Techniques for combined procurement of hearts and kidneys with satisfactory early function of renal allografts.

Methods for combination of donor nephrectomy with donor cardiectomy are outlined. The satisfactory early function of 29 of 34 transplanted kidneys harvested with these techniques supports their wider application and should encourage their wider acceptance

A review of standard pharmacological therapy for adult asthma - Steps 1 to 5

The aim of pharmacological therapy for asthma is to improve symptoms and lung function and minimise the risk of asthma attacks. The intensity of treatment is based on the level of asthma control and the potential risk of future deterioration. In the British asthma guidelines, treatments are divided into Step One to Five, with each Step signifying a need for an increase in therapy in response to symptoms or to prevent exacerbations. Treatments comprise of inhaled or systemic medications. Inhaled therapy includes short-acting and long-acting medication to improve symptoms and inhaled corticosteroids which reduce airway inflammation. Systemic treatments include medications which act on specific biological pathways, such as the leukotriene or IgE pathways, or systemic corticosteroids. In choosing a particular therapy, treatment benefits are balanced by the potential risks of medication-related adverse effects. This review will provide a practical guide to the key pharmacological therapies for adult asthma at Steps One to Five based on British guidelines and consider future options for new treatments

Elucidation of Hepatitis C Virus Transmission and Early Diversification by Single Genome Sequencing

A precise molecular identification of transmitted hepatitis C virus (HCV) genomes could illuminate key aspects of transmission biology, immunopathogenesis and natural history. We used single genome sequencing of 2,922 half or quarter genomes from plasma viral RNA to identify transmitted/founder (T/F) viruses in 17 subjects with acute community-acquired HCV infection. Sequences from 13 of 17 acute subjects, but none of 14 chronic controls, exhibited one or more discrete low diversity viral lineages. Sequences within each lineage generally revealed a star-like phylogeny of mutations that coalesced to unambiguous T/F viral genomes. Numbers of transmitted viruses leading to productive clinical infection were estimated to range from 1 to 37 or more (median = 4). Four acutely infected subjects showed a distinctly different pattern of virus diversity that deviated from a star-like phylogeny. In these cases, empirical analysis and mathematical modeling suggested high multiplicity virus transmission from individuals who themselves were acutely infected or had experienced a virus population bottleneck due to antiviral drug therapy. These results provide new quantitative and qualitative insights into HCV transmission, revealing for the first time virus-host interactions that successful vaccines or treatment interventions will need to overcome. Our findings further suggest a novel experimental strategy for identifying full-length T/F genomes for proteome-wide analyses of HCV biology and adaptation to antiviral drug or immune pressures

Protein trafficking through the endosomal system prepares intracellular parasites for a home invasion

Toxoplasma (toxoplasmosis) and Plasmodium (malaria) use unique secretory organelles for migration, cell invasion, manipulation of host cell functions, and cell egress. In particular, the apical secretory micronemes and rhoptries of apicomplexan parasites are essential for successful host infection. New findings reveal that the contents of these organelles, which are transported through the endoplasmic reticulum (ER) and Golgi, also require the parasite endosome-like system to access their respective organelles. In this review, we discuss recent findings that demonstrate that these parasites reduced their endosomal system and modified classical regulators of this pathway for the biogenesis of apical organelles

The effect of posterior capsule repair upon post-operative hip dislocation following primary total hip arthroplasty

<p>Abstract</p> <p>Background</p> <p>Herein, we evaluated, retrospectively, the effect of posterior capsular repair upon postoperative hip dislocation subsequent to total hip arthroplasty (THA) incorporating a posterolateral approach.</p> <p>Methods</p> <p>A total of 181 patients undergoing 204 primary non-complicated THA surgical procedures in the period from January 2000 to October 2005 inclusively were included in this study. The patients were separated into two groups by whether the posterior capsular repair had been incorporated in the surgical procedure. For the surgeon did not commence repairing the posterior capsule until July, 2003, all members in the group that did not undergo posterior capsular repair (142 hips from 131 patients) were collected since January, 2000 to July, 2003, while the members in the group that underwent posterior capsular repair (62 hips from 52 patients) were followed since July, 2003, to October, 2005. With a minimum follow-up period of 12 months, we evaluated the early post-operative dislocation rate.</p> <p>Results</p> <p>The early postoperative hip-dislocation rate for the group who did not undergo posterior capsular repair appeared to be substantially greater (6.38% versus 0%) than the corresponding figure for the group the members of which underwent posterior capsular repair. In addition, patient demographics and the orientation of acetabular components for the replaced hip joints, as presented in postoperative radiographs, did not differ between the two groups.</p> <p>Conclusion</p> <p>Thus, surgeons should include posterior capsular repair as an important step in the surgical procedures of posterolateral approach for all THA in order to reduce the likelihood of early hip dislocation subsequent to THA.</p

Contribution of proteasome-catalyzed peptide cis-splicing to viral targeting by CD8⁺ T cells in HIV-1 infection

Peptides generated by proteasome-catalyzed splicing of noncontiguous amino acid sequences have been shown to constitute a source of nontemplated human leukocyte antigen class I (HLA-I) epitopes, but their role in pathogen-specific immunity remains unknown. CD8⁺ T cells are key mediators of HIV type 1 (HIV-1) control, and identification of novel epitopes to enhance targeting of infected cells is a priority for prophylactic and therapeutic strategies. To explore the contribution of proteasome-catalyzed peptide splicing (PCPS) to HIV-1 epitope generation, we developed a broadly applicable mass spectrometry-based discovery workflow that we employed to identify spliced HLA-I–bound peptides on HIV-infected cells. We demonstrate that HIV-1–derived spliced peptides comprise a relatively minor component of the HLA-I–bound viral immunopeptidome. Although spliced HIV-1 peptides may elicit CD8⁺ T cell responses relatively infrequently during infection, CD8⁺ T cells primed by partially overlapping contiguous epitopes in HIV-infected individuals were able to cross-recognize spliced viral peptides, suggesting a potential role for PCPS in restricting HIV-1 escape pathways. Vaccine-mediated priming of responses to spliced HIV-1 epitopes could thus provide a novel means of exploiting epitope targets typically underutilized during natural infection