tbuckley/cabot-search huggingface dataset:
The Occupational Burden of Mental Disorders in the U.S. Military: Psychiatric Hospitalizations, Involuntary Separations, and Disability
Authors: Charles W Hoge, Holly E Toboni, Stephen C Messer, Nicole Bell, Paul Amoroso, David T Orman
Journal: American Journal of Psychiatry (2005)

A recent study showed that among U.S. military personnel, mental disorders were the leading medical correlate of separation from military service. The reasons for this association have not been determined. The purpose of this study was to characterize the risk and reasons for service separation for soldiers hospitalized with mental disorders compared with those hospitalized for other illnesses.Population-based electronic health care data were linked with data on separations and disability. The authors constructed a cohort of 13,971 U.S. Army soldiers first hospitalized in 1998 and followed them for up to 2 years following this first hospitalization.The rate of service separation 6 months after first hospitalization was 45% among personnel whose primary hospital discharge diagnosis was a mental disorder, 27% among those with a secondary mental disorder discharge diagnosis, and 11% among those hospitalized for all other medical conditions. Separation from military service due to medical disability, misconduct and other legal problems, unauthorized work absences, behavior related to personality disorders, and alcohol rehabilitation failure was significantly more common following hospitalization for a mental disorder than for other medical conditions. Mental disorders were also significantly associated with medical separations in which there was evidence that the condition existed prior to service.In the military, the occupational impact of mental disorders compared with other medical conditions appears to be mediated not only by greater disease chronicity and severity but also by a variety of behavioral problems including misconduct, legal problems, unauthorized absences, and alcohol/drug-related problems. The study also points to the difficulties inherent in screening for mental disorders prior to entry into military service.
DNA Replication Licensing Factors and Aurora Kinases are Linked to Aneuploidy and Clinical Outcome in Epithelial Ovarian Carcinoma
Authors: Anjana A. Kulkarni, Marco Loddo, Elisabetta Leo, Mohammed Rashid, Kathryn L. Eward, Thomas R. Fanshawe, Jessica Butcher, Alison Frost, Jonathan A. Ledermann, Gareth H. Williams, Kai Stoeber
Journal: Clinical Cancer Research (2007)

Abstract Purpose: DNA replication licensing factors and Aurora kinases play critical roles in maintaining genomic integrity. We used multiparameter analyses of these cell cycle regulatory proteins to investigate their role in the progression of epithelial ovarian carcinoma (EOC). Experimental Design: In a cohort of 143 patients, we linked the protein expression profiles of the proliferation marker Ki67, the replication licensing factors Mcm2 and geminin, and the Aurora A and B kinases to tumor DNA ploidy status and clinical outcome. Results: Ki67, Mcm2, geminin, and Aurora A and B are significantly associated with tumor grade and ploidy status (P &amp;lt; 0.0001). Aurora A and its substrate H3S10ph are also significantly associated with Federation of International Obstetricians and Gynecologists tumor stage (P = 0.006 and P = 0.002, respectively). Aurora A and tumor ploidy status are predictive of disease-free survival in this cohort [hazard ratio (HR), 1.29; 95% confidence intervals (95% CI), 1.06-1.58, P = 0.01 and HR, 1.80 (1.05-3.08), P = 0.03, respectively], with Aurora A of particular prognostic importance in early stage disease [HR, 1.72 (1.19-2.48), P = 0.004 for disease-free survival and HR, 1.81 (1.14-2.87), P = 0.01 for overall survival]. Conclusions: Our data show that Ki67, Mcm2, geminin and Aurora A and B can be used as an adjunct to conventional prognostic indicators and as an aid to develop a tumor progression model for EOC. Dysregulation of Aurora A seems to be an early event in EOC with a key role in tumor progression. In view of present drug development programs for specific Aurora kinase inhibitors, our findings have important implications for the use of Aurora A as a biomarker and as a potential therapeutic target.
W. Berger, V. Dietz, et al "Haltung und Bewegung beim Menschen"
Authors: E. H. De Rose
Journal: British Journal of Sports Medicine (1984)

This book deals with the physiological bases of the human posture and movements as well as their applications to athletic performance and motor disturbances in certain neurological disorders.Using mechanical, electromyographic (EMG) and electroencephalographic (EEG) methods, posture, balancing, gait, falling, motorleaming and athletic training are studied.Muscular strength is studied by EMG analysis in jumps, running and landing.The authors describe how monitoring EMG activity can lead to improved training conditions with optimal utilisation of reflex activity in athletic performance.Some disorders of gait and postural equilibrium due to lesions of sensory-motor systems are discussed, as well as cerebral palsy in infants and spasticity in adults.
Metabolism of methylmalonic acid in rats. Is methylmalonyl-coenzyme a racemase deficiency symptomatic in man?
Authors: J A Montgomery, O A Mamer, C R Scriver
Journal: Journal of Clinical Investigation (1983)

