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Biomedical subjects

M Roth

Publications and source records attributed to M Roth.

At least 73 records · Page 4Linked to original sources
PubMed2000

Optomotor and neuropsychological performance in old age.

While a delayed initiation of visually guided saccades with increasing age has been documented in a number of studies, little research has been done on the control of antisaccades. The present study investigates aging effects on the control of visually guided saccades (prosaccades) and antisaccades as well as a selection of neuropsychological functions by the cross-sectional comparison of 14, 22, and 16 participants aged 20-35 years, 59-73 years, and 74-88 years, respectively. The geriatric and neurological status of the elder participants (including evidence from computed tomography, electroencephalography, and neurological soft signs) was assessed. In four task blocks of 200 trials each, pro- and antisaccades were elicited under the 200-ms-gap and overlap conditions. Left- and right-sided stimuli were presented in random order at 4 degrees, and the order of the task blocks was varied within each age group. In addition, the Wisconsin card-sorting test (WCST) and working memory, go-nogo discrimination, alertness, and stimulus-response incompatibility tests were administered. Participants aged 59-73 years exhibited widespread reductions of optomotor and neuropsychological performance, with greatest effect sizes of age differences in the optomotor parameters and the WCST measures. A further decay after the age of 73 years was discernible in those optomotor functions reflecting saccade disinhibition (in particular, directional errors during the antisaccade task and premature responses) and the performance in some neuropsychological tests. In line with previously published reports, variance in optomotor performance could be explained by two factors, accounting for a total of 76% of the age variance. Our results suggest that the investigation of saccade control may be a highly sensitive tool for neurodevelopmental aging research.

Adult↗
PubMed2000

[Symptomatic true aneurysm of a venous bypass with compression of the right atrium].

A symptomatic true aneurysm of a saphenous vein graft to the right coronary artery in a female patient twelve years after bypass surgery is presented. Beating heart surgery included resection of the aneurysmatic saphenous vein graft, reconstruction of the right atrium and coronary artery bypass grafting to the right coronary artery. The symptoms of aneurysms of vein grafts, the diagnostic procedures and the surgical treatment are discussed.

Aged↗
PubMed2000

Do patients want minimally invasive aortic valve replacement?

OBJECTIVE: Access to aortic valve can be performed through small incisions. However, a considerable advantage of this approach has not been proven by randomized studies so far. We wanted to elucidate the opinion of patients when they are informed objectively about advantages and disadvantages of minimally invasive approach prior to operation. METHODS: This prospective study was performed with 27 patients undergoing isolated aortic valve replacement. These patients were informed prior to operation by the same resident concerning objective data. A photograph was shown illustrating a patient with postoperative wound after a standard- and a mini-incision, respectively. After the interview the patient could decide between full and partial sternotomy. RESULTS: After the interview 21/27 (78%) patients preferred to have a full sternotomy (group F) and 6/27 (22%) patients (group P) decided to have a partial sternotomy. Comments of group F: surgeon should have best exposure (n=15); cosmetics aspects unimportant (n=14); operation time as short as possible (n=7). Group P: cosmetic aspects important (n=6). Significant differences between groups (group F vs. group P): age (years), 69.1+/-1.5 vs. 49.2+/-7.3 (P=0.024); operation time (min), 142+/-7 vs. 189+/-15 (P=0.002); CK (IU/l), 111+/-11 vs. 374+/-114 (P=0.0007); CKMB (IU/l), 17+/-2 vs. 45+/-17 (P=0.006); ICU-stay (days), 2.6+/-0.2 vs. 3.2+/-0.2 (P=0.044). Pericardial effusion requiring drainage was observed in two patients of group P. One patient of group P suffered myocardial infarction. CONCLUSION: When patients are informed objectively about advantages and disadvantages of minimal invasive aortic valve surgery only a smaller number decides to have a mini incision. The patients preferring short incisions are significantly younger since cosmetic aspects are more important. Longer duration of operation may be due to longer hemostasis based on limited exposure. Air bubbles due to inadequate de-airing might be responsible for higher CK and CK-MB levels in group P.

Adult↗
PubMed2000

The effect of leukocyte-depleted blood cardioplegia in patients with severe left ventricular dysfunction: a randomized, double-blind study.

