Biomedical subjects

M Geyer

Publications and source records attributed to M Geyer.

At least 55 records · Page 3Linked to original sources

PubMed1999

[Coping with disease in the elderly - the effect of perceived control, subjective morbidity, social support and socio-demographic variables].

In a community sample of 165 elderly aged 61 to 96 years (mean 69.65 years) from East and West Germany, present diseases, subjective health, impairments, health-related control-beliefs, social support (F-SOZU; Sommer & Fydrich, 1989), and health related coping-styles ("Bern Coping Styles Questionnaire" BEFO; Heim et al., 1991) were assessed. By means of a stepwise multiple regression analysis, the differential impact of control beliefs, subjective morbidity, subjective health, social support, social integration, social burden, and socio-demographic variables (age, sex, educational level) was analyzed. Elderly with little health related impairments, emotional support, and a relatively high educational level tried to cope with diseases by lowering the affective burden by cognitive and behavioral strategies. A growing number of diseases, a high level of practical help by others, but also a high degree of social burden were the best predictors for a health related coping strategy that is characterized by avoiding the preoccupation with the disease and by searching for emotional support. A health related coping style that is characterized by lamentation, brooding, and resignation was predicted best by poor subjective health, a high degree of social burden, and a low educational level.

Adaptation, Psychological↗

PubMed1999

Ca2+ sensitivity of stunned myocardium after skinning using retrograde infusion of detergent.

Myofilament Ca2+ desensitization contributes to the contractile dysfunction of ischemic/reperfused ("stunned") myocardium. We examined the presence of reduced Ca2+ sensitivity of isometric force in chemically skinned fibers obtained from stunned myocardium using different modes of applying the detergent Triton X-100. Langendorff-perfused rat hearts underwent 20 min ischemia/20 min reperfusion, which caused a 35 +/- 3% decrease in left ventricular developed pressure, compared to continuously perfused control hearts. Stunned and control hearts were randomly allocated to two different permeabilization protocols: In group A, trabeculae were dissected and immersed in skinning solution containing 1% Triton X-100 for 20 min. Group B hearts remained fixed to the aortic cannula and skinning solution was infused retrogradely for 6 min prior to dissection of trabeculae. Extraction of cytosolic marker proteins was more complete in group-B than in group-A preparations. Group-A preparations from stunned hearts exhibited significant Ca2+ desensitization (pCa50 = 5.07 and 5.15 in stunned and control myocardium, respectively). In group B no such difference was observed, all preparations showing higher Ca2+ sensitivity and maximum force than group-A preparations (pCa50 = 5.32 in stunned versus 5.33 in control hearts). Prolonging group-A skinning to 150 min also abolished the difference in Ca2+ sensitivity between stunned and control myocardium. In conclusion, compared to a conventional protocol, skinning by perfusion results in more complete permeabilization and better preservation of myocardial contractile function. Ischemia/reperfusion at this moderate degree of contractile dysfunction induces Ca2+ desensitization at least partially by factors that can be extracted by thorough skinning.

Animals↗

PubMed1999

Activation of Vav by Nef induces cytoskeletal rearrangements and downstream effector functions.

Nef of primate lentiviruses is critical for high levels of viremia and the progression to AIDS. Nef associates with and activates a serine/threonine kinase (Nef-associated kinase [NAK]) via the small GTPases Rac1 and Cdc42. We identified the protooncogene and guanine nucleotide exchange factor Vav as the specific binding partner of Nef proteins from HIV-1 and SIV. The interaction between Nef and Vav led to increased activity of Vav and its downstream effectors. Both cytoskeletal changes and the activation of c-Jun N-terminal kinase (JNK) were observed. Furthermore, a dominant-negative Vav protein inhibited NAK activation and viral replication. Thus, the interaction between Nef and Vav initiates a signaling cascade that changes structural and physiological parameters in the infected cell.

Amino Acid Sequence↗

PubMed1999

[Subjective assessment of self health and subjective morbidity in Germany. Results of a representative demographic survey].

