Evaluation of the measurement of lysate homocysteine in patients with symptomatic arterial disease and in healthy volunteers.
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Adolescent↗
Biomedical subjects
B Müller
Publications and source records attributed to B Müller.
Immunohistological analysis of cytokine expression in human osteoarthritic and healthy cartilage.
OBJECTIVE: To investigate osteoarthritic cartilage in comparison to normal cartilage in humans for the presence of the most relevant cytokines/growth factors known to be important for degradation and formation of new cartilage. METHODS: Cartilage from knee or hip joints was obtained from 10 patients with osteoarthritis (OA) and from 7 age matched control patients with intact cartilage. Additionally, normal cartilage from 2 young patients (12 and 17 years old) was obtained after knee traumas. Immunohistological staining of cartilage sections was performed using antibodies for the following cytokines/growth factors: tumor necrosis factor alpha (TNF-alpha), interleukin 1alpha (IL-1alpha), IL-1beta, interferon-gamma, IL-6, IL-4, IL-10, transforming growth factor beta1 (TGF-beta1), insulin-like growth factor I (IGF-I), IGF-II, platelet derived growth factor AA (PDGF-AA), and PDGF-BB. RESULTS: Immunohistochemical stainings were positive for all cytokines in OA cartilage, while only a faint or no staining was found in healthy cartilage. Activated chondrocytes expressing most of the cytokines were located in the middle and partly in the lower layer of cartilage, with the exception of IGF-I, which was expressed exclusively in the upper cartilage layer close to the surface. More chondrocytes stained positive for TNF-alpha than for IL-1, and expression of the degrading cytokine TNF-alpha was inversely correlated to the expression of the regulatory cytokines IL-4, IL-10, and TGF-beta. CONCLUSION: The most relevant cytokines known to be involved in cartilage metabolism are produced by chondrocytes themselves. They are upregulated in OA cartilage, suggesting that they serve some regulatory function and could be a target for future treatment.
Adolescent↗
Different cumulative pregnancy rates in patients with repeated IVF- or ICSI cycles: possible influence of a male factor.
The low rate of ongoing pregnancies in IVF cycles leads to a high number of repeated cycles in couples with previously failed attempts. Therefore it would be helpful to have a prediction about the chance of becoming pregnant in a repeated cycle. In a retrospective study the data of about 4246 cycles were analysed. Because the pregnancy rates in IVF- and ICSI cycles are generally different, these two groups were distinguished between and the outcome in patients with one, two or more attempts was analysed. The rate of ongoing pregnancies per patient was lower after IVF (24.9%) than after ICSI (32.9%), but was similar or even slightly increased in patients with more than one attempt. On the other hand, there was a high pregnancy rate with ICSI in the first two cycles (35.9%), but patients with more than two ICSI cycles had a significantly lower chance of becoming pregnant (20.7%). Factors that are known to influence the pregnancy rate, such as stimulation protocol, oocyte quality or number of transferred embryos, were similar in all groups. However, significantly reduced embryo quality with successive cycles was only observed in ICSI patients. There might be a negative selection of patients with poor embryo quality and previously failed attempts after ICSI, possibly due to an andrological factor. The differences between IVF- and ICSI patients are based on treatment indications, and andrological diseases are the predominant indication for ICSI. Although no correlation was found between changes in conventional sperm parameters and number of treated cycles, there might be a subgroup of andrological patients selected by repeatedly failed ICSI cycles. Chromosomal or genetic disturbances in spermatozoa of this subgroup could be the reason for failure.
Adult↗
[Treatment with Kava--the root to ocombat stress].
Kava-kava (Piper methysticum), a shrub which grows on the islands of the Pacific Ocean, contains the so-called kavapyrones as active substances; these have been pharmacologically investigated in detail and are comparable with the benzodiazepine tranquilizers with regard to their mode and strength of action. The good tolerance and absence of both the soporific effect and risk of dependence should be emphasized. The present article describes the origin and history of the kava plant as well as its pharmacology, action, possibilities for therapeutic use, and significance in medical practice. Also discussed are the advantages of the standardized kavapyrone complex of active substances as a modern phyto-anxiolytic and daily tranquilizer for nervous anxiety, tension, and agitation states.
