dl had a significantly higher rate of recurrent bleeding. The rate of complications during the hospital stay was 22% (n = 87), in-hospital mortality 17% (n = 68). The rates of recurrent bleeding (28 vs. 20%), complications (24 vs. 18%) and mortality (20 vs. 14%) were significantly higher for bleeding varices than for peptic ulcers. Patients with other causes of acute GI hemorrhage developed a recurrence of bleeding in 13%, complications in 26% and had a mortality rate of 19%. Bleeding varices as well as bleeding peptic ulcers and other causes of acute GI hemorrhage still have a high mortality and require intensive medical surveillance besides diagnostic and therapeutic endoscopy.

Acute Disease↗

PubMed1996

Antipsoriatic anthrones with modulated redox properties. 3. 10-thio-substituted 1,8-dihydroxy-9(10H)-anthracenones as inhibitors of keratinocyte growth, 5-lipoxygenase, and the formation of 12(S)-HETE in mouse epidermis.

The synthesis of a series of 1,8-dihydroxy-9(10H)-anthracenones bearing sulfur-linked substituents in the 10-position is described. These compounds were evaluated for their ability to inhibit the growth of the human keratinocyte cell line HaCaT and the 5- and 12-lipoxygenase enzymes in bovine polymorphonuclear leukocytes and mouse epidermal homogenate, respectively. In addition, the following redox properties of the compounds were determined: reactivity against 2,2-diphenyl-1-picrylhydrazyl, generation of hydroxyl radicals as measured by deoxyribose degradation, and inhibition of lipid peroxidation in model membranes. Compounds 4e and 4h of this series compare favorably in the cellular assays with the antipsoriatic anthralin. They have the combined inhibitory action against leukotriene B4 and 12(S)-HETE formation and are highly potent antiproliferative agents against keratinocyte growth. In contrast to anthralin, 4h, 1,8-dihydroxy-10-[(4-hydroxyphenyl)thio]-9(10H)-anthracenone, is not cytotoxic as documented by the LDH activity released from cytoplasm of keratinocytes and does not enhance lipid peroxidation in model membranes.

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

PubMed1996

Rapid identification of phosphopeptide ligands for SH2 domains. Screening of peptide libraries by fluorescence-activated bead sorting.

A method for the identification of high-affinity ligands to SH2 domains by fluorescence-activated bead sorting (FABS) was established. Recombinant SH2 domains, expressed as glutathione S-transferase (GST) fusion proteins, were incubated with a phosphotyrosine (Y*)-containing peptide library. 6.4 x 10(5) individual peptides of nine amino acids in length (EPX6Y*X19X7X19X7X6) were each displayed on beads. Phosphopeptide interaction of a given SH2 domain was monitored by binding of fluorescein isothiocyanate-labeled antibodies directed against GST. High-fluorescence beads were isolated by flow cytometric sorting. Subsequent pool sequencing of the selected beads revealed a distinct pattern of phosphotyrosine-containing motifs for each individual SH2 domain: the SH2 domain of the adapter protein Grb2 predominantly selected beads with the sequence Y*ENDP, whereas the C-terminal SH2 domain of the tyrosine kinase Syk selected Y*EELD, each motif representing the most frequently found residues C-terminal to the phosphotyrosine. For deconvolution studies, soluble phosphopeptides comprising variations of the Grb2 motifs were resynthesized and analyzed by surface plasmon resonance.

Amino Acid Sequence↗

PubMed1996

Cytotoxic and chemotactic potencies of several aldehydic components of oxidised low density lipoprotein for human monocyte-macrophages.

We have investigated the cytotoxic and chemotactic potencies of malondialdehyde (MDA), hexanal, 4-hydroxyhexenal (HHE), 4-hydroxynonenal (HNE) and 4-hydroxyoctenal (HOE), which are aldehydes found in oxidised low density lipoprotein (LDL), for human monocyte-macrophages. They were toxic in the following order: hexanal<HHE= HOE< HNE. HNE was toxic at 20 microM and chemotactic at 2.5 microM. The other aldehydes tested had no chemoattractant activity. Our results suggest that HNE arising from LDL oxidation could attract monocytes into the human atherosclerotic lesion. A direct cytotoxic role of aldehydes in foam cell death in the lesion is less likely.

Aldehydes↗

PubMed1996

Inactivation of mouse epidermal 12-lipoxygenase by anthralin--implications for the role of oxygen radicals.

