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Biomedical subjects

R Meyer

Publications and source records attributed to R Meyer.

At least 73 records · Page 4Linked to original sources

Different types of aortic stenosis and simulation of their morphological-hydrodynamic interdependence--in vitro study with allografts and stenotic valve models.

Biological valves display a dependence of valve resistance and valve area on flow and a phase shift between systolic flow through the valves and pressure difference across the valves. The pressure-flow relations of stenosed valves raise questions about the "best measure of stenosis". There is a need for quantitative evaluation of the hydrodynamic performance of homografts and allografts. In the present paper, we report on in vitro studies of the hydrodynamic behavior of homografts from human donors, allografts from different animal species as well as three valve models. Valve model I was designed to simulate flow-dependence of valve area, valve model II was designed to simulate restricted valve opening independent of flow, and valve model III was designed to simulate a flow-dependent movement of valve root in flow direction. Among other aspects, the effect of increased viscosity of the test fluid on the pressure difference and the effects of water absorption by valve tissue on valve characteristics were investigated. The results of the present studies clearly indicate that any biological valve may be modelled as a serial connection of a model I type valve and a model II type valve. From the results, the dependence of the characteristic pressure-flow relationship of a valve on valve size and valve distensibility can be clearly seen and the clinical significance of the characteristic coefficients of the pressure-flow relationship of a valve can be elucidated. Further, it was shown that the characteristic phase shift between flow and pressure difference displayed by biological valves is due to their movable valve plane similar to that of valve model III.

Animals↗

Increased level of HSP27 but not of HSP72 in human heart allografts in relation to acute rejection.

BACKGROUND: Increased expression of heat shock proteins (HSPs) was assumed during cardiac allograft rejection. To find evidence for this in man, we quantified HSP27 and HSP72 in cardiac allograft biopsies. METHODS: In parallel to histological assessment of rejection, HSP27 was quantified by Western blotting in a total of 43 biopsies sampled from 3 patients. HSP72 was analyzed in parallel in 30 of the 43 cases. For comparison, HSPs were analyzed in myocardium. RESULTS: HSP27 was significantly higher in rejecting cardiac allografts than in non-rejecting allografts and non-failing myocardium (1.52 +/- 0.25 vs. 0.83 +/- 0.11 vs. 0.50 +/- 0.05 microg/mg protein). Similarity for HSP72 (6.27 +/- 1.54 vs. 4.06 +/- 1.03 vs. 6.27 +/- 0.76 microg/mg protein) was not found. CONCLUSION: For the first time in humans with cardiac allograft rejection, increased expression of HSP27, which could be important for cardiac self-protection, was demonstrated. For the lack of increased HSP72 expression, the influence of the cyclosporine A treatment was discussed.

Acute Disease↗

Sequence and analysis of chromosome 5 of the plant Arabidopsis thaliana.

The genome of the model plant Arabidopsis thaliana has been sequenced by an international collaboration, The Arabidopsis Genome Initiative. Here we report the complete sequence of chromosome 5. This chromosome is 26 megabases long; it is the second largest Arabidopsis chromosome and represents 21% of the sequenced regions of the genome. The sequence of chromosomes 2 and 4 have been reported previously and that of chromosomes 1 and 3, together with an analysis of the complete genome sequence, are reported in this issue. Analysis of the sequence of chromosome 5 yields further insights into centromere structure and the sequence determinants of heterochromatin condensation. The 5,874 genes encoded on chromosome 5 reveal several new functions in plants, and the patterns of gene organization provide insights into the mechanisms and extent of genome evolution in plants.

Animals↗

Negative regulation of alkylation-induced sister-chromatid exchange by poly(ADP-ribose) polymerase-1 activity.

One of the earliest responses to DNA damage in eukaryotic cells is activation of poly(ADP-ribose) polymerase-1 (PARP-1), a DNA strand break-dependent nuclear enzyme which covalently modifies proteins with poly(ADP-ribose). Here, we show that conditional over-expression of PARP-1 in stably transfected hamster cells, which causes cellular over-accumulation of poly(ADP-ribose) by several-fold, strongly suppresses alkylation-induced sister-chromatid exchange (SCE), while cytotoxicity of alkylation treatment is slightly enhanced. Viewed together with the known potentiation of SCE by abrogation of PARP-1 activity, our results provide evidence that PARP-1 activity is an important regulator of alkylation-induced SCE formation, imposing a control that is strictly negative and commensurate with the level of enzyme activity.

