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Biomedical subjects

K Müller

Publications and source records attributed to K Müller.

At least 181 records · Page 10Linked to original sources

Nongenomic effects of aldosterone on phosphocreatine levels in human calf muscle during recovery from exercise.

Nongenomic in vitro effects of aldosterone on the sodium-proton antiport and intracellular second messengers have been described in human mononuclear leukocytes, vascular smooth muscle cells, and endothelial cells. To test the potential physiological relevance of these effects, an in vivo 31P magnetic resonance spectroscopy study on the human calf at rest and during exercise was performed in 10 healthy volunteers receiving either 1 mg aldosterone or placebo iv in a double blind, randomized, cross-over trial. Spectra were analyzed for phosphocreatine, ATP, phosphomonoesters, inorganic intracellular phosphate, and intracellular pH. Resting values remained unchanged by aldosterone. After isometric contraction of the calf (50% body weight for 3 min), phosphocreatine recovered to significantly higher levels after application of aldosterone compared with placebo. Other parameters were not significantly changed by aldosterone. Effects appeared immediately after isometric contraction and, thus, occurred within 8 min of aldosterone administration. They are, therefore, likely to represent the first contemporary evidence of nongenomic in vivo effects of aldosterone in man. These findings also point to an involvement of aldosteron in the acute stress adaptation of cellular oxidative metabolism in human muscle physiology.

Adult↗

Autoantibodies to IL-1 alpha in sera from umbilical cords, children, and adults, and from patients with juvenile chronic arthritis.

Antibodies against interleukin-1 alpha (aAb-IL-1 alpha) have previously been demonstrated in sera of healthy adults and in patients with inflammatory diseases. In the present investigation the occurrence of aAb-IL-1 alpha was examined by second antibody precipitation technique in sera from umbilical cords (n = 11), children (n = 45), and adults (n = 20), as well as in 51 patients with juvenile chronic arthritis (JCA) of pauciarticular (n = 34), polyarticular (n = 8), or systemic onset type (n = 9). RESULTS. The frequency of positive sera was significantly lower in children than in cord blood and adults as were the levels of aAb-IL-1 alpha (p < 0.0001). In the non-neonatal group of individuals the levels of aAb-IL-1 alpha correlated positively with age (r = 0.394, p = 0.0015). The frequency of sera positive for aAb-IL-1 alpha was higher in the JCA patients, as were the levels (p < 0.005), and correlated positively with disease activity as evaluated by joint score and visual analogue score.

Adult↗

[Donor site defect after removal of free and pedicled forearm flaps: functional and cosmetic results].

The donor-site defect poses a special problem in free and pedicled forearm flaps. A multi-center-study of seven departments for Hand and Plastic Surgery in Germany and Switzerland studied the problem and showed the functional and cosmetic results. 342 questionnaires were checked. 267 patients came for a follow-up examination. 83.9% of them were satisfied with the result of the operation. Restrictions of movement in the wrist, forearm, and elbow appeared to be very rare. Half of the patients considered the donor-site defect to be ugly. Nearly the same number objected to preoperative information about the appearance of the donor-site defect. Based on the results of this study, we can still recommend the radial forearm flap for small and medium size soft-tissue defects, delicate technique of closure of the donor site defect provided.

Esthetics↗

[Determination of concentration and emission of gases relevant to animal and environmental hygiene in different systems for fattening of pigs with the aid of multigas monitoring].

Multigasmonitoring is a method to measure continuously gases relevant from the view point of animal and environmental hygiene with high sampling rate and to calculate emission. The methodical procedure has been described by example from different deep litter systems with additives and slatted floor system with liquid manure storage for fattening pigs. It has been shown that the emission of ammonia from an obviously good working deep litter system can be lowered by approximately 30% in comparison with slatted floor. The mean concentration of nitrous oxide in deep litter system with additives was approximately 2 ppm, whereas in the liquid manure system the N2O concentration was less than the outdoor value.

Air Pollution↗

Tunneled, double lumen Broviac catheters are useful, efficient and safe in children undergoing peripheral blood progenitor cell harvesting and transplantation.

