ALTERATIONS IN PROTEIN AND NUCLEIC ACID METABOLISM OF LYMPHOMA 6C3HED-OG CELLS IN MICE GIVEN GUINEA PIG SERUM

Lymphoma 6C3HED-OG cells, known from previous work to be susceptible to the effects of guinea pig serum in vivo and dependent upon extrinsic asparagine for protein synthesis and growth in vitro, remained for the most part morphologically intact and countable in the electronic cell counter following exposures of 1 and 2 hr to the effects of heated (56°C, 30 min) guinea pig serum injected into the peritoneal cavities of mice in which the lymphoma cells were growing rapidly; after exposures of 4 and 6 hr the bulk of the -OG cells remained still intact and countable in the cell counter, though by this time a small proportion of them (5 to 12%) proved stainable with eosin in wet preparations) hence were presumably nonviable. After 12, 16, and 24 hr of exposure, however, the bulk of the -OG cells were either lysed or fragmented, to the extent that they did not register in the cell counter. Morphologic studies of the cells exposed 16 and 24 hr to the effects of heated guinea pig serum in vivo, disclosed that most of the cells then remaining were either frankly necrotic or greatly altered otherwise, marked vacuolation of the cytoplasm being the most conspicuous alteration in cells not yet obviously necrotic. Long before the bulk of the Lymphoma 6C3HED-OG cells had become conspicuously changed morphologically following exposure to the effects of heated guinea pig serum in vivo, they manifested striking alterations in protein metabolism, as was disclosed by "pulse" studies with radioactive valine. For example, the protein metabolism of -OG cells, as measured by their incorporation of L-valine-C14, was sharply curtailed following 15 min of exposure to heated guinea pig serum in vivo, as compared with valine incorporation by cells labeled immediately after exposure to the guinea pig serum. Following exposure to heated guinea pig serum during 60 min, -OG cells incorporated less than half as much L-valine-C14 as did cells labeled immediately after exposure, and the incorporation of L-valine-C14 was still less after 120 min of exposure. By contrast, Lymphoma -RG1 cells, known from previous work to be wholly insusceptible to the effects of guinea pig serum in vivo and independent of need for extrinsic asparagine for protein synthesis and growth in vitro, showed no curtailment whatever of protein synthesis following exposures to the effects of heated guinea pig serum in vivo during periods of 15, 60, and 120 min. Reasons are given for considering the prompt inhibition of protein synthesis in the asparagine-dependent -OG cells a direct result of asparagine-deprivation induced in vivo by the injected guinea pig serum, the L-asparaginase of which presumably converted the available L-asparagine of the host to L-aspartic acid that was not taken up by the -OG cells. The synthesis of deoxyribonucleic acid by Lymphoma 6C3HED-OG cells, as measured by the incorporation of thymidme-H3, determined with the aid of liquid scintillation counting and autoradiography, was also altered by exposure of the lymphoma cells to the effects of heated guinea pig serum in vivo, though not during exposures of 15 and 60 min; only after an exposure of 120 min did the population of -OG cells incorporate notably less thymidine-H3 than did control populations, though after 240 min of exposure the -OG cells incorporated less than one-fifth as much tritiated thymidineas had -OG cells exposed to heated guinea pig serum for 60 min or to heated horse serum for periods up to 240 min. Autoradiographs indicated that DNA synthesis by -OG cells normally proceeds at an intense level that leads to some 60% of these cells being heavily labeled in autoradiographs at any given time; after exposure to the effects of heated guinea pig serum during 2 and 4 hr in vivo, however, the lymphoma cells lost their ability to incorporate enough tritiated thymidine to become heavily labeled, but approximately the same proportion of them (56 to 58%) retained their ability to incorporate sufficient tritiated thymidine to become lightly labeled. The possibility is considered that the inhibition of DNA synthesis in the asparagine-dependent -OG cells exposed to the effects of heated guinea pig serum in vivo may be secondary to the previously manifest inhibition of protein synthesis. Further, in tests of ribonucleic acid metabolism of Lymphoma 6C3HED-OG cells after exposure to the effects of heated guinea pig serum in vivo during periods of 15, 60, 120, and 240 min, the findings indicated that the ability of the lymphoma cells to synthesize RNA, as measured by their capacity to incorporate uridine-5-H3, remained unaltered during the exposures of 15, 60, and 120 min, but was substantially reduced following 240 min of exposure. The findings are considered in relation to the probability, disclosed in part by previous studies, that heated guinea pig serum brings about its effects upon Lymphoma 6C3HED-OG cells in vivo by providing active L-asparaginase in large amounts, which presumably converts the available (extracellular) asparagine of the host to aspartic acid, the latter not being taken up by the lymphoma cells in vivo or in vitro. Hence it seems likely that heated guinea pig serum in this way brings about a state of asparagine deprivation that is responsible for the sequential metabolic and morphologic alterations that become manifest in asparagine-dependent Lymphoma 6C3HED-OG cells following their exposure to the effects of guinea pig serum in vivo, as here described