Alkylation↗

Effect of the knobbed acrosome defect in bovine sperm on IVF and embryo production.

An IVF and culture system was used to determine the effect of the knobbed acrosome defect in bovine spermatozoa on fertilization and early embryonic development. Three bulls affected with knobbed acrosomes were identified as K+ (flattened acrosome), K2+ (indented acrosome) or K3+ (deep indentation of the acrosome) based on the predominant type of acrosomal aberration present in sperm of the respective bulls. After swim-up, all semen traits, except for acrosome morphology, were similar between bulls with varying degrees of the knobbed acrosome defect and a control bull, C. The mean number of spermatozoa bound to the zona pellucida was lower (P< 0.05) for the bulls with the knobbed acrosome defects (40.3 +/- 2.3, 29.5 +/- 1.6, 14.6 +/- 1.3, respectively, for Bulls K+, K2+ and K3+) than for Bull C (52.3 +/- 2.3). The percentages of zonae pellucidae penetrated by spermatozoa from Bulls K+ (51.2%), K2+ (49.5%) and K3+ (37.1%) were lower than that of Bull C (84.5%). No sperm with knobbed acrosome defects were found to have penetrated the zona pellucida. Fertilization rates for bulls with the knobbed acrosome defect, K+ (63.0%), K2+ (62.7%) and K3+ (22.6%), were significantly lower than that of the control bull (82.8%). Percentages of cleaved embryos, morulae and blastocysts produced were also lower for the bulls with knobbed acrosomes than that of the control bull. Results indicate that sperm with the knobbed acrosome defect had a reduced ability to bind to the zona pellucida, depending upon the severity of the defect, and that these aberrant spermatozoa did not penetrate the zona pellucida. The apparently normal spermatozoa coexisting in the inseminate of bulls with a high percentage of knobbed spermatozoa were also functionally deficient; oocytes penetrated by these spermatozoa had a reduced potential for fertilization, and resulting zygotes had a reduced ability for cleavage and embryonic development to the blastocyst stage. The results of the present study do not support the hypotheses that the knobbed acrosome defect is compensable.

Acrosome↗

[Metastasizing malignant germ cell tumor of the testis with infiltration of the thoracic aorta--a case for metastasis surgery].

HISTORY AND FINDINGS: A 33-year-old man was admitted 7 years after a testicular teratomatous carcinoma had first been diagnosed, treated by a right orchiectomy and two-stage radical retroperitoneal lymphadenectomy. Five years later the first mediastinal metastases were treated with high-dosage chemotherapy and autologous germ-cell transplantation, and remaining paraaortic--mediastinal tumour tissue was resected. Two years later another tumour at that site was only partially resected. A curing treatment seemed impossible, because the aortic wall had been invaded. TREATMENT AND COURSE: Five months after re-thoracotomy the metastasis and the invaded aortic segment were resected, the latter replaced by a vascular prosthesis. Histology indicated metastasis of a malignant teratoma of intermediate type. There has been no evident recurrence in the last 20 months. CONCLUSION: Combined orchidectomy, lymphadenectomy, high-dosage chemotherapy with cisplatin and autologous germ-cell transplantation at present constitute the standard treatment of malignant testicular germ-cell tumour. In case of metastatic infiltration of vital structures, such as the aortic wall, special operative procedures can prolong the period of remission when the success of a standard treatment seems limited.

Adult↗

Estrogen receptor alpha rapidly activates the IGF-1 receptor pathway.

Estrogen and insulin-like-growth factor 1 (IGF-1) are potent mitogenic stimuli that share important properties in the control of cellular proliferation. However, the coupling between the signaling cascades of estrogen receptors alpha and beta and the IGF-1 receptor (IGF-1R) is poorly understood. Therefore, we selectively transfected estrogen receptor alpha or beta in COS7 and HEK293 cells, which contain IGF-1R. In presence of estrogen receptor alpha but not beta, 17beta-estradiol (E2) rapidly induces phosphorylation of the IGF-1R and the extracellular signal-regulated kinases 1/2. Furthermore, upon stimulation with E2, estrogen receptor alpha but not beta bound rapidly to the IGF-1R in COS7 as well as L6 cells, which express all investigated receptors endogenously. Control experiments in the IGF-1R-deficient fibroblast cell line R(-) showed that after stimulation with E2 only estrogen receptor alpha bound to the transfected IGF-1R. Overexpression of dominant negative mitogen-activated protein kinases kinase inhibited this effect. Finally, estrogen receptor alpha but not beta is required to induce the activation of the estrogen receptor-responsive reporter ERE-LUC in IGF-1-stimulated cells. Taken together, these data demonstrate that ligand bound estrogen receptor alpha is required for rapid activation of the IGF-1R signaling cascade.

