Intellectual development after treatment in children with acute leukemia and brain tumor

Background: The influence of central nervous system (CNS)‐directed chemotherapy on intelligence remains controversial. In this study, we investigated the influence of treatment on intellectual development in acute lymphoblastic leukemia (ALL) and brain tumor patients undergoing CNS‐directed treatments. Methods: Among patients treated in the Department of Pediatrics, St Luke's International Hospital between April 2000 and March 2009, the subjects were 38 patients with ALL or brain tumors who underwent regular Wechsler intelligence tests. Results: The subjects consisted of 26 patients with ALL and 12 with brain tumors. Prophylactic cranial irradiation was not performed in patients with ALL, whereas it was done for all those with brain tumor. In patients with ALL, the IQ 1 year later was not changed from the start of treatment. In those with brain tumors, the verbal IQ 1 year later was significantly lower than that at the start of treatment. In patients with ALL, intelligence tests were performed 3 years after the start of treatment and there were no marked changes between the two time‐points (n= 11). In those with a brain tumor, intellectual functions further decreased after the completion of treatment to as late as 5 years after the initiation of treatment (n= 7). Conclusions: There is no intellectual impairment in any patient with ALL at post‐treatment follow‐up 3 years after the start of treatment, while intelligence is serially reduced in brain tumor patients. An innovative intervention may be needed for this group of patients.     

Activity-inducible protein Homer1a/Vesl-1S promotes redistribution of postsynaptic protein Homer1c/Vesl-1L in cultured rat hippocampal neurons

In cultured rat hippocampal neurons, overexpression of Homer1a/Vesl-1S, an inducible protein upregulated by seizure or long-term potentiation, caused a reduction of punctate distribution of a postsynaptic protein Homer1c/Vesl-1L, without significant decrease in its total amount. Clusters of F-actin were also decreased. Treatments of cells with BDNF or a proteasome inhibitor, which cause increase in the expression level of endogenous Homer1a, also resulted in the reduction of Homer1c puncta. These results indicate that the accumulation of Homer1a, either exogenously expressed or endogenously induced, caused redistribution and dispersion of postsynaptic clusters of Homer1c and F-actin, suggesting an important role of Homer1a in synaptic remodeling.     

骨骼肌介电行为的理论模型仿真

在 10 0 Hz～ 10 0 MHz范围内 ,应用椭圆壳介电理论模型 ,经过模拟仿真蛙骨骼肌细胞的介电行为 ,确定了蛙骨骼肌细胞的椭圆壳模型各相参数。为将来对骨骼肌疲劳、肌营养不良和肌肉萎缩等病症的模型分析奠定理论基础。     

Negative regulation by SHPS-1 of Toll-like receptor-dependent proinflammatory cytokine production in macrophages

SHPS-1 is a transmembrane protein predominantly expressed in macrophages. The possible role of SHPS-1 in regulation of Toll-like receptor (TLR)-dependent production of proinflammatory cytokines by macrophages has remained unknown, however. We now show that expression either of a mutant version of mouse SHPS-1 (SHPS-1–4F) in which the four tyrosine phosphorylation sites in the cytoplasmic region are replaced by phenylalanine or of a chimeric protein comprising the extracellular and transmembrane regions of human CD8 fused to the cytoplasmic region of SHPS-1–4F (CD8–4F) markedly promoted the production of tumor necrosis factor-α (TNF-α) or interleukin-6 (IL-6) induced by lipopolysaccharide (LPS) or polyinosinic-polycytidylic acid [poly(I : C)] in RAW264.7 macrophages. In contrast, expression of a mutant form of SHPS-1 that lacks most of the cytoplasmic region did not promote such responses. Expression of SHPS-1–4F promoted the LPS- or poly(I : C)-induced activation of NF-κB. LPS and poly(I : C) each induced the tyrosine phosphorylation of SHPS-1 through a Src family kinase and the association of SHPS-1 with SHP-1 and SHP-2. These results suggest that LPS or poly(I : C) induces tyrosine phosphorylation of SHPS-1 and the association of SHPS-1 with SHP-1 and SHP-2 in a manner dependent on a Src family kinase. SHPS-1 then negatively regulates TLR4- or TLR3-dependent cytokine production through inhibition of NF-κB-dependent signaling.     

