Biomedical subjects
Publications and source records attributed to C Burger.
A program to provide exposure to geriatrics as a teaching nursing home project was initiated at a large urban university medical center. Positive experiences, changes of attitude, and personal growth were noted among those involved in teaching, learning, and care of patients. A description of the program, its expansion, and plans for the future are detailed.
Explore the source record for details and available documents.
The comparative analysis of Ig class switch recombination in a priori IgG/IgA-expressing myelomas and hybridomas, in switch variants and in activated normal B cells shows the following characteristics of class switch recombination in activated B cells: It is prevented during most of B cell ontogeny. It happens on both IgH loci of activated and switched B cells. The recombination is programmed in that on both IgH loci of switched cells the same switch regions recombine with Smu. This is true at least for the IgG1 pathway. IgM-expressing cells show no class switch recombination on the inactive IgH locus. Thus, physiological class switch recombination is a programmed rather than a random event and is controlled as such. The initial stages of class switching and the molecules involved in these are largely unclear: What is the nature of the protection of switch regions and how is this protection abrogated? Do specific recombinases exist? What is the role of large transcription units? Is the specificity of class switch recombination a result of specific "opening" of the DNA for transcription? Do all B cells use the same switch mechanism? What is the role of switch factors (such as lymphokines)? These and more questions await answers and although a variety of switch scenarios could be discussed at present a detailed speculation seems premature.
Nine commonly studied Simian virus 40 (SV40)-transformed rodent cell lines were screened for tumor (T) antigens defective in SV40 DNA replication using a simple polyethylene glycol-mediated cell fusion assay. Each line contained a functional origin of SV40 DNA replication, as shown by fusion with Cos 1 cells. Fusion with uninfected monkey cells revealed that T antigens from two lines lacked detectable replicative activity, while T antigens from five other lines exhibited only very weak replicative activity. One line, and a tumor cell line derived from it, expressed T antigen with wild-type replication activity. Biochemical analysis of these proteins revealed defects in DNA binding activity and ATPase activity. One line expressed large T antigen defective in both activities. All of the lines contained complexes of T antigen with the cellular protein p53 and all of the T antigens exhibited nucleotide-binding activity. The results indicate that some of these lines may constitute a useful source of new replication-defective T antigens.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Large tumor antigen (T antigen) occurs in at least three different oligomeric subclasses in cells infected or transformed by simian virus 40 (SV40): 5-7 S, 14-16 S, and 23-25 S. The 23-25 S form is complexed with a host phosphoprotein (p53). The DNA binding properties of these three subclasses of T antigen from nine different cell lines and free p53 protein were compared using an immunoprecipitation assay. All three subclasses of T antigen bound specifically to SV40 DNA sequences near the origin of replication. However, the DNA binding activity varied between different cell lines over a 40- to 50-fold range. The 23-25 S and 14-16 S forms from most of the cell lines tested bound much less SV40 origin DNA than 5-7 S T antigen. The free p53 phosphoprotein did not bind specifically to any SV40 DNA sequences.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Simian virus 40 (SV40)-infected and -transformed cell contain, in addition to the virus-coded tumour antigens, one or more 48K to 56K host tumour antigens. At least part of this class of host proteins exists as a fast-sedimenting complex with the SV40 large T antigen. The host proteins associated with the large T antigen in SV40-transformed monkey, mouse and human cells and SV40-infected monkey cells were compared by two-dimensional gel electrophoresis and V8 partial proteolysis peptide mapping. Although these proteins differed slightly in apparent mol. wt. and peptide pattern, they migrated identically in isoelectric focusing gels. These results suggest that the cellular proteins associated with large T antigen in different hosts are very closely related to each other. Despite their similarities, the 55K proteins from different host cells form complexes of different stabilities with large T antigen, as judged by spontaneous dissociation of the complexes during storage, and the fractions of the 55K cellular protein and large T antigen found free and in the complexed form in each different host cell.
