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Biomedical subjects

F Müller

Publications and source records attributed to F Müller.

At least 181 records · Page 10Linked to original sources
PubMed1995

DNA polymerase delta holoenzyme: action on single-stranded DNA and on double-stranded DNA in the presence of replicative DNA helicases.

DNA polymerase delta requires proliferating cell nuclear antigen and replication factor C to form a holoenzyme efficient in DNA synthesis. We have analyzed three different aspects of calf thymus DNA polymerase delta holoenzyme: (i) analysis of pausing during DNA synthesis, (ii) replication of double-stranded DNA in the absence of additional factors, and (iii) replication of double-stranded DNA in the presence of the two known replicative DNA helicases from simian virus 40 and bovine papilloma virus. DNA polymerase delta holoenzyme replicated primed single-stranded DNA at a rate of 100-300 nucleotides/min, partially overcoming multiple pause sites on DNA. While Escherichia coli single-strand DNA binding protein helped DNA polymerase delta pass through pause sites, the DNA polymerase delta itself appeared to dissociate from the template in the absence of synthesis or when encountering pause sites. Proliferating cell nuclear antigen likely remained on the template. DNA polymerase delta holoenzyme could perform limited strand displacement synthesis on double-stranded gapped circular DNA, and this reaction was not stimulated either by replication protein A or by E. coli single-strand DNA binding protein. DNA polymerase delta holoenzyme could efficiently cooperate with replicative DNA helicases from simian virus 40 (large T antigen) and bovine papilloma virus 1 (protein E1) in replication through double-stranded DNA in a reaction that required replication protein A or E. coli single-strand DNA binding protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacteriophage T4↗
PubMed1995

[Can HIV infection be treated with antioxidants?].

Several recent reports have indicated high levels of reactive oxygen species, causing oxidative stress, in the pathogenesis of HIV infection. Oxidative stress may lead to enhanced HIV replication in infected cells and may also aggravate the immunodeficiency by reduction of cellular immunity and possibly by increased programmed cell death of lymphocytes. Moreover, reduced levels of antioxidants have been found in patients with HIV infection. This raises the question of whether antioxidant therapy might be beneficial in patients with HIV infection. Until now, only a few preliminary, clinical studies have been completed. Further clinical trials are needed to assess the possible role of antioxidants in the treatment of HIV infection.

Antioxidants↗
PubMed1995

1H-NMR microscopy of tablets.

A 1H-nuclear magnetic resonance (NMR) microscopy method was utilized for the first time to determine the porosity distribution of physically intact tablets. The main advantage of this newly developed method was that porosity cross sections through whole tablets or specific locations could be obtained without mechanically destroying the tested tablet. This was achieved by filling tablet cavities with silicone oil under vacuum. The amount of silicone oil locally within the tablet was then determined by 1H-NMR microscopy, revealing the inverse inner structure. To reduce the measuring time, a paramagnetic gadolinium complex was added to the silicone oil. The cross sectional signals produced by 1H-NMR microscopy through the tablet were transformed into a color image by a specially designed computer graphic program. To improve the signal-noise ratio an algorithm of 3D-filtering was introduced. The maximal spatial resolution achieved with this method was about 95 microns for a cube's edge length corresponding to some 380,000 positions in a 9-mm-diameter compression-coated tablet. Uneven porosity distributions within tablets, cracks, or cavities could be visualized with this newly developed method. Different compaction mechanisms were observed with plastic- or brittle-type tablets. The different states of densification during compaction of powders could be detected. The integrity of compression coatings was determined to be dependent on the pressure load and the location of the core within the coat.

Magnetic Resonance Imaging↗
PubMed1995

Reduced serum level of transforming growth factor-beta in patients with IgA deficiency.

Seventeen patients with IgA deficiency, 13 subjects with selective IgA deficiency and 4 with a combined IgA and IgG2 deficiency, were assessed for serum levels of cytokines relevant for B cell differentiation. Transforming growth factor (TGF)-beta was quantified by bioassay and interleukin (IL)-4, IL-6, and IL-7 by immunoassay. The serum levels of TGF-beta were significantly lower in patients with IgA deficiency than in healthy blood donors. Of the patients with IgA deficiency, 4 had detectable IL-4 levels while 4 of the others had detectable IL-6 levels in serum. IL-4 and IL-6 were not detected in the controls. Serum IL-7 levels were similar in patients and controls. A significant, negative correlation was found between serum TGF-beta and the number of circulating B lymphocytes in the patients with IgA deficiency. No association was found between serum cytokine levels and the occurrence of infections at the time of study. Since TGF-beta has been implicated in IgA isotype switching in man, and our study demonstrates an association between low serum TGF-beta levels and IgA deficiency, dysregulation of TGF-beta might be a contributing factor in the pathogenesis of IgA deficiency.

