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Biomedical subjects

Volker Schmidt

Publications and source records attributed to Volker Schmidt.

15 recordsLinked to original sources

Measurement of the bending strength of vapor-liquid-solid grown silicon nanowires.

The fracture strength of silicon nanowires grown on a [111] silicon substrate by the vapor-liquid-solid process was measured. The nanowires, with diameters between 100 and 200 nm and a typical length of 2 microm, were subjected to bending tests using an atomic force microscopy setup inside a scanning electron microscope. The average strength calculated from the maximum nanowire deflection before fracture was around 12 GPa, which is 6% of the Young's modulus of silicon along the nanowire direction. This value is close to the theoretical fracture strength, which indicates that surface or volume defects, if present, play only a minor role in fracture initiation.

Computer Simulation↗

ThromboFix platelet stabilizer: advances in clinical platelet analyses by flow cytometry?

UNLABELLED: Platelet flow cytometry is restricted by spontaneous platelet activation in unfixed samples or by significant alterations of platelet performance caused by the use of fixatives. Aim of this study was to evaluate the new platelet stabilizer ThromboFix for clinical diagnostics. METHODS: Whole blood samples with or without addition of a weak (ADP) or strong (TRAP-6) agonist were fixed with either ThromboFix or paraformaldehyde (PFA) and stored for different periods of time for up to 7 days. Samples were then incubated with either CD41 and CD62P or CD42b and CD45 monoclonal antibodies and analyzed by flow cytometry. RESULTS: The numbers of platelets, microparticles and aggregates remained stable for 7 days after treatment with ThromboFix but not with PFA due to an increasing aggregate formation after 3 days. Platelet activation was restricted to less than 1% of CD62P positive events in resting samples without a significant difference compared to an unfixed reference sample. Fixation, however, significantly reduced CD62P expression after stimulation (P < 0.05). Stabilized by ThromboFix, the level of platelet activation remained unchanged in resting and ADP stimulated samples for 7 days but decreased moderately with time after a strong stimulation with TRAP-6 (P < 0.01). After PFA fixation, intact CD62P antigen disappeared from the platelet surface within hours (P < 0.01). ThromboFix reduced the formation of platelet-leukocyte conjugates significantly (P < 0.05) and, in contrast to PFA, failed to stabilize the already formed conjugates. CONCLUSION: In clinical situations without immediate access to a flow cytometer, ThromboFix is helpful in the flow cytometric analysis of the platelet activation marker CD62P. It should not be used for the investigation of platelet-leukocyte conjugate formation.

Adenosine Diphosphate↗

Fitting of random tessellation models to keratin filament networks.

The role of specific structural patterns in keratin filament networks for regulating biophysical properties of epithelial cells is poorly understood. This is at least partially due to a lack of methods for the analysis of filament network morphology. We have previously developed a statistical approach to the analysis of keratin filament networks imaged by scanning electron microscopy. The segmentation of images in this study resulted in graph structures, i.e. tessellations, whose structural characteristics are now further investigated by iteratively fitting geometrical statistical models. An optimal model as well as corresponding optimal parameters are detected from a given set of possible random tessellation models, i.e. Poisson-Line tessellations (PLT), Poisson-Voronoi tessellations (PVT) and Poisson-Delaunay tessellations (PDT). Using this method, we investigated the remodeling of keratin filament networks in pancreatic cancer cells in response to transforming growth factor alpha (TGFalpha), which is involved in pancreatic cancer progression. The results indicate that the fitting of random tessellation models represents a suitable method for the description of complex filament networks.

Algorithms↗

Diameter-dependent growth direction of epitaxial silicon nanowires.

We found that silicon nanowires grown epitaxially on Si (100) via the vapor-liquid-solid growth mechanism change their growth direction from 111 to 110 at a crossover diameter of approximately 20 nm. A model is proposed for the explanation of this phenomenon. We suggest that the interplay of the liquid-solid interfacial energy with the silicon surface energy expressed in terms of an edge tension is responsible for the change of the growth direction. The value of the edge tension is estimated by the product of the interfacial thickness with the surface energy of silicon. For large diameters, the direction with the lowest interfacial energy is dominant, whereas for small diameters the surface energy of the silicon nanowire determines the preferential growth direction.

Anisotropy↗

A disease complex associated with pigeon circovirus infection, young pigeon disease syndrome.