This study presents selected results from the poll of a representative cross-section of the German population during the Spring of 1996 was subjective data on health and illness investigated, inter alia. The majority of the questioned subjects stated good health with low impairment of their general condition by their general conditions by their health. Compared with data from 1975, people have the impression that their health is in a better state, but, on the other hand, more significantly inparied by their health. East Germans claim a somewhat lower state of health and more impairment than West Germans; the same results were found for women in comparison with men and elderly persons compared with younger subjects. There is no difference between East and West Germans with respect the frequency of disease, but there were more illnesses with a clear morphological correlation reported by East-Germans. West Germans report more functional infirmities or troubles. One of the most striking results was the high frequency of cardiovascular disorders in East Germany. The influence of social support and social status on the subjective assessment of one's own health and subjective morbidity is of only low importance.

Adolescent↗

PubMed1999

[The situation of young people in Germany--results of a representative population survey].

Youth and adolescence is one of great periods of upheaval during a human lifetime. Separation from parents and forming a stable individual identity are major themes. The present study outlines results relevant to this issue taken from three representative surveys of German population. The average results for various psycho-social parameters applying to young people in the country as a whole reflect a well-integrated, relatively contented and stable generation. Differentiating these results according to place of residence (East vs. West Germany) demonstrates, firstly, that psycho-social gap between East and West is closing faster among the younger generation than among the older sections of the population and, secondly, that East German youth is particularly burdened by special problems. The diminishing role of family as a stabilizing "counterpole" in the face of increasing objective difficulties and the possible consequences of this trend for young people is discussed in connection with the findings.

Adolescent↗

PubMed1999

[Critical review of the categorical structures of the core Conflictual Relationship Theme Method (CCRT)].

The CCRT-method developed by Lester Luborsky is the most widespread and best established method to assess relationship structures in the field of psychodynamic psychotherapy research. Although its categorical structures are criticised in many different ways there have not been any attempts to modify them. This article points out the inconsistency of the current categorical system and demonstrates first approaches to alternative solutions. For this purpose genetic algorithms are used. Their application in psychotherapy research is demonstrated here for the first time.

Algorithms↗

PubMed1998

Expression of vascular endothelial growth factor during the development of cardiac hypertrophy in spontaneously hypertensive rats.

Left ventricular hypertrophy (LVH) is often associated with an impaired maximal coronary blood flow and increases the vulnerability of the heart tissue to ischaemia. In this study, the correlation between coronary blood flow and expression of the vascular endothelial growth factor (VEGF) mRNA was investigated. Using both haemodynamic measurements and analysis of mRNA, we have demonstrated that during development of LVH, in spontaneously hypertensive rats (SHR), an impaired maximal coronary flow at 12 weeks of age is associated with low levels of VEGF mRNA. However, in older SHR (32 weeks) with stabilised hypertrophy and a normal maximal coronary flow response, VEGF mRNA levels are increased 3-fold. These results suggest that the mechanism for the impaired flow, observed in some types of cardiac hypertrophy, might involve an inadequate growth of the coronary vessels due to insufficient activation of the VEGF gene.

Animals↗

PubMed1998

Repeated testing of prepulse inhibition and habituation of the startle reflex: a study in healthy human controls.

The aim of this study was to examine the effect of repeated testing on prepulse inhibition (PPI) and habituation of the startle reflex. Fifteen healthy control subjects (eight males, mean age 30 years; seven females, mean age 29 years) were tested on three occasions across the same day separated by a minimum of 2 h. An acoustic probe of 40-msec bursts of 116 dB(A) white noise over a continuous background noise of 70 dB(A) was presented binaurally through headphones and the eye-blink component of the startle response was measured taking electromyographic recordings from the right orbicularis oculi. The test session was identical at each time point and consisted of two blocks of 12 randomly mixed trials of four pulse-alone, four 60-msec prepulse and four 120-msec prepulse trials enclosed by two blocks each of six pulse-alone trials. There was huge variation in individual response magnitude that was independent of subsequent PPI in both women and men. Women showed greater PPI in the second half of sessions with the 120-msec prepulse only; but PPI was not altered significantly in either group between sessions across the day. In general, there was good test-retest reliability of PPI especially within trial type. Normal reflex habituation occurred across sessions and this effect was preserved in sessions across the day. Latency of response was significantly reduced in a session by the 60-msec trial type compared to the 120-msec trial type, as previously reported. Our results suggest that measures of PPI and habituation of the startle response are appropriate and reliable for a within-subject, test-retest design.

