A synthetic random basic copolymer with promiscuous binding to class II major histocompatibility complex molecules inhibits T-cell proliferative responses to major and minor histocompatibility antigens in vitro and confers the capacity to prevent murine graft-versus-host disease in vivo.

Graft-versus-host disease (GVHD) is a T-cell-mediated disease of transplanted donor T cells recognizing host alloantigens. Data presented in this report show, to our knowledge, for the first time that a synthetic copolymer of the amino acids L-Glu, L-Lys, L-Ala, and L-Tyr (molecular ratio, 1.9:6.0:4.7:1.0; Mr, 6000-8500) [corrected], termed GLAT, with promiscuous binding to multiple major histocompatibility complex class II alleles is capable of preventing lethal GVHD in the B10.D2 --> BALB/c model (both H-2d) across minor histocompatibility barriers. Administration of GLAT over a limited time after transplant significantly reduced the incidence, onset, and severity of disease. GLAT also improved long-term survival from lethal GVHD: 14/25 (56%) of experimental mice survived > 140 days after transplant compared to 2/26 of saline-treated or to 1/10 of hen egg lysozyme-treated control mice (P < 0.01). Long-term survivors were documented to be fully chimeric by PCR analysis of a polymorphic microsatellite region in the interleukin 1beta gene. In vitro, GLAT inhibited the mixed lymphocyte culture in a dose-dependent fashion across a variety of major barriers tested. Furthermore, GLAT inhibited the response of nylon wool-enriched T cells to syngeneic antigen-presenting cells presenting minor histocompatibility antigens. Prepulsing of the antigen-presenting cells with GLAT reduced the proliferative response, suggesting that GLAT inhibits antigen presentation.

Human protein Sam68 relocalization and interaction with poliovirus RNA polymerase in infected cells.

A HeLa cDNA expression library was screened for human polypeptides that interacted with the poliovirus RNA-dependent RNA polymerase, 3D, using the two-hybrid system in the yeast Saccharomyces cerevisiae. Sam68 (Src-associated in mitosis, 68 kDa) emerged as the human cDNA that, when fused to a transcriptional activation domain, gave the strongest 3D interaction signal with a LexA-3D hybrid protein. 3D polymerase and Sam68 coimmunoprecipitated from infected human cell lysates with antibodies that recognized either protein. Upon poliovirus infection, Sam68 relocalized from the nucleus to the cytoplasm, where poliovirus replication occurs. Sam68 was isolated from infected cell lysates with an antibody that recognizes poliovirus protein 2C, suggesting that it is found on poliovirus-induced membranes upon which viral RNA synthesis occurs. These data, in combination with the known RNA- and protein-binding properties of Sam68, make Sam68 a strong candidate for a host protein with a functional role in poliovirus replication.

Systemic immunization with papillomavirus L1 protein completely prevents the development of viral mucosal papillomas.

Infection of mucosal epithelium by papillomaviruses is responsible for the induction of genital and oral warts and plays a critical role in the development of human cervical and oropharyngeal cancer. We have employed a canine model to develop a systemic vaccine that completely protects against experimentally induced oral mucosal papillomas. The major capsid protein, L1, of canine oral papillomavirus (COPV) was expressed in Sf9 insect cells in native conformation. L1 protein, which self-assembled into virus-like particles, was purified on CsCl gradients and injected intradermally into the foot pad of beagles. Vaccinated animals developed circulating antibodies against COPV and became completely resistant to experimental challenge with COPV. Successful immunization was strictly dependent upon native L1 protein conformation and L1 type. Partial protection was achieved with as little as 0.125 ng of L1 protein, and adjuvants appeared useful for prolonging the host immune response. Serum immunoglobulins passively transferred from COPV L1-immunized beagles to naive beagles conferred protection from experimental infection with COPV. Our results indicate the feasibility of developing a human vaccine to prevent mucosal papillomas, which can progress to malignancy.

The human papilloma virus 16E6 gene sensitizes human mammary epithelial cells to apoptosis induced by DNA damage.

