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Biomedical subjects

A Beyer

Publications and source records attributed to A Beyer.

At least 37 records · Page 2Linked to original sources

Lysophosphatidic acid, a novel lipid growth factor for human thyroid cells: over-expression of the high-affinity receptor edg4 in differentiated thyroid cancer.

Lysophosphatidic acid (LPA) is a small lipid mediator with pleiotropic biological activities, e.g., the regulation of cellular proliferation and various aspects of cellular physiology. Signal transduction is achieved by binding to 2 high-affinity receptors, EDG2 and EDG4, and a group of low-affinity receptors, EDG1-7, all belonging to the superfamily of G protein-coupled receptors. We examined the growth-regulatory effects of LPA in primary cultures of 8 goiters and 1 papillary thyroid cancer. We further assessed mRNA expression of high-affinity receptors EDG2 and EDG4 in 14 normal thyroids, 29 papillary thyroid cancers, 7 follicular thyroid cancers and 13 goiters by quantitative RT-PCR. We also identified mRNA expression of phospholipase A(2) and LPA acyltransferase in fresh thyroid tissues derived from various sources. At concentrations of 10, 50 and 150 microM, LPA induced a 2-fold rise of proliferation (p < 0.001) and acted as strongly as thyrotropin. The combination of LPA and TSH produced significant synergistic effects compared with each substance alone (p < 0.05). Normal thyroid, goiter and papillary or follicular thyroid cancer expressed 2 high-affinity cognate LPA receptors, EDG2 and EDG4. EDG4 receptor mRNA expression was increased 3-fold in differentiated thyroid cancer (p < 0.01), both papillary (p < 0.01) and follicular (p < 0.05), compared to normal thyroid or goiter. Overall expression of EDG2 receptor was unchanged in malignancy; however, increased EDG2 expression in individual samples correlated with lymphonodular metastasis (p = 0.01). Thus, lipid mediators are a novel class of factors involved in the control of proliferation in the human thyroid. Altered mRNA expression of the high-affinity LPA receptor EDG4 suggests a role in the pathogenesis of differentiated thyroid cancer.

Acyltransferases↗

Long-range transport potential of semivolatile organic chemicals in coupled air-water systems.

Ongoing deliberations on the regulation of semivolatile organic chemicals require the assessment of chemical transport in atmospheric and marine systems. The characteristic travel distance was proposed as a measure for the transport potential in air and water. However, the existing definition treats the transport processes separately. It is shown that combined transport in coupled air-ocean systems can accelerate the overall transport into remote regions. Concentration ratios in air and water change with distance from sources depending on the initial concentration ratio and on the difference between the transport velocities. A measure is suggested facilitating the chemical screening with respect to transport potentials in such air-ocean systems. A case study for alpha and gamma-hexachlorocyclohexane shows that the suggested measure qualitatively reveals the transport potentials of these chemicals and exemplifies possible concentration patterns.

Air Movements↗

Increased catecholamine levels in urine in subjects exposed to road traffic noise: the role of stress hormones in noise research.

The nocturnal excretion of catecholamines in urine was studied in 30-45-year-old women whose bedroom and/or living room were facing streets of varying traffic volume. The traffic volume of the streets was used as an indicator of noise exposure; adrenaline and noradrenaline concentrations were assessed as indicators of the outcome of the physiological stress. Significant associations between traffic volume and noradrenaline concentrations in urine were found with regard to the exposure of the bedroom (not the living room), indicating a higher chronic physiological arousal in noise-exposed subjects as compared to less exposed. Subjective measures of disturbance due to traffic noise were positively correlated with the noradrenaline level. However, this was only found in subjects where closing the window could not reduce the perceived disturbance, which points to the effectiveness of individual coping mechanisms. Stress hormones are useful indicators to study associations, mechanisms, and interactions between noise, health outcomes, and effect modifiers in epidemiological noise research.

Adaptation, Psychological↗

Clinical and physiologic evaluation of stellate ganglion blockade for complex regional pain syndrome type I.