We prospectively evaluated performance, efficiency, safety and compliance of large-bore central venous catheters (Cook TPN; Cook (Switzerland) AG) introduced via saphenous veins in 32 children and infants elected to undergo peripheral blood progenitor cell (PBPC) harvesting and transplantation (PBPCT). With these catheters a flow rate (25-65 ml/min) adequate for leukapheresis was achieved in all patients. There were no important catheter-related complications during harvest. The total duration of catheter placement was 4569 days (median, 139 days; range, 8-268 days). During this period which included conditioning and PBPCT, we observed five mechanical complications and 12 septic episodes not necessarily catheter-related (0.11 and 0.26 events per 100 catheter days, respectively). All infections resolved after systemic antibiotic treatment. There was no exit or tunnel area infection, and no catheter had to be removed due to infection. Two catheters were replaced because of displacement. Tunneled double lumen Broviac catheters introduced via saphenous veins were not only efficient and safe, they were also well accepted by children and young adults undergoing PBPC harvesting and transplantation.

Adolescent↗

1,25-Dihydroxyvitamin D3 as a natural regulator of human immune functions.

1,25-dihydroxyvitamin D3 (1,25-D3) modulates lymphocyte and macrophage functions in vitro. These effects are exerted through production of 1,25-D3 by antigen-presenting monocytes/macrophages (MO) and binding to vitamin D receptors expressed in MO and in activated, but not in resting T-lymphocytes. 1,25-D3 inhibits production of MO-derived cytokines such as interleukin-1 alpha, interleukin-6, and tumor necrosis factor alpha at the post-transcriptional level, most likely by reducing the half-life of specific mRNAs. The proliferation of T-cells and their release of cytokines such as IL-2 and interferon gamma are also suppressed by 1,25-D3, partly as a result of the reduced production of T-cell-activating cytokines (interleukin-1 alpha, tumor necrosis factor alpha), but also because of a direct effect on the T-cells. Although 1,25-D3 has no apparent effect on B-lymphocytes, the T-cell suppression indirectly inhibits antibody production by B-cells. The CD45R0+ subset of T-helper cells is relatively more sensitive than the CD45RA+ subset to the inhibitory effects of 1,25-D3. The CD45R0+ subset plays a key role in immune activation and in the pathogenesis of many autoimmune disease. 1,25-D3 acts as an important local regulator of T-cell functions and thus modulates several immunological effector functions. The actions of 1,25-D3 are distinct from those of commonly used immunosuppressants, and vitamin D3 analogs are therefore potentially useful as alternatives to conventional immunosuppressive therapies.

Calcitriol↗

Novel 10-substituted antipsoriatic anthrones as inhibitors of epidermal 12-lipoxygenase and lipid peroxidation in membranes.

The ability of novel 10-substituted anthrones to inhibit 12-lipoxygenase (12-LO) in mouse epidermal homogenate and lipid peroxidation in both bovine brain phospholipid liposomes and erythrocyte ghosts was investigated, and compared with their ability to inhibit 5-lipoxygenase (5-LO) in bovine leukocytes. The compounds were fairly potent inhibitors of epidermal 12-LO, in addition to their strong inhibitory effects against leukocyte 5-LO. Although the antipsoriatic drug, anthralin, predominantly inhibited epidermal 12-LO, the novel derivatives were more selective 5-LO inhibitors. Compounds with free phenolic groups in the attached aromatic ring were also potent inhibitors of nonenzymatic lipid peroxidation in both sources of lipid substrate. This property was not correlated with their ability to inhibit the 5- and 12-LO pathways, suggesting that their mechanism of 5-/12-LO inhibition is not simply due to scavenging of peroxyl radicals generated at the active site of the enzymes. The compounds are dual-purpose inhibitors and may play a protective role against oxidative damage to psoriatic skin, in addition to their antiinflammatory 5-LO and 12-LO inhibitory properties.

Administration, Topical↗

Modification of DNA bases by anthralin and related compounds.

