Expression of cyclic ADP-ribose-synthetizing CD38 molecule on human platelet membrane

CD38 is a cell surface molecule widely used as a marker for immature and activated lymphocytes. It has been recently shown that CD38 displays three enzymatic activities: hydrolysis of NAD+ to ADP-ribose, synthesis of cyclic ADP-ribose from NAD+, and hydrolysis of cyclic ADP- ribose to ADP-ribose. Thus, CD38 plays a key role in the synthesis of cyclic ADP-ribose, a calcium-mobilizing compound. We investigate here the expression and cellular localization of CD38 in human platelets using a specific monoclonal antibody. Results showed that CD38 is expressed by human platelet membranes. Moreover, we show that platelet CD38 possesses NAD glycohydrolase, ADP-ribose cyclase, and cyclic ADP- ribose hydrolase activities. This finding indicates that the calcium- mobilizing agent cyclic ADP-ribose can be synthetized by human platelets and raises the question about the possible role of CD38 expression and enzymatic activities in the signal transduction pathways leading to platelet activation.     

Effects of CD34+ cell selection and perfusion on ex vivo expansion of peripheral blood mononuclear cells

Ex vivo expansion of peripheral blood mononuclear cells (MNCs), cultured both directly and after selection for CD34+ cells, was compared in static and continuously perfused cultures containing interleukin (IL)-3, IL-6, granulocyte colony-stimulating factor (G- CSF), and stem cell factor (SCF). Cultures inoculated with either MNCs or CD34+ cells produced cells that were remarkably similar after 10 days of culture, as evidence by cell morphology, expression of CD34, CD33, CD15, and CD11b, and the fractions of cells giving rise to colony- forming units granulocyte-monocyte (CFU-GM) and long-term culture- initiating cells (LTC-IC). Static and perfusion cultures gave similar average total cells and CFU-GM expansions for both MNC and CD34+ cell cultures. However, those samples that performed poorly in static culture performed at near-normal levels in perfusion. In addition, perfusion supported higher LTC-IC numbers for both MNC and CD34+ cell cultures. While total cell expansion was about ten times greater in CD34+ cell cultures (approximately 100-fold), CFU-GM expansion (approximately 20-fold) was similar for both MNC and CD34+ cell cultures. The similar distribution of cell types produced in MNC and CD34+ cell cultures allows direct comparison of total and colony- forming cell production. After 15 days in perfusion, MNC cultures produced 1.5-, 2.6-, and 2.1-fold more total cells, CFU-GM, and LTC-IC, respectively, than the same sample selected and cultured as CD34+ cells. Even if the CD34+ selection process was 100% efficient, CFU-GM production would be 1.5-fold greater for MNCs than for CD34+ cells.     

Lack of interference by heparin with thrombolysis or binding of tissue- type plasminogen activator to thrombi

Coronary thrombolysis with t-PA is generally implemented with concomitant administration of heparin. However, results of studies in vitro suggest that heparin competes with fibrin for binding of tissue- type plasminogen activator (t-PA), augments activation of free plasminogen, decreases fibrin specificity, and impairs thrombolysis. To define the biological implications of these observations, we characterized effects of therapeutic concentrations of heparin on the binding of t-PA to thrombi formed in whole blood, effects of heparin on activation of plasminogen by t-PA in plasma, and effects of heparin on thrombolysis induced by t-PA in a clot lysis system designed to simulate conditions in vivo. The amount of t-PA bound to thrombi was not affected by heparin (0, 0.5, 1.0, and 5.0 U/mL). When t-PA activity was selectively and irreversibly inhibited by D-Phe-Pro-Arg- chloromethyl ketone (PPACK) the amount of t-PA-PPACK bound was similarly unaffected by heparin. Thrombolysis measured by 125I- fibrin(ogen) release and by reduction of mass of thrombi were not altered by heparin. Heparin did not affect plasminogen consumption induced by t-PA. Plasma concentrations of alpha-2-antiplasmin after exposure of blood to t-PA were less depressed with increasing concentrations of heparin. Thus, heparin in therapeutic concentrations does not interfere with binding of t-PA to thrombi, augment activation of free plasminogen, or inhibit thrombolysis. Accordingly, it appears likely that concomitant administration of heparin will not impair thrombolysis with t-PA implemented clinically.     

View-invariant representations of familiar objects by neurons in the inferior temporal visual cortex

A view-invariant representation of objects in the brain would have many computational advantages. Here we describe a population of single neurons in the temporal visual cortex (IT) that have view-invariant representations of familiar objects. Ten real plastic objects were placed in the monkeys' home cages for a period of time before neurophysiological experiments in which neuronal responses were measured to four views of each object. The macaques performed a visual fixation task, and had never been trained in object discrimination. The majority of the visual neurons recorded were responsive to some views of some objects and/or to the control stimuli, as would be expected from previous studies. However, a small subset of these neurons were responsive to all views of one or more of the objects, providing evidence that these neurons were coding for objects, rather than simply for individual views or visual features within the image. This result was confirmed by information theoretic analyses, which showed that the neurons provided information about which object was being seen, independently of the view. The coding scheme was shown to be sparse distributed, with relatively independent information being provided by the different neurons. Hypotheses about how these view-invariant cells are formed are described.      

Prospective randomized study of the efficacy of hydrogel, hydrocolloid, and saline solution—moistened dressings on the management of pressure ulcers

A total of 67 patients with pressure ulcers were randomized into one of three treatment modalities: hydrogel sheet dressing, hydrocolloid, or wet-to-moist gauze. Safety, efficacy, and physical attributes of the three dressings were evaluated. No statistical significance was found in wound healing rate among the three treatments. Hydrogel sheets were advantageous in allowing wound visualization without dressing or wound disruption.     

Evaluating the emotions of patients with chronic low back pain. A preliminary examination

The Emotions Scale (EMS) was developed to assess responses of patients with CLBP to pain in terms of positive and negative emotions. Such an evaluation may be able to provide an insight into the effectiveness of a rehabilitation programme in patients with CLBP. To determine the final number of factors, an initial principal component analysis without rotation was conducted. The EMS developed and validated in the present study for patients with CLBP is a tool that can be applied by all specialists and in all medical or rehabilitation settings because it is short and concise. At the same time it includes most of the main emotions affected by CLBP, so that with one tool, many assessments can be performed. The EMS may be used in controlled trials, or in observational and survey studies. The results revealed that two factors explained 56.31% of the total variance. Cronbach α coefficients were: 0.92 for factor “negative emotions” (12 items, e.g. “weak”) and 0.90 for factor “positive emotions” (8 items, e.g. “cheer”). Importantly, the component correlation matrix of the specific analysis showed a negative correlation between these two factors.