In activation of 12-lipoxygenase (12-LO) in mouse epidermal homogenate by the antipsoriatic drug anthralin has been studied in detail. In view of the chemical instability of anthralin in a physiological buffer, the biological effects ascribed to the molecule itself may be related to some of its breakdown products. However, the inhibitory activity could not be attributed to the known stable oxidation product of anthralin, danthron, which did not decrease (12-LO activity. Addition of the antioxidants 2,6-di-tert-butyl-4-methylphenol (BHT) or beta-carotene, or the hydroxyl radical scavenger sodium benzoate, protected against anthralin-mediated 12-LO inactivation, suggesting that pro-oxidant species derived from anthralin play a key role in the inhibitory action. Even though inhibitory effects of anthralin against catalase and superoxide dismutase (SOD) have been observed under the conditions applied in this study, these antioxidant enzymes also partially prevented the inhibition of 12-LO by anthralin when added to the incubation mixtures. Control experiments without anthralin revealed that the oxygen radical scavengers and antioxidant enzymes, themselves, did not appreciably influence epidermal 12-LO activity. A mechanism underlying the inactivation of epidermal 12-LO by anthralin is proposed, which involves active oxygen species formed during the auto-oxidation of the drug.

Animals↗

PubMed1996

2-Anthracenonyl acetic acids as 5-lipoxygenase inhibitors.

The synthesis of 2-substituted anthracenonyl acetic acid (2-AA) derivatives is described. The key step is the Marschalk reaction of 1-hydroxy-8-methoxy-anthracenedione with glycolic acid. After protection of the resulting 2-anthracenonyl acetic acid derivative, the 2-monoalkylated derivatives are selectively obtained by direct alkylation. The methodology proves quite general and allows for the introduction of various substituents onto the 2-position of the carboxylic side chain. Reduction of the anthracenediones proceeds with concomitant protecting group removal and provides final 2-AA products in good yields. The results of initial biological studies demonstrate enhanced 5-lipoxygenase inhibition compared to anthralin.

Acetates↗

PubMed1996

The soft tissue cover of the mandibular condyle: age-related changes in high buoyant density proteoglycans, free tissue water and remodelling activity.

Age-related changes in the relative proportion of high buoyant density proteoglycans of the soft tissue cover of the mandibular condyle of domestic pigs and the chemical composition of these proteoglycans were investigated by biochemical methods. The relative proportion of high buoyant density proteoglycans has been shown to decrease with age, with their chemical composition varying as follows: With age, the relative proportions of protein increased, galactosamine decreased, glucosamine was similar in newborns and juveniles, but clearly increased in adults, galactosamine plus glucosamine decreased. As measured by 1H-NMR-relaxation spectroscopic methods, the concentration of free tissue water of the soft tissue cover of the mandibular condyle decreased with age. Its mobility, however, was greater in newborns than in juveniles, but similar in juveniles and adults. The concentration of free tissue water, but not its mobility, correlated weakly with relative proportions of polyanionic side chains (e.g. chondroitin sulphate plus keratan sulphate chains) of the high buoyant density proteoglycans. By affecting the concentration of free tissue water and in turn of matrix solutes and cellular environments, the high buoyant density proteoglycans of the soft tissue cover of the mandibular condyle seem to be involved in regulation of age-related changes in the adaptive remodelling activity of the mandibular condyle.

Aging↗

PubMed1996

Transverse mobility of aminophospholipids in the plasma membrane of ram sperm cells.

The transbilayer movement of aminophospholipids in the plasma membrane of ram sperm cells was investigated using spin-labeled lipid analogues. After incorporation, spinlabeled phosphatidylserine (SL-PS) and phosphatidyl-ethanolamine (SL-PE) rapidly disappeared from the exoplasmic monolayer. Even at lower temperatures (10 degrees C) the inward movement of SL-PE is fast. The initial velocities of the internalization of SL-PS and SL-PE were compared with those of ram and human erythrocytes.

Acrosome↗

PubMed1996

High volumetric yields of functional dimeric miniantibodies in Escherichia coli, using an optimized expression vector and high-cell-density fermentation under non-limited growth conditions.

Functional bivalent miniantibodies, directed against the epidermal growth factor receptor, accumulated to more than 3 gl-1 in high-cell-density cultures of Escherichia coli RV308(pHKK) on a pilot scale. The miniantibodies consist of scFv fragments with a C-terminal hinge followed by a helix-turn-helix motif, which homodimerizes in vivo. The improved expression vector pHKK is characterized by the hoklsok suicide system, improving plasmid maintenance, and the inducible lac pl o promoter system with the very strong T7g10 Shine-Dalgarno sequence. The expression unit is flanked by terminators. The prototrophic RV308 cells were cultivated in glucose mineral salt medium and reached a cell density of 145 g dry biomass l-1 after 33 h. After induction, growth continued almost unchanged for a further 4 h with concomitant miniantibody formation. In the fedbatch phase, the concentration of glucose was kept almost constant at the physiological level of approximately 1.5 gl-1, using on-line flow injection analysis for control. Surprisingly, E. coli RV308(pHKK) did not accumulate significant amounts of the metabolic by-product acetate under these unlimited aerobic growth conditions.

Acetates↗

PubMed1996

Antipsoriatic anthrones: aspects of oxygen radical formation, challenges and prospects.