Modification of bases in calf thymus DNA by treatment with the antipsoriatic drug anthralin was studied. The products of DNA bases were identified and their yields measured by gas chromatography-mass spectrometry with selected ion monitoring. Treatment of calf thymus DNA with anthralin significantly enhanced the amount of modified bases above control levels. Purine bases were modified to products identical with those known to be typical of DNA damage induced by hydroxyl radicals. The yields of Fapy-adenine, 8-hydroxyadenine, Fapy-guanine, and 8-hydroxyguanine were maximally increased at an anthralin concentration of 75 microM. A variety of structural analogues of anthralin were also tested at 75 microM were either weaker or stronger hydroxylating agents. It is likely that damage to DNA bases induced by anthrones contributes to their antiproliferative activity. The pharmacological implications of these characteristics of the action of anthralin on DNA bases are discussed.

Adenine↗

Tetravalent miniantibodies with high avidity assembling in Escherichia coli.

We have designed tetravelent miniantibodies assembling in the periplasm of Escherichia coli. They are based on single-chain Fv fragments, connected via a flexible hinge to an amphipathic helix which tetramerizes the molecule. The amphipathic helix is derived from the coiled coil helix of the transcription factor GCN4, in which all hydrophobic a positions of every heptad repeat have been exchanged to leucine and all d positions to isoleucine. Gel filtration shows tetramer assembly of the miniantibody even at low concentrations. As expected, the functional affinity (avidity) of the tetravalent miniantibody is higher in ELISA and BIAcore measurements than that of the bivalent construct and the gain is dependent on surface epitope density.

Amino Acid Sequence↗

Cyclical treatment of osteopenic ovariectomized adult rats with PTH(1-34) and pamidronate.

Administration of PTH(1-34) at low intermittent doses stimulates bone formation in vivo. However, the new bone is quickly resorbed after drug withdrawal. Following the concept of lose, restore, and maintain, we studied the possibility of maintaining the PTH(1-34)-mediated new bone by APD post-treatment and the effect of a second PTH(1-34)-APD cycle in osteopenic ovariectomized (OVX) adult rats. Eighty OVX rats (6-months-old, 3 months after OVX) and 10 sham-operated rats were divided into nine groups. One OVX group was killed as baseline (BL). Five OVX groups were injected with PTH(1-34) (20 micrograms/kg/day, subcutaneously) for 3 weeks (5 days/week). The remaining two OVX groups and the sham group (S) were injected with saline as controls. One PTH(1-34) group (A) and one control group (B) were then killed. Three PTH(1-34) groups were post-treated with APD injections (250 micrograms/kg/day, subcutaneously) for 5 days; the remaining PTH(1-34) group, the other control group, and group S were injected with saline; and all these groups were left untreated for 3 weeks. At the end, one PTH-APD group (C), the PTH-saline group (D), and the saline-saline group (E) were killed. Another PTH-APD cycle was applied to the remaining two PTH-APD groups, with group F killed after the second PTH treatment and group G killed after two complete cycles. We found a 90% increase in cancellous bone volume (Cn.BV/TV) and a 28% increase in trabecular thickness (Tr.Th) in group A over group B.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

MAB, a generally applicable molecular force field for structure modelling in medicinal chemistry.

The mathematical formulation, parametrization scheme, and structural results of a new, generally applicable molecular force field are presented. The central features are a scheme for automatic parameter assignments, the consistent united-atom approximation, the absence of atom types other than elements, the replacement of electrostatic terms by geometrical hydrogen-bonding terms, the concomitant lack of a need for partial atomic charge assignment and the strict adherence to a finite-range design. As a consequence of omitting all hydrogen atoms, optimal hydrogen-bond patterns are computed dynamically by appropriate network analyses. For a test set of 1589 structures, selected from the Cambridge Structural Database solely on the grounds of a given element list and criteria for high structure refinement, the agreements are on average 2 pm for bonds, 2 degrees for valence angles and 10 to 20 pm for the root-mean-square deviation of atom positions, depending somewhat on size and flexibility of the structures. More qualitative testing of large-scale structural properties of the force field on proteins and DNA oligomers revealed satisfactory performance.

