Kv11.1 channel subunit composition includes MinK and varies developmentally in mouse cardiac muscle

The Kv11.1 (also ERG1) K(+) channel underlies cardiac I(Kr), a current that contributes to repolarization in mammalian heart. In mice, I(Kr) current density decreases with development and studies suggest that changes in the structure and/or properties of the heteromultimeric I(Kr)/Kv11.1 channel are responsible. Here, using immunohistochemistry, we report that total Kv11.1 alpha subunit protein is more abundant in neonatal heart and is distributed throughout both adult and neonatal ventricles with greater abundance in epicardia. Immunoblots reveal that the alpha subunit alternative splice variant, Kv11.1a, is more abundant in adult heart while the Kv11.1b variant is more abundant in neonatal heart. Additionally, MinK channel subunit protein is shown to co-assemble with Kv11.1 protein and is more abundant in neonatal heart. In summary, Kv11.1/I(Kr) channel composition varies developmentally and the higher I(Kr) current density in neonatal heart is likely attributable to higher abundance of Kv11.1/I(Kr) channels, more specifically, the Kv11.1b splice variant.     

Emergence of influenza A H1N2 reassortant viruses in the human population during 2001

A recombinant vaccinia virus encoding rotavirus protein NSP3 driven by an internal ribosome entry site (IRES) from the encephalomyocarditis (EMC) virus was able to abate protein synthesis in BSC1 cells by 25-fold, with as much as 30% of the remaining protein synthesis being NSP3. Hence NSP3 shuts off host cell protein synthesis down to the level seen during rotavirus infection but is unable to prevent translation from EMC IRES-driven genes. This effect was abolished by deletions in the eIF4G-binding (aa 274-313) and the dimerization (aa 150-206) but not the viral mRNA-binding (aa 83-149) domains, supporting that NSP3 functions in vivo as a dimer. Binding of eIF4G by NSP3 has been implicated in interfering with mRNA 5'-3' circularization, hence such circularization is essential for translation in mammalian cells.     

Stability of variables associated with the metabolic syndrome from adolescence to adulthood: the Aerobics Center Longitudinal Study.

The purpose of the study was to examine the stability of variables associated with the metabolic syndrome from adolescence to adulthood. The sample included 48 subjects from the Aerobics Center Longitudinal Study who had one clinical visit during adolescence (mean age = 15.8 years) and a follow-up visit during adulthood (mean age = 26.6 years). The following variables were considered: treadmill time to exhaustion (TM), body mass index (BMI), waist circumference (WC), percent body fat (%BF), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), TC:HDL-C, triglycerides (TG), glucose (GLU), and systolic (SBP), diastolic (DBP), and mean (MAP) blood pressure. A composite risk factor score using variables consistent with the WHO and ATP III definition of the metabolic syndrome (WC, HDL-C, TG, MAP, and GLU) was calculated. Tracking coefficients were computed as partial correlations, controlling for length of follow-up (mean = 11 years). Tracking coefficients (r values) were moderate for all variables (TM, 0.53; BMI, 0.64; WC; 0.79;%BF, 0.44; TC, 0.62; HDL-C, 0.60; TG, 0.54; TC:HDL-C, 0.78; SBP, 0.45; and MAP, 0.41), except GLU (0.26) and DBP (0.21). The composite risk factor score also tracked moderately well (0.56) from adolescence into adulthood. The results support previous findings that variables associated with the metabolic syndrome track moderately well from adolescence to adulthood. The findings support the prevention and treatment of obesity, atherosclerosis, type 2 diabetes, and the metabolic syndrome during childhood and adolescence.     

Pulmonary artery angiosarcoma: a clinicopathologic and radiological correlation

A 69-year-old man presented with cough, shortness of breath, and fatigue. He was initially treated for allergies and then for pulmonary embolism. Radiologically, a tumor mass was found to occlude the right pulmonary artery and involve the pulmonary trunk. A right pneumonectomy was performed. Histologically, a cellular malignant spindle and epithelioid tumor with areas of necrosis and brisk mitotic activity was seen. In some areas, the tumor appeared to form vascular channels. Focal osteosarcomatous differentiation was present. Immunohistochemical studies were performed including vimentin, smooth muscle actin, desmin, CD31, CD34, S100, and pan-cytokeratin. The tumor cells were positive for CD31 and vimentin and negative for pan-cytokeratin, CD34, and S100. Two months after surgery, the patient was alive and well.     

Apoptotic body engulfment by a human stellate cell line is profibrogenic

Hepatocyte apoptosis and stellate cell activation are both features of chronic liver diseases, but a relationship between these events has not been explored. In macrophages, engulfment of apoptotic bodies induces expression of transforming growth factor-beta (TGF-beta), a profibrogenic cytokine. We examined whether a similar response occurs in stellate cells. Fluorescently labeled hepatocyte apoptotic bodies were added to cultures of primary and immortalized human stellate cells. Stellate cells, but not hepatocytes, readily engulfed apoptotic bodies in a time-dependent manner as assessed by confocal microscopy. The activation of primary and immortalized human stellate cells after incubation with apoptotic bodies, as well as their fibrogenic activity, was indicated by an increase in alpha-smooth muscle actin (primary cells), TGF-beta1, and collagen alpha1(I) mRNA (primary and immortalized cells). The profibrogenic response was dependent upon apoptotic body engulfment, because nocodazole, a microtubule-inhibiting agent, blocked both the engulfment and the increase of TGF-beta1 and collagen alpha1(I) mRNA. As described in primary rodent stellate cells, up-regulation of collagen alpha1(I) mRNA was inhibited by a PI-3K inhibitor (LY294002) and a p38 mitogen-activated protein kinase inhibitor (SB203580) in LX-1 cells. In conclusion, these data support a model in which engulfment of hepatocyte apoptotic bodies by stellate cells leads to a fibrogenic response by eliciting a kinase-signaling pathway.     