In order to collect more convincing data on the aetiological agent of young pigeon disease syndrome (YPDS), a comprehensive study was performed on pigeons in German lofts with or without outbreaks of YPDS. The investigations included examination of histories, clinical signs and pathology, as well as parasitological and microbiological analysis. Pigeons in their 4th to 12th week of life exhibited clinical signs at higher frequency and with greater severity than pigeons of other ages. Greenish liquid in the crop, proventriculus and ventriculus, and yellow fluid in the small intestine were seen more often in YPDS-affected pigeons. Escherichia coli and Klebsiella pneumoniae were isolated more frequently from these birds. Depletion of splenic and bursal lymphocytes was only seen in pigeons with YPDS. Inclusion bodies were present in various organs, especially the bursa of Fabricius. The genome of pigeon circovirus was detected in lymphoid tissues from all pigeons with YPDS. The results of this study indicate that YPDS is a multifactorial disease in which pigeon circovirus might be a crucial factor, possibly by inducing immunosuppression in infected birds.

Animals↗

Platelet activity, reactivity and platelet-leukocyte conjugate formation before and after exhaustive or moderate exercise in patients with IDDM.

Diabetes mellitus alters blood coagulation and platelet function which supports the suggestion that diabetes mellitus is a hypercoagulable state. Firstly the aim of the study was to investigate if differences in platelet activity, reactivity and platelet-leukocyte conjugate (PLC) formation can be observed in subjects with IDDM; secondly, if differences can be seen between the diabetic and control group concerning exercise-induced changes in platelet activation and conjugate formation; and thirdly, if different types of exercise lead to different patterns in platelet activation. Sixteen subjects with IDDM and 16 controls underwent a maximal step test and an endurance test (90% IAT, 45 min). Blood samples were taken after 30 min rest, and immediately and 1 h after completion of exercise. CD62P expression and differentiated platelet-leukocyte conjugates (CD45, CD14, CD41) were detected flow-cytometrically with and without stimulation with TRAP-6. The rest values of the platelet-granulocyte (PGC) and platelet-lymphocyte conjugates (PLyC) were higher (P < 0.05) in the diabetics. After exercise, platelet reactivity (CD62P-TRAP; P < 0.05) but not the activity (CD62P-unstimulated), as well as all different conjugates with or without stimulation were increased (P < 0.05) independently from the group. Differences according to the type of exercise were barely observable. IDDM without vascular complications leads to higher PCG and PLyC at rest and to identical increases in differentiated platelet-leukocyte formation after exercise in comparison with matched controls.

Adult↗

Differentiation of platelet-leukocyte conjugate formation by short term exercise.

Platelet-leukocyte conjugates are increased in cardiovascular disease, but exercise is also able to trigger platelet-leukocyte formation in healthy subjects. The aim was to investigate the heterogeneity of platelet-leukocyte conjugate formations triggered by short term exercise. 18 healthy non-smokers underwent a 90 second maximal test on a SRM cycle ergometry system and a control experiment. Blood samples were taken after 30 min rest, immediately before and after, 15 min and 1 h after exercise. The different platelet-leukocyte conjugates were detected by flow cytometry via CD45, CD14, CD16, CD41, together with CD62P antibodies for the investigation of platelet activation in the conjugates. In addition, a stimulation of conjugate formation in vitro with 8 microM TRAP-6 was initiated. Immediately after exercise platelet-granulocyte (+24%), and -lymphocyte (+17%) conjugates were increased (p<0.01), while the platelet-monocyte conjugates (+40%) were enhanced (p<0.05) 15 min after exercise. The differentiation after stimulation showed that the regular (CD14(+)16(-); +32%) and mature (CD14(+)16(+); +35%) monocytes were both increased after exercise (p<0.01) but the regular monocytes were preferred (p<0.001) in platelet-monocyte conjugate formation. In addition, these conjugates revealed the highest CD62P expression. Maximal short term exercise is useful for the investigation of platelet-leukocyte formation; e.g., it could be shown, that regular monocytes may be preferred in conjugate formation and that these conjugates revealed the highest CD62P expression.

Adult↗

Classification of prostatic carcinoma with artificial neural networks using comparative genomic hybridization and quantitative stereological data.

Staging of prostate cancer is a mainstay of treatment decisions and prognostication. In the present study, 50 pT2N0 and 28 pT3N0 prostatic adenocarcinomas were characterized by Gleason grading, comparative genomic hybridization (CGH), and histological texture analysis based on principles of stereology and stochastic geometry. The cases were classified by learning vector quantization and support vector machines. The quality of classification was tested by cross-validation. Correct prediction of stage from primary tumor data was possible with an accuracy of 74-80% from different data sets. The accuracy of prediction was similar when the Gleason score was used as input variable, when stereological data were used, or when a combination of CGH data and stereological data was used. The results of classification by learning vector quantization were slightly better than those by support vector machines. A method is briefly sketched by which training of neural networks can be adapted to unequal sample sizes per class. Progression from pT2 to pT3 prostate cancer is correlated with complex changes of the epithelial cells in terms of volume fraction, of surface area, and of second-order stereological properties. Genetically, this progression is accompanied by a significant global increase in losses and gains of DNA, and specifically by increased numerical aberrations on chromosome arms 1q, 7p, and 8p.