Identification and characterization of human thymic cortical dendritic macrophages that may act as professional scavengers of apoptotic thymocytes

We identify and characterize a special type of macrophage in the human thymic cortex that may act as professional scavengers of apoptotic thymocytes. These are large cells with clear cytoplasm, evenly distributed exclusively in the thymic cortex, and usually contain degraded nuclei in their cytoplasm. They are distinct from ordinary macrophages (OM) in the thymic cortex in expressing fascin, an actin-bundling protein specific for dendritic cells (DC), and in lacking lysozyme (LZM) and CD68. They are also different from DC in lacking major histocompatibility complex (MHC)-class II molecules. To distinguish them from OM and DC, we called them thymic cortical dendritic macrophages (TCDM). Both TCDM and OM are positive for DC-SIGN (CD209) and HAM56, whereas fascin(hi) MHC-class II(hi) medullary DC (mDC) are negative for these antigens. TCDM exhibit either dendritic or plump feature depending on cases examined. Plump TCDM usually contain several degraded nuclei, while dendritic TCDM contain one or two. These degraded nuclei are positive for active caspase-3 (aCasp-3), indicating that they are apoptotic thymocytes. In contrast to TCDM, LZM(hi) CD68(hi) OM are smaller round cells, distributed unevenly throughout the thymus, and do not contain apoptotic thymocytes at all. TCDM tend to adhere to capillaries with their dendrites or they make extensive contacts covering a large portion of the capillaries. Electron microscopic analysis confirmed the extensive contact between TCDM and capillaries and indicated that TCDM possess extremely electron-lucent, abundant cytoplasm with numerous tubulovesicular structures and secondary lysosomes. The finding of numerous condensed nuclei in most of the TCDM indicates that these cells represent a special type of fixed macrophages in the human thymic cortex, and that they play a central role in the clearance of apoptotic thymocytes.     

Gene expression analysis of common carp (Cyprinus carpio L.) lines during Cyprinid herpesvirus 3 infection yields insights into differential immune responses

Cyprinid herpesvirus 3 (CyHV-3), also known as koi herpesvirus (KHV), is the etiological agent of a virulent and lethal disease in common and koi carp. This study aimed to determine the genetic basis underlying the common carp immune response to the CyHV-3 virus. Two common carp lines (R3 and K) were infected with CyHV-3 by immersion. The R3 line presented a 20% higher survival rate compared to the K line and significantly lower viral loads as measured at day 3 post infection (p.i.). Microarray analysis using a common carp slides containing a number of 10,822 60-mer probes, revealed that 581 genes in line K (330 up-regulated, 251 down-regulated) and 107 genes in line R3 (77 up-regulated, 30 down-regulated), showed at least a 2-fold difference in expression at day 3 p.i. compared to day 0. Genes which showed at least a 4-fold difference in expression in both lines were selected as potential markers of a CyHV-3 infection in common carp. Additionally, 76 genes showed at least 2-fold differentially expression between K and R3 lines at day 3 p.i. Significantly higher expression of several immune-related genes including number of those which are involve in pathogen recognition, complement activation, MHC class I-restricted antigen presentation and development of adaptive mucosal immunity was noted in more resistant R3 line. Further real-time PCR based analysis provided evidence for higher activation of CD8(+) T cells in R3 line. This study uncovered wide array of immune-related genes involved into antiviral response of common carp toward CyHV-3. It is also demonstrated that the outcome of this severe disease in large extent could be controlled by genetic factors of the host.     

