tbuckley/cabot-search huggingface dataset:
A Case of Esophageal Duplication Cyst with a 13-year Follow-up Period
Authors: M. W. Versleijen, J. P. Drenth, F. M. Nagengast
Journal: Endoscopy (2005)

Benign esophageal cysts are very rare embryonic malformations. In adults, esophageal cysts are mostly asymptomatic. Complications can occur due to mass effects. The diagnosis can be made using endoscopic ultrasonography (EUS), which is regarded as the diagnostic test of choice. It is a matter of debate whether relatively asymptomatic esophageal duplication cysts should be removed or whether conservative management is feasible. We report here on the case of a 37-year-old woman who presented with mild upper abdominal complaints and who was found to have compression of the distal lumen on barium esophagography. It was possible to diagnose an esophageal duplication cyst with EUS. In view of the absence of symptoms, it was decided to provide conservative management. During a 13-year follow-up period, no growth of the cyst was documented, nor did symptoms develop during this period. Close EUS observation may eliminate the need for surgery in asymptomatic patients.
Interleukin 1 and interleukin 1β converting enzyme (caspase 1) expression in the human colonic epithelial barrier. Caspase 1 downregulation in colon cancer
Authors: A Jarry, G Vallette, E Cassagnau, A Moreau, C Bou-Hanna, P Lemarre, E Letessier, J-C Le Neel, J-P Galmiche, C L Laboisse
Journal: Gut (1999)

BACKGROUND Interleukin (IL) 1β converting enzyme (now known as caspase 1) is able to process pro-IL-1β into its active form and is involved in proapoptotic signalling. AIMS To characterise IL-1 and caspase 1 expression in human colonic epithelial cells. METHODS Intracellular IL-1 content (IL-1α and IL-1β) was measured by ELISA in freshly isolated human normal colonocytes. Caspase 1 expression was determined both at the mRNA level using in situ hybridisation and reverse transcription polymerase chain reaction, and at the protein level by immunoblotting experiments using antibodies specific for the proform of caspase 1 and for its cleavage forms. RESULTS Low amounts of IL-1β were found in nearly all preparations (92%), and IL-1α was detected in only 45% of human colonocyte preparations. The normal colonic epithelium strongly expressed caspase 1, both at the mRNA level and at the protein level in its latent form. In contrast, caspase 1 was not expressed in colon cancer (primary colonic adenocarcinomas and cancer cell lines). CONCLUSIONS The demonstration that the human colonic epithelial barrier is able to express caspase 1 and its substrate IL-1β reinforces the concept that, under certain conditions, the epithelium could trigger an inflammatory reaction. In addition, the finding that caspase 1 was downregulated in colonic adenocarcinomas supports the concept that disrupted apoptosis pathways may be involved in tumour formation and/or may confer resistance to treatment.
NEURONAL SUBSTRATES OF COMPLEX BEHAVIORS IN <i>C. ELEGANS</i>
Authors: Mario de Bono, Andres Villu Maricq
Journal: Annual Review of Neuroscience (2005)

A current challenge in neuroscience is to bridge the gaps between genes, proteins, neurons, neural circuits, and behavior in a single animal model. The nematode Caenorhabditis elegans has unique features that facilitate this synthesis. Its nervous system includes exactly 302 neurons, and their pattern of synaptic connectivity is known. With only five olfactory neurons, C. elegans can dynamically respond to dozens of attractive and repellant odors. Thermosensory neurons enable the nematode to remember its cultivation temperature and to track narrow isotherms. Polymodal sensory neurons detect a wide range of nociceptive cues and signal robust escape responses. Pairing of sensory stimuli leads to long-lived changes in behavior consistent with associative learning. Worms exhibit social behaviors and complex ultradian rhythms driven by Ca 2+ oscillators with clock-like properties. Genetic analysis has identified gene products required for nervous system function and elucidated the molecular and neural bases of behaviors.
Muscular imbalance and shoulder pain in volleyball attackers.
Authors: A Kugler, M Krüger-Franke, S Reininger, H H Trouillier, B Rosemeyer
Journal: British Journal of Sports Medicine (1996)

