Journal of internal medicine
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In 1998, Wallace et al. (Science 1988; 242: 1427-30) published evidence that the mutation m.11778G>A was responsible for causing Leber's hereditary optic neuropathy. This was the first account of a mitochondrial DNA mutation being irrefutably linked with a human disease and was swiftly followed by a report from Holt et al. (Nature 1988; 331: 717-9) identifying deletions in mitochondrial DNA as a cause for myopathy. During the subsequent 20 years there has been an exponential growth in 'mitochondrial medicine', with clinical, biochemical and genetic characterizations of a wide range of mitochondrial diseases and evidence implicating mitochondria in a host of many other clinical conditions including ageing, neurodegenerative illness and cancer. In this review we shall focus on the diagnosis and management of mitochondrial diseases that lead directly or indirectly to disruption of the process of oxidative phosphorylation.
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High oxygen-affinity haemoglobin variants and 2,3-diphosphoglycerate (2,3-DPG) deficiency are inherited diseases generating low tissue oxygen tension and erythropoietin-driven erythrocytosis, that characterizes the clinical phenotype of patients. Level of blood p50 (the oxygen tension at which haemoglobin is 50% saturated) is used to recognize these conditions. ⋯ This study suggests that the investigation of blood p50 level may be useful to define diagnosis in patients with isolated erythrocytosis.
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Infection of humans by the human immunodeficiency virus (HIV) causes a progressive, multifactorial impairment of the immune system eventually leading to the acquired immunodeficiency syndrome (AIDS). No cure or vaccine exists yet against HIV infection. More worrisome is the fact that despite having identified HIV as the cause of the AIDS, we still do not understand what pathogenic mechanisms lead to the debacle of the immune system. In this review we consider the extent and the limits of our knowledge of HIV pathogenesis, and how this knowledge may be used to design preventive and therapeutic approaches.
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Issues of quantity, quality and location impact the ability of CD8 T cells to mediate protection from infection. These issues are considered in light of human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) vaccination. ⋯ Arguments are made that establishing memory CD8 T cells within mucosal sites of transmission, a priori to natural infection, may be essential for conferring optimal and rapid protection. Lastly, it is proposed that heterologous prime-boost vaccination with recombinant live replicating vectors, which has the potential to induce tremendous numbers of cytolytic memory CD8 T cells within mucosal tissues, would provide a far more stringent test of the hypothesis that memory CD8 T cells could, in principal, form the basis for a preventative HIV vaccine.
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Increasing evidence supports the notion that the innate immune response, and in particular, natural killer cells play a central role in determining the quality of the host immune response to infection. In this review we highlight recent evidence that suggests that NK cells influence the clinical fate of HIV-infected individuals.