Adult↗
PubMed1995

The leucocyte protein L1 (calprotectin): a putative nonspecific defence factor at epithelial surfaces.

The L1 protein occurs at high concentrations in neutrophils, monocytes, certain reactive tissue macrophages, squamous mucosal epithelia, and reactive epidermis. It constitutes in fact about 60% of the neutrophilic cytosol protein fraction. The two L1 chains (L1H and L1L) are referred to by a bewildering collection of names, various authors having different preferences (MRP-8 and MRP-14; CFA or calgranulin A and B). The most recent proposal is calprotectin because of its calcium-binding properties and antimicrobial effect shown in vitro. L1 belongs to the S-100 protein family and may be involved in the regulation of keratinocyte proliferation and differentiation. It exists at high levels in blood and interstitial tissue fluid in several infectious, inflammatory, and malignant disorders, and it is released abundantly in foci of granulocytes and macrophages. The C-terminal sequence of the L1H chain has been shown to be identical to the N-terminus of peptides known as neutrophil immobilizing factors. Such an activity of L1 could be important for the accumulation of vital granulocytes, while L1 released from neutrophils, macrophages and epithelial cells might exert antimicrobial activity, perhaps by depriving microorganisms of zinc. The minimum inhibitory concentrations of L1 in vitro were found to be 4-32 mg/l for Candida albicans, 64 mg/l for Staphylococcus aureus, 64-256 mg/l for S. epidermidis, and 256 mg/ml for Escherichia coli and Klebsiella spp. Killing was observed at 2-4 times higher concentrations. In patients with HIV infection, those who developed oral candidiasis had significantly lower parotid L1 levels than those who did not (67 micrograms/l vs. 216 micrograms/l).

AIDS-Related Opportunistic Infections↗
PubMed1995

The effects of desipramine on thyroid hormone concentrations in rat brain.

The effects of the antidepressant desipramine on the tissue concentrations of thyroxine and triiodothyronine in 9 different regions of the brain and also in the pituitary and liver were investigated in male rats. The investigations were carried out at three different times of the light/dark cycle: 5 a.m., 1 p.m. and 11 p.m. After fourteen days' treatment with 20 mg/kg/day desipramine by gavage the concentrations of triiodothyronine in the frontal and parieto-occipital cortex were significantly higher than in the saline-treated controls, those in the hippocampus lower and those in the 6 remaining brain regions the same. In 8 areas of the brain the concentrations of thyroxine were lower in the desipramine-treated rats and the tissue ratios of triiodothyronine to thyroxine were enhanced in 6 regions. These effects are most likely the result of the action of desipramine on the activity of the isoenzyme 5'II deiodinase. This enzyme catalyzes the deiodination of thyroxine to triiodothyronine in rat brain and its activity has recently been reported to be enhanced by desipramine. The observed effects were dose-dependent and also strongly dependent upon the time within the 24 h light/dark cycle at which the hormone concentrations were measured. No effects of desipramine were seen in the pituitary or liver after 14 days' treatment, or in various areas of the central nervous system 24 h after administration. In view of the psychotropic properties of thyroid hormones, it seems possible that the observed increases in triiodothyronine concentrations, particularly in cortical areas, are involved in the mechanisms of action of desipramine.

Administration, Oral↗
PubMed1995

A 240 kDa protein represents the complete beta subunit of the cyclic nucleotide-gated channel from rod photoreceptor.