Vitamin B12-deficient and normal rats were loaded with methylmalonic (MMA) and ethylmalonic acids labeled with 13C in the carboxyl groups and with 2H in the alkyl groups. Significant fractions of the administered acids were excreted in both the B12-deficient and the normal animal, having undergone exchange of both their 13C-labeled carboxyl groups with endogenous 12C. The exchange of the alpha-1H of MMA in 2H2O at 25 degrees C and pH 7.5 was found by 1H-nuclear magnetic resonance to have a half-life of 28.3 min. These results show that a fraction of in vivo metabolism through the propionate-to-succinate pathway occurs via a shunt involving free MMA. The enzymes of this pathway are thought to utilize only coenzyme A (CoA) esters. To allow for the exchange of the second CoA-bound carboxyl group, we propose the deacylation of the once exchanged acid with spontaneous racemization (relative to the 13C-carboxyl group), followed by reacylation, thus exposing the labeled carboxyl to decarboxylation. The significance of this mechanism involving free MMA is that racemization of methylmalonyl (MM)-CoA may also occur without the intervention of MM-CoA racemase. A deficiency of this enzyme need not result in symptomatic methylmalonic aciduria.
Glucose metabolism in reperfused myocardium measured by [2-18F] 2-fluorodeoxyglucose and PET
Authors: K Kofoed
Journal: Cardiovascular Research (2000)

Objective: [2-18F] 2-fluorodeoxyglucose (FDG) is widely used to trace glucose metabolism for cardiac imaging with positron emission tomography. Because the transport and phosphorylation rates differ for glucose and FDG, a lumped constant (LC) is used to correct for these differences. The effects of ischemia and reperfusion on the LC in vivo are unknown. To determine the validity of FDG as a tracer of glucose metabolism in post-ischemic myocardium in vivo, the relationship between glucose uptake (GU) and FDG metabolic rate (FDG-MR) was assessed early post-reperfusion following a transient ischemic event. Methods: FDG metabolic rate, measured with FDG and PET, was compared to invasive measurements of substrate metabolism in reperfused and global myocardium of dogs subjected to 25 min ischemia and 2 h reperfusion. Results: The FDG metabolic rate was decreased 20±4% in reperfused relative to remote myocardium. Glucose oxidation and lactate uptake were also decreased in reperfused relative to global myocardium, by 26±6% and 60±8% respectively. Glucose uptake did not differ significantly between reperfused and global myocardium. A linear correlation between FDG metabolic rate and glucose uptake was found in both reperfused and remote myocardium. Estimates of the LC from the slopes of the regression lines were similar in reperfused and remote myocardium, 1.25 and 1.44 respectively, and did not differ significantly from the LC determined in control dogs, 1.1. Conclusions: We conclude that the FDG metabolic rate continues to correlate well with glucose metabolism in reperfused myocardium. While FDG metabolic rate was modestly decreased in the absence of a significant change in glucose uptake, large alterations in the LC are not found 2 h post-reperfusion in vivo.
Liver Injury From Tumor Necrosis Factor-α Antagonists: Analysis of Thirty-four Cases
Authors: Marwan Ghabril, Herbert L. Bonkovsky, Clarissa Kum, Tim Davern, Paul H. Hayashi, David E. Kleiner, Jose Serrano, Jim Rochon, Robert J. Fontana, Maurizio Bonacini
Journal: Clinical Gastroenterology and Hepatology (2013)
Insulin-like Growth Factor (IGF)-binding Protein-4 Inhibits Colony Formation of Colorectal Cancer Cells by IGF-independent Mechanisms
Authors: Daniela Diehl, Andreas Hoeflich, Eckhard Wolf, Harald Lahm
Journal: Cancer Research (2004)

