Transducin-alpha C-terminal peptide binding site consists of C-D and E-F loops of rhodopsin

The binding of heterotrimeric GTP-binding proteins (G-proteins) to serpentine receptors involves several independent contacts. We have deduced the points of interaction between mutant bovine rhodopsins and alphat-(340-350), a peptide corresponding to the C terminus of the alpha subunit (alphat) of bovine retinal G-protein, transducin. Direct binding of alphat-(340-350) to rhodopsin stabilizes the activated metarhodopsin II state (M II), consequently uncoupling the rhodopsin-transducin interaction. This peptide action requires two segments on the cytoplasmic domain of rhodopsin: the Tyr136-Val137-Val138-Val139 sequence on the C-D loop and the Glu247-Lys248-Glu249-Val250-Thr251 sequence on the E-F loop. We propose that a tertiary interaction of these two loop regions forms a pocket for binding the alphat C terminus of the transducin during light transduction in vivo. In most G-proteins, the C termini of alpha subunits are important for interaction with receptors, and, in several serpentine receptors, regions similar to those in rhodopsin are essential for G-protein activation, indicating that the interaction described here may be a generally applicable mode of G-protein binding in signal transduction.     

Evaluation of the effectiveness of continuous renal replacement therapy in critical patients after cardiovascular surgery

The efficacy of continuous methods of renal substitute therapy (RST) in patients with multiple organ failure is assessed. The patients were divided in 2 groups administered different types of PST. Group 1 were 16 patients subjected to RST by peritoneal dialysis, in group 2 (n = 16) GP and/or GDP were used. Hemodynamics, hematological and biochemical values, and clearance of inflammation mediators were monitored and hemohydrobalance and complications of therapy assessed in the course of RST. Both RST methods proved to be highly effective. The possibility of differentiated use of peritoneal dialysis and GP/GDP permits an individual approach to treatment, and equally high efficacy of both methods solves the problem of treating total renal insufficiency in the majority of patients with multiple organ failure following cardiovascular surgery.     

Effect of sodium nitroprusside on compound action potential thresholds in the gerbil cochlea

OBJECTIVE: Trials that do not allow rejection of the null hypothesis of no treatment effect may have had an inappropriate design. Trials are virtually never assessed for correlation between responses to different treatment modalities. METHODS: Using a hypothetical example and several published studies we examine the influence of correlation levels between treatment modalities on the sensitivity of testing. RESULTS: The level of correlation between responses to different treatment modalities is a major determinant of the sensitivity both of crossover and parallel group clinical trials. CONCLUSIONS: It is very relevant to assess a priori correlation levels between responses to the different treatment modalities of a trial. If a negative correlation is anticipated, a crossover design is likely to lack sensitivity. If a positive correlation is anticipated a parallel-group design seems less appropriate, because it would lack the extra sensitivity of accounting for the positive correlation. Both designs would seem suitable for approximately zero correlations (e.g. comparison vs baseline or vs placebo under the assumption that the number of placebo responders is negligible.     

Acquired autoimmune thrombocytopenia post-bone marrow transplantation for severe combined immunodeficiency

Children with severe combined immunodeficiency (SCID) have profoundly diminished humoral and cellular immunity resulting in death during infancy unless immune reconstitution occurs by bone marrow transplantation (BMT). Thrombocytopenia post-bone marrow transplantation can be seen in relation to infection, graft-versus-host disease (GVHD) and rarely, as an autoimmune phenomenon due to immune dysregulation. We report two cases of severe AITP following BMT for SCID. Both cases developed large intracerebral hemorrhages from which one died. Autoimmune thrombocytopenia in this setting can be life-threatening and we recommend early and active intervention.     

Pneumococcal polysaccharide vaccine in children with chronic renal disease: a prospective study of antibody response and duration

We studied the antibody response to pneumococcal serotypes 3 and 14 after pneumococcal polysaccharide vaccine was administered to 41 children with renal disease. One month after vaccination, 76% and 61% of patients achieved at least a twofold titer rise to serotypes 3 and 14, respectively; this finding was comparable to historic control values. One year after vaccination, the majority of patients retained protective antibody levels. Achieving a titer > or = 1.0 microgram/ml IgG at 1 month was highly predictive of retaining a protective antibody level > or = 0.15 microgram/ml at 1 year.