Polyamidoamine dendrimer-conjugated quantum dots for efficient labeling of primary cultured mesenchymal stem cells

Monitoring of cells in vivo after transplantation could supply important information for determining the efficacy of stem cell therapy. The use of quantum dots (QDs) has several advantages for in vivo imaging, such as remarkable resistance to photo bleaching, high fluorescence efficiency, and size-tunable emission. After they are taken up by cells via endocytosis, QDs lose their fluorescence intensity in endosomes/lysosomes at low pH because the intensity cannot survive under acidic conditions. Moreover, the amount of QD uptake by mesenchymal stem cells (MSCs) is extremely small. Therefore, for effective labeling of MSCs and long observation of MSCs labeled by QDs in vivo, it is essential both to increase cellular uptake of QDs and to promote endosomal escape into the cytosol. The polyamidoamine (PAMAM) dendrimer had plenty of cationic charge, which promoted cellular uptake though electrostatic interactions, and a "buffering capacity," which enhanced endosomal escape into the cytosol. In this study, QDs were modified with PAMAM dendrimer for the efficient labeling of MSCs by QDs. The uptake efficiency and cytosolic distribution of QDs in primary cultured MSCs were increased by the modification of the PAMAM dendrimer. The fluorescence intensity in MSCs labeled by PAMAM dendrimer-conjugated QDs lasted for a longer time in harvested culture plates or in cell-transplanted mice than that in MSCs labeled by non-conjugated QDs.     

Total sleep deprivation elevates blood pressure through arterial baroreflex resetting: a study with microneurographic technique

STUDY OBJECTIVES: Sleep deprivation has a profound effect on cardiovascular regulation through the autonomic nervous system. This study examined the effect of 24-hour total sleep deprivation on muscle sympathetic nerve activity (MSNA), which is a direct measurement of the postganglionic sympathetic efferent innervating the vascular bed in the skeletal muscle and other circulatory structures. DESIGN: The study was performed on 6 young healthy men. The factors exerting influence on MSNA, such as aging, obesity, body posture, activity, intensity of illumination, and food and beverage consumption were strictly controlled. Burst rate and burst incidence were used as parameters of MSNA. The burst rate, burst incidence, heart rate, and systolic and diastolic blood pressure were measured after total sleep deprivation and control sleep. To perform a linear regression analysis of arterial baroreflex (ABR), the incidence of MSNA bursts corresponding to a given diastolic blood pressure (%MSNA) was examined. MEASUREMENT AND RESULTS: The diastolic blood pressure was significantly higher after total sleep deprivation than after control sleep (66.5 +/- 1.7 vs 57.4 +/- 3.3 mm Hg). The burst rate (9.6 +/- 1.8 vs 13.3 +/- 2.7 bursts/min) and burst incidence (21.6 +/- 4.5 vs 30.3 +/- 8.9 bursts/100 heart beats) of MSNA were significantly lower after total sleep deprivation than after control sleep (P < .05). Analysis of the ABR disclosed a significant linear regressive relation between %MSNA and diastolic blood pressure in every subject after both total sleep deprivation and control sleep. This result implies that the ABR regulates the occurrence of MSNA bursts under different diastolic blood pressure conditions. The threshold (X-axis intercept) of the blood pressure regression line (ie, an indicator of the ABR set point) shifted by 12 +/- 4.3 mm Hg toward a higher blood pressure level after total sleep deprivation (P < .05). The ABR sensitivity, or the slope of the regression line, tended to be less steep after total sleep deprivation than after control sleep, although it was not statistically significant (P = .09). CONCLUSIONS: The diastolic blood pressure increased and both burst rate and burst incidence of MSNA decreased after total sleep deprivation. The results show that resetting of the ABR toward a higher blood pressure level occurred after total sleep deprivation. This ABR resetting probably brings about an increase in arterial blood pressure after total sleep deprivation.     

Pimet, the Drosophila homolog of HEN1, mediates 2'-O-methylation of Piwi- interacting RNAs at their 3' ends

Piwi-interacting RNAs (piRNAs) consist of a germline-specific group of small RNAs derived from distinct intergenic loci in the genome. piRNAs function in silencing selfish transposable elements through binding with the PIWI subfamily proteins of Argonautes. Here we show that piRNAs in Drosophila are 2'-O-methylated at their 3' ends. Loss of Pimet (piRNA methyltransferase), the Drosophila homolog of Arabidopsis HEN1 methyltransferase for microRNAs (miRNAs), results in loss of 2'-O-methylation of fly piRNAs. Recombinant Pimet shows single-stranded small RNA methylation activity in vitro and interacts with the PIWI proteins within Pimet mutant ovary. These results show that Pimet mediates piRNA 2'-O-methylation in Drosophila.