Organization of the ribosomal RNA gene cluster in Lytechinus variegatus. Restriction analysis and cloning of restriction fragments.
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Renal cell carcinomas belong to the small group of tumors that are able to induce antitumor responses. Here we describe two general types of cytotoxic effector lymphocytes that can eliminate autologous tumor cells and discuss the role that major histocompatibility complex encoded molecules play in governing their specificities. Improved understanding of the cellular and molecular basis of renal cell carcinoma recognition opens new avenues of research with the potential to develop better immunotherapies for patients with metastatic disease.
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Hearts from rats fed a copper-deficient (Cu-) diet have decreased levels of nuclear-encoded peptides of cytochrome c oxidase (CCO). Studies were conducted to determine whether iron deficiency would lead to a similar finding, whether mRNA transcripts and the chaperonin heat shock proteins (HSP) 60 and 70 from hearts of Cu- rats were decreased as compared with copper-adequate controls and whether synthesis of mitochondrial and nuclear encoded peptides differed as affected by diet copper. In study 1, weanling rats were assigned to one of three groups (n = 6 in each group): (1) control copper and iron adequate fed rats; (2) Cu- rats and (3) iron-deficient (Fe-) rats. Western blotting of nonmyofibrillar cardiac proteins revealed that the nuclear encoded peptides of CCO from the Cu- rats were markedly decreased as compared with control and Fe- rats. Mitochondrial encoded subunits did not appear to differ by treatment groups. Iron-deficient rats had similar nuclear encoded peptide levels as those of controls. In study 2, mRNA transcripts from Cu- (n = 4) and control copper adequate (n = 4) rats did not appear to differ for subunits II and IV, which correspond to mitochondrial and nuclear encoded subunits, respectively. In study 3, levels of HSP 60 and 70 from hearts of Cu- rats (n = 3) did not differ from Cu+ rats (n = 3). In study 4, infusion of 3H-(4,5)-leucine into the hearts of Cu+ and Cu- rats suggested there was no difference in synthesis of the nuclear encoded peptides by copper status and some indication there was enhanced breakdown of the nuclear encoded peptides among the Cu- rats. As expected, more isotope was incorporated into the mitochondria of Cu- rats than Cu+ rats. These results demonstrate an independent effect of copper upon the apparent decrease in the nuclear encoded subunits of CCO, the effect of copper upon the CCO subunits is probably post-transcriptional and that translocation of the nuclear encoded subunits from the ribosomes to the mitochondria via the chaperonin proteins is not a primary defect in explaining these observations in hearts from Cu- rats and synthesis of the nuclear encoded subunits of CCO in not impaired in copper deficiency.
The illustrated clinical and experimental results demonstrate the strong relationship between the MHC class I antigen HLA-B27 and synovial CD8+ T cells with specificity for bacterial and possible self-antigen in SpA. These new aspects obtained in recent experimental and clinical studies might also provide clues to the pathomechanisms of joint inflammation in SpA. In particular, the newly developed techniques will be of great relevance in the near future. New and more precise bioalgorithms reflecting new insights in the biology and biochemistry of proteins as recently presented [98, 99] can be helpful (e.g., a program with an improved prediction of the features of immunoproteasomes). Intracellular and secreted cytokine staining by FACScan allows examination of a great number of cells expressing certain antigens in response to certain stimuli. The analysis of T-cell responses with tetramer/peptide complexes can be useful to screen tissue sections for TCR, recognizing foreign or self-derived epitopes on those complexes loaded with selected (e.g., bacterial) peptides. Identification of arthritogenic peptides and a further understanding of the immunology of the pathomechanisms in SpA might open ways to design new peptide vaccines to prevent inflammation, autoimmunity, and other diseases by early intervention [100].
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