Anti-Anxiety Agents↗
Reduction of the bacterial load by the silver-coated endotracheal tube (SCET), a laboratory investigation.
Microaspiration enabled by high-volume-low-pressure cuffed endotracheal tubes is the most likely explanation for ventilator-associated pneumonia. To decontaminate the secretion at the proximal end of the cuff we developed a silver-coated endotracheal tube (SCET). In an in vitro model we investigated the efficacy of SCET to lower the bacterial load of secretion and aspirate. We developed a continuously contaminated and mechanically ventilated oropharynx-larynx-lung model to investigate the reduction of the bacterial count by SCET compared to controls. The model was continuously contaminated via the oropharynx-larynx with Pseudomonas aeruginosa ATCC 27853. During the investigation period of 50 hours the bacterial count of oropharynx-larynx and lung was measured as colony-forming-units/ml. In addition, the characteristic curve of silver ion release of SCET was determined. SCET significantly reduced the bacterial count in oropharynx-larynx at all timepoints (p < 0.05). In lung the bacterial count was significantly lower beginning with the 36th hour of recording (p < 0.05). A reduction of greater than 2 log was found from 28 hours on in oropharynx-larynx and from 50 hours on in lung. The release of silver ions was very rapid and was described by a mono-exponential function with a time-constant tau of about 60 minutes and a saturation concentration of 200 +/- 80 microg/l. SCET showed a significant inhibition of growth of P. aeruginosa in the continuously contaminated and mechanically ventilated oropharynx-larynx-lung model. SCET by thus might be helpful in reducing ventilator-associated pneumonia.
Bacterial Infections↗
Assembly of the D1 precursor in monomeric photosystem II reaction center precomplexes precedes chlorophyll a-triggered accumulation of reaction center II in barley etioplasts.
Assembly of plastid-encoded chlorophyll binding proteins of photosystem II (PSII) was studied in etiolated barley seedlings and isolated etioplasts and either the absence or presence of de novo chlorophyll synthesis. De novo assembly of reaction center complexes in etioplasts was characterized by immunological analysis of protein complexes solubilized from inner etioplast membranes and separated in sucrose density gradients. Previously characterized membrane protein complexes from chloroplasts were utilized as molecular mass standards for sucrose density gradient separation analysis. In etiolated seedlings, induction of chlorophyll a synthesis resulted in the accumulation of D1 in a dimeric PSII reaction center (RCII) complex. In isolated etioplasts, de novo chlorophyll a synthesis directed accumulation of D1 precursor in a monomeric RCII precomplex that also included D2 and cytochrome b(559). Chlorophyll a synthesis that was chemically prolonged in darkness neither increased the yield of RCII monomers nor directed assembly of RCII dimers in etioplasts. We therefore conclude that in etioplasts, assembly of the D1 precursor in monomeric RCII precomplexes precedes chlorophyll a-triggered accumulation of reaction center monomers.
Chlorophyll↗
[Comment on: Burchert A, Schmassman A. Evaluation of various screening and surveillance strategies in colorectal carcinoma].
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Acromegaly↗
Differential expression of major histocompatibility complex class II genes on murine macrophages associated with T cell cytokine profile and protective/suppressive effects.
Protective/suppressive major histocompatibility complex (MHC) class II alleles have been identified in humans and mice where they exert a disease-protective and immunosuppressive effect. Various modes of action have been proposed, among them differential expression of MHC class II genes in different types of antigen-presenting cells impacting on the T helper type 1 (Th1)-Th2 balance. To test this possibility, the expression of H-2 molecules from the four haplotypes H-2(b), H-2(d), H-2(k), and H-2(q) was determined on bone marrow-derived macrophages (BMDMs) and splenic B cells. The I-Ab and I-Ek molecules, both well characterized as protective/suppressive, are expressed at a high level on almost all CD11b+ BMDMs for 5-8 days, after which expression slowly declines. In contrast, I-Ad, I-Ak, and I-Aq expression is lower, peaks over a shorter period, and declines more rapidly. No differential expression could be detected on B cells. In addition, the differential MHC class II expression found on macrophages skews the cytokine response of T cells as shown by an in vitro restimulation assay with BMDMs as antigen-presenting cells. The results indicate that macrophages of the protective/suppressive haplotypes express MHC class II molecules at a high level and exert Th1 bias, whereas low-level expression favors a Th2 response. We suggest that the extent of expression of the class II gene gates the back signal from T cells and in this way controls the activity of macrophages. This effect mediated by polymorphic nonexon segments of MHC class II genes may play a role in determining disease susceptibility in humans and mice.