BACKGROUND: The propensity for leukocytes to cause reperfusion injury in patients undergoing heart surgery is widely accepted. Reperfusion injury may result in myocardial damage and unfavorable operative outcome, especially in patients with severely reduced ejection fractions. This study was performed to evaluate the impact of leukocyte filtration on the postoperative course of patients undergoing coronary bypass surgery. METHODS: Thirty-two patients with coronary artery disease and left ventricular ejection fraction less than 35% were included in this double-blind, randomized study. Two serial leukocyte removal filters (Pall BC1B filter [Pall Biomedical, Portsmouth, England], group F, 15 patients) or two dummy filters (group C, 17 patients) were connected to the blood cardioplegia line. Leukocyte count, hemodynamic measurement, and transesophageal echocardiography were performed before and after cardiopulmonary bypass. Cardiac-specific enzymes were analyzed from arterial blood during the first 72 hours and from coronary sinus blood 30 and 60 minutes after aortic unclamping. RESULTS: Patient characteristics were similar in the two groups (ejection fraction 20.9% +/- 4.3% in group C and 21.1% +/- 4.8% in group F; P =.773). No early death or perioperative myocardial infarction occurred. Leukocyte count, hemodynamic parameters, cardiac troponin T, cardiac troponin I, and creatine kinase MB mass levels in arterial blood were similar in the two groups. Group F showed lower release of cardiac troponin T from the coronary sinus 30 minutes after unclamping of the aorta (group F, 0.263 +/- 0.12 ng/mL; group C, 0.6 +/- 0.32 ng/mL; P =.005). Lower doses of dopamine were necessary after cardiopulmonary bypass (group F, 0.36 +/- 0.11 mg x kg(-1) x min(-1); group C, 0.49 +/- 0.14 mg x kg(-1) x min(-1); P =.003). A moderate increase in ejection fraction was observed at 30 minutes in both groups (group F, 30.3% +/- 6.2%; group C, 28.0% +/- 6.3%; P =.239) and a significant increase at 60 minutes in group F (group F, 32.5% +/- 6.0%; group C, 27.4% +/- 7.5%; P =.012). CONCLUSIONS: These results indicate that serial leukocyte filters connected to the blood cardioplegia line decrease myocardial cell injury and may therefore help to improve outcome of patients with severely depressed ejection fractions undergoing coronary artery bypass grafting.

Aged↗
PubMed2000

Distinct effects of Broncho-Vaxom (OM-85 BV) on gp130 binding cytokines.

BACKGROUND: Broncho-Vaxom (OM-85 BV) is known to support respiratory tract resistance to bacterial infections. In vivo and in vitro studies in animals and humans have shown that the action of the drug is based on the modulation of the host immune response, and it has been found to upregulate interferon gamma (IFN-gamma) and interleukin (IL)-2, IL-6, and IL-8. These immunomodulatory effects of the compound may explain its stimulation on T helper cells and natural killer cells. Following earlier findings that OM-85 BV induces the synthesis of IL-6, a study was undertaken to investigate its possible effect on other gp130 binding cytokines including IL-11, IL-12, leukaemia inhibitory factor (LIF), oncostatin M (OSM), and ciliary neutrophil factor (CNTF). Its modulation of the corresponding receptors of the above mentioned cytokines and of the signal transducer gp130 in human pulmonary fibroblasts and peripheral blood lymphocytes was also studied. METHODS: Transcription of cytokines was assessed by Northern blot analysis. Secretion of cytokines was analysed using commercially available enzyme linked immunosorbent assay kits. Cytokine receptors and gp130 proteins were determined by Western blot analysis. RESULTS: OM-85 BV increased the expression of IL-11 in human lung fibroblasts, but not in lymphocytes, in a dose and time dependent manner by maximal fivefold within 20 hours. The compound inhibited serum induced IL-12 expression in peripheral blood lymphocytes but did not induce OSM, LIF, or CNTF at any concentration. In lung fibroblasts the expression of the IL-6 receptor was enhanced fourfold at a concentration of 10 microg/ml OM-85 BV while that of the IL-11 receptor was not altered. In peripheral blood lymphocytes LIF receptor alpha expression was downregulated in the presence of 10 microg/ml OM-85 BV. At a concentration of 10 microg/ml OM-85 BV enhanced gp130 gene transcription fivefold and increased gp130 protein accumulation in cell membranes by 2.5 times. CONCLUSION: In vitro OM-85 BV exerts immunomodulatory action via modulation of the signal transducer gp130 and gp130 binding cytokines. The increase of IL-6 and IL-11 may explain enhanced T and B cell activity, immunoglobulin synthesis, and IgM to IgG switch. Suppression of IL-12 and LIF receptor-alpha further contributes to organ protection. With regard to gp130 mediated signalling of the investigated cytokines, OM-85 BV modifies the host immune response towards an increased sensitisation of cells to gp130 binding proteins.