Animals↗

Cellular allograft rejection affecting the donor aorta after combined heart-lung transplantation.

BACKGROUND: Infectious pseudoaneurysms of the ascending aorta are a recognized major complication after heart-lung transplantation. METHOD: This report describes an unusual and previously unreported complication, that of cellular allograft rejection, which caused a pseudoaneurysm of the donor's ascending aorta in a patient who underwent combined heart-lung transplantation. Repair was performed by primary suture after mobilization of the aortic segments. RESULT: On histological examination the resected aneurysm showed evidence of proliferative vasculitis with perivascular infiltration of the vasa vasorum by mononuclear cells. The mononuclear cells were identified as CD4+ and CD8+ by immunohistological staining. CONCLUSIONS: This report shows that cellular allograft rejection may affect the donor aorta after heart-lung transplantation and may result in pseudoaneurysm formation, even under triple-drug immunosuppression after ABO-compatible allograft transplantation.

Adult↗

Fluid mechanics of biological surfaces and their technological application.

A survey is given on fluid-dynamic effects caused by the structure and properties of biological surfaces. It is demonstrated that the results of investigations aiming at technological applications can also provide insights into biophysical phenomena. Techniques are described both for reducing wall shear stresses and for controlling boundary-layer separation. (a) Wall shear stress reduction was investigated experimentally for various riblet surfaces including a shark skin replica. The latter consists of 800 plastic model scales with compliant anchoring. Hairy surfaces are also considered, and surfaces in which the no-slip condition is modified. Self-cleaning surfaces such as that of lotus leaves represent an interesting option to avoid fluid-dynamic deterioration by the agglomeration of dirt. An example of technological implementation is discussed for riblets in long-range commercial aircraft. (b) Separation control is also an important issue in biology. After a few brief comments on vortex generators, the mechanism of separation control by bird feathers is described in detail. Self-activated movable flaps (= artificial bird feathers) represent a high-lift system enhancing the maximum lift of airfoils by about 20%. This is achieved without perceivable deleterious effects under cruise conditions. Finally, flight experiments on an aircraft with laminar wing and movable flaps are presented.

Animals↗

[Autopsy techniques in congenital heart defects. Influence of prenatal diagnosis on the planning and carrying out of autopsies].

As a result of the quality of prenatal ultrasound and the expanded experience of prenatal diagnosticians, it is possible to observe congenital heart malformations in increasingly greater detail and at an ever earlier stage of gestation [4]. Since it is on the basis of ultrasound findings that decisions to terminate pregnancies are made, it is of cardinal importance that after termination monitoring and confirmation of the prenatal diagnosis be carried out. This need can only be adequately met by autopsy. There are different methods for carrying out autopsies when there is suspicion of a congenital heart defect: a) the Anderson sequential segmental analysis as modified according to the Berlin method; b) use of a special autoptic method corresponding to the ultrasound findings, based on defining a preferred sectional plane; c) stereomicroscopically; or d) microscopically after embedding and preparation of serial microscopic sections. For the pathologist the consequence is that he has to adapt his autopsy method to the ultrasound findings and the age of the fetus. This enables him to determine an optimal, case-based autopsy strategy for each type of cardiac defect, which is essential for monitoring of the prenatal diagnosis. The present paper discusses the various autoptic methods used in cases of congenital heart malformations and the consequences for the pathologist of the continuing improvements in prenatal diagnostics.

Autopsy↗

Profile and kinetics of L-type calcium current during the cardiac ventricular action potential compared in guinea-pigs, rats and rabbits.