Abstract Effects of insulin-like growth factor-binding protein-4 (IGFBP-4) on proliferation, colony formation, and cell migration were assessed in IGF-sensitive and -insensitive colorectal cancer cell lines. In IGF-insensitive Isreco-1 cells, overexpression of IGFBP-4 reduced colony formation but not cell proliferation and migration, whereas exogenous IGF-II had no effect. In IGF-dependent LS1034 cells, IGFBP-4 inhibited all parameters of growth tested, whereas IGF-II partially restored reduced proliferation and cell migration only. In Isreco-2 cells, which lack endogenous IGF expression but are IGF sensitive, colony formation was also reduced by IGFBP-4. Therefore, specific parameters of malignant progression of colon carcinoma cells are distinctly affected by IGF-dependent and IGF-independent effects of IGFBP-4.
Carotid-Wall Intima–Media Thickness and Cardiovascular Events
Authors: Joseph F. Polak, Michael J. Pencina, Karol M. Pencina, Christopher J. O'Donnell, Philip A. Wolf, Ralph B. D'Agostino
Journal: New England Journal of Medicine (2011)

Intima-media thickness of the walls of the common carotid artery and internal carotid artery may add to the Framingham risk score for predicting cardiovascular events.We measured the mean intima-media thickness of the common carotid artery and the maximum intima-media thickness of the internal carotid artery in 2965 members of the Framingham Offspring Study cohort. Cardiovascular-disease outcomes were evaluated for an average follow-up of 7.2 years. Multivariable Cox proportional-hazards models were generated for intima-media thickness and risk factors. We evaluated the reclassification of cardiovascular disease on the basis of the 8-year Framingham risk score category (low, intermediate, or high) after adding intima-media thickness values.A total of 296 participants had a cardiovascular event. The risk factors of the Framingham risk score predicted these events, with a C statistic of 0.748 (95% confidence interval [CI], 0.719 to 0.776). The adjusted hazard ratio for cardiovascular disease with a 1-SD increase in the mean intima-media thickness of the common carotid artery was 1.13 (95% CI, 1.02 to 1.24), with a nonsignificant change in the C statistic of 0.003 (95% CI, 0.000 to 0.007); the corresponding hazard ratio for the maximum intima-media thickness of the internal carotid artery was 1.21 (95% CI, 1.13 to 1.29), with a modest increase in the C statistic of 0.009 (95% CI, 0.003 to 0.016). The net reclassification index increased significantly after addition of intima-media thickness of the internal carotid artery (7.6%, P<0.001) but not intima-media thickness of the common carotid artery (0.0%, P=0.99). With the presence of plaque, defined as intima-media thickness of the internal carotid artery of more than 1.5 mm, the net reclassification index was 7.3% (P=0.01), with an increase in the C statistic of 0.014 (95% CI, 0.003 to 0.025).The maximum internal and mean common carotid-artery intima-media thicknesses both predict cardiovascular outcomes, but only the maximum intima-media thickness of (and presence of plaque in) the internal carotid artery significantly (albeit modestly) improves the classification of risk of cardiovascular disease in the Framingham Offspring Study cohort. (Funded by the National Heart, Lung, and Blood Institute.).
Lessons from type I interferons in ulcerative colitis
Authors: A. Kaser, R. S. Blumberg
Journal: Gut (2011)

Ulcerative colitis (UC) is a complex polygenic disease that arises in the context of as yet unknown environmental factors.1 One biological pathway that has arisen as being important to UC, but not Crohn's disease (CD), is that associated with dysregulated CD1d-restricted, natural killer T (NKT) cell responses.2–4 CD1d-restricted NKT cells are a specialised subset of T cells that recognise lipid antigens presented by CD1d, a non-polymorphic major histocompatibility complex (MHC) class I-related molecule, on antigen-presenting cells. Upon ligation of their T cell receptor (TCR), NKT cells immediately release a large spectrum of cytokines such as interferon γ (IFNγ), interleukin 4 (IL-4), IL-13 and many others. The lipid ligands responsible for NKT cell activation in UC are however unknown, but probably include both endogenous and exogenous lipids from microbes.4

The mechanistic relationship between NKT cells and UC derives mostly from animal models and correlative human studies.2 The earliest observations on the ontogeny of these concepts was the recognition that CD1d is expressed on mouse and human intestinal epithelial cells5 6 and that CD1d on epithelial cells is functionally able to activate NKT cells.7 These studies were later followed by the discovery that NKT cells secreting IL-13 were critical for the induction of experimental colitis resembling human UC.2 Subsequent careful studies of colonic lamina propria T cells obtained from patients with UC confirmed a similar CD1d-dependent upregulation of IL-13 secretion. These studies not only …
Ironic insult added to copper injury
Authors: M L Schilsky
Journal: Hepatology (1997)