Acoustic Stimulation↗

PubMed1997

NMR structure of inactivation gates from mammalian voltage-dependent potassium channels.

The electrical signalling properties of neurons originate largely from the gating properties of their ion channels. N-type inactivation of voltage-gated potassium (Kv) channels is the best-understood gating transition in ion channels, and occurs by a 'ball-and-chain' type mechanism. In this mechanism an N-terminal domain (inactivation gate), which is tethered to the cytoplasmic side of the channel protein by a protease-cleavable chain, binds to its receptor at the inner vestibule of the channel, thereby physically blocking the pore. Even when synthesized as a peptide, ball domains restore inactivation in Kv channels whose inactivation domains have been deleted. Using high-resolution nuclear magnetic resonance (NMR) spectroscopy, we analysed the three-dimensional structure of the ball peptides from two rapidly inactivating mammalian K. channels (Raw3 (Kv3.4) and RCK4 (Kv1.4)). The inactivation peptide of Raw3 (Raw3-IP) has a compact structure that exposes two phosphorylation sites and allows the formation of an intramolecular disulphide bridge between two spatially close cysteine residues. Raw3-IP exhibits a characteristic surface charge pattern with a positively charged, a hydrophobic, and a negatively charged region. The RCK4 inactivation peptide (RCK4-IP) shows a similar spatial distribution of charged and uncharged regions, but is more flexible and less ordered in its amino-terminal part.

Amino Acid Sequence↗

PubMed1997

The subjective shoulder rating system.

We developed a subjective shoulder rating system (SSRS) and tested its reliability against a recognized system (Constant-Murley Score) and a four-point verbal rating scale in 200 patients (mean age 43 years, range 18-71 years; 83 women and 117 men; 48 anterior shoulder reconstructions, 123 subacromial decompressions, 29 manipulations under anesthesia). Within the study period of 1 year, patients completed the SSRS preoperatively and at 1 and 2 weeks, also at 3, 6, and 12 months. The examination according to the Constant-Murley Score was performed preoperatively and at 3 and 12 months. Linear regression showed a highly significant correlation between the SSRS and the Constant-Murley Score (r = 0.83, n = 592, P < 0.001). Ninety-seven percent of the SSRS forms were completed and returned. The average time to complete the SSRS form was 55 s (range 20-310 s) as compared with an experienced examiner requiring an average of 410 s (range 190-720 s) to complete the Constant-Murley Score. The time difference was highly significant (P < 0.001).

Adolescent↗

PubMed1997

GEFs, GAPs, GDIs and effectors: taking a closer (3D) look at the regulation of Ras-related GTP-binding proteins.

Cell biology depends on the interactions of macromolecules, such as protein-DNA, protein-protein or protein-nucleotide interactions. GTP-binding proteins are no exception to the rule. They regulate cellular processes as diverse as protein biosynthesis and intracellular membrane trafficking. Recently, a large number of genes encoding GTP-binding proteins and the proteins that interact with these molecular switches have been cloned and expressed. The 3D structures of some of these have also been elucidated.

Animals↗

PubMed1997

Structure of the Ras-binding domain of RalGEF and implications for Ras binding and signalling.

The solution structure of the Ras-binding domain (RBD) of Ral guanine-nucleotide exchange factor RalGEF was solved by NMR spectroscopy. The overall structure is similar to that of Raf-RBD, another effector of Ras, although the sequence identity is only 13%. 15N chemical shifts changes in the complex of RalGEF-RBD with Ras indicate an interaction similar to the intermolecular beta-sheet observed for the complex between Ras and Raf-RBD.

Amino Acid Sequence↗

PubMed1996

Linear free energy relationships in the intrinsic and GTPase activating protein-stimulated guanosine 5'-triphosphate hydrolysis of p21ras.