Animals↗
Synthesis, anticonvulsant activity, and structure-activity relationships of sodium channel blocking 3-aminopyrroles.
Starting from the corresponding acetophenone and glycine derivatives, a series of new 3-aminopyrroles was synthesized in few steps. Using this procedure with hydrazine and hydroxylamine instead of the glycinates provides access to 3-aminopyrazoles and 5-amino 1,2-oxazoles. The various derivatives were tested for anticonvulsant activity in a variety of test models. Several compounds exhibit considerable activity with a remarkable lack of neurotoxicity. 4-(4-Bromophenyl)-3-morpholinopyrrole-2-carboxylic acid methyl ester, 3, proved to be the most active compound. It was protective in the maximal electroshock seizure (MES) test in rats with an oral ED50 of 2.5 mg/kg with no neurotoxicity noted at doses up to 500 mg/kg. Compound 3 blocks sodium channels in a frequency-dependent manner. The essential structural features which could be responsible for an interaction with an active site of the voltage-dependent sodium channel are established within a suggested pharmacophore model.
Animals↗
Modulating the Th1/Th2 balance in inflammatory arthritis.
The balance between Th1 and Th2 cells regulates the choice between inflammatory and antibody-mediated immune responses. To an increasing extent this balance is thought to involve the participation of antigen-presenting cells, rather than the entirely autonomous activity of T cells and their cytokines. Here we survey current opinion concerning the working of this balance, and its condition in rheumatoid arthritis and the other inflammatory arthritides. The contrast between Lyme arthritis and reactive arthritis is particularly illuminating, since one is triggered by extracellular and the other by intracellular infection. We describe current approaches to the modulation of this balance. Guided by the principles that genetic polymorphism is likely to identify relevant genes, that any cytokine gene picked up by a virus must matter and that natural immunosuppressive activity at mucosal surfaces should be worth exploiting, we identify as particularly worthy of attention: (i) IL-10, (ii) inhibitors of IL-12 production, (iii) inhibitors of CD40 ligand expression and (iv) oral and nasal tolerance. Other protective T cell subsets are touched on, and the impact of oligonucleotide arrays mentioned.
Animals↗
Net efflux of citrate in Penicillium simplicissimum is mediated by a transport protein.
Penicillium simplicissimum excreted citrate, isocitrate, and succinate when grown in a strongly buffered medium [1 M Mes (pH 6) or 1 M Hepes (pH 7.3)]. Growth in a weakly buffered medium did not lead to citrate excretion despite a similar intracellular citrate concentration. When nongrowing, citrate-excreting hyphae were aerated in a glucose solution, the following steady-state intracellular concentrations of organic acids were measured: succinate (25 mM); citrate, isocitrate, malate, and fumarate (all less than 5 mM). After 2 h of incubation, the extracellular concentrations of these acids were [micromol (g dry wt.)-1]: isocitrate [100], citrate [60], succinate [30], and malate, fumarate, and alpha-ketoglutarate [<5]. The excretion of citrate was due neither to an unspecific change in the permeability of the plasma membrane nor to simple diffusion of undissociated citric acid. The involvement of a transport protein in citrate excretion was indicated because N-ethylmaleimide and sodium azide inhibited citrate excretion strongly despite an unchanged outward-directed citrate gradient. Arguments are given why efflux via a citrate uptake carrier is not considered probable. These results indicate that citrate is excreted by P. simplicissimum via a transport protein that probably specifically mediates the efflux of citrate.
Azides↗
A comparison of psychological and pharmacological treatment of pediatric migraine.