Programmed cell death (apoptosis) is a normal physiological process, which could in principle be manipulated to play an important role in cancer therapy. The key importance of p53 expression in the apoptotic response to DNA-damaging agents has been stressed because mutant or deleted p53 is so common in most kinds of cancer. An important strategy, therefore, is to find ways to induce apoptosis in the absence of wild-type p53. In this paper, we compare apoptosis in normal human mammary epithelial cells, in cells immortalized with human papilloma virus (HPV), and in mammary carcinoma cell lines expressing wild-type p53, mutant p53, or no p53 protein. Apoptosis was induced with mitomycin C (MMC), a DNA cross-linking and damaging agent, or with staurosporine (SSP), a protein kinase inhibitor. The normal and HPV-transfected cells responded more strongly to SSP than did the tumor cells. After exposure to MMC, cells expressing wild-type p53 underwent extensive apoptosis, whereas cells carrying mutated p53 responded weakly. Primary breast cancer cell lines null for p53 protein were resistant to MMC. In contrast, two HPV immortalized cell lines in which p53 protein was destroyed by E6-modulated ubiquitinylation were highly sensitive to apoptosis induced by MMC. Neither p53 mRNA nor protein was induced in the HPV immortalized cells after MMC treatment, although p53 protein was elevated by MMC in cells with wild-type p53. Importantly, MMC induced p21 mRNA but not p21 protein expression in the HPV immortalized cells. Thus, HPV 16E6 can sensitize mammary epithelial cells to MMC-induced apoptosis via a p53- and p21-independent pathway. We propose that the HPV 16E6 protein modulates ubiquitin-mediated degradation not only of p53 but also of p21 and perhaps other proteins involved in apoptosis.

Lo grotesco en la creación de imágenes publicitarias

A través de esta investigación se busca analizar de que forma una categoría estética como es lo grotesco, relacionada generalmente con lo desagradable, lo inquietante, lo cómico-burlesco e, incluso, lo repugnante y lo siniestro, tiene cabida en el ámbito de la fotografía publicitaria, mediante la observación de una tendencia estética que se caracteriza por un uso de lo grotesco sobre todo fantástico, y en la que confluyen algunos de los valores que le han sido atribuidos por diferentes autores a lo largo del tiempo, con otros nuevos que se adecuan a su contexto publicitario. De esta forma, en primer lugar, y para llegar al momento en que lo grotesco adquiere, finalmente, entidad propia, se debe comenzar por el estudio de la belleza, la cual es considerada una de las ideas principales del pensamiento filosófico durante un largo período de tiempo, hasta que entra en crisis en el siglo XVIII a la par que nace la estética como disciplina, e irrumpen nuevas categorías a tener en cuenta en la reflexión sobre el arte, entre las que se encuentra lo grotesco. Así, lo grotesco surge como término en el siglo XV, proveniente de la palabra italiana gruta, ya que se utilizó inicialmente para designar ciertas ornamentaciones encontradas en el sepultado palacio de la Domus Aurea, construido por Nerón en el siglo I. Esas pinturas fueron imitadas por varios pintores del XV y asentado ya el término como sustantivo, vio como era adjetivado y se extendía por toda Europa, relacionándose, además, con numerosas concepciones como lo ridículo o lo bizarro, o manifestaciones cómico artísticas como la Comedia del Arte o los grabados de Callot. Entonces, llegado el siglo XVIII y esa mencionada ampliación del gusto estético en el Romanticismo, y con el apoyo de autores como Friedrich Schlegel, Ruskin y sobre todo Victor Hugo, lo grotesco surge como categoría estética independiente aunque limítrofe con otras, como lo sublime, lo feo y lo cómico, entre las que este estudio analiza sus relaciones y sus distinciones para profundizar en la compleja naturaleza de lo grotesco...

Efterladte philosophiske skrifter.

Pref. signed: J.F.W. Schlegel.

C. F. Gellerts sämmtliche werke ...

6.-9. th. edited by J. A. Schlegel and G. L. Heyer.

Ueber die neuere Geschichte; Vorlesungen gehalten zu Wien im Jahre 1810.

Pages 561-562 bound in incorrect order.

Das Ich-Problem der Romantik : die historische Stellung Friedrich Schlegels innerhalb der modernen Geistesgeschichte /

Mode of access: Internet.

Geschichte der alten und neuen Literatur. Vorlesungen, gehalten zu Wien im Jahre 1812

Mode of access: Internet.

Philosophie de l'histoire /

Contiene : Tom. 1

Vollständige Mühlenbaukunst nach den neuesten wichtigsten Erfingungen und Verbesserungen, mit besonderer Berücksichtigung der amerikanischen und schweizerischen Kunstmühlen. Nebst Anleitung gewöhnliche Mahlmühlen nach dem amerikanischen System einzurichten. Praktisches Lehrbuch ...

Mode of access: Internet.