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Biomedical subjects

K Schindler

Publications and source records attributed to K Schindler.

At least 37 records · Page 2Linked to original sources

Complex response to periodic inhibition in simple and detailed neuronal models.

Constant current injection with superimposed periodic inhibition gives rise to phase locking as well as chaotic activity in rat neocortical neurons. Here we compare the behavior of a leaky integrate-and-fire neural model with that of a biophysically realistic model of the rat neuron to determine which membrane properties influence the response to such stimuli. We find that only the biophysical model with voltage-sensitive conductances can produce chaotic behavior.

Animals↗

Signaling through the interaction of membrane-restricted stem cell factor and c-kit receptor tyrosine kinase: genetic evidence for a differential role in erythropoiesis.

Mutations of the receptor tyrosine kinase c-kit or its ligand stem cell factor (SCF), which is encoded as a soluble and membrane-associated protein by the Steel gene in mice, lead to deficiencies of germ cells, melanocytes, and hematopoiesis, including the erythroid lineage. In the present study, we have used genetic methods to study the role of membrane or soluble presentation of SCF in hematopoiesis. Bone marrow-derived stromal cells expressing only a membrane-restricted (MR) isoform of SCF induced an elevated and sustained tyrosine phosphorylation of both c-kit and erythropoietin receptor (EPO-R) and significantly greater proliferation of an erythrocytic progenitor cell line compared with stromal cells expressing soluble SCF. Transgene expression of MR-SCF in Steel-dickie (Sld) mutants resulted in a significant improvement in the production of red blood cells, bone marrow hypoplasia, and runting. In contrast, overexpression of the full-length soluble form of SCF transgene had no effect on either red blood cell production or runting but corrected the myeloid progenitor cell deficiency seen in these mutants. These data provide the first evidence of differential functions of SCF isoforms in vivo and suggest an abnormal signaling mechanism as the cause of the severe anemia seen in mutants of the Sl gene.

Animals↗

rTS gene expression is associated with altered cell sensitivity to thymidylate synthase inhibitors.

rTS is a recently discovered gene, phylogenetically conserved and found to be expressed in a wide variety of cell lines. rTS has also been found to be overexpressed in two cell lines resistant to FU and to MTX. The MTX-resistant cell line was found to have a high degree of cross resistance to several TS inhibitors. An apparent paradox to this correlation of rTS overexpression and resistance to TS inhibitors is the observation that expression of transfected rTS alpha results in enhanced sensitivity of cells to the TS inhibitor prodrug TFT and a modest increase in resistance to FUdR. Since immunoprecipitation of TS leads to the co-immunoprecipitation of two proteins within the expected molecular weight range of the two rTS proteins, it may be that both proteins bind to TS in vivo and modify its activity. Preliminary data substantiate this conclusion. It is conceivable that the ratio of the two rTS proteins associated with TS in vivo may differentially alter TS activity depending upon their stoichiometry or possibly posttranslational modification. Thus it may be possible for rTS to confer greater sensitivity to one pyrimidine analog (e.g., TFT) which is a product analog but to increase resistance or have a minor effect on a substrate analog (e.g., FdUMP) by stabilizing different conformations of TS. The structure of the rTS proteins suggests they are expected to have catalytic activity which involves proton abstraction from an alpha-carbon of a carboxyl group. Whether this enzyme activity is functional and related to pyrimidine metabolism awaits further study.

Alternative Splicing↗

[The effect of very low and moderate fiber levels on metabolism in the cecum of growing rabbits].

Investigations with 15N'-labelled urea were carried out to find out the influence of the amount of fibre on the reflux of 15N' into the caecum to take part in the caecal metabolism. Two pelleted diets, containing 9.7% (group 1 with 23% oat hulls) and 2.2% (Group 2 without oat hulls) crude fibre, with urea with 60 atom% 15N-excess (15N) used as marker were given to three White New Zealand rabbits each group. Group 1 and 2 consumed 109 and 72 g fresh matter per rabbit and day, respectively. Daily 15N'-intake per rabbit was 307 mg in group 1 and 279 mg in group 2. Most of 15N' was eliminated directly via the urine. The daily faecal excretion in group 1 and 2 was 5.3 and 2.3 mg 15N', respectively. Only about 20 to 30% of 15N' and volatile fatty acids in the caecum and higher amounts of 15N' in muscles were found. The animals of this group consumed nearly the total amount of faeces by caecotrophy. Therefore 24 g of group 2 was still satisfying compared to 33 g live weight gain/rabbit and day of group 1. It is concluded that the animals of group 2 could compensate the low fibre level within a period of about 20 days by a more efficient utilization, the consumption of crude protein and starch being 18 and 12% lower than in group 1, respectively. Feed intake and health status were not evidently affected. The results are in contradiction to the common knowledge.

