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Biomedical subjects

K Müller

Publications and source records attributed to K Müller.

At least 217 records · Page 12Linked to original sources
PubMed1994

The antipsoriatic Mahonia aquifolium and its active constituents; I. Pro- and antioxidant properties and inhibition of 5-lipoxygenase.

The effects of the extract of the bark of Mahonia aquifolium and its main constituents (berberine, berbamine, oxyacanthine) on 5-lipoxygenase, lipid peroxidation in phospholipid liposomes induced by 2,2'-azo-(bis-2-amidinopropane), deoxyribose degradation, and their reactivities against the free radical 2,2-diphenyl-1-picrylhydrazyl have been studied. The extract of M. aquifolium inhibits 5-LO with an IC50 value of 50 microM, whereas no appreciable effects were observed by its constituent alkaloids. Reactivity against DPPH increased in the following order: berberine < M. aquifolium < oxyacanthine, berbamine. Pro-oxidant effects by M. aquifolium or its constituents can be excluded, since deoxyribose degradation was not influenced as determined by the release of malondialdehyde. The most prominent feature of M. aquifolium is its efficacy in inhibition of lipid peroxidation (IC50 = 5 microM) which was not mediated by the alkaloids berberine, berbamine, and oxyacanthine.

Animals↗
PubMed1994

Immunogenicity and evolutionary variability of epitopes within IgA1 protease from serogroup A Neisseria meningitidis.

Five murine epitopes were defined and mapped within IgA1 protease produced by Neisseria meningitidis. Epitopes 1 and 2 were present in IgA1 protease from all strains, and from Neisseria gonorrhoeae. Epitopes 3 through to 5 varied between subgroups of serogroup A meningococci, but have remained constant over decades within the subgroups, except for epitope 4, which changed between 1983 and 1987 during the spread of subgroup III meningococci from Asia to Africa. Binding of monoclonal antibodies to epitopes 1, 4 and 5 neutralized enzymatic function. Human sera containing antibodies to IgA1 protease as a result of natural infection inhibited binding of monoclonal antibodies to epitope 4 but not to the other epitopes.

Animals↗
PubMed1993

Antipsoriatic anthrones with modulated redox properties. 1. Novel 10-substituted 1,8-dihydroxy-9(10H)-anthracenones as inhibitors of 5-lipoxygenase.

The syntheses, the biological evaluation, and the structure-activity relationships of a novel series of 1,8-dihydroxy-9(10H)-anthracenones bearing acyl-, alkyl-, or alkylidene-linked aromatic substituents in the 10-position are described. The phenylacyl and phenylalkylidene analogs were far more potent inhibitors of 5-lipoxygenase (5-LO) from bovine polymorphonuclear leukocytes (IC50 values in the 10(-7) M range) than the antipsoriatic drug anthralin, whereas phenylalkyl analogs were only weak inhibitors. Among the active compounds were both potent generators of hydroxyl radicals, as determined by deoxyribose degradation, and strong reducers of the stable free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH). However, several derivatives of this series maintained 5-LO inhibitory activity but did not generate hydroxyl radicals and were not reactive with DPPH. In particular, phenylacyl analogs were also 6 times more efficient in inhibition of lipid peroxidation in model membranes than anthralin. Structure-activity relationships have shown that the presence of free phenolic groups in the attached aromatic ring is beneficial but not required for 5-LO inhibitory potency. The inhibitory potency in the 10-phenylacyl series increased with the length of the acyl chain with three methylene units being the optimum, suggesting a specific enzyme interaction which would not be expected for nonspecific redox inhibitors.

Administration, Topical↗
PubMed1993

Hydroxyl radical damage to DNA sugar and model membranes induced by anthralin (dithranol).