1. Antipsoriatic anthrones are among the most commonly used topical agents for the treatment of psoriasis. 2. These drugs generate reactive oxygen species during their auto-oxidation under physiological conditions. 3. Recent studies have indicated that activation of molecular oxygen by anthrones may play a critical role in their mechanism of action at the molecular level. 4. This article summarizes the evidence pointing toward the significance of oxygen activation and radical formation in the antipsoriatic action and induction of skin inflammation of anthrones. 5. Also, the role of oxygen radical formation in the development of novel anthrones devoid of inflammatory and staining properties is discussed.

Administration, Topical↗

PubMed1996

Benzophenanthridine alkaloids of Chelidonium majus; I. Inhibition of 5- and 12-lipoxygenase by a non-redox mechanism.

The benzophenanthridine alkaloids sanguinarine and chelerythrine of Chelidonium majus, L. (Papaveraceae), are potent inhibitors of 5-lipoxygenase in polymorphonuclear leukocytes and 12-lipoxygenase in mouse epidermis, while the activity of soybean lipoxygenase is not influenced. The extract of the herb of Ch.majus also inhibits the 5-LO enzyme. Chelidonine, which cannot form pseudobases, is inactive against LO enzymes. Pro- and antioxidant actions of benzophenanthridine alkaloids can be excluded from the lack of deoxyribose degradation, reactivity against free radicals and inhibition of lipid peroxidation, suggesting that the inhibitory effects against LO enzymes appear to be due to specific enzyme interaction rather than a nonspecific redox mechanism.

Alkaloids↗

PubMed1996

Benzophenanthridine alkaloids of Chelidonium majus; II. Potent inhibitory action against the growth of human keratinocytes.

The benzophenanthridine alkaloids sanguinarine and chelerythrine of Chelidonium majus, L. (Papaveraceae), were tested for their action against the growth of human keratinocytes. Cell proliferation was independently determined by directly counting the cells and in the colorimetric MTT assay. Sanguinarine potently inhibited cell growth with an IC50 of 0.2 microM. Chelidonine, the main alkaloid of Ch. majus, was much less efficient. The extract of the herb of Ch. majus was also effective with an IC50 of 1.9 microM, calculated on the basis of its alkaloid content in terms of chelidonine. Keratinocytes were further tested for their susceptibility for the action of sanguinarine and chelerythrine on plasma membrane integrity, which resulted in a twofold increase in lactate dehydrogenase (LDH) activity as compared to controls. On the other hand, the activity of the extract of the herb of Ch. majus was due to cytostatic rather than cytotoxic effects, as LDH release was unchanged as compared to controls.

Alkaloids↗

PubMed1996

In vitro cytokine production and phenotype expression by blood mononuclear cells from umbilical cords, children and adults.

Age related differences in immunological reactions include variations in the in vitro functions of blood mononuclear cells (MNC). In an attempt to understand the mechanism behind these differences we examined age related differences in the phenotype profiles of MNC in parallel with the in vitro production of interleukin IL-6, tumour necrosis factor alpha (TNF alpha) and interferon gamma (IFNg) in neonates, children and adults. In cultures without added polyclonal activators IL-6 and TNF alpha levels in children were 3-6 times higher than those of umbilical cords and adults. However, using optimal in vitro stimulation (E. coli lipopolysaccharide (LPS), phytohaemmagglutinin or pokeweed mitogen (PWM)) no significant differences in the levels of these cytokines were observed. The levels of IFNg in PWM driven cultures followed a different pattern with comparable levels in children and adults, and unmeasurable levels in cord blood MNC. Flow cytometry analysis of the phenotypic distribution of MNC revealed age related differences in the expression of CD3, CD4, CD8, CD14, CD19, CD45RA, CD45R0, CD2, LFA-1, ICAM-1 and LFA-3. Correlation studies did not indicate that the observed differences in cytokine production could be ascribed to differences in the frequency of monocytes, T cells or B cells. The TNF alpha levels in suboptimally stimulated cultures correlated negatively with the expression of LFA-3 and positively with CD45RA, while IFNg correlated positively with CD2, LFA-1, CD45R0 and CD8. In conclusion, the study provides evidence of age related differences in the production of TNF alpha, IL-6 and IFNg among neonates, children and adults. These differences may to some extent be caused by differences in the expression of cell surface molecules involved in cellular interactions and signalling.

Adult↗

PubMed1996

Familial aggregation of spelling disability.

This study examined the familial aggregation of spelling disability in a sample of 32 German school-aged children and their relatives. The influence of two different diagnostic criteria (low-achievement criterion, and regression-based IQ-discrepancy criterion) on the rate of affectedness was investigated. Results revealed that 52.3-61.9% of the sibs and 26-34% of the parents were spelling disabled. Little evidence was found for an influence of the diagnostic criterion on the rate of affectedness.

Achievement↗