The substantial interspecies differences in mammalian cardiac action potentials (APs) are attributed primarily to variations in K+ currents. In a comparative study on isolated ventricular myocytes from guinea-pigs, rabbits and rats, we investigated the influence of the species-based AP differences on the time course of the L-type Ca2+ current (ICa,L). In addition, we tested whether also species-dependent properties of the ICa,L contribute to its time course during the AP. In patch-clamp measurements, ICa,L was characterised using conventional square pulses and digitised APs as command voltages. Special interest was directed to the analysis of the actual time courses of ICa,L, and L-type channel activation and inactivation during APs. Although species-specific differences in AP shape strongly influence the amplitude and the time course of ICa,L, divergence in L-type channel inactivation was found as well. In each species ICa,L inactivation was related to Ca2+ influx via L-type channels. However, while L-type channels showed similar Ca2+ dependency in the rabbit and the rat, a 2-times higher Ca2+ influx was necessary to achieve a given degree of inactivation in the guinea-pig. Thus, inactivation of ICa,L is delayed in the guinea-pig, thereby contributing to the prolonged AP plateau in this species. Comparing the actual time course of ICa,L, and L-type channel activation and inactivation revealed that, in each species, fading of ICa,L during final repolarisation was caused by deactivation (i.e. closure of the channel's d-gate) rather than inactivation.

Action Potentials↗

Comparing the German versions of the Strengths and Difficulties Questionnaire (SDQ-Deu) and the Child Behavior Checklist.

The Strengths and Difficulties Questionnaire (SDQ) is a brief behavioural screening questionnaire that can be completed in about 5 minutes by the parents and teachers of 4-16 year olds. The scores of the English version correlate well with those of the considerably longer Child Behavior Checklist (CBCL). The present study compares the German versions of the questionnaires. Both SDQ and CBCL were completed by the parents of 273 children drawn from psychiatric clinics (N = 163) and from a community sample (N = 110). The children from the community sample also filled in the SDQ self-report and the Youth Self Report (YSR). The children from the clinic sample received an ICD-10 diagnosis if applicable. Scores from the parent and self-rated SDQ and CBCL/YSR were highly correlated and equally able to distinguish between the community and clinic samples, with the SDQ showing significantly better results regarding the total scores. They were also equally able to distinguish between disorders within the clinic sample, the only significant difference being that the SDQ was better able to differentiate between children with and without hyperactivity-inattention. The study shows that like the English originals, the SDQ-Deu and the German CBCL are equally valid for most clinical and research purposes.

Adolescent↗

Comparison of porcine xenografts and homografts for pulmonary valve replacement in children.

BACKGROUND: Due to the limited availability of homografts, different alternatives are used for replacement of the pulmonary valve. This study investigates the value of porcine stentless pulmonary xenografts in pediatric cardiac patients. METHODS: Twenty-three pediatric xenograft (size 10 to 21 mm) recipients were compared with 23 homograft (size 9 to 21 mm) recipients. RESULTS: Hospital mortality was 2 of 23 patients in the xenograft group and 3 of 23 in the homograft group (NS). Six out of 20 xenografts and 1 of 19 homografts were stenotic after 1 year (p = 0.011). Xenograft stenoses were mainly located at the distal anastomosis, while the leaflets were preserved. Homografts showed valvular stenoses and wall calcification. The 1 year freedom from reoperation was 77% in the xenograft and 93% in homograft recipients (NS), and from transcatheter intervention 84% and 100% (p = 0.004), respectively. Transcatheter intervention in 7 xenograft patients and 1 homograft recipient improved stenosis gradients from 65 to 40 mm Hg (mean) in 6 out of 8 patients. Explanted xenografts showed a loss of elastic membranes and proliferating connective tissue scars coated with activated endothelium. CONCLUSIONS: Xenografts demonstrated a higher incidence of supravalvular obstructions, which were possibly due to unfavorable hemodynamics at the distal anastomosis. Histological findings additionally indicated a pronounced immunological response. Interventional angioplasty lowered the rate of reoperation. Thus, the use of xenografts in children can be accepted as a second choice when a homograft is unavailable.

Animals↗

Oxidative stress in the human heart is associated with changes in the antioxidative defense as shown after heart transplantation.