The cyclic nucleotide-gated channel from rod photoreceptors is composed of two distinct subunits (alpha and beta). The properties of the alpha subunit, which can form functional channels by itself, are modified by coexpression with a homologous polypeptide, designated the beta subunit. However, the alpha subunit from rod photoreceptor membranes copurifies with a 240 kDa protein that is significantly larger than this putative beta subunit. We now demonstrate by peptide sequencing and by cloning and functional expression of cDNA that the 240 kDa protein represents the complete beta subunit with an unusual bipartite structure. The N-terminal part is essentially identical to a glutamic acid-rich protein (GARP), whereas the C-terminal part is highly homologous to the previously cloned human "beta subunit." Expression of the complete beta subunit in HEK 293 cells results in a polypeptide with the same apparent molecular weight as the 240 kDa protein of the native rod channel. Coexpression of the alpha subunit with the full-length beta subunit yields hetero-oligomeric channels with properties characteristic of the native channel.

Amino Acid Sequence↗
PubMed1995

Bovine hereditary cardiomyopathy: an animal model of human dilated cardiomyopathy.

UNLABELLED: Bovine hereditary cardiomyopathy (bCMP) displays clinical characteristics of human idiopathic dilated cardiomyopathy (DCM). We studied isometric force of contraction in right ventricular trabeculae, plasma and tissue catecholamines, beta- and alpha 1-adrenoceptor density, Gi proteins and adenylyl cyclase activity in eight hearts with bCMP and eight control hearts (right and left atria and ventricles each). RESULTS: Compared to control, the potency of isoprenaline in bCMP was eight-fold decreased, whereas the maximal positive inotropic effect of isoprenaline as well as the efficacy and potency of calcium were unchanged. Plasma noradrenaline was increased by 240%. Tissue noradrenaline and adrenaline were decreased by 36-63% and 58-69%, whereas dopamine was increased by 105-218%. beta-adrenoceptor density was drastically reduced by 90%, but binding affinity was unchanged. alpha-Adrenoceptor density and binding affinity were unchanged. Total PTX-substrates were increased in bCMP by 28-99%. Basal adenylyl cyclase activity was decreased by 36-47%. Similarly, stimulation by GTP, GMPPNP, isoprenaline, sodium fluoride, manganese or forskolin was attenuated by 26-62% (atria) and 45-66% (ventricles). In conclusion, we found marked activation of the sympatho-adrenergic system, downregulation of beta-adrenoceptors, upregulation of Gi proteins, global desensitization of adenylyl cyclase and selective subsensitivity to beta-adrenergic inotropic stimulation. These results closely resemble the characteristic alterations in the beta-adrenoceptor-G protein-adenylyl cyclase pathway in human heart failure, indicating that they are general features of heart failure. The similarity to human DCM, the inheritance and the availability of large tissue samples make bCMP a suitable model for human DCM.

Adenylate Cyclase Toxin↗
PubMed1995

Studies on adaptation to complete dentures. Part II: Oral stereognosis and tactile sensibility.

High oral perception is thought to contribute to poor adaptation to new dentures. The aim of this study was to evaluate the oral stereognosis and tactile sensibility in edentate subjects and relate these to patient age and capability of adaptation to new prostheses. A total of 67 patients were provided with new complete dentures 2-3 weeks before the experiment. In 54 subjects, the oral stereognosis was evaluated by 12 different test-pieces, which were placed unseen on the tongue and had to be recognized. In 38 patients, the oral tactile sensibility was determined in the premolar area using copper foils. The capability of adaptation was evaluated by a questionnaire. Denture retention was assessed by clinical examination. The number of correctly identified test-pieces and the average identification time were related to the age, but no relation was found to patients' capability of adaptation. The tactile sensibility was found to be impaired with age and diminished capability of adaptation. Both adaptation and oral tactile sensibility were significantly lower in subjects with poor lower-denture retention. In conclusion, the results cannot support a relationship between high oral stereognosis and adaptation problems. However, good denture retention facilitates the adaptation process.

Adaptation, Psychological↗
PubMed1995

Comparative studies on check-bite and central-bearing-point method for the remounting of complete dentures.

Thirty-six complete dentures were remounted both with check-bite as well as central-bearing-point (CBP) registration. The mandibular or denture position was registered in the condylar area three times with each method. Two independent operators carried out the registrations. One half of patients had their occlusion equilibrated according to the check-bite registration, the other half in the central-bearing-point position. After individual determination of the hinge axis the upper dentures were mounted by a face-bow transfer into a Dentatus articulator. A total of six registrations was performed and repeatedly compared in the condylar area in three dimensions using a computer supported measuring device. The reproducibility of the check-bite registration was 0.37 +/- 0.33 mm, with a maximum of 1.77 mm. For the central-bearing-point method this was 0.29 +/- 0.26 mm with a maximum of 1.56 mm. The mean difference in condylar position between both methods was 0.66 +/- 0.55 mm with a maximum of 4.02 mm. A third independent operator re-examined 30 of the patients 2-3 weeks after the remounting and evaluated the adaptation to the new dentures. Those patients whose dentures were equilibrated with the central-bearing-point method tended to cope better with their dentures and suffered on average from fewer pressure spots.