OBJECTIVE: The efficacy of peripheral sympathetic interruption after stellate ganglion blockade was assessed by a sympathetic function test. Results were compared with clinical signs such as temperature changes, pain reduction, and the development of Horner syndrome to evaluate the correlation with clinical investigations. DESIGN: Stellate ganglion blockade with local anesthetics was carried out via an anterior paratracheal approach in 33 patients suffering from complex regional pain syndrome type I. Patients were examined before and after the procedure. For assessment of sympathetic nervous function, the vasoconstrictor response to sympathetic stimuli was assessed using laser Doppler flowmetry. Clinical parameters like surface temperature changes (thermography), pain relief (visual analogue scale), and Horner syndrome were monitored. RESULTS: Twenty-three (70%) of 33 patients developed an increase in temperature difference between the treated hand and the contralateral hand of more than 1.5 degreesC after the procedure, which is a clinical sign of sympathicolysis. In 48% (n = 11) of these patients, the sympathetic function test showed an undisturbed sympathetic nervous function. In 10 patients, no significant increase in temperature difference was observed. Although these patients presented with a normal sympathetic vasoconstrictor response, 4 felt pain relief of more than 50%, suggesting a placebo effect. Only 7 patients with pain relief revealed both clinical sympathicolysis and extinguished sympathetic nervous function and qualified for sympathetically maintained pain. CONCLUSIONS: Clinical investigation is not reliable in the assessment of stellate ganglion blockade. Proof of sympathetically maintained pain based on pain relief after stellate ganglion blockade is not conclusive.

Adult↗

Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs.

With the complete human genomic sequence being unraveled, the focus will shift to gene identification and to the functional analysis of gene products. The generation of a set of cDNAs, both sequences and physical clones, which contains the complete and noninterrupted protein coding regions of all human genes will provide the indispensable tools for the systematic and comprehensive analysis of protein function to eventually understand the molecular basis of man. Here we report the sequencing and analysis of 500 novel human cDNAs containing the complete protein coding frame. Assignment to functional categories was possible for 52% (259) of the encoded proteins, the remaining fraction having no similarities with known proteins. By aligning the cDNA sequences with the sequences of the finished chromosomes 21 and 22 we identified a number of genes that either had been completely missed in the analysis of the genomic sequences or had been wrongly predicted. Three of these genes appear to be present in several copies. We conclude that full-length cDNA sequencing continues to be crucial also for the accurate identification of genes. The set of 500 novel cDNAs, and another 1000 full-coding cDNAs of known transcripts we have identified, adds up to cDNA representations covering 2%--5 % of all human genes. We thus substantially contribute to the generation of a gene catalog, consisting of both full-coding cDNA sequences and clones, which should be made freely available and will become an invaluable tool for detailed functional studies.

3' Untranslated Regions↗

Comparing representations of the environmental spatial scale of organic chemicals.

Long-range transport potential is one of the criteria proposed to identify chemicals as persistent organic pollutants. Here, different approaches to determine the spatial scale of an environmental area or region that can be impacted by an emitted chemical are investigated. A ranking of chemicals according to the spatial range R on a limited scale, as suggested by Scheringer, is equivalent to the characteristic travel distance L according to Bennett et al. on a linear, open scale. However, the methods are different with respect to the weighting of differences between the chemicals and according to their comparability with persistence. The characteristic travel distance L and the overall persistence are both plotted on open log-linear scales, whereas the spatial range R is represented on a limited scale. Various approaches of how to account for the mode of entry of chemicals are compared, and it is argued that relative measures are more appropriate to describe the long-range transport potential of chemicals than absolute numbers.

Environment↗

[Continuous peridural analgesia vs patient - controlled intravenous analgesia for pain therapy after thoracotomy].