Controlling the hydrolysis rate of GTP bound to guanine nucleotide binding proteins is crucial for the right timing of many biological processes. Theoretical, structural, and functional studies have demonstrated that in p21ras the substrate of the reaction, GTP itself, plays a central role by acting as the base catalyst. This substrate-assisted reaction mechanism was analyzed with the help of linear free energy relationships (LFERs). Here we present experimental data that further support the proposed mechanism. We extend the LFER analysis to a wide range of oncogenic as well as nontransforming Ras mutants. It is illustrated that almost all Ras variants follow the observed LFER and thus also the same reaction path. Further, the reduced GTPase reaction rate that characterizes the oncogenic effect of many of the p21 mutants found in human tumors seems to be a consequence of a slightly reduced pKa of the gamma-phosphate group of bound GTP. Factors causing a pKa deviation of just 0.5 unit are enough to slow the intrinsic GTPase reaction rate significantly, and the system may exhibit as a consequence of this an oncogenic potential. Interestingly, we also found oncogenic mutations that do not follow the regular LFER. This suggests that the oncogenic effect of distinct Ras mutants has a different physical origin. The results presented might aid in the design of drugs aimed at reactivating the GTPase reaction of many oncogenic p21ras mutants. We also analyzed the stimulated GTPase reaction of p21ras by the GTPase activating protein (GAP) and the GTPase reaction of Rap1A, a Ras-related GTP binding protein, with similar approaches. The corresponding results indicate that the GAP-stimulated GTPase as well as the Rap1A-catalyzed reaction seem to follow the same substrate-assisted reaction mechanism. However, the correlation coefficient for the GAP-catalyzed reaction is different from the corresponding coefficient for the intrinsic reaction. While the intrinsic reaction exhibits a Brønsted slope of beta = 2.1, the corresponding value for the GAP-activated reaction is beta = 4.9.

Binding Sites↗

PubMed1996

Polyamine spider toxins and mammalian N-methyl-D-aspartate receptors. Structural basis for channel blocking and binding of argiotoxin636.

Recombinant N-methyl-D-aspartate receptors composed of NR1/NR2A subunits were expressed in Xenopus oocytes to analyse the voltage-dependent and use-dependent channel blocking activity of argiotoxin636. Functional assays demonstrate that the toxin competes with other open channel blockers such as Mg2+ and MK-801. Direct binding or competition assays using radiolabeled ligands and isolated rat brain membranes, in contrast, reveal no specific binding or yield binding constants which differ by orders of magnitude from the IC50 values of the functional assays. One explanation is that argiotoxin636 does not bind with high affinity to the inhibitory site in the N-methyl-D-aspartate-receptor channel under in vitro conditions when membranes are depolarised. The structure of argiotoxin636 was investigated by NMR spectroscopy. In solution the positively charged argiotoxin636 acquires an extended conformation and its dimensions might allow permeation deep into the channel. In the absence of direct structural information on the channel protein, the detailed analysis of blockade in conjunction with structural information, as provided here, may be of aid in the deduction of structural features of glutamate-receptor channel ion pores.

Animals↗

PubMed1996

Conformational transitions in p21ras and in its complexes with the effector protein Raf-RBD and the GTPase activating protein GAP.

31P NMR revealed that the complex of p21ras with the GTP analog GppNHp.Mg2+ exists in two conformational states, states 1 and 2. In wild-type p21ras the equilibrium constant K1(12) between the two states is 1.09. The population of these states is different for various mutants but independent of temperature. The activation enthalpy delta H ++ and activation entropy delta S ++ for the conformational transitions were determined by full-exchange matrix analysis for wild-type p21ras and p21ras(S65P). For the wild-type protein one obtains delta H ++ = 89 +/- 2 kJ mol-1 and delta S ++ = 102 +/- 20 J mol-1 K-1 and for the mutant protein delta H ++ = 93 +/- 7 kJ mol-1 and delta S ++ = 138 +/- 30 J mol-1 K-1. The study of various p21ras mutants suggests that the two states correspond to different conformations of loop L2, with Tyr-32 in two different positions relative to the bound nucleotide. High-field EPR at 95 GHz suggest that the observed conformational transition does not directly influence the coordination sphere of the protein-bound metal ion. The influence of this transition on loop L4 was studied by 1H NMR with mutants E62H and E63H. There was no indication that L4 takes part in the transition described in L2, although a reversible conformational change could be induced by decreasing the pH value. The exchange between the two states is slow on the NMR time scale (< 10 s-1): at approximately pH 5 the population of the two states is equal. The interaction of p21ras-triphosphate complexes with the Ras-binding domain (RBD) of the effector protein c-Raf-1, Raf-RBD, and with the GTPase activating protein GAP was studied by 31P NMR spectroscopy. In complex with Raf-RBD the second conformation of p21ras (state 2) is stabilized. In this conformation Tyr-32 is located in close proximity to the phosphate groups of the nucleotide, and the beta-phosphate resonance is shifted upfield by 0.7 ppm. Spectra obtained in the presence of GAP suggest that in the ground state GAP does not interact directly with the nucleotide bound to p21ras and does not induce larger conformational changes in the neighborhood of the nucleotide. The experimental data are consistent with a picture where GAP accelerates the exchange process between the two states and simultaneously increases the population of state 1 at higher temperature.