Meditation-State Functional Connectivity (msFC): Strengthening of the Dorsal Attention Network and Beyond

Meditation practice alters intrinsic resting-state functional connectivity (rsFC) in the default mode network (DMN). However, little is known regarding the effects of meditation on other resting-state networks. The aim of current study was to investigate the effects of meditation experience and meditation-state functional connectivity (msFC) on multiple resting-state networks (RSNs). Meditation practitioners (MPs) performed two 5-minute scans, one during rest, one while meditating. A meditation naïve control group (CG) underwent one resting-state scan. Exploratory regression analyses of the relations between years of meditation practice and rsFC and msFC were conducted. During resting-state, MP as compared to CG exhibited greater rsFC within the Dorsal Attention Network (DAN). Among MP, meditation, as compared to rest, strengthened FC between the DAN and DMN and Salience network whereas it decreased FC between the DAN, dorsal medial PFC, and insula. Regression analyses revealed positive correlations between the number of years of meditation experience and msFC between DAN, thalamus, and anterior parietal sulcus, whereas negative correlations between DAN, lateral and superior parietal, and insula. These findings suggest that the practice of meditation strengthens FC within the DAN as well as strengthens the coupling between distributed networks that are involved in attention, self-referential processes, and affective response

The extramural metastasis might be categorized in lymph node staging for colorectal cancer

<p>Abstract</p> <p>Background</p> <p>The objective of this study is to assess the clinical significance and prognostic impact of extramural metastasis in colorectal carcinoma and establish an optimal categorization in the staging system.</p> <p>Methods</p> <p>To determine the frequency and prognostic significance of extramural metastasis, from 2000 to 2005, a total of 1,215 patients with colorectal cancer who underwent surgical resection were recruited into this study. Individual demographic and clinicopathologic data were collected including tumor stage, nodal stage, tumor histology, degree of tumor differentiation, and presence of lymphovascular invasion. After surgery, all patients received standard treatments and follow-up, which were closed in April 2010.</p> <p>Results</p> <p>EM was detected in 167 (13.7%) patients and in 230 (1.8%) of the 12,534 nodules retrieved as 'lymph nodes'. The incidence of extramural metastasis was significantly higher in patients with large tumors, deeper invasive depth and more lymph node metastasis (P < 0.001). After curative operation, overall survival was significantly worse for patients with extramural metastasis than those without (P < 0.001). Multivariate analysis identified extramural metastasis as an independent prognostic factor (RR = 2.1, 95%CI:1.5-3.0). By using the Akaike information criterion (AIC), N staging was capable of predicting survival outcome with the highest accuracy when both nodal involvement and extramural metastasis were treated together as N factors(AIC = 1025.3).</p> <p>Conclusion</p> <p>Extramural metastasis might be diagnosed as replaced lymph nodes in the process of classification, thus forming a new categorization.</p

Genetic effects on gene expression across human tissues

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of diseas

Genetic effects on gene expression across human tissues

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of disease