Adjuvants, Immunologic↗
PubMed2000

Hypoxia modifies the effect of PDGF on glycosaminoglycan synthesis by primary human lung cells.

Hypoxia, a consequence of interstitial lung diseases, may lead to secondary pulmonary hypertension and pulmonary vascular remodeling. Hypoxia induces activation and proliferation of lung cells and enhances the deposition of extracellular matrix including glycosaminoglycans (GAGs). To elucidate the cell biological mechanisms underlying the development of secondary pulmonary hypertension, we studied the effect of hypoxia on GAG synthesis by human lung cells. GAG synthesis was measured by incorporation of [(3)H]glucosamine; GAGs were isolated, purified, and characterized with GAG-degrading enzymes. Fibroblasts and vascular smooth muscle cells (VSMCs) synthesized hyaluronic acid, heparan sulfate, and chondroitin sulfates, whereas dermatan sulfate was found only in fibroblasts. Hypoxia did not influence the size or charge of the individual GAGs. However, hypoxia inhibited platelet-derived growth factor-induced [(3)H]glucosamine incorporation in secreted GAGs, especially hyaluronic acid, in VSMCs. In contrast, it stimulated GAG secretion, specifically heparan sulfate, by fibroblasts. Our results indicate that hypoxia induces modifications in GAG synthesis by human lung VSMCs and fibroblasts that may be correlated to pathophysiological manifestations in lung diseases causing hypoxia.

Cell Hypoxia↗
PubMed2000

Interleukin-6 stimulates LDL receptor gene expression via activation of sterol-responsive and Sp1 binding elements.

Inflammatory or malignant diseases are associated with elevated levels of cytokines and abnormal low density lipoprotein (LDL) cholesterol metabolism. In the acute-phase response to myocardial injury or other trauma or surgery, total and LDL cholesterol levels are markedly decreased. We investigated the effects of the proinflammatory cytokine interleukin (IL)-6 on LDL receptor (LDL-R) function and gene expression in HepG2 cells. IL-6 dose-dependently increased the binding, internalization, and degradation of (125)I-LDL. IL-6-stimulated HepG2 cells revealed increased steady-state levels of LDL-R mRNA. In HepG2 cells transiently transfected with reporter gene constructs harboring the sequence of the LDL-R promoter extending from nucleotide -1563 (or from nucleotide -234) through -58 relative to the translation start site, IL-6 dose-dependently increased promoter activity. In the presence of LDL, a similar relative stimulatory effect of IL-6 was observed. Studies using a reporter plasmid with a functionally disrupted sterol-responsive element (SRE)-1 revealed a reduced stimulatory response to IL-6. In gel-shift assays, nuclear extracts of IL-6-treated HepG2 cells showed an induced binding of SRE binding protein (SREBP)-1a and SRE binding protein(SREBP)-2 to the SRE-1 that was independent of the cellular sterol content and an induced binding of Sp1 and Sp3 to repeat 3 of the LDL-R promoter. Our data indicate that IL-6 induces stimulation of the LDL-R gene, resulting in enhanced gene transcription and LDL-R activity. This effect is sterol independent and involves, on the molecular level, activation of nuclear factors binding to SRE-1 and the Sp1 binding site in repeat 2 and repeat 3 of the LDL-R promoter, respectively.

Blotting, Northern↗
PubMed2000

Biotin-avidin microplate assay for the quantitative analysis of enzymatic methylation of DNA by DNA methyltransferases.