The study was designed to demonstrate--for the first time in humans--that oxidative stress in the heart indicated by lipid peroxidation is associated with time-dependent changes in the enzymatic antioxidative defense. For this purpose, we analyzed the oxygen radical metabolism in 69 myocardial biopsies (taken between the fifth day and 6 years after transplantation) of 31 heart transplant recipients who were suspected of suffering from increased formation of oxygen radicals in the allograft. The levels of lipid peroxides (LPO), glutathione peroxidase (GSH-Px), total-, copper/zinc- and manganese superoxide dismutase (t-SOD, CuZnSOD, MnSOD) were compared in 3 post-transplantation periods (5-90 d vs. 91-365 d vs. >1 y). Significantly increased LPO levels were found (0.27+/-0.04 vs. 0. 13+/-0.02 vs. 0.27+/-0.04 nmol/mg protein) in the first and third period. Increased activities of GSH-Px (39.8+/-3.8 vs. 30.2+/-4.1 vs. 76.7+/-6.5 mU/mg protein), t-SOD (1.57+/-0.10 vs. 1.30+/-0.14 vs. 2.44+/-0.23 U/mg protein) and CuZnSOD (1.09+/-0.08 vs. 0.93+/-0.13 vs. 2.05+/-0.21 U/mg protein) occurred only in the third period. For calculation of time courses more precisely, the single data with respect to time were analyzed with a curve fitting program. Except for the first period, the allograft LPO and GSH-Px levels rose for up to 6 years after transplantation. However, the t-SOD and CuZnSOD activities switched from increase to decrease in the third period. The study provided indication for: first, the potency of the human heart to time-limited increase of the enzymatic antioxidative defense, and secondly, the inability of human heart allografts--despite this adaptation--for complete prevention of myocardial oxidative stress.

Adult↗

The adaptation of perimuscular connective tissue during distraction osteogenesis.

It is not known whether the decreased range of motion observed during distraction osteogenesis results from the lack of adaptation of muscle or from fibrosis in the perimysium. The adaptation of the perimysium in the tibialis anterior muscle in skeletally immature rabbits using two distraction regimens (0.7 and 1.4 mm/day with 15% lengthening) was characterized. The resulting data indicate that during distraction osteogenesis, the muscle adapts by reorganization of its connective tissue. At a lengthening rate of 1.4 mm/day, there is perimysial fibrosis without major cellular pathologic abnormalities in the muscle fibers. The increase in perimysial thickness is characterized by an increase of collagen Type I. In addition, collagen Type I is deposited around the endomysium. The increase in total collagen and its cross-linking are dependent on the lengthening rate. The faster lengthening rate also leads to a significant decreased passive plantar flexion. Supplemental growth of the tibia was not observed, and a lack of adaptation in the muscle (based on resting length) was not seen. Together, the data suggest that decreased range of motion during distraction osteogenesis may be a function of the adaptation of the perimysium rather than of the muscle fibers.

Adaptation, Physiological↗

Bayesian reconstruction of chaotic dynamical systems

We present a Bayesian approach to the problem of determining parameters of nonlinear models from time series of noisy data. Recent approaches to this problem have been statistically flawed. By applying a Markov chain Monte Carlo algorithm, specifically the Gibbs sampler, we estimate the parameters of chaotic maps. A complete statistical analysis is presented, the Gibbs sampler method is described in detail, and example applications are presented.

Journal Article↗

Identification of the mob genes of plasmid pSC101 and characterization of a hybrid pSC101-R1162 system for conjugal mobilization.

Similarities in DNA base sequence indicate that pSC101 and R1162 encode related systems for conjugal mobilization, although these plasmids are otherwise very different. The mob region of pSC101 was cloned, and two genes that are required for transfer were identified. One gene, mobA, encodes a protein similar in amino acid sequence to the DNA processing domain of the R1162 MobA protein. The other gene, mobX, is within the same transcriptional unit as the pSC101 mobA and is located just downstream, at the same position occupied by mobB in R1162. Despite this, the MobB and MobX proteins do not appear to be closely related based on a comparison of their amino acid sequences. Complementation analysis indicated that neither of the pSC101 Mob proteins could substitute for, or be replaced by, their R1162 counterparts, nor were they active together at the R1162 origin of transfer (oriT). However, the full set of R1162 Mob proteins did recognize the pSC101 oriT. A hybrid system for mobilization, active at the R1162 oriT site, was constructed. This system consists of MobX and a chimeric protein made up of the DNA cleaving-ligating domain of the R1162 MobA protein joined to a fragment of pSC101 MobA. Previous results suggested that MobB and a region of MobA distinct from the DNA processing domain together formed a functional unit in transfer. The present results support this model because the chimeric MobA, although active on R1162 oriT, requires the pSC101 protein MobX for efficient plasmid mobilization.

Amino Acid Sequence↗