The antipsoriatic anthrones anthralin and butantrone caused degradation of the DNA sugar deoxyribose in the presence of ferric salt. The degradation was substantially inhibited by iron-binding hydroxyl radical scavengers, iron chelators, superoxide dismutase (SOD) and catalase, suggesting a mechanism in which antipsoriatic anthrones generate hydroxyl radicals via the Fenton reaction or an iron-catalysed Haber-Weiss reaction. Butantrone was markedly less efficient at generating hydroxyl radicals than anthralin. Using bovine brain phospholipid liposomes as model membranes to study the effects of antipsoriatic anthrones on lipid peroxidation, the peroxidation of liposomal membranes in the presence of ferric salt was maximally enhanced by anthralin and butantrone at 12.5 and 5 microM, respectively. Higher concentrations of the drugs resulted in less peroxidation. Chain-breaking antioxidants and iron chelators strongly decreased anthralin-enhanced lipid peroxidation, suggesting the involvement of hydroxyl, peroxyl or alkoxyl radicals. In contrast to their stimulatory effects on liposomal membrane peroxidation, both anthralin and butantrone diminished Fe3+/ascorbate-induced lipid peroxidation in liposomes. Butantrone was more effective as an inhibitor of lipid peroxidation than was anthralin. The antioxidant properties of antipsoriatic anthrones were determined in terms of their reactivities with the stable free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH). Antioxidant activity of antipsoriatic anthrones requires the presence of free hydroxyl groups at C-1 and C-8 and at least one hydrogen atom at C-10 of the anthrone nucleus. The role of active oxygen species produced by antipsoriatic anthrones and the biological effects on cellular targets are discussed with respect to the mode of action and manifestation of side effects of these drugs.

Animals↗
PubMed1993

Two histone H1-encoding genes of the green alga Volvox carteri with features intermediate between plant and animal genes.

Southern hybridization indicated the presence of at least two and possibly four histone H1-encoding genes occurring as singlets in the Volvox carteri genome. Two of these genes, H1-I and H1-II, have been cloned and characterized. Their coding sequences are each interrupted by three introns, but only the position of the second intron is identically conserved in both H1-I and H1-II. The encoded 260-amino-acid (aa) (H1-I) and 240-aa (H1-II) polypeptides possess the typical tripartite organization of animal H1 histones, with variable N- and C-terminal domains flanking a conserved 'globular' DNA-binding domain. Extensive differences in their variable regions suggest that H1-I and H1-II (62% identity) represent two isotypes with different functions. A prominent KAPKAP-KAA motif in the H1-I N-terminal region, similarly seen in single H1 variants of a mosquito and a nematode, has a putative function in packing condensed subtypes of chromatin. Different from higher plants, but like animals, the H1 genes of V. carteri possess a typical 3' palindrome for mRNA processing, resulting in non-polyadenylated mRNAs. Transcription initiates 33 nucleotides (nt) (H1-I) and 26 nt (H1-II) downstream of typical TATA boxes. A putative 20-bp conserved enhancer element upstream of each TATA box closely resembles the consensus sequence associated with the nucleosomal histone-encoding genes in V. carteri [Müller et al., Gene 93 (1990) 167-175] and suggests stringent regulation. Accordingly, transcription of H1 was shown to be restricted to late embryogenesis, when new flagella are produced. We discuss the inferred accessory role of histone H1 proteins in stabilizing axonemal microtubules, as has been recently observed in sea urchin flagella [Multigner et al., Nature 360 (1992) 33-39].

Amino Acid Sequence↗
PubMed1993

Ontogeny is different for explicit and implicit memory in humans.

This study was aimed to clarify in how far ontogenetic development is different for declarative/explicit compared to procedural/implicit learning. These two memory subsystems are differentially affected in a number of pathological conditions. Sixty-one children between the age of 5 and 10 years were tested on a verbal story recall and non-verbal pictorial recall task, representing explicit memory. To test for implicit memory, a motor mirror tracking task and a non-motor tower-of-hanoi puzzle were used. Both explicit memory tasks showed a clear developmental profile with an increase in the number of recalled items for immediate, late and delayed recall with adult values not reached before the age of 9-10 years. In contrast, there were no age differences for both implicit memory tasks. The study demonstrates that explicit and implicit memory follow different maturational trends and further corroborate the notion of two different memory systems.

Adolescent↗
PubMed1993

Effects of oxygen radicals, hydrogen peroxide and water-soluble singlet oxygen carriers on 5- and 12-lipoxygenase.