Adenocarcinoma↗

Short-term exercise and platelet activity, sensitivity to agonist, and platelet-leukocyte conjugate formation.

Strenuous exercise may be partially responsible for cardio-vascular events. The aim was to investigate the platelet activity, reactivity and different platelet-leukocyte-conjugate formation following maximal short-term exercises. Fifteen healthy non-smokers underwent three isokinetic maximal tests on a SRM cycle ergometry system with durations of 15, 45 and 90 s. Blood samples were taken after a 30-min rest, immediately before and after exercise, and 15 min and 1 h after completion of exercise. Platelets were detected flow-cytometrically by CD41, and activated platelets by CD62P. In addition, stimulation of the platelets in vitro with 7.5 microM TRAP-6 was initiated. For testing platelet-leukocyte-conjugates, antibodies against CD45, CD14 and CD41 were used. After the exercise tests the percent of non-stimulated CD62P-positive platelets (%PC) was unchanged. In contrast, an increase in %PC (CD62P) TRAP-6 stimulated (15-s test: 37.2+/-10.3 to 46.2+/-12.3%, P < 0.05; 90-s test: 40.6+/-9.5 to 51.7+/-10.2%, P < 0.01) and in platelet-granulocyte, platelet-lymphocyte, and platelet-monocyte conjugate formation 15 min after exercise (45- and 90-s test; P < 0.05) were observed in comparison with the changes on the control day. The changes nearly reversed 1 h after exercise. Maximal short-term exercise only leads to a moderate increase of platelet reactivity and to an increase in the different platelet-leukocyte conjugates. The implications of the changes in platelet-leukocyte conjugate formation should be investigated in future studies.

Adult↗

Paraformaldehyde fixation induces a systematic activation of platelets.

In whole blood flow cytometric platelet assays sample fixation using paraformaldehyde (PFA) is considered very advantageous to prevent spontaneous activation of platelets in vitro. However, fixation is an important variable in activation assays and its influence on platelets is poorly understood. Using a direct immunofluorescence labelling technique and whole blood flow cytometry, the effect of PFA fixation was investigated for 4 different epitopes on platelet surface each of which mirrors a different aspect of platelet activation, namely P-selectin (CD62P), GP IIbIIa complex (CD41), the fibrinogen binding site of the activated GP IIaIIIb complex (PAC-1) and GP Ib-V-IX complex (CD42b). Platelets fixed with PFA (0.5%) before antibody labelling showed significant (P<0.01) increases in mean fluorescence intensity (MFI) of CD62P (1.10 +/- 0.14 vs. 0.94 +/- 0.12 arbitrary units of fluorescence), CD41 (27.3 +/- 6.3 vs. 15.6 +/- 2.1) and PAC-1 (6.21 +/- 1.25 vs. 0.55 +/- 0.12) when compared to unfixed samples. At the same time, MFI of CD42b was reduced from 28.2 +/- 1.6 to 22.6 +/- 2.3 (P<0.01). When fixation was initiated after antibody labelling, we observed less prominent increases in MFI of CD41 (P<0.05) and PAC-1 (P<0.05) while there was no significant difference for CD62P and rather a moderate rise in CD42b than a decrease (P<0.05). Because these alterations cannot be explained by unspecific effects only, it must be concluded that PFA induces a systematic stimulation of platelets. The lowest in vitro platelet activation was found when antibody labelling was started immediately after blood sampling and when samples were analysed within 10 minutes after being stored without fixation of 4 degrees C in the dark.

Biomarkers↗

Identification of Cis-regulatory elements in the mouse Pax9/Nkx2-9 genomic region: implication for evolutionary conserved synteny.

We previously reported close physical linkage between Pax9 and Nkx2-9 in the human, mouse, and pufferfish (Fugu rubripes) genomes. In this study, we analyzed cis-regulatory elements of the two genes by comparative sequencing in the three species and by transgenesis in the mouse. We identified two regions including conserved noncoding sequences that possessed specific enhancer activities for expression of Pax9 in the medial nasal process and of Nkx2-9 in the ventral neural tube. Remarkably, the latter contained the consensus Gli-binding motif. Interestingly, the identified Pax9 cis-regulatory sequences were located in an intron of the neighboring gene Slc25a21. Close examination of an extended genomic interval around Pax9 revealed the presence of strong synteny conservation in the human, mouse, and Fugu genomes. We propose such an intersecting organization of cis-regulatory sequences in multigenic regions as a possible mechanism that maintains evolutionary conserved synteny.

