Species-specific tissue antigens. II. A human species-specific antigen possessing esterase activity

An esterase that is limited in species distribution to human and monkey tissues was demonstrated by enzymoimmunoelectrophoresis and enzymoimmunodiffusion. The monkey esterase exhibited a slightly faster electrophoretic mobility than the human tissue esterase. An antigenically identical esterase found in concentrated human urine had a mobility slightly more anodal than the human tissue esterase. Despite the differences in electrophoretic mobility among the human tissue esterase, urinary esterase and monkey tissue esterase, they all reacted in enzymoimmunodiffusion with antiserum to cellular or urinary esterase to produce lines of immunologic identity. Tissues of the other species tested did not exhibit the human cathodal esterase.     

CNK and HYP form a discrete dimer by their SAM domains to mediate RAF kinase signaling

RAF kinase functions in the mitogen-activated protein kinase (MAPK) pathway to transmit growth signals to the downstream kinases MEK and ERK. Activation of RAF catalytic activity is facilitated by a regulatory complex comprising the proteins CNK (Connector enhancer of KSR), HYP (Hyphen), and KSR (Kinase Suppressor of Ras). The sterile alpha-motif (SAM) domain found in both CNK and HYP plays an essential role in complex formation. Here, we have determined the x-ray crystal structure of the SAM domain of CNK in complex with the SAM domain of HYP. The structure reveals a single-junction SAM domain dimer of 1:1 stoichiometry in which the binding mode is a variation of polymeric SAM domain interactions. Through in vitro and in vivo mutational analyses, we show that the specific mode of dimerization revealed by the crystal structure is essential for RAF signaling and facilitates the recruitment of KSR to form the CNK/HYP/KSR regulatory complex. We present two docking-site models to account for how SAM domain dimerization might influence the formation of a higher-order CNK/HYP/KSR complex.     

Enteric-Release Budesonide May Be Useful in the Management of Non-Responsive Celiac Disease

Digestive Diseases and Sciences - Non-responsive celiac disease (NRCD) has many aetiologies, including gluten exposure. Budesonide may be used for refractory celiac disease (RCD) and celiac crisis....     

Angiotensin-converting enzyme inhibitors in adults after the Mustard procedure

Angiotensin-converting enzyme inhibitors had no significant effect on cardiopulmonary exercise function in 14 patients who had undergone a Mustard operation for transposition of the great arteries. In some patients aerobic capacity improved and maximum systolic blood pressure decreased.     

Management and treatment of hepatitis C virus in patients with HIV and hepatitis C virus coinfection: A practical guide for health care professionals

Concomitant HIV and hepatitis C virus (HCV) is a common yet complex coinfection. The present document is a practical guide for treating HCV infection in people coinfected with HIV. Effective antiretroviral therapies have prolonged survival rates for HIV-infected people over the past decade, which have made latent complications of HCV major causes of morbidity and mortality in these patients. Advances in the treatment of HCV (eg, combined pegylated interferon and ribavirin) offer the possibility of eradicating HCV infection in coinfected persons. The treatment of HCV must be considered in all cases. Intensive management of the adverse effects of HCV treatment is one of the factors for the success of these therapies. HCV eradication is predicted to decrease the mortality associated with coinfection and reduce the toxicity of HIV treatment.     

Line-up Member Similarity Influences the Effectiveness of a Salient Rejection Option for Eyewitnesses

Visually salient line-up rejection options have not been systematically studied with adult eyewitnesses. We explored the impact of using a non-verbal, salient rejection option on adults' identification accuracy for line-ups containing low- or high-similarity fillers. The non-verbal, salient rejection option had minimal impact on accuracy in low-similarity line-ups, but in high-similarity line-ups its inclusion increased correct rejections for target-absent line-ups as well as incorrect rejections in target-present line-ups, relative to a verbal rejection condition. The improved performance in target-absent line-ups suggests that adults, like children, may experience pressure to choose and guess during difficult tasks. This pressure is reduced when a prominent non-verbal rejection option is displayed in the line-up. However, the salient rejection option also appears to increase the attractiveness of avoiding a difficult choice between the target and highly similar fillers. Implications of these findings for the experimental literature and justice system are discussed.     

KSR stimulates Raf-1 activity in a kinase-independent manner

Kinase suppressor of Ras (KSR) is an evolutionarily conserved component of Ras-dependent signaling pathways. Here, we find that murine KSR (mKSR1) translocates from the cytoplasm to the plasma membrane in the presence of activated Ras. At the membrane, mKSR1 modulates Ras signaling by enhancing Raf-1 activity in a kinase-independent manner. The activation of Raf-1 is mediated by the mKSR1 cysteine-rich CA3 domain and involves a detergent labile cofactor that is not ceramide. These findings reveal another point of regulation for Ras-mediated signal transduction and further define a noncatalytic role for mKSR1 in the multistep process of Raf-1 activation.