OBJECTIVES: Continuous epidural analgesia (EA) and patient-controlled intravenous analgesia (PCA) are widely used for postoperative pain control. Studies indicate that both analgesic regimens provide good analgesia after major surgery. However, because of the following reasons it is still unclear whether one of the two modes of application is superior. First, there are conflicting data regarding the differences in pain relief and drug use between epidural and intravenous administration of opioids. Second, in many studies epidural analgesia is performed by a combination of local anaesthetics and opioids. Third, reduced morbidity was observed only in some of the studies, in which epidural analgesia provided better pain relief than systemic opioid supply. Despite these conflicting results, EA with local anaesthetics and fentanyl as well as PCA with piritramid, a highly potent mu-agonist, are routinely used in Germany. The purpose of this study was to compare these two treatments for analgesic efficacy, pulmonary function, incidence of side effects and complications in patients undergoing thoracotomy. METHODS: In this prospective randomized trial 50 patients were included. For postoperative pain control 25 patients (EA group) received thoracic epidural infusion of local anaesthetics (bupivacaine 0.125% or ropivacaine 0,2%) and fentanyl 4,5 microg/ml with a flow rate of 4-10 ml/h. 25 patients received intravenous PCA with piritramid (bolus 2, 5 mg, lock out 15 minutes, maximum of 25 mg/4 h, no background infusion). RESULTS: Analgesia at rest and while coughing, as evaluated by visual analogue scale, was significantly better in the EA group. EA also resulted in superior values of pulmonary function tests, general condition and a lower incidence of sedation and nausea. In contrast, patients with EA reported distinctly more pruritus than patients with PCA. Duration of hospital stay was shorter in the EA group, but this difference did not reach statistical significance. There was one atelectasis in the EA group. No major complications related to EA or PCA were observed. CONCLUSION: In this study EA with local anaesthetics and fentanyl provided superior postoperative pain control and a lower incidence of sedation and nausea compared to intravenous PCA with piritramid, but there was no superiority as to pulmonary complications and duration of hospital stay.

Analgesia, Patient-Controlled↗

[Diagnostic criteria and new classification of the cervical spine syndrome].

OBJECTIVES: Pain and functional disorders of the neck are widely diagnosed as "cervical spine syndrome". As this diagnosis is not able to sufficiently specify the different symptoms, a new classification with five pain syndromes, created empirically, was developed. The aim of this study is to evaluate the predictive values of the diagnostic criteria respectively clinical findings of patients diagnosed with cervical spine syndrome. METHODS: Within the two year time frame of the study all patients diagnosed with "cervical spine syndrome", which presented themselves at the clinic, were included. The statistic analysis was performed in multiple steps: univariate analyses, bivariate variable screening and the use of the logistic regression model. RESULTS: Within two years 653 patients previously diagnosed as suffering from cervical spine syndrome presented at the clinic; 332 of them were included in the study. According to the diagnostic criteria they were attached to one of the five pain syndromes. The statistical analysis showed in 17 of 35 evaluated diagnostic criteria a significant association to one of the five subgroups of the cervical spine syndrome. CONCLUSION: The statistical analyses revealed significant associations between diagnostic criteria which were assessed by clinical examination and the five subgroups of the cervical spine syndrome. The identified predictors represent the typical syndrome-associated diagnostic criteria of a certain syndrome-subgroup.

English Abstract↗

Continuous axillary brachial plexus analgesia with low dose morphine in patients with complex regional pain syndromes.

In this prospective pilot study, nine patients suffering from complex regional pain syndrome of the arm were treated with morphine 0.16 mg h-1 (3.84 mg day-1) applied continuously through an axillary brachial plexus catheter. In all of them an oral analgesic medication including the less potent opioid tramadol had not provided sufficient pain relief. During regional treatment, patients were kept in hospital and physiotherapy was carried out frequently in order to improve strength and function of the affected arm. Pain at rest and during movement as well as grip strength were assessed at first visit, during morphine infusion and at a long-term follow-up visit. All assessments improved significantly during plexus analgesia. There were no major opioid related side-effects. The results from this pilot study indicate that continuous axillary brachial plexus analgesia with low dose morphine might be beneficial in patients suffering from complex regional pain syndrome of the arm.

Adult↗

[Posterior corneal curvature after penetrating keratoplasty before and after suture removal].

