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Histone acetylation has been implicated with the pathogenesis of neuropsychiatric disorders and targeting histone deacetylases (HDACs) using HDAC inhibitors was shown to be neuroprotective and to initiate neuroregenerative processes. However, little is known about the role of individual HDAC proteins during the pathogenesis of brain diseases. HDAC1 was(More)
The present investigation extends our initial evaluation of the evolution of antigen selection mechanisms for antibodies of a "single" specificity. The binding sites of 11 mouse anti-PC antibodies produced in response to the bacterium P. morganii or the nematode A. suum were characterized for both hapten and hapten plus carrier specificity. All of the(More)
Biochemical and serological studies were performed on more than 400 anti- phosphocholine (PC) hybridoma proteins (HP) derived from six strains of mice; 26 of these HP were examined in detail. All HP possessed specificity for PC, and all those tested contained an H-chain idiotypic determinant, V(H)-PC, which is shared by PC-binding myeloma proteins (BMP) and(More)
Neurotrophic factors have raised hopes to be able to cure symptoms and to prevent progressive neurodegeneration in devastating neurological diseases. Gene therapy by means of viral vectors can overcome the hurdle of targeted delivery, but its current configuration is irreversible and thus much less controllable than that of classical pharmacotherapies. We(More)
Gene therapy, in its current configuration, is irreversible and does not allow control over transgene expression in case of side effects. Only few regulated vector systems are available, and none of these has reached clinical applicability yet. The mifepristone (Mfp)-regulated Gene Switch (GS) system is characterized by promising features such as being(More)
The present investigation extends our immunochemical characterization of binding site heterogeneity among a large series of monoclonal anti-phosphocholine (PC) antibodies. Hybridoma proteins (HP) from eight genetically distinct strains are included in this study, yet no strain specific characteristics are observed. These HP, as previously shown (5), are(More)
Phosphocholine-specific antibodies in mice are composed of three families of antibodies, the T15, the M603 and the M511, which are constructed by combinatorial association of a VH4 H chain and one of three different L chains, VK22, VK8 and VK24, respectively. Antiidiotypic antisera can be generated which (1) recognize all members of a family, i. e. anti-T15(More)
Spontaneously nalidixic acid-resistant lines (NAr lines) were selected from a V79 Chinese hamster cell line and phenotypically characterized. NAr lines showed an increased doubling time, a higher number of spontaneous SCE, and more interestingly, decreased DNA topoisomerase II activity. These lines were also cross-resistant to the eukaryotic topoisomerase(More)
Some HGPRT spontaneous revertants were isolated from a mutant line (E2) of V79 Chinese hamster cells and phenotypically characterized. Dot-Blot hybridization with a 32P-labelled HGPRT probe revealed an increase in the number of HGPRT sequences in some of these revertants, suggesting the occurrence of gene amplification. Cytogenetic analysis performed in(More)
Topoisomerase II inhibitors such as etoposide (VP16) are able to stabilize the enzyme-DNA complex by trapping the topoisomerase on DNA without affecting its strand-break activity. To test if this inhibition resulting in chromosomal breakage via double-strand breaks could underlie gene amplification, we performed VP16 treatments followed by selection for(More)