Computers↗

The organization structure and regulatory elements of Chlamydomonas histone genes reveal features linking plant and animal genes.

The genome of the green alga Chlamydomonas reinhardtii contains approximately 15 gene clusters of the nucleosomal (or core) histone H2A, H2B, H3 and H4 genes and at least one histone H1 gene. Seven non-allelic histone gene loci were isolated from a genomic library, physically mapped, and the nucleotide sequences of three isotypes of each core histone gene species and one linked H1 gene determined. The core histone genes are organized in clusters of H2A-H2B and H3-H4 pairs, in which each gene pair shows outwardly divergent transcription from a short (< 300 bp) intercistronic region. These intercistronic regions contain typically conserved promoter elements, namely a TATA-box and the three motifs TGGCCAG-G(G/C)-CGAG, CGTTGACC and CGGTTG. Different from the genes of higher plants, but like those of animals and the related alga Volvox, the 3' untranslated regions contain no poly A signal, but a palindromic sequence (3' palindrome) essential for mRNA processing is present. One single H1 gene was found in close linkage to a H2A-H2B pair. The H1 upstream region contains the octameric promoter element GGTTGACC (also found upstream of the core histone genes) and two specific sequence motifs that are shared only with the Volvox H1 promoters. This suggests differential transcription of the H1 and the core histone genes. The H1 gene is interrupted by two introns. Unlike Volvox H3 genes, the three sequenced H3 isoforms are intron-free. Primer-directed PCR of genomic DNA demonstrated, however, that at least 8 of the about 15 H3 genes do contain one intron at a conserved position. In synchronized C. reinhardtii cells, H4 mRNA levels (representative of all core histone mRNAs) peak during cell division, suggesting strict replication-dependent gene control. The derived peptide sequences place C. reinhardtii core histones closer to plants than to animals, except that the H2A histones are more animal-like. The peptide sequence of histone H1 is closely related to the V. carteri VH1-II (66% identity). Organization of the core histone gene in pairs, and non-polyadenylation of mRNAs are features shared with animals, whereas peptide sequences and enhancer elements are shared with higher plants, assigning the volvocalean histone genes a position intermediate between animals and plants.

Amino Acid Sequence↗

Vitamin D3 metabolism in patients with rheumatic diseases: low serum levels of 25-hydroxyvitamin D3 in patients with systemic lupus erythematosus.

1,25-dihydroxyvitamin D3 (1,25(OH)2 D3) has been shown to modulate lymphocyte activation in vitro. Through binding to specific receptors 1,25-(OH)2 D3 inhibits proliferation, immunoglobulin production and the release of cytokines. Moreover, 1,25-(OH)2 D3 is efficiently produced by activated monocytes. These findings suggest that 1,25-(OH)2 D3 may play a role as a regulator of immunological activation. Consequently, we found it of interest to study the serum levels of the two major metabolites of vitamin D3 in patients with systemic lupus erythematosus (SLE) (n = 21), rheumatoid arthritis (RA) (n = 29) and osteoarthritis (n = 12). In patients with SLE the levels of 25-OH D3 were below those of the healthy controls (p = 0.0008) and OA (p = 0.0168). The levels 1,25-(OH)2 D3 corresponded to normal levels. There were no significant correlations between 25-OH D3 levels and clinical or paraclinical disease manifestations. Further, the phenotypic distribution of Gc-globulin, which binds vitamin D3 metabolites in circulation, was normal. The serum concentrations of 1,25-(OH)2 D3 and 25-OH D3 in patients with RA and OA corresponded to those of the controls. Although the cause of the reduced 25-OH D3 levels in SLE patients is unclear, possible beneficial effects of administration of vitamin D to these patients should be considered.

Adult↗

Thermal acclimation and dietary lipids alter the composition, but not fluidity, of trout sperm plasma membrane.