Several clinical studies have suggested that excess hepatic iron accumulation is a progressive factor in some liver diseases including chronic viral hepatitis and hemochromatosis. However, it is not known whether iron–induced hepatotoxicity may be directly involved in hepatitis, cirrhosis, and liver cancer. The Long–Evans Cinnamon (LEC) rat, which accumulates excess copper in the liver as in patients with Wilson's disease, is of a mutant strain displaying spontaneous hemolysis, hepatitis, and liver cancer. We found previously that LEC rats harbored an additional abnormality: accumulation of as much iron as copper in the liver. In the present study, we compared the occurrence of hepatitis and liver cancer in LEC rats fed an iron–deficient diet (ID) with those in rats fed a regular diet (RD). The RD group showed rapid increments of hepatic iron concentrations as the result of hemolysis, characteristics of fulminant hepatitis showing apoptosis, and a 53% mortality rate. However, no rats in the ID group died of fulminant hepatitis. Hepatic iron, especially “free” iron concentration and the extent of hepatic fibrosis in the ID group were far less than those of the RD group. At week 65, all rats in the RD group developed liver cancer, whereas none did in the ID group. These results suggest that the accumulation of iron, possibly by virtue of synergistic radical formation with copper, plays an essential role in the development of fulminant hepatitis, hepatic fibrosis, and subsequent hepatocarcinogenesis in LEC rats.
<i>ERCC1</i> and <i>ERCC2</i> Polymorphisms Predict Clinical Outcomes of Oxaliplatin-Based Chemotherapies in Gastric and Colorectal Cancer: A Systemic Review and Meta-analysis
Authors: Ming Yin, Jingrong Yan, Eva Martinez-Balibrea, Francesco Graziano, Heinz-Josef Lenz, Hyo-Jin Kim, Jacques Robert, Seock-Ah Im, Wei-Shu Wang, Marie-Christine Etienne-Grimaldi, Qingyi Wei
Journal: Clinical Cancer Research (2011)

Nucleotide excision repair (NER) modulates platinum-based chemotherapeutic efficacy by removing drug-produced DNA damage. To summarize published data on the association between polymorphisms of NER genes (ERCC1 and ERCC2) and responses to oxaliplatin-based chemotherapies, we carried out a meta-analysis of gastric and colorectal cancer for commonly studied polymorphisms ERCC1 rs11615C>T and ERCC2 rs13181T>G.In 17 previously published studies, 1,787 cancer patients were treated with the oxaliplatin-based regimen. Primary outcomes included therapeutic response (TR; i.e., complete response + partial response vs. stable disease + progressive disease), progression-free survival (PFS), and overall survival (OS). We calculated OR or HR with 95% CIs to estimate the risk or hazard.We found consistent and clinically substantial risk or hazard for TR, PFS, and OS in the oxaliplatin-treated gastric and colorectal cancer patients with an ethnic discrepancy. For ERCC1 rs11615C>T, the T allele was associated with reduced response and poor PFS and OS in Asians (TR: OR = 0.53 and 95% CI = 0.35-0.81; PFS: HR = 1.69 and 95% CI = 1.05-2.70; and OS: HR = 2.03 and 95% CI = 1.60-2.59). For ERCC2 rs13181T>G, the G allele was associated with reduced response and poor PFS and OS in Caucasians (TR: OR = 0.56 and 95% CI = 0.35-0.88; PFS: HR = 1.41 and 95% CI = 1.02-1.95; and OS: HR = 1.42 and 95% CI = 1.11-1.81).NER ERCC1 rs11615C>T and ERCC2 rs13181T>G polymorphisms are useful prognostic factors in oxaliplatin-based treatment of gastric and colorectal cancer. Larger studies and further clinical trials are warranted to confirm these findings.
Cost effectiveness of interferon or peginterferon with ribavirin for histologically mild chronic hepatitis C
Authors: R Grieve
Journal: Gut (2005)