Subclasses of simian virus 40 large T antigen in simian virus 40-transformed and -infected cells separated by zone velocity sedimentation in sucrose density gradients have been characterized. Three forms of large T antigen were distinguished: a 5 to 6S form, a 14 to 16S form, and a 23 to 25S form. These forms appeared to differ biochemically and biologically. Differential labeling experiments suggested that the 5 to 6S form was less highly phosphorylated than the faster-sedimenting forms. The 23 to 25S form which was complexed with one or more host phosphoproteins, as reported recently (D. P. Lane and L. V. Crawford Nature [London] 268:261-263, 1979; F. McCormick and E. Harlow, J. Virol. 34: 213-224, 1980), was prominent in extracts of transformed cells, but was also detected in productively infected cells. Pulse-chase experiments suggested that the 5 to 6S large T antigen is a precursor of the more stable, faster-sedimenting forms of T antigen. Monkey cells infected with a tsA mutant of simian virus 40 at 41 degrees C contained only 5 to 6S large T antigen, implying that this form is not active in the initiation of simian virus 40 DNA replication. In pulse-chase, shift-down experiments, DNA replication resumed, and the 5 to 6S large T antigen which had accumulated at 41 degrees C was partially converted at 33 degrees C to a fast-sedimenting form. However, shift-up experiments demonstrated that the fast-sedimenting large T antigen, once formed, remained stable at 41 degrees C, although it was unable to function in initiation. These experiments suggest that different biological functions of large T antigen may be carried out by different subclasses of this protein.
We evaluated platelet aggregation in vitro in blood samples drawn simultaneously from aorta and coronary sinus. Platelet aggregation was significantly lower in the coronary venous blood than in the aortic blood in patients with coronary artery disease. Lower platelet counts were also observed in coronary venous blood. No such differences were seen in subjects with normal coronary arteries. Oral administration of aspirin eliminated the differences in platelet aggregation and counts across the myocardial vascular bed. These observations suggest that platelet sequestration in the myocardial vasculature may be related to the presence of disease in the coronary arteries.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
BACKGROUND: Although only poor data exist on changes in myocardial blood flow (MBF) under acute hypoxia, patients with known coronary artery disease are advised not to exceed a moderate altitude exposure of about 2000 m above sea level. METHODS AND RESULTS: We measured MBF with positron emission tomography using O-15--labeled water in 8 healthy human volunteers (aged 26 +/- 3 years [mean +/- SD]) at baseline (450 m above sea level, Zurich, Switzerland) and during acute hypoxic hypoxemia induced by inhalation of 2 hypoxic gas mixtures corresponding to altitudes of 2000 and 4500 m. MBF remained unchanged at 2000 m (increase of 10%, not significant) but increased significantly at 4500 m (62%, P <.001), exceeding the relative increase in rate pressure product. CONCLUSIONS: Our results may explain why exposure to an altitude of 2000 m (corresponding to the cabin pressure in most airplanes during flight) is clinically well tolerated, even by patients with reduced coronary flow reserve, such as those with coronary artery disease. However, at an altitude of 4500 m, MBF increases significantly, supporting the recommendation that patients with impaired flow reserve avoid exposure to higher altitudes.
Analysis software for medical image data tends to be expensive and usable only in a restricted environment. Therefore the aim of the current project was to implement a flexible framework for medical image processing and visualization which is portable among platforms and open to different data formats including DICOM 3.0. The software was designed as a set of tools which encapsulate specialized functionality. The tools are full stand alone applications, but they are also able to present a co-operating environment within which images and other information are communicated in real time. Currently, the emphasis is on quantitative analysis of PET data by kinetic modelling. However, general viewing capabilities are included, and the design is flexible enough that other types of processing can easily be integrated by simply plugging in Java classes. The software is successfully applied to PET data quantitation in clinical research studies and even patient studies. Portability was aimed at by encoding the programs in Java. Experience shows that the implementation of such a complex and computationally demanding Java application is feasible. Although there are major portability issues to consider, configurations can be found on which the software runs stably and at a speed comparable to C code if just-in-time compilation is available.