A comparison was carried out of the efficacy of psychological and drug treatments for children with migraine. Forty-three children aged between 8 and 16 years (mean age: 11.3 years) who suffered from migraine received either progressive relaxation or cephalic vasomotor feedback, both with stress management training, or metoprolol, a beta-blocker. Psychological treatment was administered in ten sessions lasting six weeks and the drug treatment lasted ten weeks. Relaxation and stress management training reduced the headache index (frequency x intensity of headache episodes), more effectively than metoprolol with cephalic vasomotor feedback and stress management training in between. An overall improvement over time was found with regard to frequency and intensity of headache episodes and analgesics intake. When comparing pre- to post-treatment data, children treated with relaxation training improved significantly in headache frequency and intensity, whereas those treated with cephalic vasomotor feedback improved significantly in headache frequency and duration as well as mood. The clinical improvement was stable at an 8-months follow-up.
Adolescent↗
The spatial distribution of pulmonary lesions in severe ARDS. An autopsy study of 35 cases.
The present study was undertaken in order to describe the local distribution and temporal course of pulmonary lesions in severe ARDS. We investigated a total of 35 patients (22 females), ranging in age from 2 to 51 years, who suffered from ARDS III and IV and were treated by extracorporeal CO2 removal and low frequency positive pressure ventilation (ECCO2-R). The extent of acute and chronic diffuse alveolar damage was assessed on histologic gross sections in the ventral, central and dorsal zone of the upper and lower lobes. The lesions showed a characteristic uniform distribution. Areas with chronic DAD were predominantly situated in the ventral portions of the upper lobes. Acute DAD predominated in the dorsal and basal areas of the lung. The extent of acute and chronic DAD was virtually independent of the duration of disease. Hemorrhage occurred at the interface zone between chronic and acute DAD and made up a significant volume portion of the lung tissue, ranging between 8% (lower lobes) and 42% (upper lobes). We conclude that the progression of acute DAD to chronic DAD is mainly determined by local factors (hydrodynamic and hydrostatic forces, intraalveolar pressure) that differ within the lung, whereas the duration of disease plays a minor role. Parenchymal hemorrhage occurs at the interface between areas of acute and chronic DAD and may therefore primarily be due to an increased susceptibility of the pulmonary parenchyma to mechanical stress.
Adolescent↗
A 5'-3' exonuclease activity involved in forming the 3' products of histone pre-mRNA processing in vitro.
Histone RNA 3' processing in vitro produces one or more 5' cleavage products corresponding to the mature histone mRNA 3' end, and a group of 3' cleavage products whose 5' ends are mostly located several nucleotides downstream of the mRNA 3' end. The formation of these 3' products is coupled to the formation of 5' products and dependent on the U7 snRNP and a heat-labile processing factor. These short 3' products therefore are a true and general feature of the processing reaction. Identical 3' products are also formed from a model RNA containing all spacer nucleotides downstream of the mature mRNA 3' end, but no sequences from the mature mRNA. Again, this reaction is dependent on both the U7 snRNP and a heat-labile factor. Unlike the processing with a full-length histone pre-mRNA, this reaction produces only 3' but no 5' fragments. In addition, product formation is inhibited by addition of cap structures at the model RNA 5' end, indicating that product formation occurs by 5'-3' exonucleolytic degradation. This degradation of a model 3' product by a 5'-3' exonuclease suggests a mechanism for the release of the U7 snRNP after processing by shortening the cut-off histone spacer sequences base paired to U7 RNA.
Animals↗
New sialyltransferase inhibitors based on CMP-quinic acid: development of a new sialyltransferase assay.
Quinic acid (4) was transformed into phosphitamides 6, 14, and 15, which could be readily linked to 5'-O-unprotected cytidine derivative 7; ensuing oxidation of the obtained phosphite triesters with tert-butylhydroperoxide furnished the corresponding phosphate triesters 8, 16, and 17, respectively. Hydrogenolytic debenzylation of the phosphate moiety, base catalysed removal of acetyl protective groups, and basic hydrolysis of the methylester of the quinic acid moiety furnished CMP-Neu5Ac analogues 1-3. In order to measure their inhibition of sialyltransferases, a nonradioactive sialyltransferase assay [employed for alpha(2-6)-sialyltransferase from rat liver (EC 2.4.99.1)] based on reversed-phase HPLC separation of UV-labelled acceptor 20 (p-nitrophenyl glycoside of N-acetyllactosamine) from the UV-labelled product 21 (p-nitrophenyl glycoside of sialyl alpha(2-6')-N-acetyllactosamine) and p-nitrophenylalanine as internal standard was developed. The assay reproduced the reported K(M) values for CMP-Neu5Ac and N-acetyllactosamine and the Ki values for CDP. 1 and 2 turned out to be potent sialyltransferase inhibitors.
