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E Schnell

Publications and source records attributed to E Schnell.

12 recordsLinked to original sources

Dynamics of learning and recall at excitatory recurrent synapses and cholinergic modulation in rat hippocampal region CA3.

Hippocampal region CA3 contains strong recurrent excitation mediated by synapses of the longitudinal association fibers. These recurrent excitatory connections may play a dominant role in determining the information processing characteristics of this region. However, they result in feedback dynamics that may cause both runaway excitatory activity and runaway synaptic modification. Previous models of recurrent excitation have prevented unbounded activity using biologically unrealistic techniques. Here, the activation of feedback inhibition is shown to prevent unbounded activity, allowing stable activity states during recall and learning. In the model, cholinergic suppression of synaptic transmission at excitatory feedback synapses is shown to determine the extent to which activity depends upon new features of the afferent input versus components of previously stored representations. Experimental work in brain slice preparations of region CA3 demonstrates the cholinergic suppression of synaptic transmission in stratum radiatum, which contains synapses of the longitudinal association fibers.

Animals

Laminar selectivity of the cholinergic suppression of synaptic transmission in rat hippocampal region CA1: computational modeling and brain slice physiology.

ACh may set the dynamics of cortical function to those appropriate for learning new information. In models of the putative associative memory function of piriform cortex, selective suppression of intrinsic but not afferent fiber synaptic transmission by ACh prevents recall of previous input from interfering with the learning of new input (Hasselmo, 1993). Selective cholinergic suppression may play a similar role in the hippocampal formation, where Schaffer collateral synapses in stratum radiatum (s. rad) may store associations between activity in region CA3 and the entorhinal cortex input to region CA1 terminating in stratum lacunosum-moleculare (s. l-m). A computational model of region CA1 predicts that for effective associative memory function of the Schaffer collaterals, cholinergic suppression of synaptic transmission should be stronger in s. rad than in s. l-m. In the hippocampal slice preparation, we tested the effect of the cholinergic agonist carbachol (0.01-500 microM) on synaptic transmission in s. rad and s. l-m. Stimulating and recording electrodes were simultaneously placed in both layers, allowing analysis of the effect of carbachol on synaptic potentials in both layers during the same perfusion in each slice. Carbachol produced a significantly stronger suppression of stimulus-evoked EPSPs in s. rad than in s. l-m at all concentrations greater than 1 microM. At 100 microM, EPSP initial slopes were suppressed by 89.1 +/- 3.0% in s. rad, but only by 40.1 +/- 4.1% in s. l-m. The muscarinic antagonist atropine (1 microM) blocked cholinergic suppression in both layers. These data support the hypothesis that synaptic modification of the Schaffer collaterals may store associations between activity in region CA3 and the afferent input to region CA1 from the entorhinal cortex. In simulations, feedback regulation of cholinergic modulation based on activity in region CA1 sets the appropriate dynamics of learning for novel associations, and recall for familiar associations.

Animals

Overexpression of the pseudoautosomal gene MIC2 in Ewing's sarcoma and peripheral primitive neuroectodermal tumor.

Ewing's Sarcoma (ES), the second most frequent bone tumor in childhood and adolescence, and the probably closely related peripheral primitive neuroectodermal tumor (pPNET) share a unique cytogenetic translocation between chromosomes 11 and 22. Both of them expose high amounts of a glycoprotein on their cell surface, which can be specifically detected by the mAb HBA-71. The cDNA coding for the HBA-71 antigen was isolated by screening a cDNA expression library constructed from a pPNET-derived cell line. Nucleotide sequencing revealed the HBA-71 antigen to be the product of the pseudoautosomal gene MIC2 previously identified by the mAb 12E7 in haematopoietic cells. This antigen is a glycoprotein with a molecular weight of about 29,000 and is expressed in low amounts in most human cell lines and probably normal tissues and tumors with only a few exceptions. In T-cells the antigen is involved in cell adhesion processes. In ES- and pPNET-derived cell lines MIC2 expression is significantly enhanced. No gross changes in posttranslational modification could be observed. The high expression results in easy and specific detection of the antigen in immunocytochemical analysis of paraffin embedded tissue sections making HBA-71 a useful tool in tumor diagnosis.

12E7 Antigen

[Benefits of routine automatic blood picture differentiation].

The benefits of automated blood smear differential cell counting as a supplementary laboratory examination have been studied. The investigations focussed on patients of whom hematology requisitions were limited to total leukocyte count and hemoglobin determination. The specimens were derived from patients of departments of surgery and obstetrics and gynecology. For specimen collection the vacutainer system was used. The blood smears were prepared in a Coulter Electronics slide spinner, stained with a Hematek II slide stainer and analyzed in the Coulter Electronics Diff 3-50 cell classifier. A total of 1700 blood smears were examined. Following processing of each sample, the classification of each cell was inspected. Corrections were performed, if necessary, and the number of classification changes performed for each smear was registered. Using the in-house normal ranges, 34.5% were pathological smears. Since this group included a large number of borderline cases, new discrimination limits for clinically relevant pathological findings were set empirically. According to these wider ranges, the fraction of pathological slides amounted to 15.2%. Among these, immature granulocytes, eosinophilia and lymphopenia were the most frequent pathological findings. Microscopic control proved in 57.6% of the total number of smears. This complemental procedure was not found to be time-consuming.

Automation

[Automatic blood smear differentiation using the Coulter Electronics Diff 3-50 system].

The Coulter Electronics Diff 3-50 consists of a slide spinner, a slide stainer and a cell classifier. The cell analyzer is composed of an optical system with a microscope, microprocessor, video camera and printer. The system used in this laboratory is supplemented by a video monitor. The Diff 3-50 analyzes blood cells according to the classical criteria used in hematology. It classifies 11 types of nucleated blood cells and it processes an average of 45 blood smears per hour. It features a visual control of each cell classified with a built-in mechanism for change of classification by the operator if necessary. Moreover, the system estimates leukocyte and platelet count and generates a quantitative estimate of platelet number. Blood smears of 507 blood samples from patients admitted to the hospital were included in the present study. They were analyzed twice, first by the Diff 3-50, and secondly by visual checking of the automatic classification of each cell. The results of the two procedures were then compared. The findings indicate an overall false negative error of 1.4% and an overall false positive error of 4.3%. Major differences were found, though not consistently, only when the classification by the Diff 3-50 of the band neutrophils was compared with the visual classification performed by the operator. Lymphocytes and monocytes correlated well when both procedures were compared. Blasts present in 5 blood smears were recognized by the classifier. The Diff 3-50 identified immature granulocytes in 47 out of 48 cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Cell Count

Metabolic transformation of colchicine, IV[1]. On the interaction of colchicine and colchiceine with sulfhydryl compounds.

The interaction of colchicine and one of its metabolites, O10-demethylcolchicine (colchiceine), with sulfhydryl compounds was studied in several experimental systems. Colchiceine protects reduced glutathione from oxidation by atmospheric oxygen. Inactivation of enzymes with catalytically essential sulfhydryl groups is prevented by colchiceine. In affinity chromatographic experiments, Agarose-bound colchiceine adsorbs sulfhydryl enzymes which may be eluted specifically by SH-compounds like mercaptoethanol. No such effects are shown by colchicine. The data demonstrate a novel type of biochemical reactivity in the metabolite colchiceine with potential biological relevance.

Adenosine Deaminase