Animals↗

Platelet activity, sensitivity to agonist, and platelet--leukocyte conjugate formation after long-term exercise.

For rehabilitation training it is recommended that the intensity of exercise should be distinctly below the individual anaerobic threshold (IAT). We investigated platelet activity, reactivity and platelet-leukocyte conjugate formation following a stardardized treadmill (TR) ergometer test at 90% IAT for 60-120 min. Seventeen healthy male non-smokers underwent TR. Blood samples were taken after a 30-min rest, immediately after exercise, and 2 h after exercise completion. Platelets were detected flow cytometrically by CD41 in whole blood, activated platelets by CD62P. In addition, stimulation of platelets in vitro with 7.5 microM TRAP-6 was performed. For testing platelet-leukocyte conjugates, antibodies against CD45 and CD41 were used. After TR the percent of non-stimulated CD62P-positive platelets (%PC) remained unchanged (1.65 +/- 0.56 to 1.73 +/- 0.79%PC) (mean +/- SD). In contrast, an increase (P<0.05) from 31.9 +/- 13.5 to 37.4 +/- 15.0 %PC in CD62P, TRAP-6 stimulated and enhanced (P<0.01) platelet-leukocyte conjugates (11.7 +/- 3.7 to 16.1 +/- 6.9, CD41-%PC) after TR were observed. Both changes were independent of thrombin generation measured by F1+2 and TAT, and reversible after 2 h. Long-term exercise (90% IAT) on a treadmill ergometer only leads to a moderate increase of platelet reactivity and platelet-leukocyte conjugates. The determination of platelet-leukocyte conjugates may offer the possibility to detect an early activation stage of platelets in vivo.

Adult↗

[A hopeless case?].

In a hollow covered with earth, a herb gatherer discovered a severely decomposed corpse mutilated by scavenging animals. Only small areas of the skin had remained intact. A conspicuous tattoo could still be distinguished on the left upper arm. Despite concrete evidence of violence (fracture in the occipital bone, subdural hemorrhage with a volume of 20 ml), the exact cause of death could no longer be established. Police enquiries identified a person in whom such a conspicuous tattoo had been photographed in an earlier criminal case. Eventually, the deceased person could be identified by DNA analysis of a stored blood alcohol specimen. Considered together, the autopsy findings and the results of the investigation of traces of blood on the putative tool used in the crime indicated that the man had been struck dead and the body had afterwards been buried in the wood. Although the prospects of success had been initially slight, it was not only possible to identify the victim, but also to reconstruct the crime.

Adult↗

[The efficacy of different oral dosage forms of furazolidone for E. coli infections in carrier pigeons].

The clinical efficiacy of furazolidon for treatment of E. coli-induced gastro-intestinal infections in racing pigeons was investigated. 36 adult pigeons were treated with 2 different oral modes of application (capsule/drinking water) with a daily therapeutic dosage of 12.5 mg furazolidon/pigeon. The pigeons used for this study (Columba livia f. domestica) originated from conventional breeders and were housed in 3 different groups (control-, capsule- and powder-group) in different stables. After infection with an E. coli-strain (O150:H8) that proved to be pathogenic for pigeons, the animals developed clinical signs of disease within 2 days. After onset of disease the treatment with furazolidon for 5 days started. This phase was followed by an adspectory phase for 6 days. The negative identification of the E. coli O150:H8 was determined as main parameter for the clinical efficiacy of the treatment with furazolidon. This parameter showed a highly significant (p = 0.0001) difference between both groups treated with furazolidon and the control group. In both groups treated with furazolidon the E. coli strain could not be isolated after the end of the treatment. An improvement of clinical signs was seen 24 hours after treatment via capsule and 48 hours after treatment via drinking water formulation. The time difference might be caused by the high concentration of furazolidon in the capsules due to the single daily application. Considering the inaccurate dosing via drinking water that results from the varying drinking water intake in pigeons, the application by capsule should be prefered. Both furazolidon preparations proved to be effective in treating gastro-intestinal E. coli-infections in racing pigeons in a dosage of 12.5 mg/pigeon for 5 days, however, best results were obtained by application via capsule.

Administration, Oral↗