Non-life-threatening sepsis: report of two cases

Streptococcus bovis is one of the nonenterococcal species included among the streptococci group D. It is part of the normal bowel flora in humans and animals, but it is also responsible for infectious diseases (10-15% of all cases of bacterial endocarditis). Many cases of bacteremia and metastatic abscesses (spleen, liver, soft tissues, bone, meninges, endocardium) caused by S. bovis were reported as associated with digestive tract diseases, mainly colonic disease, and, in particular colonic neoplasms, or chronic liver diseases. A role in carcinogenesis has been suggested for this microorganism. The authors report two cases of S. bovis sepsis, one associated with colonic neoplasm and the other with liver cirrhosis and gastric carcinoma. Discussion is focused on probable mechanisms that favor gastric colonization and systemic diffusion of S. bovis from the gut in patients with gastrointestinal neoplasms or chronic liver disease and provides clinical recommendations for patients with S. bovis infections.     

Primary cardiac T-cell lymphoma

Primary cardiac lymphoma (PCL), defined as a lymphoma clinically mimicking cardiac disease, with the bulk of the tumor located intrapericardially, is extremely rare in immunocompetent patients. Clinical manifestations vary depending on sites of involvement in the heart and include chest pain, arrhythmias, pericardial effusion, and heart failure. Diagnosis is often difficult and may require invasive procedures; in some cases, diagnosis is not made until autopsy. Histologically, nearly all cases of PCL reported thus far have been of B-cell origin. In this report, we describe a case of PCL of T-cell origin in an adult immunocompetent patient, the second reported in the literature to the best of our knowledge, and provide a brief overview of the features of previously published PCL cases.     

Crystal structure of a eukaryotic zinc-dependent histone deacetylase, human HDAC8, complexed with a hydroxamic acid inhibitor

Histone deacetylases (HDACs) are a family of enzymes involved in the regulation of gene expression, DNA repair, and stress response. These processes often are altered in tumors, and HDAC inhibitors have had pronounced antitumor activity with promising results in clinical trials. Here, we report the crystal structure of human HDAC8 in complex with a hydroxamic acid inhibitor. Such a structure of a eukaryotic zinc-dependent HDAC has not be described previously. Similar to bacterial HDAC-like protein, HDAC8 folds in a single alpha/beta domain. The inhibitor and the zinc-binding sites are similar in both proteins. However, significant differences are observed in the length and structure of the loops surrounding the active site, including the presence of two potassium ions in HDAC8 structure, one of which interacts with key catalytic residues. CD data suggest a direct role of potassium in the fold stabilization of HDAC8. Knockdown of HDAC8 by RNA interference inhibits growth of human lung, colon, and cervical cancer cell lines, highlighting the importance of this HDAC subtype for tumor cell proliferation. Our findings open the way for the design and development of selective inhibitors of HDAC8 as possible antitumor agents.