Adaptation, Physiological↗
PubMed1995

Studies on adaptation to complete dentures. Part I: Oral and manual motor ability.

The assessment of an edentate patient's ability to adapt to new dentures is still a problem in prosthetic treatment. In this study the oral and manual motor abilities were compared with a patient's ability to adapt in 60 experienced denture wearers who had new dentures inserted 2-3 weeks before the experiment. To assess the oral muscular co-ordination ability a modification of the muscular ability (MA) test was used. To determine the manual motor ability a 'pinhole-board' test and a 'margin-cutting' test were employed. The degree of adaptation to the new dentures was assessed by a questionnaire. The results show that a patient's age only roughly indicates the capability of adaptation. In contrast to the manual motor ability, the oral motor ability seems to correlate to the patient's adaptation to new dentures (r = 0.55). The manual motor ability was clearly more strongly (r = 0.61) age-related than the oral motor ability (r = 0.33). The permanent altered oral perception through denture wearing and a training effect by the permanent challenge of intra-oral denture management are discussed.

Adaptation, Physiological↗
PubMed1995

Long-term lipid-based total parenteral nutrition activates mononuclear cells and modulates membrane lipid composition in pigs.

In previous studies we have found lung granulomas in pigs on long-term soybean-based total parenteral nutrition (TPN). In the present study we have investigated activities and membrane lipids of cells known to participate in a granulomatous process. Pigs were given TPN with soybean emulsion for 7 weeks, controls were given saline intravenously and consumed a similar caloric load in a standard oral diet. Spontaneous nitroblue tetrazolium (NBT) reduction increased 204% in peripheral blood mononuclear cells (MNC) from TPN animals compared to controls (p < 0.05), and 161% (p = 0.05) in alveolar macrophages. The spontaneous lymphocyte mitogen response (LMR) rate in MNC increased 299% (p < 0.05). Endotoxin-stimulated procoagulant activity in MNC tended to increase in TPN animals. Acid phosphatase and lysozyme production in alveolar macrophages were not significantly changed. The serum neopterin level at the end of the observation was 7.0 nmol l-1 in TPN animals compared to 3.9 nmol l-1 in controls (p < 0.01), while interleukin-1 and tumour necrosis factor were not detectable. These findings indicated in vivo activation of peripheral blood monocytes, lymphocytes and alveolar macrophages in pigs on TPN. The membrane lipid contents of linoleic acid (18:2, n-6) increased, while arachidonic acid (20:4, n-6) tended to decrease both in MNC and lung tissue. Thus, linoleic acid conversion did not lead to accumulation of arachidonate in the cell membranes. Direct effects on monocytes, lymphocytes and alveolar macrophages of TPN particles, and altered cell membrane function, due to linoleic acid enrichment, are tentative explanations for the raised cell responses. Such cell activation may have contributed to the formation of granulomas.

Acid Phosphatase↗
PubMed1995

[Possibilities and limits of a new color technique: ultrasound angiography--results of the "Heidelberg Round Table Discussion"].