Cloning, Molecular↗

PubMed1996

Chlorophyll fluorescence biosensor for the detection of herbicides.

A biosensor is described for the detection of triazine and phenylurea herbicides in drinking water by kinetic measurements of endogenous chlorophyll fluorescence in isolated chloroplasts from higher plants. The pocket-size device uses a diode laser for simultaneous excitation of sample and reference channels, and photodiodes for detection of the emitted light. The biological material can be supplied as a freeze-dried powder, stable for 21 days at room temperature, for 6 weeks at 4 ( degrees )C or for at least 9 months at -20 ( degrees )C. The detection of 0.1 microg/l of a single herbicide, as required by European Community legislation on drinking water quality, can be achieved without prior extraction of the sample.

Journal Article↗

PubMed1996

[Osteolysis of the lateral clavicle after Tossy II injury in ice hockey players].

Injuries of the acromioclavicular joint in hockey mainly occur after trauma directly to the shoulder joint. E.g. at a fall against the border, onto the ground or in case of a body check. Tossy-III-lesions lead directly to surgery meanwhile type Tossy-II-lesions are mainly treated conservatively. Despite healing of the acromioclavicular ligaments often acromioclavicular joint pain remains despite conservative treatment because of discuss lesions or a osteolysis of the lateral end of the clavicle. The resection of the lateral end of the clavicle with certain pain relief, very good functional results and quick full level participation in hockey has been shown as the method of choice in our patients.

Acromioclavicular Joint↗

PubMed1996

[A new osteoblast cell culture system for standardized testing of biomaterials].

For in vitro testing of new biomaterials cultured fibroblasts are employed. In the case of the agar diffusion test survival of cells is involved in the presence of the material to be tested. Further statements on the biological effects of a biomaterial require the use of cell cultures adapted to the tissue concerned and the underlying problem being investigated. In the present study, an osteoblast cell culture system with which implant surfaces in contact with bone can be tested as required by the relevant standards is described. Test bodies made of titanium, polystyrene or copper were used in the conventional agar diffusion test, and were also overgrown with fibroblasts or a cell line of foetal human osteoblasts. For the agar diffusion test, the test criterion was the extent of the inhibition area on staining with neutral red, while for the overgrowth, the mean cell diameter and the number of cells was employed. The phenotype of the osteoblast cell line was determined immunohistochemically by means of alkaline phosphatase or immunohistologically by means of collagen I and osteocalcin. Calcification was demonstrated using the v. Kossa stain. In the case of the osteoblasts, a differentiation of a collagen I and alkaline phosphatase-positive phenotype over an osteocalcin-positive phenotype to an increase in calcium deposition was shown. As in the case of the agar diffusion test, direct overgrowth also revealed no cytotoxic effect for titanium and polystyrene. In contrast, a cytotoxic effect consisting in a decrease in the number of cells and also a left shift in the size distribution was observed for copper. The standard deviations of the individual tests were less for overgrowth than for the agar diffusion test. The culture system for osteoblast cells thus meets the criteria of the EN/DIN 30993-5 in terms of the quality and accuracy of the results obtained. In addition to excluding direct cytotoxicity, this test system offers a new possibility of examining the influence of the material on cell growth. Consequently, it permits a repeatable examination of proliferation and differentiation of the osteoblasts on each material surface.

Animals↗