Inhibition of 5-lipoxygenase from bovine polymorphonuclear leukocytes and 12-lipoxygenase from bovine platelets by active oxygen species has been studied. Oxygen radicals and hydrogen peroxide markedly inhibited 12-lipoxygenase, whereas 5-lipoxygenase activity was only moderately influenced. Singlet oxygen liberated from water-soluble naphthalene endoperoxides was without effect.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1993

Demonstration of Borrelia burgdorferi infection in a child with Guillain-Barré syndrome.

A 4.5-year-old child suffered from rapidly evolving motor weakness with paresthesia and radicular pain in both legs, accompanied by an isolated elevation of protein levels in CSF. Isoelectric focusing revealed oligoclonal IgG produced in the cerebrospinal compartment only. The diagnosis of Guillain-Barré syndrome was confirmed by electrophysiological studies. High antibody titres against Borrelia burgdorferi in the serum and specific antibodies in the CSF were demonstrable by ELISA and immunoblotting. B. burgdorferi specific DNA fragments were demonstrated in urine and CSF by means of a nested polymerase chain reaction (PCR), thus providing the borrelial aetiology and indicating B. burgdorferi infection. Complete recovery was observed after treatment with high dose immunoglobulin and ceftriaxone and control urine specimens were PCR negative.

Antibodies, Bacterial↗
PubMed1993

An assessment of the in vitro hepatocyte micronucleus assay.

The in vitro hepatocyte micronucleus assay was tested for its practicability and its usefulness in detecting mutagens. The assay protocol developed by Alati et al. (1989) was shown to give reproducible levels of proliferating hepatocytes and the formation of micronuclei could be readily assessed by fluorescence microscopy. Epidermal growth factor and insulin were used as mitogens, yielding mitotic indices of 2.4 +/- 0.74% after 72 h of culture. The high number of 8.0 +/- 3.33% micronucleated hepatocytes in control cultures at that time, typically for in vitro stimulated hepatocytes, is probably due to disordered mitoses frequently leading to chromosome loss. The direct acting mutagen N-methyl-N'-nitro-N-nitrosoguanidine and the clastogens cyclophosphamide and retrorsine, which require metabolic activation, induced dose dependent increases in the frequencies of micronucleated hepatocytes. The carcinogen 2-AAF also yielded significantly enhanced rates of micronuclei. The non-mutagen KCl as well as the peroxisome proliferator clofibrate, which is considered to be a non-genotoxic hepatocarcinogen, yielded consistently negative results. Problems occurred when chemicals exerting strong cytotoxic effects were tested in this assay. The mutagen and hepatocarcinogen aflatoxin B1 did not enhance the number of micronucleated hepatocytes. Rather a reduction of micronuclei and of mitoses was observed at AFB1 concentrations considered positive in other genotoxicity assays. Hepatocyte proliferation seems to be highly susceptible to the cytotoxic action of chemicals. A decrease in the proliferating activity of hepatocytes can obviously prevent the detection of mutagenic effects. Further studies on the in vitro hepatocyte micronucleus assay are necessary to clarify its role in mutagenicity testing.

Animals↗
PubMed1993

1,25-dihydroxyvitamin D3 selectively reduces interleukin-2 levels and proliferation of human T cell lines in vitro.

1,25-Dihydroxyvitamin D3 (1,25-(OH)2D3) inhibits the proliferation of mitogen-stimulated human mononuclear cells (MNC) as well as the production of a number of proinflammatory cytokines, including interleukin (IL)-1 alpha, IL-6, tumour necrosis factor-alpha, IL-2, interferon-gamma (IFNg) and lymphotoxin (LT). These effects are most likely mediated via specific vitamin D receptors expressed by monocytes and activated T lymphocytes. In the present study we have evaluated the ability of 1,25-(OH)2D3 to affect proliferation and cytokine production by human T cell lines stimulated by anti-CD3 antibodies or anti-CD3 plus anti-CD28 antibodies. 1,25-(OH)2D3 selectively reduced the supernatant levels of IL-2, while the IFNg and LT levels were unaffected. This was followed by a time- and dose-dependent reduction in proliferation. Although the expression of high affinity IL-2 receptors (IL-2R) (p75) was unaffected, exogenously added IL-2 failed to restore proliferation. The study demonstrates that human T cell lines, in the absence of accessory cells, may be a direct target for 1,25-(OH)2D3, resulting in a specific reduction of IL-2 levels and inhibition of proliferation. The mechanism by which 1,25-(OH)2D3 inhibits proliferation most likely involves interference with activation signals at the IL-2R level or at a post IL-2R level.