The effect of a long-term adaptation of rainbow trout to 8 and 18 degrees C combined with a corn oil- or a fish oil-supplemented diet on the characteristics of the spermatozoan plasma membrane was investigated. The experiment lasted up to 22 mon during which spermatozoa were collected from the mature males. Spermatozoan plasma membranes were isolated by nitrogen cavitation, and the cholesterol content, phospholipid composition and fatty acid pattern were investigated. Membrane viscosity was assessed on whole cells by electron spin resonance using spin-labeled phospholipids. Neither diet nor rearing temperature influenced the cholesterol content of the plasma membrane nor the phospholipid class distribution. The rearing temperature of the broodstock only slightly affected the phospholipid fatty acids. A minor decrease in 18:0 and increase in monounsaturated fatty acids was observed for the cold-adapted fish. These modifications were not sufficient to affect membrane fluidity, and we conclude that trout spermatozoa do not display any homeoviscous adaptations in these conditions. On the contrary, the dietary fatty acid intake greatly modified the fatty acid profile of plasma membrane phospholipids. The fish oil-fed trout displayed a much higher n-3/n-6 fatty acid ratio than did the corn oil-fed ones, but the 22:6n-3 levels remained unchanged. Modifications in plasma membrane composition by the diet were obtained although neither of the two diets was deficient in essential fatty acids. The enrichment in n-3 fatty acids, however, did not affect plasma membrane fluidity which was unchanged by the diets.

Acclimatization↗

Reduction of nitroxides by anthralin and some of its derivatives.

In DMSO solution, anthralin and its C-10 monosubstituted derivatives reduce nitroxides to the corresponding hydroxylamine derivatives, which are not further transformed. The reaction rate depends on the solvent used, the nitroxide, and the structure of the reducer. It is faster in DMSO than in DMF, piperidine type of nitroxides are reduced faster than the pyrrolidine type, and the substitution on C-10 of anthralin has a significant influence on the reaction rate. Anthralin derivatives without protons at C-10 are not able to reduce nitroxides.

Administration, Topical↗

Abnormal distributions of T-lymphocyte subsets in the cerebrospinal fluid of patients with acute schizophrenia.

We analysed the percentages of CD4+ and CD8+ T lymphocytes in the cerebrospinal fluid (CSF) from 31 acutely ill schizophrenic patients. The psychotic patients had in their CSF clearly altered proportions of CD4+ and/or CD8+ T cells. As compared to the distribution of T cell subsets in the CSF from non-psychotic controls, the schizophrenic patients displayed both abnormally high and abnormally low frequencies of CD4+ and/or CD8+ cells. Changes in the distribution of T cell subsets corresponding to those seen in the CSF were not observed in paired blood samples from schizophrenic patients.

Acute Disease↗

Estrogen dose required to maintain parathyroid hormone mediated bone gain in osteopenic ovariectomized rats is probably higher than in preventive treatment with estrogen.

Successful prevention of bone loss in ovariectomized rats with 17 beta-estradiol (E2) at 10 micrograms/kg/d has been reported. Here we show that E2 dose twice that much is not enough to maintain PTH(1-34) mediated bone gain. Three-month-old female Wistar rats were ovariectomized and fed with regular rodent chow and water ad libitum. Three months later they were divided into 9 groups (5-8 per group) and treated cyclically with PTH(1-34) (20 micrograms/kg/d sc, 5d/w for 3w) and E2 (20 micrograms/kg/d sc, 5d/w for 4w). There were also a baseline group and five vehicle control groups. Cancellous bone volume (Cn.BV/TV) of distal femoral metaphyses was measured by computer-aided histomorphometry on trichrome stained thin sections, and 24-hour fasted urine was analyzed for pyridinoline/creatinine (PYR/CREA) by immunoassay. Histomorphometric results showed that PTH(1-34) progressively increased Cn.BV/TV but E2 failed to maintain them. Urinary PYR/CREA results showed that E2-treated groups had lower values. We conclude that E2 dose > 20 micrograms/kg/d is required to maintain the PTH mediated bone gain.

Analysis of Variance↗