Biomedical subjects
D Fabian
Publications and source records attributed to D Fabian.
Control of thymocyte proliferation via redox-regulated expression of glycolytic genes.
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Functional studies by site-directed mutagenesis on the role of Sp1 in the expression of the pyruvate kinase M and aldolase A genes.
During the cell cycle of mitogen stimulated rat thymocytes, an 8-10-fold induction of glycolytic enzymes and a corresponding increase in the mRNA levels has been observed. This prompted us to study the transcriptional regulation of the rat aldolase A and pyruvate kinase M genes. cis-Regulatory elements of both promoters were evaluated by site-directed mutagenesis of promoter/luciferase constructs and transient transfections of rat hepatoma FTO2B cells. Furthermore, the binding proteins were identified by mobility shift assays in the presence of specific antibodies. In the aldolase AH1 promoter, five binding sites for Sp1 and Sp3 and a TPA responsive element were identified as essential for transcriptional regulation. Most of the promoter activity can be attributed to these regulatory elements. In the pyruvate kinase M promoter three out of five binding sites of Sp1 and Sp3 (B box and GC boxes 1 and 3) turned out to be functional in the transfection assays whereas the disruption of GC box 2 had no effect, and the disruption of the GC box 4 had only a minor effect on the promoter activity. Both promoters are stimulated by Sp1 as well as Sp3, as judged by cotransfection experiments of Drosophila SL2 cells. Therefore, the Sp1- and Sp3-directed transcription provides a means for common regulatory mechanism of the aldolase A and the pyruvate kinase M genes.
Epstein-Barr virus and lymphoma.
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Borrelia burgdorferi induces chemokines in human monocytes.
Lyme disease is clinically and histologically characterized by strong inflammatory reactions that contrast the paucity of spirochetes at lesional sites, indicating that borreliae induce mechanisms that amplify the inflammatory response. To reveal the underlying mechanisms of chemoattraction and activation of responding leukocytes, we investigated the induction of chemokines in human monocytes exposed to Borrelia burgdorferi by a dose-response and kinetic analysis. Lipopolysaccharide (LPS) derived from Escherichia coli was used as a positive control stimulus. The release of the CXC chemokines interleukin-8 (IL-8) and GRO-alpha and the CC chemokines MIP-1alpha, MCP-1, and RANTES was determined by specific enzyme-linked immunosorbent assays, and the corresponding gene expression patterns were determined by Northern blot analysis. The results showed a rapid and strong borrelia-inducible gene expression which was followed by the release of chemokines with peak levels after 12 to 16 h. Spirochetes and LPS were comparably effective in stimulating IL-8, GRO-alpha, MCP-1, and RANTES expression, whereas MIP-1alpha production preceded and exceeded chemokine levels induced by LPS. Unlike other bacteria, the spirochetes themselves did not bear or release factors with intrinsic chemotactic activity for monocytes or neutrophils. Thus, B. burgdorferi appears to be a strong inducer of chemokines which may, by the attraction and activation of phagocytic leukocytes, significantly contribute to inflammation and tissue damage observed in Lyme disease.
Boosting your financial health.
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[A.R.G.U.S. A model for an interactive visual field and visual pathway atlas].
A.R.G.U.S. is a data base that connects visual field defects directly with possible lesion sites that are presented graphically. By means of a touch screen or "mouse," scotomata can be depicted on a VDU, while on a second monitor the computer program simultaneously shows the resulting defects in the visual pathway. It is possible to page through different sections of the visual pathway; the lesion is probably located in the section where the affected fibers lie the closest to each other and where the non-affected fibers are the farthest apart. Additionally, the VDU depicting the visual pathway can show the surrounding anatomic structures in the form of brain sections. Even in these sections, lesions can be superimposed interactively; the resulting scotomata are simultaneously depicted on the "visual field VDU." Anatomic and functional details can be displayed by touching the structure of interest. If necessary, a video clip can be activated in the same way. New anatomic findings can be considered by modifying the course of the fibers of the visual pathway. This new technique is especially helpful in distributing comprehensive neuro-ophthalmological knowledge.
