CD39 activity correlates with stage and inhibits platelet reactivity in chronic lymphocytic leukemia

Background  

Chronic lymphocytic leukemia (CLL) is characterized by accumulation of mature appearing lymphocytes and is rarely complicated by thrombosis. One possible explanation for the paucity of thrombotic events in these patients may be the presence of the ecto-nucleotidase CD39/NTDPase-1 on the surface of the malignant cells in CLL. CD39 is the major promoter of platelet inhibition in vivo via its metabolism of ADP to AMP. We hypothesize that if CD39 is observed on CLL cells, then patients with CLL may be relatively protected against platelet aggregation and recruitment and that CD39 may have other effects on CLL, including modulation of the disease, via its metabolism of ATP.     

Triploidy syndrome: A report on two live-born (69, XXY) and one still-born (69, XXX) infants

Two live-born cases, 69,XXY and one stillbirth, 69,XXX are reported. Further evidence is presented to delineate the triploidy syndrome. Common external and internal features which characterize the triploidy syndrome are low-set ears, hypertelorism, colobomata, syndactyly, simian creases, microphallus, undescended testes, scrotal aplasia, anomalous heart and hypoplasia of kidneys and adrenals. The triploidy syndrome encompasses features found in trisomies 13, 18 and 21. We suggest that the abnormal development of the triploidy infants is the result of the mentioned trisomies and their subsequent effect on the remaining genome.     

Interaction of a Motor Response, and Reaction Time and Time Estimation Tasks, on Heart Rate and Skin Conductance

The influence of motor responding and typical psychophysiological tasks on heart rate was tested by manipulating motor requirements of reaction time (RT) and time estimation (TE) tasks. Thirty-four volunteers were assigned randomly to four groups. Two groups squeezed a hand dynamometer at the start of a trial and the other two groups squeezed at the finish of the trial. The force of the squeeze was also manipulated: either 3 kg (3) or 7 kg (7). The four groups were Start 3, Start 7, Finish 3, and Finish 7. All subjects participated in the TE and RT tasks. The dependent variables were measurements of forearm flexor muscle tension, heart rate and skin conductance. It was found that the manipulations of when and with what force a person squeezed the dynamometer resulted in reliable group differences in muscle tension. The magnitude of acceleratory components of the triphasic (acceleration-deceleration-acceleration) cardiac response was amplified by tension. The magnitude of the deceleratory component seemed to depend on both muscle tension and stimulus processing. Except for the magnitude of the response-bound deceleration, RT and TE produced very similar heart rate responses, and skin conductance did not differ among groups. The data were interpreted as providing evidence that motor response acts as an amplifier for the phasic HR produced by common psychological paradigms.     

Genome-wide examination of myoblast cell cycle withdrawal during differentiation.

Skeletal and cardiac myocytes cease division within weeks of birth. Although skeletal muscle retains limited capacity for regeneration through recruitment of satellite cells, resident populations of adult myocardial stem cells have not been identified. Because cell cycle withdrawal accompanies myocyte differentiation, we hypothesized that C2C12 cells, a mouse myoblast cell line previously used to characterize myocyte differentiation, also would provide a model for studying cell cycle withdrawal during differentiation. C2C12 cells were differentiated in culture medium containing horse serum and harvested at various time points to characterize the expression profiles of known cell cycle and myogenic regulatory factors by immunoblot analysis. BrdU incorporation decreased dramatically in confluent cultures 48 hr after addition of horse serum, as cells started to form myotubes. This finding was preceded by up-regulation of MyoD, followed by myogenin, and activation of Bcl-2. Cyclin D1 was expressed in proliferating cultures and became undetectable in cultures containing 40% fused myotubes, as levels of p21(WAF1/Cip1) increased and alpha-actin became detectable. Because C2C12 myoblasts withdraw from the cell cycle during myocyte differentiation following a course that recapitulates this process in vivo, we performed a genome-wide screen to identify other gene products involved in this process. Using microarrays containing approximately 10,000 minimally redundant mouse sequences that map to the UniGene database of the National Center for Biotechnology Information, we compared gene expression profiles between proliferating, differentiating, and differentiated C2C12 cells and verified candidate genes demonstrating differential expression by RT-PCR. Cluster analysis of differentially expressed genes revealed groups of gene products involved in cell cycle withdrawal, muscle differentiation, and apoptosis. In addition, we identified several genes, including DDAH2 and Ly-6A, whose expression specifically was up-regulated during cell cycle withdrawal coincident with early myoblast differentiation.     

Modulation of activity in medial frontal and motor cortices during error observation

We used measures of the human event-related brain potential (ERP) to investigate the neural mechanisms underlying error processing during action observation. Participants took part in two conditions, a task execution condition and a task observation condition. We found that activity in both the medial frontal cortex and the motor cortices, as measured via the error-related negativity and the lateralized readiness potential, respectively, was modulated by the correctness of observed behavior. These data suggest that similar neural mechanisms are involved in monitoring one's own actions and the actions of others.     