PURPOSE: After penetrating keratoplasty (PK), peripheral swelling effects, malapposition of the graft in the recipient bed and suture tension may result in a changed ratio of curvature between anterior and posterior corneal surface. The purpose of this pilot study was to assess the posterior corneal curvature after PK with and without sutures and to compare this data to the posterior curvature of normal individuals. PATIENTS AND METHODS: In this cross-sectional study, 44 eyes after PK with a double running 16-bite diagonal antitorque suture in place (mean age 37 +/- 14 years, spherical equivalent (SEQ) -0.1 +/- 3.2 diopters (D)), 36 eyes with "all-sutures-out" (mean age 40 +/- 18 years, SEQ -0.8 +/- 3.5 D), and 464 normal control eyes (mean age 34 +/- 16 years, SEQ -0.3 +/- 2.2 D) were included. Based on Orbscan slit scanning topography analysis the following parameters were assessed: posterior power, posterior astigmatism, and posterior asphericity in various segments. RESULTS: With sutures in place the posterior central power ranged from -7.36 to -4.53 (mean -5.90 +/- 0.62) D, astigmatism ranged from 0.13 to 1.15 (mean 0.42 +/- 0.20) D, and asphericity ranged from 0.20 to 2.97 (mean 1.13 +/- 0.76, 56% oblate). With "all-sutures-out" the central power ranged from -7.56 to -4.93 (mean -6.41 +/- 0.53) D, astigmatism ranged from 0.13 to 1.15 (mean 0.39 +/- 0.19) D, and asphericity ranged from 0.26 to 3.04 (mean 1.25 +/- 0.76, 44% oblate). In the control group the central power ranged from -7.20 to -4.90 (mean -6.01 +/- 0.29) D, astigmatism ranged from 0.01 to 1.04 (mean 0.12 +/- 0.10) D, and asphericity ranged from 0.33 to 3.13 (mean 1.06 +/- 0.37, 47% oblate). Mean negative posterior power in grafts with "all-sutures-out" was significantly greater than in grafts with "all-sutures-in" and normal controls (p < 0.001), but showed no difference between the two latter groups (p = 0.56). Posterior astigmatism did not differ significantly comparing grafts with and without sutures (p = 0.44). However, astigmatism was significantly higher in grafts than in the control group (p < 0.0001). Asphericity did not differ significantly comparing grafts with and without sutures (p = 0.49) or comparing grafts to controls (p > 0.38). CONCLUSIONS: Except for the amount of astigmatism, the posterior corneal curvature of grafts with a double running suture in place does not seem to differ significantly from that of normal corneas. The removal of a double running suture tends to steepen the central posterior curvature. Knowledge about the individual posterior corneal curvature may have a favorable impact on the precision of intraocular lens power calculation for cataract surgery in eyes after PK.

Adult↗

Production of IL-6 and MCP-1 by the human peritoneum in vivo during major abdominal surgery.

Both inflammatory and anti-inflammatory mediators are released into the circulation during major abdominal surgery. In addition, some of these mediators have been detected postoperatively in peritoneal fluids. Thus, it appears that the peritoneum may be a potential source of circulating immunomodulators following major abdominal surgery. With this in mind, we quantified the intraoperative production of interleukin (IL)-6 and monocyte chemoattractant protein-1 (MCP-1) by human peritoneum. A small chamber was sewed to the parietal peritoneum of 19 patients at the beginning of the operation. This chamber was perfused with buffered salt solution, and the perfusate was collected hourly and assayed for IL-6 and MCP-1 concentrations by enzyme-linked immunosorbent assay. Expression of the corresponding mRNAs was determined by reverse-transcription polymerase chain reaction from additional peritoneal biopsies taken at the beginning and at the end of operation. Peritoneal production of IL-6 and MCP-1 started within the first hour of operation and continued with increasing amounts of up to 435 (43-1925) pg/cm2/h [median (range)] of IL-6 and 435 (59-1930) pg/cm2/h of MCP-1. There was induction of peritoneal IL-6 and MCP-1 mRNA expression. A suppressed MCP-1 production was seen only in one patient who suffered from severe septic complications in the postoperative course. Using a new technique that allows for the quantification of local cytokine production in vivo, we demonstrated that the peritoneum rapidly reacts to abdominal surgery with increased production of IL-6 and MCP-1. Early detection of impaired production may help to identify patients at risk of postoperative septic complications.

Abdomen↗

Cloning, characterisation, and functional expression of the Mus musculus SKD1 gene in yeast demonstrates that the mouse SKD1 and the yeast VPS4 genes are orthologues and involved in intracellular protein trafficking.