Dose and dose rate effects of whole-body proton irradiation on leukocyte populations and lymphoid organs: part I.

The goal of part I of this study was to evaluate the effects of whole-body proton irradiation on lymphoid organs and specific leukocyte populations. C57BL/6 mice were exposed to the entry region of the proton Bragg curve to total doses of 0.5 gray (Gy), 1.5 Gy, and 3.0 Gy, each delivered at a low dose rate (LDR) of 1 cGy/min and high dose rate (HDR) of 80 cGy/min. Non-irradiated and 3 Gy HDR gamma-irradiated groups were included as controls. At 4 days post-irradiation, highly significant radiation dose-dependent reductions were observed in the mass of both lymphoid organs and the numbers of leukocytes and T (CD3(+)), T helper (CD3(+)/CD4(+)), T cytotoxic (CD3(+)/CD8(+)), and B (CD19(+)) cells in both blood and spleen. A less pronounced dose effect was noted for natural killer (NK1.1(+) NK) cells in spleen. Monocyte, but not granulocyte, counts in blood were highly dose-dependent. The numbers for each population generally tended to be lower with HDR than with LDR radiation; a significant dose rate effect was found in the percentages of T and B cells, monocytes, and granulocytes and in CD4(+):CD8(+) ratios. These data indicate that mononuclear cell response to the entry region of the proton Bragg curve is highly dependent upon the total dose and that dose rate effects are evident with some cell types. Results from gamma- and proton-irradiated groups (both at 3 Gy HDR) were similar, although proton-irradiation gave consistently lower values in some measurements.     

Culex restuans (Diptera: Culicidae) relative abundance and vector competence for West Nile Virus

The abundance and vector competence of Culex restuans Theobald and Culex pipiens L. were compared to determine the relative importance of these species as West Nile virus (WNV) vectors in the northeastern United States. Abundance was estimated from egg raft collections at 12 sites in Albany, Suffolk, and Richmond counties, New York, during July, August, and September 2002 and 2003. Cx. restuans was more abundant than Cx. pipiens in both urban and rural areas, comprising 86% of 1,623 egg rafts collected. Vector competence for WNV was estimated after feeding on an artificial bloodmeal and in vitro transmission assays. The vector competence of the two species for WNV was similar, but the dynamics of infection seems to be mosquito species dependent. These findings suggest an important role for Cx. restuans in WNV transmission cycles in New York.     

The ventral tegmental area revisited: is there an electrophysiological marker for dopaminergic neurons?

The ventral tegmental area (VTA) and in particular VTA dopamine (DA) neurons are postulated to play a central role in reward, motivation and drug addiction. However, most evidence implicating VTA DA neurons in these functions is based on indirect electrophysiological characterization, rather than cytochemical identification. These physiological criteria were first established in the substantia nigra pars compacta (SNc), but their validity in the VTA is uncertain. In the current study we found that while 88 ± 2% of SNc neurons labelled by the neuronal marker NeuN were co-labelled for the catecholamine enzyme tyrosine hydroxylase (TH), a much smaller percentage (55 ± 2%) of VTA neurons co-expressed TH. In addition, using in vitro whole-cell recordings we found that widely accepted physiological criteria for VTA DA neurons, including the hyperpolarization-activated inwardly rectifying non-specific cation current ( I _h), spike duration, and inhibition by DA D2 receptor agonists, do not reliably predict the DA content of VTA neurons. We could not distinguish DA neurons from other VTA neurons by size, shape, input resistance, I _h size, or spontaneous firing rate. Although the absence of an I _h reliably predicted that a VTA neuron was non-dopaminergic, and I _h(−) neurons differ from I _h(+) neurons in firing rate, interspike interval (ISI) standard deviation, and ISI skew, no physiological property examined here is both sensitive and selective for DA neurons in the VTA. We conclude that reliable physiological criteria for VTA DA neuron identification have yet to be determined, and that the criteria currently being used are unreliable.     

Effects of spontaneously chosen crank rate variations on electromyographic responses in sub-maximal arm exercise in inexperienced subjects

The aim of the present study was to compare electromyographic responses during arm exercises with a crank rate chosen spontaneously (T_S) or set at 20% below or above (T_–20, T₊₂₀) the spontaneously chosen crank rate (SCCR). Ten male physical education students performed arm exercises with intensities ranging from 20% to 80% of maximal power. Muscular activity levels were analysed for the biceps brachii and the triceps brachii muscles using integrated rectified surface electromyography (iEMG). All values were presented as the mean and standard deviation. During T_S, the sum of iEMG for the two muscles studied was significantly (P<0.05) lower than during T₊₂₀ for each power output. No significant differences were observed in iEMG values between T_S and T_–20. The hypothesis that SCCR relates to a minimisation of muscle activation during an upper body exercise was not confirmed. Variations superior or inferior to a 20% increase of the iEMG responses do not influence it. Moreover, the selection of crank rates depends on the power output and the SCCR increased significantly (P<0.05) with increasing power output.