An assay is described to measure methylation of biotinylated oligonucleotide substrates by DNA methyltransferases using [methyl-3H]-AdoMet. After the methylation reaction the oligonucleotides are immobilized on an avidin-coated microplate. The incorporation of [3H] into the DNA is quenched by addition of unlabeled AdoMet to the binding buffer. Unreacted AdoMet and enzyme are removed by washing. To release the radioactivity incorporated into the DNA, the wells are incubated with a non-specific endonuclease and the radioactivity determined by liquid scintillation counting. As an example, we have studied methylation of DNA by the EcoRV DNA methyltransferase. The reaction progress curves measured with this assay are linear with respect to time. Methylation rates linearly increase with enzyme concentration. The rates are comparable to results obtained with the same enzyme using a different assay. The biotin-avidin assay is inexpensive, convenient, quantitative, fast and well suited to process many samples in parallel. The accuracy of the assay is high, allowing to reproduce results within +/- 10%. The assay is very sensitive as demonstrated by the detection of incorporation of 0.8 fmol methyl groups into the DNA. Under the experimental conditions, this corresponds to methylation of only 0.03% of all target sites of the substrate. Using this assay, the DNA methylation activity of some M.EcoRV variants could be detected that was not visible by other in vitro methylation assays.

Avidin↗
PubMed2000

Zinc fingers: DNA binding and protein-protein interactions.

The zinc finger domain is a very ubiquitous structural element whose hallmark is the coordination of a zinc atom by several amino acid residues (cysteines and histidines, and occasionally aspartate and glutamate). These structural elements are associated with protein-nucleic acid recognition as well as protein-protein interactions. The purpose of this review is to examine recent data on the DNA and protein binding properties of a few zinc fingers whose three dimensional structure is known.

Animals↗
PubMed2000

A dynamic bubble trap reduces microbubbles during cardiopulmonary bypass: a case study.

Microemboli passing to the cerebral circulation during cardiopulmonary bypass can contribute to postoperative neurologic dysfunction. Many studies conclude that air microbubbles predominantly are responsible for this problem. A dynamic bubble trap (DBT) was developed to diminish the number of microbubbles in the arterial line of extracorporeal circulation. The DBT is able to substantially reduce the number of air microbubbles, as shown in two patients undergoing coronary artery bypass grafting, where a high number of microbubbles was assessed. Although a 40-micron arterial filter was used, many bubbles larger than 40 microns occurred in the arterial line. The DBT reduced the number of large microbubbles from 2,267 to 67 in patient 1 and from 897 to 61 in patient 2.

Aged↗
PubMed1999

Glycosaminoglycan analysis in brain stems from animals infected with the bovine spongiform encephalopathy agent.

Increasing evidence suggests that the pathological alterations observed in brains affected by neurodegenerative disorders such as Creutzfeldt-Jakob disease and Alzheimer's disease also involve changes in glycosaminoglycans (GAGs). In the present study, we have isolated, purified, and characterized total GAGs from brain stems of healthy cows or those infected with the bovine spongiform encephalopathy (BSE) agent and we report on the differences between the two groups. Purification of the GAGs was achieved by gel filtration after homogenization, delipidation, and sequential treatment with pronase, DNase, and alkali borohydride. Fractionation of the total GAGs by Superose 6 gel filtration and HPLC revealed four major fractions, with average molecular masses of 360, 180, 15, and 2.3 kDa, respectively, both in controls and infected tissues. Enzymatic characterization, using GAG-degrading enzymes, showed that in both infected and normal brain stems, the 360- and 180-kDa fractions correspond to hyaluronic acid, which was also the most abundant GAG, while the 15-kDa fractions correspond to chondroitin sulfates as well as heparan sulfate and dermatan sulfate, the latter being the least prominent GAG. Electrophoresis on cellulose acetate membranes revealed that the relative ratio of GAGs was not significantly modified in infected brain stems, compared to controls. However, total GAGs in infected brain stems was significantly decreased by approximately 40%, compared to controls, and this decrease applied equally to all of the above GAG fractions. The diminution observed in total GAGs in infected brain stems is in good agreement with the recently reported neuroprotective role of certain GAG molecules and offers an additional criterion for differential diagnosis of BSE-infected animals.

Alzheimer Disease↗
PubMed1999

Crystal structure of the oxidised and reduced acidic cytochrome c3from Desulfovibrio africanus.