Spectral electroencephalographic correlates of iron status: Tired blood revisited

For some time, clinical reports have described impairment of affective and cognitive functions in iron deficient persons. Recent studies suggest that both brain biochemistry and cognitive performance capacity may be disrupted by inadequate intake of dietary iron, but the relationship of the possible neurophysiological effects to psychological ones is unclear. To examine the relationship of iron status to simultaneous measures of cortical activation and cognitive performance, 8 channels of electroencephalographic (EEG) data were recorded during a resting period and during the performance of several cognitive tasks in two groups of men. The EEG data were spectrally analyzed, and measures of total power and frequency of peak power in each of several bands of the power spectrum for each channel were used as predictors in multiple regression analyses with serum iron and serum ferritin as alternative criteria. Measures of power in the delta frequency in the resting period appeared relevant to iron status in both groups, perhaps indicating alertness or arousal level. Consistently in these regressions, the asymmetry of the EEG appeared relevant to iron and ferritin. These findings suggest that the combination of EEG and performance measures may help characterize the neuropsychological effects of trace element nutrition.     

Cytokine induction of heat shock protein in human granulosa-luteal cells

The infiltration of leukocytes is a characteristic feature ofluteolysis in humans. Leukocytes are known to generate physiologicalinducers of cell stress such as cytokines which have been implicatedas mediators of functional luteal regression. In cells exposedto stress, a response characterized by an increase in heat shockprotein (HSP) synthesis occurs. Recently, the induction of HSP-70in rat luteal cells has been shown to inhibit luteinizing hormone(LH) and cAMP-sensitive progesterone production, possibly byinterfering with the translocation of cholesterol to the mitochondrialcytochrome P450_SCC. We therefore investigated whether HSP-70is induced in human granulosa-luteal cells and its relationshipto steroidogenesis. [³⁵S]Methionine labelling showed an increasein a 70 kDa protein after heat treatment which was demonstratedto be HSP-70 by Western analysis using monoclonal antibodiesagainst the constitutive and inducible forms of HSP-70. Inductionof HSP-70 in human granulosa-luteal cells was also seen withinterferon (IFN) (10 ng/ml), tumour necrosis factor (TNF)-     

Self-esteem and causal attributions for success and failure in children

In a comparison of causal attributions following success and failure in hypothetical social, athletic, and academic situations, high self-esteem grade school children were more likely than low self-esteem children to attribute their success to ability and their failure to either lack of effort or bad luck. Low self-esteem children, on the other hand, attributed their success more often than high self-esteem children to good luck (and in social situations to effort and task ease as well) and their failure to lack of ability. Whereas prior studies that focused only on the internal-external dimension found that low and high self-esteem children differed in their attributional style to success but not to failure, the present study found that when distinctions between behavioral and characterological attributions (stability and globality dimensions) were included, the two groups differed significantly in response to both success and failure. Although perhaps not generalizable beyond the present attribution measure, the most pronounced attribution differences between low and high self-esteem children were observed in the social domain, the least in the academic domain, with athletics falling in between. Finally, it was found that sex and age (within the limited fourth- to sixth-grade range examined in the present study) did not alter the overriding difference in attributional style between low and high self-esteem children.This study is based on a doctoral dissertation submitted by the first author under the supervision of the last author in partial fulfillment of the requirements for the Ph.D. degree at the University of Vermont.     

Race disparities in genetic alterations within Wilms tumor specimens

BackgroundWilms tumor (WT) affects Black children disproportionately. Genetic aberrations within WT specimens that contribute to this disparity have not been reported.MethodsThe Therapeutically Applied Research to Generate Effective Treatments (TARGET) database was queried for WT patient and genomic features. Clinical and genetic variables were compared by race.ResultsWithin the discovery set (enriched for adverse events; N = 94 White, 19 Black, 14 Other/unreported patients), Black children were more likely to present with advanced stage disease (p = 0.019). Within the validation set (primarily a random sampling of NWTS-5; N = 360 White, 92 Black, 72 Other/Unreported), Black children appeared older at diagnosis (p = 0.050), had decreased median follow-up time (p<0.0005) and were over-represented (17.4%) relative to the concurrent U.S. Census (12.8%). Among the 37 target genes sequenced, ACTB (p = 0.030) and DICER1 (p = 0.026) mutations were more common in Black patient specimens, whereas DGCR8 (p = 0.041) mutations were more common in White patient specimens. White patient specimens were more likely to contain one or multiple targeted mutations (p = 0.026).ConclusionWithin the TARGET database, Black children were over-represented and harbored WT specimens containing more frequent ACTB and DICER1 mutations. In contrast, WT from White children contained overall more mutations in targeted genes and specifically in DGCR8.Level of EvidenceIII.