For patients with mild chronic hepatitis C the cost effectiveness of antiviral therapy is unknown.To assess whether antiviral therapy (either interferon alpha or peginterferon alpha combined with ribavirin) is cost effective at a mild stage compared with waiting and only treating those cases who progress to moderate disease.Cases with mild chronic hepatitis C.A cost effectiveness model which estimates long term costs and outcomes for patients with mild chronic hepatitis C. The model uses effectiveness and cost data from the UK mild hepatitis C randomised controlled trial, combined with estimates of disease progression and cost from observational studies.Antiviral treatment at a mild rather than a moderate stage improved outcomes measured by quality adjusted life years (QALYS) gained. The mean cost per QALY gained from antiviral treatment with interferon alpha-2b and ribavirin, compared with no treatment at a mild stage, was 4535 pounds sterling (7108 dollars) for patients with genotype non-1 and 25,188 pounds sterling (39,480 dollars) for patients with genotype 1. Providing peginterferon alpha-2b and ribavirin at a mild rather than a moderate stage was also associated with a gain in QALYS; the costs per QALY gained were 7821 pounds sterling (12,259 dollars) for patients with genotype non-1 and 28,409 pounds sterling (44,528 dollars) for patients with genotype 1.For patients with chronic hepatitis C, it is generally more cost effective to provide antiviral treatment at a mild rather than a moderate disease stage. For older patients (aged 65 years or over) with genotype 1, antiviral treatment at a mild stage is not cost effective.
Subtype 2 of angiotensin II receptors controls pressure-natriuresis in rats.
Authors: M Lo, K L Liu, P Lantelme, J Sassard
Journal: Journal of Clinical Investigation (1995)

Angiotensin II recognizes two receptor subtypes, AT1 and AT2, both of them having been recently cloned. Although AT2 receptors represent 5-10% of angiotensin II receptors in the kidneys of adult rats, their function remains unknown. In the present work, we examined the possible contribution of AT2 receptors to the regulation of pressure-natriuresis in anesthetized rats infused either with the specific AT2 antagonist PD 123319, or with CGP 42112B, an AT2 ligand with agonistic properties. The effects of PD 123319 were examined in a preparation with stable levels of angiotensin II, and in which AT1 receptors were blocked by the specific antagonist losartan. The effects of CGP 42112B were studied in rats deprived of endogenous angiotensin II. AT2 receptor blockade with PD 123319 did not change the renal blood flow while it increased the diuresis and natriuresis. These effects persisted even after full AT1 receptor blockade with losarfan. CGP 42112B did not modify the renal blood flow, but dose-dependently decreased urine flow and natriuresis. These results show that, contrary to AT1 receptors, renal AT2 receptors have no effect on total renal blood flow, but blunt the pressure-natriuresis, thus demonstrating that this receptor subtype is involved in a function of importance for body fluid and blood pressure regulation.
A 25-Signal Proteomic Signature and Outcome for Patients With Resected Non–Small-Cell Lung Cancer
Authors: Kiyoshi Yanagisawa, Shuta Tomida, Yukako Shimada, Yasushi Yatabe, Tetsuya Mitsudomi, Takashi Takahashi
Journal: JNCI Journal of the National Cancer Institute (2007)

Among patients with non-small-cell lung cancer (NSCLC), those with poor prognosis cannot be distinguished from those with good prognosis.Matrix-assisted laser desorption-ionization mass spectrometry was used to analyze protein profiles of 174 specimens from NSCLC tumors and 27 specimens from normal lung tissue and to derive a prognosis-associated proteomic signature. Frozen resected tissue specimens were randomly divided into a training set (116 NSCLC and 20 normal lung specimens) and an independent, blinded validation set (58 NSCLC and seven normal lung specimens). Mass spectrometry signals from training set specimens that were differentially associated with specimens from patients with a high risk of recurrence (i.e., who died within 5 years of surgical treatment because of relapse) compared with those from patients with a low risk of recurrence (i.e., alive with no symptoms of relapse after a median follow-up of 89 months) were selected by use of the Fisher's exact test, the Kruskal-Wallis test, and the significance analysis of microarray test. These signals were used to build an individualized, weighted voting-based prognostic signature. The signature was then validated in the independent dataset. Survival was assessed by multivariable Cox regression analysis. Proteins corresponding to individual signals were identified by ion-trap mass spectrometry coupled with high-performance liquid chromatography. All statistical tests were two-sided.From 2630 mass spectrometry signals from specimens in the training cohort, we derived a signature of 25 signals that was associated with both relapse-free survival and overall survival. Among stage I NSCLC patients in the validation set, the signature was statistically significantly associated with both overall survival (hazard ratio [HR] of death for patients in the high-risk group compared with those in the low-risk group = 61.1, 95% confidence interval [CI] = 8.9 to 419.2, P<.001) and relapse-free survival (HR of relapse = 11.7, 95% CI = 3.1 to 44.8, P<.001). Proteins corresponding to signals in the signature were identified that had various cellular functions, including ribosomal protein L26-like 1, acylphosphatase, and phosphoprotein enriched in astrocytes 15.We defined a mass spectrometry signature that was associated with survival among NSCLC patients and appeared to distinguish those with poor prognosis from those with good prognosis.