Primary Intestinal Lymphoma in Crohn's Disease: Minute Tumor with a Fatal Outcome

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75263/1/j.1572-0241.1992.tb02897.x.pd

Phase separation due to quantum mechanical correlations

Can phase separation be induced by strong electron correlations? We present a theorem that affirmatively answers this question in the Falicov-Kimball model away from half-filling, for any dimension. In the ground state the itinerant electrons are spatially separated from the classical particles.Comment: 4 pages, 1 figure. Note: text and figure unchanged, title was misspelle

Gribov Problem for Gauge Theories: a Pedagogical Introduction

The functional-integral quantization of non-Abelian gauge theories is affected by the Gribov problem at non-perturbative level: the requirement of preserving the supplementary conditions under gauge transformations leads to a non-linear differential equation, and the various solutions of such a non-linear equation represent different gauge configurations known as Gribov copies. Their occurrence (lack of global cross-sections from the point of view of differential geometry) is called Gribov ambiguity, and is here presented within the framework of a global approach to quantum field theory. We first give a simple (standard) example for the SU(2) group and spherically symmetric potentials, then we discuss this phenomenon in general relativity, and recent developments, including lattice calculations.Comment: 24 pages, Revtex 4. In the revised version, a statement has been amended on page 11, and References 14, 16 and 27 have been improve

Acute Loss of Iron-Sulfur Clusters Results in Metabolic Reprogramming and Generation of Lipid Droplets in Mammalian Cells

Iron–sulfur (Fe-S) clusters are ancient cofactors in cells and participate in diverse biochemical functions, including electron transfer and enzymatic catalysis. Although cell lines derived from individuals carrying mutations in the Fe-S cluster biogenesis pathway or siRNA-mediated knockdown of the Fe-S assembly components provide excellent models for investigating Fe-S cluster formation in mammalian cells, these experimental strategies focus on the consequences of prolonged impairment of Fe-S assembly. Here, we constructed and expressed dominant–negative variants of the primary Fe-S biogenesis scaffold protein iron–sulfur cluster assembly enzyme 2 (ISCU2) in human HEK293 cells. This approach enabled us to study the early metabolic reprogramming associated with loss of Fe-S–containing proteins in several major cellular compartments. Using multiple metabolomics platforms, we observed a ∼12-fold increase in intracellular citrate content in Fe-S–deficient cells, a surge that was due to loss of aconitase activity. The excess citrate was generated from glucose-derived acetyl-CoA, and global analysis of cellular lipids revealed that fatty acid biosynthesis increased markedly relative to cellular proliferation rates in Fe-S–deficient cells. We also observed intracellular lipid droplet accumulation in both acutely Fe-S–deficient cells and iron-starved cells. We conclude that deficient Fe-S biogenesis and acute iron deficiency rapidly increase cellular citrate concentrations, leading to fatty acid synthesis and cytosolic lipid droplet formation. Our findings uncover a potential cause of cellular steatosis in nonadipose tissues

Resection Status, Age and Nodal Involvement Determine Survival among Patients Receiving Adjuvant Chemoradiotherapy in Pancreatic Adenocarcinoma

Context Pancreas cancer can potentially be cured by resection, but the role of adjuvant chemotherapy and/or chemoradiation has been controversial. Objectives To better define clinicopathological factors that may serve as predictive and/or prognostic variables. Patients Between 1984 and 2006, we retrospectively analyzed 91 patients with pancreas cancer treated with pancreaticoduodenectomy or total pancreatectomy followed by adjuvant 5-fluorouracil-based chemoradiation at the University of Pennsylvania. Final pathological coding including margin status was confirmed by a pathologist. Interventions Patients were treated with 48.6 to 63.0 Gy, and 96.7% completed their prescribed radiation dose. Main outcome measures The prognostic significance of demographic factors, stage, year of surgery, tumor location, grade, resection status, and number of positive lymph nodes on overall survival were examined. Results With a median follow-up of 6.5 years, the overall median survival was 2.3 years (95% CI 1.5-3.2 years), and the 5-year overall survival was 28.9%. In multivariate analysis, completeness of resection (P<0.001), fewer number of positive lymph nodes (0 vs. 1-2 vs. 3 or more) (P=0.004), and age less than, or equal to, 60 years (P=0.006) were all independently associated with improved overall survival. The overall survival reported in this study compares favorably with the results of other single-institution studies and with the RTOG 97-04 trial. Conclusions Adjuvant 5-FU-based chemoradiation following radical pancreatectomy can be delivered safely and results in comparatively good overall survival. The results of this analysis underscore the importance of resection status, number of involved lymph nodes and patient age as prognostic characteristics. These factors may be considered stratification variables for future post-pancreatectomy adjuvant therapy trials

Electron spin dynamics in quantum dots and related nanostructures due to hyperfine interaction with nuclei

We review and summarize recent theoretical and experimental work on electron spin dynamics in quantum dots and related nanostructures due to hyperfine interaction with surrounding nuclear spins. This topic is of particular interest with respect to several proposals for quantum information processing in solid state systems. Specifically, we investigate the hyperfine interaction of an electron spin confined in a quantum dot in an s-type conduction band with the nuclear spins in the dot. This interaction is proportional to the square modulus of the electron wave function at the location of each nucleus leading to an inhomogeneous coupling, i.e. nuclei in different locations are coupled with different strength. In the case of an initially fully polarized nuclear spin system an exact analytical solution for the spin dynamics can be found. For not completely polarized nuclei, approximation-free results can only be obtained numerically in sufficiently small systems. We compare these exact results with findings from several approximation strategies.Comment: 26 pages, 9 figures. Topical Review to appear in J. Phys.: Condens. Matte

