In a series of papers 1,2,3, Lawrence Schulman presented examples which demonstrate the compatibility of opposite arrows of time in various situations. In a previous letter to this journal 4 I ...questioned some of them for not being realistic in spite of being logically correct. Schulman replied 5 to these objections in a letter directly succeeding my one. I am here trying to clarify some aspects of the dispute, thereby further explaining and supporting my previous conclusions.
A novel method was developed to isolate immunogenic peptides (CD8+ T-cell epitopes) from class I complexes expressed at the cell surface of viable cells. Cells treated at pH 3.3 with ...citrate-phosphate buffer for periods as short as 15 s remained viable and became phenotypically class I deficient. Qualitative loss of class I determinants was verified both serologically and by the incapacity of acid-treated cells to be lysed by class I-restricted cytolytic T lymphocytes (CTLs) in contrast to non-acid-treated controls. Flow cytometric analysis of acid-treated cells suggests that class I heavy chains remain associated with the cell membrane, while the class I light chain (beta 2-microglobulin) is absent. Since the physical dissociation of beta 2-microglobulin from class I heavy chain is correlated with the release of previously class I-bound peptides, we examined acid-eluted cell-free supernatants for the presence of immunogenic peptides. Peptides were acid eluted from an influenza A strain-infected, HLA-A2+ cell line and were subsequently fractionated by reverse-phase high performance liquid chromatography (RP-HPLC). These fractionated peptides were examined for their capacity to sensitize an HLA-A2+ B cell line to lysis mediated by an influenza A matrix peptide- (Flu M1 57-68) specific, HLA-A2-restricted CTL line. A single peak of biologic activity was identified in HPLC fractions 47 and 48 derived from influenza-infected cells. These fractions contained a peptide of M(r) 968 with a sequence similar to the Flu M1 58-66 sequence GILGFVFTL. The application of this technique to other T-cell-based systems may aid in the definition of peptide epitopes relevant to viral, autoimmune, or neoplastic disorders.
The introduction of spinor and other massive fields by “quantizing” particles (corpuscles) is conceptually misleading. Only spatial fields must be postulated to form the fundamental objects to be ...quantized (that is, to define a formal
basis for all quantum states), while apparent “particles” are a mere consequence of decoherence. This conclusion is also supported by the nature of gauge fields.
Vaccines for colorectal cancer Zeh, Herbert J; Stavely-O'Carroll, Kevin; Choti, Michael A
Trends in Molecular Medicine,
07/2001, Letnik:
7, Številka:
7
Book Review, Journal Article
Recenzirano
Despite recent advances in the treatment of colorectal cancer, the overall survival rate for those patients with advanced locoregional disease remains less than 50%. Although adjuvant systemic ...chemotherapy has improved survival of these patients, more effective therapies are needed. Immunotherapy is an approach that could have a particular role in the adjuvant therapy of colorectal cancer. There is now convincing evidence that the immune system can specifically recognize and destroy malignant cells. Although both antibody- and T-cell-mediated anti-tumor responses have been documented, the cellular immune response with its direct cytotoxic mechanisms is felt to be the principal anti-tumor arm of the immune system. Analysis of the T cells that recognize tumors has led to the identification and characterization of many tumor-associated antigens including several colorectal antigens. Current approaches to developing a vaccine for colorectal cancer use our expanded understanding of these tumor-associated antigens and the conditions that allow development of an effective cellular immune response to them.
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