Ultrastructural quantification of cell death after injurious compression of bovine calf articular cartilage

OBJECTIVE: It has been suggested that chondrocyte death by apoptosis may play a role in the pathogenesis of cartilage destruction in osteoarthritis, but the results of in-vivo and in-vitro investigations have been conflicting. To investigate further the cell death in our in-vitro model for traumatic joint injury, we performed a quantitative analysis by electron microscopy (EM) of cell morphology after injurious compression. For comparison, the TUNEL assay was also performed. DESIGN: Articular cartilage explant disks were harvested from newborn calf femoropatellar groove. The disks were subjected to injurious compression (50% strain at a strain rate of 100%/s), incubated for 3 days, and then fixed for quantitative morphological analysis. RESULTS: By TUNEL, the cell apoptosis rate increased from 7 +/- 2% in unloaded controls to 33 +/- 6% after injury (P=0.01; N=8 animals). By EM, the apoptosis rate increased from 5 +/- 1% in unloaded controls to 62 +/- 10% in injured cartilage (P=0.02, N=5 animals). Analysis by EM also identified that of the dead cells in injured disks, 97% were apoptotic by morphology. CONCLUSIONS: These results confirm a significant increase in cell death after injurious compression and suggest that most cell death observed here was by an apoptotic process.

Phase I trial of combretastatin A4 phosphate (CA4P) in combination with bevacizumab in patients with advanced cancer

The vascular disrupting agent (VDA) combretastatin A4 phosphate (CA4P) induces significant tumor necrosis as a single agent. Preclinical models have shown that the addition of an anti-VEGF antibody to a VDA attenuates the revascularization of the surviving tumor rim and thus significantly increases antitumor activity.

Evidence of viral adaptation to HLA class I-restricted immune pressure in chronic hepatitis C virus infection

Cellular immune responses are an important correlate of hepatitis C virus (HCV) infection outcome. These responses are governed by the host's human leukocyte antigen (HLA) type, and HLA-restricted viral escape mutants are a critical aspect of this host-virus interaction. We examined the driving forces of HCV evolution by characterizing the in vivo selective pressure(s) exerted on single amino acid residues within nonstructural protein 3 (NS3) by the HLA types present in two host populations. Associations between polymorphisms within NS3 and HLA class I alleles were assessed in 118 individuals from Western Australia and Switzerland with chronic hepatitis C infection, of whom 82 (69%) were coinfected with human immunodeficiency virus. The levels and locations of amino acid polymorphisms exhibited within NS3 were remarkably similar between the two cohorts and revealed regions under functional constraint and selective pressures. We identified specific HCV mutations within and flanking published epitopes with the correct HLA restriction and predicted escaped amino acid. Additional HLA-restricted mutations were identified that mark putative epitopes targeted by cell-mediated immune responses. This analysis of host-virus interaction reveals evidence of HCV adaptation to HLA class I-restricted immune pressure and identifies in vivo targets of cellular immune responses at the population level.

The James Lind Library: explaining and illustrating the evolution of fair tests of medical treatments

The James Lind Library (www.jameslindlibrary.org) has been established to improve public and professional general knowledge about fair tests of treatments in healthcare and their history. Its foundation was laid ten years ago at the Royal College of Physicians of Edinburgh, and its administrative centre is in the College's Sibbald Library, one of the most important collections of historic medical manuscripts, papers and books in the world. The James Lind Library is a website that introduces visitors to the principles of fair tests of treatments, with a series of short, illustrated essays, which are currently available in English, Arabic, Chinese, French, Portuguese, Russian and Spanish. A 100-page book-- Testing Treatments--is now available free through the website, both in English and in Arabic and Spanish translations. To illustrate the evolution of ideas related to fair tests of treatments from 2000 BC to the present, the James Lind Library contains key passages and images from manuscripts, books and journal articles, many of them accompanied by commentaries, biographies, portraits and other relevant documents and images, including audio and video files. New material is being added to the website continuously, as relevant new records are identified and as methods for testing treatments evolve. A multinational, multilingual editorial team oversees the development of the website, which currently receives tens of thousands of visitors every month.

The COLOSS BEEBOOK Volume I, Standard methods for Apis mellifera research: Introduction

The COLOSS BEEBOOK is a practical manual compiling standard methods in all fields of research on the western honey bee, Apis mellifera. The COLOSS network was founded in 2008 as a consequence of the heavy and frequent losses of managed honey bee colonies experienced in many regions of the world (Neumann and Carreck, 2010). As many of the world’s honey bee research teams began to address the problem, it soon became obvious that a lack of standardized research methods was seriously hindering scientists’ ability to harmonize and compare the data on colony losses obtained internationally. In its second year of activity, during a COLOSS meeting held in Bern, Switzerland, the idea of a manual of standardized honey bee research methods emerged. The manual, to be called the COLOSS BEEBOOK, was inspired by publications with similar purposes for fruit fly research (Lindsley and Grell, 1968; Ashburner 1989; Roberts, 1998; Greenspan, 2004).

The COLOSS BEEBOOK Volume I: Standard Methods for Apis mellifera Research

In recent years, declines of honey bee populations have received massive media attention worldwide, yet attempts to understand the causes have been hampered by a lack of standardisation of laboratory techniques. Published as a response to this, the COLOSS BEEBOOK is a unique collaborative venture involving 234 bee scientists from 34 countries, who have produced the definitive guide to how to carry out research on honey bees. It is hoped that these volumes will become the standards to be adopted by bee scientists worldwide. Volume I includes approximately 1,100 separate protocols dealing with the study of the honey bee, Apis mellifera. These cover anatomy, behavioural studies, chemical ecology, breeding, genetics, instrumental insemination and queen rearing, pollination, molecular studies, statistics, toxicology and numerous other techniques

Aristeas the Tourist

"Herodotus the Tourist" was the title given by James Redfield to his inquiry into Herodotus's ethnological system (Classical Philology, 80.2, 1985: 97-118). Redfield's insights, together with François Hartog's monograph The mirror of Herodotus (University of California Press, 1988), definitively modified our interpretation of Herodotus's Histories. In the present paper, I analyse the so-called Letter of Aristeas from a narratological perspective, suggesting that the anonymous author of the Letter deliberately constructed his main character ("Aristeas") as a Herodotus-like figure, who visits Judea and Jerusalem as yet another "tourist". In so-doing, the author's pseudo-ethnographic text produces a specific Jewish self-definition and identity in the Hellenistic period, mirroring both Greek representations of the Jews as a people of philosophers, and a Jewish interpretation of the ideal bios philosophikos, best typified through the Jewish compliance with the Mosaic legislation.