Direct and reversible inhibitory effect of the tetrapeptide acetyl-N- Ser-Asp-Lys-Pro (Seraspenide) on the growth of human CD34+ subpopulations in response to growth factors

The tetrapeptide Acetyl-N-Ser-Asp-Lys-Pro (AcSDKP, Seraspenide; Ipsen- Biotech, Paris, France), an inhibitor of murine spleen colony-forming units reduces the number and the percentage in DNA synthesis of progenitors from human unfractionated bone marrow. To determine whether AcSDKP may directly affect the growth potential of purified progenitors even at the most primitive level, CD34+HLA-DRhigh and CD34++HLA-DRlow cells were highly purified by cell sorting. Then, CD34+ subsets were stimulated in liquid culture with combinations of growth factors (GFs) and AcSDKP was added for 20 hours or 6 days and cells plated in methylcellulose. After a 20-hour incubation, we show that AcSDKP (at 10(-10) mol/L) significantly inhibits the colony formation of both CD34+ subsets. Moreover, when added daily for 6 days, AcSDKP: (1) reduces the proliferation of both CD34+ cell fractions stimulated by 3 or 7 GFs, and (2) decreases the number of progenitors generated from the CD34+HLA-DRhigh and CD34++HLA-DRlow cell fractions. Furthermore, we show for the first time, using both high proliferative potential cell and long-term culture initiating cell assays, that AcSDKP inhibits the most primitive cells contained in the CD34++HLA-DRlow subpopulation. Finally, by using limiting dilution assays we demonstrated that AcSDKP acts directly at a single cell level and that its inhibitory effect is reversible and dose dependent.     

Carrier detection in hemophilia A: a cooperative international study. I. The carrier phenotype

Eight laboratories in six countries cooperated to clarify several issues concerning the phenotypes of heterozygous carriers of hemophilia "A." Plasma levels of factor VIII (F.VIII:C, formerly VIII:C) and von Willebrand factor (VWF:Ag, formerly VIIIR:Ag) of carriers and normal women were determined by various "in-house" methods; a single lyophilized plasma standard was used for all assays. Analysis of the collated data from 336 carriers (296 obligatory carriers and 40 sporadic carriers) and 137 normal women showed that there was no difference in the F.VIII:C levels of "paternal" carriers (women who had obtained the abnormal gene from their fathers) and "maternal" carriers. Neither was there a difference in the VWF:Ag levels of normal women and either type of carrier. Age was found to have a significant effect on both F.VIII:C and VWF:Ag, values being higher at very young and very old ages, the minima occurring in the 25- to 30-year range. ABO blood type had a striking effect. Women of types A, B, and AB (designated non- O in the study), both normals and carriers, had significantly higher levels of both factors than did women of type O. Analysis by laboratories showed that differences in mean levels of both factors between laboratories were highly significant. It was concluded that age, ABO blood type, and laboratory variation should be taken into account in carrier detection.     

Differential effects of nitric oxide on erythroid and myeloid colony growth from CD34+ human bone marrow cells

Nitric oxide (NO) is a reactive molecule with numerous physiologic and pathophysiologic roles affecting the nervous, cardiovascular, and immune systems. In previous work, we have demonstrated that NO inhibits the growth and induces the monocytic differentiation of cells of the HL- 60 cell line. We have also demonstrated that NO inhibits the growth of acute nonlymphocytic leukemia cells freshly isolated from untreated patients and increases monocytic differentiation antigens in some. In the present work, we studied the effect of NO on the growth and differentiation of normal human bone marrow cells in vitro. Mononuclear cells isolated from human bone marrow were cultured in semisolid media and treated with the NO-donating agents sodium nitroprusside (SNP) or S- nitroso-acetyl penicillamine (SNAP) (0.25 to 1 mmol/L). Both agents decreased colony-forming unit-erythroid (CFU-E) and colony-forming unit- granulocyte macrophage (CFU-GM) formation by 34% to 100%. When CD34+ cells were examined, we noted that these cells responded to SNP and SNAP differently than did the mononuclear cells. At a concentration range of 0.25 to 1 mmol/L, SNP inhibited the growth of CFU-E by 30% to 75%. However, at the same concentration range, SNP increased the number of CFU-GM by up to 94%. At concentrations of 0.25 to 1 mmol/L, SNAP inhibited the growth of CFU-E by 33% to 100%. At a concentration of 0.25 mmol/L, SNAP did not affect CFU-GM. At higher concentrations, SNAP inhibited the growth of CFU-GM. Although SNP increased intracellular levels of cGMP in bone marrow cells, increasing cGMP in cells by addition of 8-Br-cGMP (a membrane permeable cGMP analogue) did not reproduce the observed NO effects on bone marrow colonies. These results demonstrate that NO can influence the growth and differentiation of normal human bone marrow cells. NO (generated in the bone marrow microenvironment) may play an important role modulating the growth and differentiation of bone marrow cells in vivo.     