The mouse SKD1 protein displays a high degree of sequence identity (62%) to the yeast Vps4 protein, which is involved in the transport of proteins out of a prevacuolar/endosomal compartment. We isolated the mouse SKD1 locus and found that the SKD1 gene is split into 11 exons covering a region of 29kb of the genome. Interestingly, the exon/intron structure reflects to a certain degree the proposed domain structure of the protein, since the 5' located coiled-coil region and the AAA domain are flanked by introns. Analysis of the promoter region, which revealed features common for 'housekeeping genes', is consistent with previous results of a mouse multi-tissue Northern blot, confirming that SKD1 is a ubiquitously expressed gene. Expression of the full-length SKD1 cDNA in a vps4 disrupted yeast strain suppressed the temperature-sensitive growth defect of the vps4 mutant strain. Overexpression of wild type and expression of mutant Vps4 and SKD1 proteins, harbouring single amino acid exchanges in their AAA domains, induced a dominant-negative vacuolar protein sorting defect in wild type yeast cells, indicating that mouse SKD1 protein and yeast Vps4p fulfil similar functions.

ATPases Associated with Diverse Cellular Activitie↗

GRC5 and NMD3 function in translational control of gene expression and interact genetically.

The yeast gene, GRC5 (growth control), is a member of the highly conserved QM gene family, the human member of which has been associated with the suppression of Wilms' tumor. GRC5 encodes ribosomal protein L10, which is thought to play a regulatory role in the translational control of gene expression. A revertant screen identified four spontaneous revertants of the mutant grc5-1ts allele. Genetic and phenotypic analysis showed that these represent one gene, NMD3, and that the interaction of NMD3 and GRC5 is gene-specific. NMD3 was previously identified as a component of the nonsense-mediated mRNA decay pathway. The point mutations within NMD3 reported here may define a domain important for the functional interaction of Grc5p and Nmd3p.

Alleles↗

Intravenous titration with morphine for severe cancer pain: report of 28 cases.

BACKGROUND: In a multicenter study, 28 patients with cancer pain and insufficient pain relief with analgesic treatment according to step II of the guidelines of the World Health Organization (WHO) were switched to oral slow-release morphine. METHODS: Patients received intravenous morphine through a patient-controlled pump (PCA) for the first 24 hours (bolus = 1 mg, lockout interval = 5 minutes, maximum dose = 12 mg/hour). From day 2 patients were treated with oral slow-release morphine. Daily doses were calculated from the requirements of the day before. Breakthrough pain was treated with PCA until stable doses were reached (<2 boluses/day) and then with oral immediate-release morphine solution. Pain intensity was reported in a diary four times a day, in addition to mood, activity, and quality of sleep once daily. RESULTS: Mean duration until adequate pain relief reported (<30 on a 101-step numerical scale; NRS) was 5 hours (range = 80-620 minutes). Mean pain intensity was reduced from 67 NRS to 22 NRS. Mean doses of oral morphine were 133 mg/day initially and then 154 mg/day on day 14. Serious adverse events such as respiratory depression were not observed. Two patients terminated the study due to progressive symptoms of gastrointestinal obstruction. Seventy-five percent of the patients evaluated the effectiveness of the analgesic regime as good. CONCLUSIONS: Dose finding with intravenous PCA may be appropriate for a small minority of patients with severe pain. Higher treatment costs and the risk of complications are drawbacks of this method compared with conventional oral titration.

Administration, Oral↗

Conformational study of the HIV-1 reverse transcriptase inhibitor 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT).

The conformations of the HIV-1 reverse transcriptase inhibitor 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) are calculated by semiempirical and mainly by ab initio methods in order to estimate the potential for the rotation around the carbon sulfur single bond. The results are compared to X-ray structures of HEPT associated to the HIV-1 reverse transcriptase. The NMR spectra of the compound are calculated to obtain some information about its structure in solution. The structure of HEPT in the complex is analysed to study the intermolecular interactions between the inhibitor and the surrounding protein, which determine the geometry of the inhibition complex.

Anti-HIV Agents↗