Sonographic diagnostics has been essentially enlarged by blood flow measurements with the color Doppler technique. Nevertheless, the method has certain limitations, especially when employed to visualize extremely slow blood flow velocities, which occur e.g. in malignant tumors due to neovascularization. Recently, a new technique, the so-called angio-color procedure, has been presented, which is supposed to overcome the above-mentioned limitations. The way of coding the signal differs considerably from that in conventional color Doppler: The amplitude is color coded, not the frequency deviations. Results and first experiences with the new procedure in various domains were discussed at a 'Heidelberg Round Table' and are summarized in the present article. In the obstetrics/gynecology there are clear advantages in the representation of blood flow in the placenta. In eutrophic fetuses a blood flow over the entire placental breadth was detected, in dystrophic fetuses, however, only on the margins of the placenta. Conventional color Doppler could not visualize blood flow in the placenta at all. Blood flow assessment in the fetal organs also provided different results with the two procedures: the angio-color method showed color pixels even in the peripheral areas. In 8 malignant breast tumors the same observation was made, the angio-color procedure seemed to visualize more color pixels. In 4 of 6 benign lesions blood flow could be measured with the traditional color Doppler, but in 5 of 6 patients with the angio-color Doppler. This was also observed in ovarian tumors. Angio-color representation of renal transplants with normal function resulted in blood flow information reaching deep into the renal capsule, whereas in cases of renal transplants with impaired function a clearly reduced perfusion was visualized. These differences were not so evident with the conventional Doppler method. In lymph node diagnosis, too, marked differences between malignant and reactive lymph nodes could be visualized. In the diagnosis of arteriosclerotic plaques, blood flow in the residual lumen could also be detected more exactly with the angio-color technique. Color representation of liver tumors also showed a higher color signal density with ultrasound angiography. In summary, ultrasound angiography can provide additional information in the color representation of vessels with slow flow velocities. However, an obvious problem is the unability to quantify detected low blood flow. The new procedure will not replace but usefully complete the established sonographic techniques.

Arteriosclerosis↗
PubMed1994

Tas, a retrotransposon from the parasitic nematode Ascaris lumbricoides.

The cloned retrotransposon Tas OE3 from the genome of the parasitic nematode Ascaris lumbricoides was completely sequenced. The element is flanked by long terminal repeats (LTR) and contains three distinct regions encoding putative proteins typical for retroid elements. The first region, ORF1, encodes a putative Gag protein including a 'Leu zipper', a nucleic acid binding motif, as well as an aspartic protease domain. The second region contains an incomplete ORF (ORF2) with sequence similarities to known retroviral reverse transcriptases (RT), ribonucleases H and integrases. A third ORF, which is located adjacent to the 3' LTR, might encode an env-like protein. Based on amino-acid sequence analysis of the RT domain, Tas falls into a new subgroup of LTR-containing retrotransposons.

Amino Acid Sequence↗
PubMed1994

Caenorhabditis elegans unc-51 gene required for axonal elongation encodes a novel serine/threonine kinase.

Mutations in the unc-51 gene of the nematode Caenorhabditis elegans result in various abnormalities in axonal elongation and axonal structures. We cloned the unc-51 gene by tagging with the transposon Tc1. The wild-type unc-51 gene, which rescued the mutant phenotypes, encodes a novel serine/threonine kinase of 856 amino acids. Mutation sites were identified in the unc-51 gene of six mutants. A Lys-->Met mutation created in vitro in the kinase domain led to the loss of rescuing activity and was dominant negative, indicating that the kinase domain of Unc-51 is essential for the function. Expression of an unc-51/lacZ fusion gene was observed in many neurons at all stages. We propose that protein phosphorylation by the unc-51 product is important for axonal elongation and possibly for axonal guidance.

Alleles↗
PubMed1994

Release of cytokines, soluble cytokine receptors, and interleukin-1 receptor antagonist after intravenous immunoglobulin administration in vivo.

We investigated the in vivo effects of one bolus injection (400 mg/kg) of intravenous immunoglobulin (IVIG) on a number of cytokines, soluble cytokine receptors, and interleukin-1 receptor antagonist (IL-1Ra) in plasma in 12 patients with primary hypogammaglobulinemia. A significant and rapid increase in plasma levels of IL-6, IL-8, and tumor necrosis factor alpha (TNF alpha) was seen within 1 hour after IVIG infusion. This increase was accompanied by a more prolonged elevation in levels of both types of soluble TNF receptors (sTNFRs), which remained elevated throughout the study period (44 hours) although they reached peak levels within 1 hour. After an initial increase in the ratio between TNF alpha and sTNFRs, this ratio decreased to values significantly lower than baseline values 20 and 44 hours postinfusion with approximately 600-fold molar excess of sTNFRs to TNF alpha (trimer). Although only a modest but statistically significant increase in plasma levels of IL-1 beta was seen, IVIG infusion was followed by a marked increase in plasma levels of IL-1Ra with 1,000-fold molar excess of IL-1Ra to IL-1 beta in some patients. The demonstrated effects of IVIG infusion on the cytokine network, particularly the induction of IL-1Ra and sTNFRs release, might be important for the therapeutic effects of IVIG in several immune-mediated disorders.

Adult↗