Antitumor activity of phytic acid (inositol hexaphosphate) in murine transplanted and metastatic fibrosarcoma, a pilot study.
We have previously reported that phytic acid (inositol hexaphosphate or InsP6), a natural constituent of cereal diet, when administered in drinking water exerts a consistent antitumor effect on experimental colon cancer in vivo. The objective of this study was to determine whether InsP6 has similar anti-neoplastic effect on other tumor models, such as murine fibrosarcoma. We report that intraperitoneal injection of InsP6 reduces growth of subcutaneously transplanted fibrosarcoma (FSA-1) in mice, prolongs survival of tumor-bearing mice and reduces the number of pulmonary metastases. Since InsP6 is a common constituent of our diet and has very little or no toxic effects, in addition to being chemopreventive, it could have potential use in therapy of cancer as well.
Screening for hypothermia in the ambulatory elderly. The Maine experience.
This study investigated the prevalence of low body temperatures in 97 elderly and 20 nonelderly subjects. To the best of our knowledge, no earlier survey has been conducted with a North American population. To ensure comparability with the British National Survey performed in 1973, urine temperatures were collected as a proxy measure of core temperatures. The urine-collecting funnel was modified to minimize cooling artifact introduced by the device. Study subjects were selected from an internal medicine clinic that serves the poor, a federally subsidized housing project, and a subsidized housing project in northernmost Maine. A youthful population (mean age, 32.3 years) was chosen to provide a comparative population to elderly participants (mean age, 73.9 years). Based on the British National Survey, the expected prevalence of low body temperatures (less than 35.5 degrees C) was 10%. The present study detected no low body temperatures, and the average urine and mouth temperatures were 0.3 and 0.19 degree C warmer, respectively, than those in the British National Survey. Youthful subjects were not significantly different from elderly participants. There appears to be no evidence from this study that low early-morning basal body temperature (less than 35.5 degrees C) is a common geriatric occurrence in ambient room temperature.
Pre- and postoperative gait analysis in patients with spastic diplegia: a preliminary report.
The benefits of using computerized gait analysis to plan and evaluate operations were assessed by studying the data from 20 children with spastic diplegia and examining the changes in estimated external work of walking, stride length, walking velocity, and joint rotations pre- and postoperatively. Of the 20 patients, 13 improved, 6 were unchanged, and 1 was worse. None of the patients walked in a crouch postoperatively. By clinical evaluation, 19 of the 20 patients were better. Thus objective gait analysis imposed much more stringent criteria for improvement. Computerized gait analysis has enabled us to be more objective in the evaluation and documentation of outcome.
Differential calcium requirements for growth of mouse skin epithelial and fibroblast cells.
Concentration of extracellular Ca++ optimum for growth of cell types of mesodermal origin have been reported to be up to 100-fold higher than concentrations optimal for epidermal or other epithelial lining cells. In order to examine Ca++ requirements of epithelial v. fibroblastic cells derived from a common tissue source, prior to prolonged culture, freshly isolated mouse epidermal keratinocytes, hair follicle cells and dermal fibroblasts were plated at high density or at clonal density in medium ranging from 0.014 to 1.4 mM Ca++. Epithelial skin cells grew best at Ca++ levels below 0.1 mM while dermal fibroblasts grew best at a Ca++ concentration of 1.4 mM. The epithelial cell types exhibited marked morphologic changes in response to Ca++, while the fibroblasts did not. These results suggest that the variations in Ca++ response between lining epithelium and mesenchymal cells resulted from inherent differences in these cell types, but a mechanism for such differential effects has not yet been defined.
[Hepatobiliary and renal excretion of Rotop-EHIDA--animal experimental studies].
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[Age factors in the clinical symptomatology of myocardial infarct].
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The use of a cellulose-derived immunoadsorbent for the purification of guinea pig anti-trinitrophenyl antibody.
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Cervical auriculars; congenital chondro-cutaneous appendages of the neck.
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