Amino Acids↗

[Studies on rumen fermentation with special reference to the volatile fatty acid production rate in ewes during reproduction. 2. Production rate of volatile fatty acids and rumen volume].

Methods and results of the measuring of the rumen volume and the passage rate as well as the dependence of the production of volatile fatty acids on the parameters mentioned are described. The correlative relations between rumen volume on the one hand and feed passage on the other hand to the production quotas are investigated. Passage rates and rumen volumes were determined with the help of the isotope dilution method. In the course of reproduction rumen volumes of 7.81, 6.41, 8.91, 7.11 in experiment 1 and 5.41, 5.81, 9.51 and 4.71 in experiment 2 were measured in the sequence early stage of gestation, late stage of gestation, lactation and the period between pregnancies. The average total production of volatile fatty acids within 12 hours amounted to 475 mmol, 265 mmol, 313 mmol and 351 mmol in experiment 1 and 155 mmol, 175 mmol, 271 mmol and 144 mmol in experiment 2 in the same sequence. The average passage duration of the feed through the digestive tract of the ewes was 32.4 h in experiment 1 and 33.6 h in experiment 2. The relatively high feed intake of the ewes resulted in a short passage duration and could be a cause of the low production quotas of the volatile fatty acids.

Animals↗

[Reanastomosis of the rabbit fallopian tube with fibrinogen concentrate].

In order to investigate the use of fibrin glue in reconstructive surgery of the oviduct, tubal reanastomosis was performed with homologous fibrinogen concentrate in 26 rabbits. The contralateral tube was clamped. The pregnancy rate was 25%. No adhesions were seen in the area of the anastomosis on examination of the abdomen 3 months after operation.

Animals↗

Morphology of rabbit oviduct after reanastomosis with fibrin glue.

We examined the site of experimental reanastomosis with fibrin glue in rabbit oviducts 3 months after the operation with light and scanning electron microscopy. Local tissue reaction was minimal, no fibrin clots were seen and inflammatory reactions were almost absent. On scanning electron microscopy ciliated cells were reduced in number. Morphologic changes at the site of anastomosis after the use of fibrin glue appear comparable to the alterations seen after the use of microsutures.

Animals↗

[Rumen fermentation with special reference to volatile fatty acid production during reproduction. 1. Methods and results of volatile fatty acid levels and production rates in vitro].

The target of the investigations was to register part of the synthesis performance in the rumen of ewes during the complete reproduction cycle. With the help of in-vitro experiments with artificial rumen the concentration and production rates of volatile fatty acids in the rumen fluid were measured. From the experiments the measured data of fertility-accentuated crossbreeding (experiment 1) and crossbreeding (experiment 2) ewes were contrasted. The average concentrations of volatile fatty acids in ewes are 95.4 m mol/l in experiment 1 and 109.2 m mol/l in experiment 2 during the early stage gestation, 121.4 m mol/l in experiment 1 and 99.8 m mol/l in experiment 2 in the last stage stage of gestation, 129.6 m mol/l in experiment 1 and 112.8 m mol/l in experiment 2 during lactation and 106.6 m mol/l in experiment 1 and 112.9 m mol/l in experiment 2 during the dry period. The production rates of volatile fatty acids calculated form their concentration amount to 4.8 m mol/l X h in experiment 1 and 2.6 m mol/l X h in experiment 2 in the early stage of gestation, 3.5 m mol/l X h in experiment 1 and 3.1 m mol/l X h in experiment 2 in the last stage of gestation, 3.2 m mol/l X h in experiment 1 and 2.7 m mol/l X h in experiment 2 during lactation and 3.7 m mol/l X h in experiment 1 and 2.9 m mol/l X h in experiment 2 in the dry period. The correlation between the concentration and the production rate of volatile fatty acids is not significantly negative in either of the ewe experiments. The scattering of the individual values is wide so that the individual influence of the test animals as well as the influence of the in-vitro method used permit the conclusion that a significant statement on the influence of the genotype and the stage of reproduction on the production rates cannot be made.

Animals↗