Differing effects of prosaccades and antisaccades on postural stability

The goal of the study was to examine the effect of different types of eye movements on postural stability. Ten healthy young adults (25 ± 3 years) participated in the study. Postural control was measured by the TechnoConcept© platform and recorded in Standard Romberg and Tandem Romberg conditions while participants performed five oculomotor tasks: two fixation tasks (central fixation cross, without and with distractors), two prosaccade tasks toward peripheral targets displayed 4° to the left or to the right of the fixation cross (reactive saccades induced by a gap 0 ms paradigm and voluntary saccades induced by an overlap 600 ms paradigm) and one antisaccade task (voluntary saccade made in the opposite direction of the visual target). The surface, the length, and the mean speed of the center of pressure were analyzed. We found that saccadic eye movements improved postural stability with respect to the fixation tasks. Furthermore, antisaccades were found to decrease postural stability compared to prosaccades (reactive as well as voluntary saccades). This result is in line with the U-shaped nonlinear model described by Lacour et al. (Neurophysiol Clin 38:411–421, 2008), showing that a secondary task performed during a postural task could increase (prosaccade task) or decrease (antisacade task) postural stability depending on its complexity. We suggest that the different degree of attentional resources needed for performing prosaccade or antisaccade tasks are, most likely, responsible for the different effect on postural control.     

Rhodium effects on Pt anode materials in a direct alkaline ethanol fuel cell

The development of efficient catalysts for ethanol oxidation in alkaline medium requires a synthetic approach that may prevent the surfactant molecules from being adsorbed at the catalytic sites and decreasing the electrochemical performance of the final direct ethanol fuel cell. Toward this goal, the recently reported surfactant-less Bromide Anion Exchange (BAE) method, appears as a promising route to conveniently aim at preparing PtRh alloys dispersed on carbon substrates. The catalysts prepared herein by the BAE method were characterized physicochemically to obtain structural information on the PtRh/C nanomaterials, their morphology (size and shape), and their chemical and surface composition. Electrochemical behavior and properties of these electrodes were then investigated in a half-cell before the implementation of a direct ethanol fuel cell (DEFC) in a home-made anion exchange membrane Teflon cell. The analysis of the electrolytic solution in the anodic compartment by chromatography revealed that acetate was the major reaction product and the carbonate amount increased with the Rh content in the bimetallic composition. With 2.8–3.6 nm particle sizes, the Pt₅₀Rh₅₀/C catalyst exhibited the highest activity towards the ethanol electrooxidation.

The development of efficient catalysts for ethanol oxidation in alkaline medium requires an approach that avoids surfactant molecules from being adsorbed at active sites and decreasing the electrochemical performance of the direct ethanol fuel cell.     

Immune Reconstitution Inflammatory Syndrome Secondary to Mycobacterium kansasii Infection in a Kidney Transplant Recipient

Nontuberculous mycobacteria (NTM) infection is a challenging diagnosis for clinicians in solid organ transplantation. Immune reconstitution inflammatory syndrome (IRIS) is so far unreported in this context. We report here the case of a renal transplant recipient who developed Mycobacterium kansasii–associated lymphadenitis complicated by IRIS while undergoing reduction of his immunosuppressive therapy. For IRIS, the patient required low‐dose steroids and an increase in global immunosuppression, in association with NTM antibiotherapy.