Antibodies↗
PubMed1993

Mycobacterium hiberniae sp. nov.

Strains of a new type of slowly growing scotochromogenic, rose-pink-pigmented mycobacterium were isolated repeatedly from sphagnum vegetation, true moss, and soil in Ireland. These strains grew at 22, 31, and 37 degrees C but not at 45 degrees C and possessed acid phosphatase and arylsulfatase activities. They reduced nitrate, tolerated 0.1% NaNO2, did not split amides, and were resistant to most of the antituberculous drugs tested, except ethambutol. They did not form acid from glucose and mannose. Their internal phenetic similarity was 97.08% +/- 2.07%. The whole mycolate pattern confirmed the homogeneity of the taxa sharing similar mycolate types with several other mycobacterial species. However, on the basis of the nature of the major pyrolysis esters, the taxon appeared unique. The phylogenetic analysis based on evolutionary distance values revealed that the strains belong to a new species of slowly growing mycobacteria. The DNA-DNA hybridization values confirmed that these strains differ significantly from Mycobacterium nonchromogenicum, M. terrae, M. triviale, and M. thermoresistibile. The strains produced a unique rose-pink pigment and were nonpathogenic for mice, guinea pigs, and rabbits, but they provoked a nonspecific hypersensitivity reaction to bovine tuberculin in guinea pigs and cattle. Hence, they are considered a member of a new species of nonpathogenic slowly growing mycobacteria, for which the name Mycobacterium hiberniae is proposed. Strain Hi 11 is the type strain, a culture of which has been deposited in the American Type Culture Collection as strain ATCC 49874.

Bacterial Typing Techniques↗
PubMed1993

Cerebrospinal fluid and MRI findings in three patients with multiple sclerosis and systemic lupus erythematosus.

Three patients fulfilling the diagnostic criteria of both multiple sclerosis (MS) and systemic lupus erythematosus (SLE) were examined clinically, immunologically and by magnetic resonance imaging (MRI). In all three patients MRI showed several high-signal lesions compatible with MS and, additionally, non-specific small white matter lesions suggesting small vessel occlusion were seen. In CSF the cytoimmunological abnormalities were variable and showed only slight to moderate immunoactivation within the CNS at the time of sampling.

Adult↗
PubMed1993

IGF-I and pamidronate increase bone mineral density in ovariectomized adult rats.

Effects induced by insulin-like growth factor I (IGF-I) and/or the bisphosphonate pamidronate (APD) on bone mineral density (BMD) of the lumbar spine and proximal and midshaft tibia were studied in adult rats made osteopenic by ovariectomy, using dual-energy X-ray absorptiometry. IGF-I, which was administered by osmotic minipumps implanted subcutaneously for 6 wk, caused a dose-dependent increase of BMD at the three investigated sites. A 4-wk course of IGF-I, followed by intermittent cyclical APD administration, induced significant increases of BMD at the levels of spine and proximal tibia. At midshaft tibia, where cortical bone predominates, BMD was increased by IGF-I only. In conclusion, IGF-I increased BMD at sites with trabecular and/or cortical bone, whereas the APD influence was mainly detectable in the former site only.

Absorptiometry, Photon↗
PubMed1993

Trichlorobromomethane-induced changes of purine nucleotides in hepatocytes.

The changes in nucleotide content during CBrCl3 treatment were investigated. In the first 5-10 minutes a significant ATP decrease was detected. The GTP loss leading to 57% of the initial level after 10 min surpasses the ATP loss which leads to 70% of the initial value after 10 min. The increase in uric acid is not only the result of CBrCl3 induced reaction, because of no significant changes in adenine and hypoxanthine values. The uric acid pool reflected different influx and efflux processes. These changes were compared with nucleotide degradation and accumulation of nucleotide degradation products during anoxia.

Adenosine Triphosphate↗