Animals↗
Effect of air pollutants on the pulmonary surfactant system.
Air pollutants have been recognized to influence the structure and function of the surfactant system. Agents that have received the most attention include ozone, nitrogen dioxide, hyperoxia, diesel exhaust, tobacco smoke, silica and fibrous materials such as asbestos. The deleterious effects of air pollutants on the surfactant system depend on the size of the agent, on its solubility in aqueous solutions and chemical reactivity and on its concentration and the duration of exposure. Hereby the following general rules apply: the smaller the agent's size and the less water soluble the pollutant is, the greater the tendency to reach the alveoli during breathing. In addition, the reactivity also determines the depth of penetration into alveoli. Compounds with high reactivity such as O3, which also fulfil the earlier rules, will react with the upper respiratory tract compared with compounds with slightly reduced reactivity, such as NO2, which will penetrate the alveoli. The common consequence of exposure to air pollutants is an accumulation of surfactant phospholipids and surfactant-specific proteins in the bronchoalveolar lavage fluid. These components also are structurally altered, mainly by oxidant gases, resulting in impairment of their biological activity. Thus, for surfactant phospholipids, there is impaired adsorption to the air-liquid interface due to oxidation of their fatty acids. Also, surfactant protein A, regarded as a modulator of the surfactant system, shows impaired functions after exposure to oxidants. It is likely that in addition to the effects described in this review not all effects are known because the molecular effects of several key components (e.g. SP-B and C) have not been well studied.
Air Pollutants↗
NAD(P)H oxidase activity in cultured human podocytes: effects of adenosine triphosphate.
Reactive oxygen species contribute to glomerular damage and proteinuria. In this study, we show that cultured human podocytes produce superoxide in response to extracellular adenosine triphosphate (ATP), and we identified the oxidases involved in this process. Adenosine triphosphate (10-4 M for 4 hr) raised superoxide production from 1.28 +/- 0.15 to 2.67 &/- 0.34 nmol/mg protein/min. Studies with podocyte homogenates revealed activation of both nicotinamide adenine dinucleotide (NADH; from 2.65 +/- 0.23 to 7.43 +/- 0.57) and nicotinamide adenine dinucleotide phosphate (NADPH) dependent oxidases [from 1.74 +/- 0.13 to 4.05 +/- 0.12 (nmol O2/mg protein/min)] by ATP. Activity of xanthine-oxidases was low and unchanged by ATP. Activation of the plasma-membrane bound NAD(P)H oxidases by ATP was time and dose dependent. Reverse transcribed-polymerase chain reaction (RT-PCR) studies with primers derived from monocyte sequences amplified mRNA for the NADPH oxidase subunits p22phox, p47phox, gp91phox, and p67phox, and the latter was transiently increased by ATP. Experiments with actinomycin D and cycloheximide suggested that ATP modulates enzyme activity at the transcriptional and translational levels. In conclusion, NAD(P)H dependent, membrane associated oxidases represent the major superoxide source in human podocytes. Activation of NAD(P)H oxidase by ATP might be secondary to increased mRNA expression of the NADPH oxidase subunit gp67phox.
Adenosine Triphosphate↗
Persistence of human herpesvirus 7 in normal tissues detected by expression of a structural antigen.
Human herpesvirus 7 (HHV-7) infection in histologically normal human tissues was investigated by immunohistochemical detection of the 85-kDa tegument phosphoprotein (pp85) encoded by the U14 gene. So far, two cell types were recognized as sites of HHV-7 infection in vivo: CD4+ T lymphocytes, believed to be the site of latent infection, and epithelial cells of salivary glands, the site of productive infection and viral shedding. Unexpectedly, cells expressing the HHV-7 structural antigen were detectable in lungs, skin, and mammary glands. Morphologically and phenotypically, they were distinct from lymphocytes. Liver, kidney, and tonsils were positive, although the number of HHV-7-positive cells was low. Large intestine, spleen, and brain were negative. Different from the current notion of the state of HHV-7 in humans, the results show that a variety of tissues harbor cells at a late stage of infection and suggest that HHV-7 causes a persistent rather than a true latent infection.
Antigens, Viral↗