Unique among sulphate-reducing bacteria, Desulfovibrio africanus has two periplasmic tetraheme cytochromes c3, one with an acidic isoelectric point which exhibits an unusually low reactivity towards hydrogenase, and another with a basic isoelectric point which shows the usual cytochrome c3reactivity. The crystal structure of the oxidised acidic cytochrome c3of Desulfovibrio africanus (Dva.a) was solved by the multiple anomalous diffraction (MAD) method and refined to 1.6 A resolution. Its structure clearly belongs to the same family as the other known cytochromes c3, but with weak parentage with those of the Desulfovibrio genus and slightly closer to the cytochromes c3of Desulfomicrobium norvegicum. In Dva.a, one edge of heme I is completely exposed to the solvent and surrounded by a negatively charged protein surface. Heme I thus seems to play an important role in electron exchange, in addition to heme III or heme IV which are the electron exchange ports in the other cytochromes c3. The function of Dva.a and the nature of its redox partners in the cell are thus very likely different. By alignment of the seven known 3D structures including Dva.a, it is shown that the structure which is most conserved in all cytochromes c3is the four-heme cluster itself. There is no conserved continuous protein structure which could explain the remarkable invariance of the four-heme cluster. On the contrary, the proximity of the heme edges is such that they interact directly by hydrophobic and van der Waals contacts. This direct interaction, which always involves a pyrrole CA-CB side-chain and its bound protein cysteine Sgammaatom, is probably the main origin of the four-heme cluster stability. The same kind of interaction is found in the chaining of the hemes in other multihemic redox proteins.The crystal structure of reduced Dva. a was solved at 1.9 A resolution. The comparison of the oxidised and reduced structures reveals changes in the positions of water molecules and polar residues which probably result from changes in the protonation state of amino acids and heme propionates. Water molecules are found closer to the hemes and to the iron atoms in the reduced than in the oxidised state. A global movement of a chain fragment in the vicinity of hemes III and IV is observed which result very likely from the electrostatic reorganization of the polypeptide chain induced by reduction.

Amino Acid Sequence↗
PubMed1999

[Current therapeutic strategies in acute coronary syndrome. New and established drug and interventional therapy].

Therapeutic options in acute coronary syndrome (unstable angina pectoris/non-Q-wave myocardial infarction), as also in acute Q-wave infarction, include conservative medical and mechanical-interventional measures. Early hospitalization for surveillance and induction of treatment is always necessary. Administration of oxygen, analgesia, sedation and treatment with nitrates, beta blockers or calcium antagonists, acetylsalicylic acid (ASA) and heparin are the basic measures. As alternatives to ASA, the new ADP antagonists, ticlopidine, clopidogrel, and as an alternative to heparin, hirudin or low-molecular-weight heparins can be used. If this does not result in rapid clinical stabilisation (here, transient ST-T changes in the ECG and the detection of troponine I or T represent major risk indicators) the new glycoprotein-IIb/IIIa receptor antagonists may be employed as highly potent platelet aggregation inhibitors. In addition, the patients should then undergo coronary angiography prior to interventional treatment of the underlying coronary stenosis.

Angina, Unstable↗
PubMed1999

On the substrate specificity of DNA methyltransferases. adenine-N6 DNA methyltransferases also modify cytosine residues at position N4.

Methylation of DNA is important in many organisms and essential in mammals. Nucleobases can be methylated at the adenine-N6, cytosine-N4, or cytosine-C5 atoms by specific DNA methyltransferases. We show here that the M.EcoRV, M.EcoRI, and Escherichia coli dam methyltransferases as well as the N- and C-terminal domains of the M. FokI enzyme, which were formerly all classified as adenine-N6 DNA methyltransferases, also methylate cytosine residues at position N4. Kinetic analyses demonstrate that the rate of methylation of cytosine residues by M.EcoRV and the M.FokI enzymes is reduced by only 1-2 orders of magnitude in relation to methylation of adenines. This result shows that although these enzymes methylate DNA in a sequence specific manner, they have a low substrate specificity with respect to the target base. This unexpected finding has implications on the mechanism of adenine-N6 DNA methyltransferases. Sequence comparisons suggest that adenine-N6 and cytosine-N4 methyltransferases have changed their reaction specificity at least twice during evolution, a model that becomes much more likely given the partial functional overlap of both enzyme types. In contrast, methylation of adenine residues by the cytosine-N4 methyltransferase M.BamHI was not detectable. On the basis of our results, we suggest that adenine-N6 and cytosine-N4 methyltransferases should be grouped into one enzyme family.

Adenine↗