Sex and adverse events of adjuvant chemotherapy in colon cancer: an analysis of 34,640 patients in the ACCENT database

BACKGROUND: Adjuvant chemotherapy is a standard treatment option for patients with stage III and high-risk stage II colon cancer. Sex is one of several factors responsible for the wide inter-patient variability in drug responses. Amalgamated data on the effect of sex on the toxicity of current standard adjuvant treatment for colorectal cancer are missing. METHODS: The objective of our study was to compare incidence and severity of major toxicities of fluoropyrimidine- (5FU or capecitabine) based adjuvant chemotherapy, with or without oxaliplatin, between male and female patients after curative surgery for colon cancer. Adult patients enrolled in 27 relevant randomized trials included in the ACCENT (Adjuvant Colon Cancer End Points) database, a large, multi-group, international data repository containing individual patient data, were included. Comparisons were conducted using logistic regression models (stratified by study and treatment arm) within each type of adjuvant chemotherapy (5FU, FOLFOX, capecitabine, CAPOX, and FOLFIRI). The following major toxicities were compared (grade III or IV and grade I-IV, according to National Cancer Institute Common Terminology Criteria [NCI-CTC] criteria, regardless of attribution): nausea, vomiting, nausea or vomiting, stomatitis, diarrhea, leukopenia, neutropenia, thrombocytopenia, anemia, and neuropathy (in patients treated with oxaliplatin). RESULTS: Data from 34 640 patients were analyzed. Statistically significant and clinically relevant differences in the occurrence of grade III or IV nonhematological {especially nausea (5FU: odds ratio [OR] = 2.33, 95% confidence interval [CI] = 1.90 to 2.87, P < .001; FOLFOX: OR = 2.34, 95% CI = 1.76 to 3.11, P < .001), vomiting (5FU: OR = 2.38, 95% CI = 1.86 to 3.04, P < .001; FOLFOX: OR = 2.00, 95% CI = 1.50 to 2.66, P < .001; CAPOX: OR = 2.32, 95% CI = 1.55 to 3.46, P < .001), and diarrhea (5FU: OR = 1.35, 95% CI = 1.21 to 1.51, P < .001; FOLFOX: OR = 1.60, 95% CI = 1.35 to 1.90, P < .001; FOLFIRI: OR = 1.57, 95% CI = 1.25 to 1.97, P < .001)} as well as hematological toxicities (neutropenia [5FU: OR = 1.55, 95% CI = 1.37 to 1.76, P < .001; FOLFOX: OR = 1.96, 95% CI = 1.71 to 2.25, P < .001; FOLFIRI: OR = 2.01, 95% CI = 1.66 to 2.43, P < .001; capecitabine: OR = 4.07, 95% CI = 1.84 to 8.99, P < .001] and leukopenia [5FU: OR = 1.74, 95% CI = 1.40 to 2.17, P < .001; FOLFIRI: OR = 1.75, 95% CI = 1.28 to 2.40, P < .001]) were observed, with women being consistently at increased risk. CONCLUSIONS: Our analysis confirms that women with colon cancer receiving adjuvant fluoropyrimidine-based chemotherapy are at increased risk of toxicity. Given the known sex differences in fluoropyrimidine pharmacokinetics, sex-specific dosing of fluoropyrimidines warrants further investigation

Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use.

Tobacco and alcohol use are leading causes of mortality that influence risk for many complex diseases and disorders1. They are heritable2,3 and etiologically related4,5 behaviors that have been resistant to gene discovery efforts6-11. In sample sizes up to 1.2 million individuals, we discovered 566 genetic variants in 406 loci associated with multiple stages of tobacco use (initiation, cessation, and heaviness) as well as alcohol use, with 150 loci evidencing pleiotropic association. Smoking phenotypes were positively genetically correlated with many health conditions, whereas alcohol use was negatively correlated with these conditions, such that increased genetic risk for alcohol use is associated with lower disease risk. We report evidence for the involvement of many systems in tobacco and alcohol use, including genes involved in nicotinic, dopaminergic, and glutamatergic neurotransmission. The results provide a solid starting point to evaluate the effects of these loci in model organisms and more precise substance use measures

Lung Function after the Minimal Invasive Pectus Excavatum Repair (Nuss Procedure)

Background The Nuss procedure was introduced at our center in 1999. The operation was mainly performed for cosmesis. Little information is available regarding the influence of this operation on lung function. Methods The aim of this study, a prospective analysis, was to analyze the effect of the Nuss procedure on lung function variables. Between 1999 and 2007 a total of 203 patients with pectus excavatum were treated with the Nuss procedure, of whom 145 (104 male, 41 female) were located at Emma Children’s Hospital. In the latter subset of consecutive patients, static lung function variables [total lung capacity (TLC), functional residual capacity (FRC), vital capacity (VC)] and dynamic lung function variables [forced expired volume in 1 s (FEV1), maximum expiratory flow (MEF50)] were performed using spirometry and body box measurements at four time points: prior to operation Some of these data were presented at the International Surgical Week