In overhead sports such as volleyball, baseball, or tennis shoulder problems are very common. The aim of this study was to identify features which may correlate with shoulder problems in volleyball attackers.30 competitive volleyball attackers (mean age 25 years) were included in the study; 15 were suffering from shoulder pain and 15 had no history of shoulder pain. The results were compared with those of a control group of 15 recreational athletes without any overhead sports activities.Volleyball attackers have a different muscular and capsular pattern at the playing shoulder compared to the opposite shoulder. Their playing shoulder is depressed, the scapula lateralised, and the dorsal muscles and the posterior and inferior part of the shoulder capsule shortened. These differences were of more significance in volleyball attackers with shoulder pain than in volleyball players without shoulder pain. In contrast to recreational athletes without any overhead sports activity, there were no significant difference in the comparison of the two shoulders. The histories, clinical and sonographic findings did not reveal further typical features for volleyball attackers with shoulder pain.Muscular balance of the shoulder girdle is very important in this sport. It is therefore imperative to include adequate stretching and muscular training programme for the prevention, as well as for therapy, of shoulder pain in volleyball attackers.
Ras activation of Erk restores impaired tonic BCR signaling and rescues immature B cell differentiation
Authors: Sarah L. Rowland, Corinne L. DePersis, Raul M. Torres, Roberta Pelanda
Journal: The Journal of Experimental Medicine (2010)

B cell receptors (BCRs) generate tonic signals critical for B cell survival and early B cell development. To determine whether these signals also mediate the development of transitional and mature B cells, we examined B cell development using a mouse strain in which nonautoreactive immunoglobulin heavy and light chain–targeted B cells express low surface BCR levels. We found that reduced BCR expression translated into diminished tonic BCR signals that strongly impaired the development of transitional and mature B cells. Constitutive expression of Bcl-2 did not rescue the differentiation of BCR-low B cells, suggesting that this defect was not related to decreased cell survival. In contrast, activation of the Ras pathway rescued the differentiation of BCR-low immature B cells both in vitro and in vivo, whereas extracellular signal-regulated kinase (Erk) inhibition impaired the differentiation of normal immature B cells. These results strongly suggest that tonic BCR signaling mediates the differentiation of immature into transitional and mature B cells via activation of Erk, likely through a pathway requiring Ras.
Molecular Pathways: Targeting Mdm2 and Mdm4 in Cancer Therapy
Authors: Qin Li, Guillermina Lozano
Journal: Clinical Cancer Research (2012)

Abstract The p53 tumor suppressor is activated in response to cellular stresses to induce cell-cycle arrest, cellular senescence, and apoptosis. The p53 gene is inactivated by mutations in more than 50% of human tumors. In addition, tumor cells dampen p53 activities via overexpression of p53-negative regulators, in particular 2 structurally related proteins, Mdm2 and Mdm4. And yet, Mdm2 and Mdm4 possess p53-independent activities, which also contribute to tumor formation and progression. Given that Mdm2 and Mdm4 inhibit p53 activities to promote tumor development, small molecules and peptides were developed to abrogate the inhibition of p53 by Mdm proteins. Antitumor activities of these molecules have already been confirmed in preclinical studies and early-phase clinical trials. These research endeavors and clinical advances constitute the main focus of this review. Clin Cancer Res; 19(1); 34–41. ©2012 AACR.
Effect of Posthemorrhagic Anemia on the Renal Circulation of the Unanesthetized Rabbit
Authors: GORDON S. STOKES, PAUL I. KORNER
Journal: Circulation Research (1964)

In the unanesthetized rabbit made acutely anemic by bleeding with plasma replacement, there was no change in renal blood flow (RBF), a reduction in glomerular filtration rate (GFR), and a reduction in renal vascular resistance with a fall in the filtration fraction. There was evidence of renal tissue hypoxia and reduction in renal PAH extraction ratio. The extraction ratio was 97% at a hematocrit ratio of 34.5%, 91% at a hematocrit of 11.5%, and 84% with hematocrits between 6 and 10%. The effects of carboxyhemoglobinemia at normal blood viscosity were compared with the effects of anemia; a smaller reduction in renal PAH extraction ratio was found and there was no reduction in filtration fraction. The reductions in renal vascular resistance and filtration fraction in anemia were partly reversed by breathing 100% O 2 , viscosity changes again being minimized. It was concluded that renal tissue hypoxia and reduction in red cell concentration contribute in varying degrees to the changes in the renal vascular bed and the PAH extraction ratio.
The significance of fat droplet size and the prognostic value of hyaluronic acid in non-alcoholic fatty liver disease (NAFLD): a biopsy based analysis
Authors: G. Masterton, L. Y. C. Ngoh, A. Lockman, P. C. Hayes, J. Plevris
Journal: Gut (2011)

<h3>Introduction</h3> There are little data regarding the significance of fat droplet size or degree of hepatic steatosis in NAFLD. Microvesicular steatosis is thought to be rare in NAFLD. The aims of this study were to assess the prevalence of microvesicular steatosis and determine whether droplet size and amount of steatosis are clinically relevant. A further aim was to determine if hyaluronic acid (HA), a non-invasive marker of fibrosis, was helpful in discriminating fibrosis in NAFLD. <h3>Methods</h3> A database of liver biopsies performed between 1998 and 2009 at the Royal Infirmary of Edinburgh was interrogated and patients with NAFLD identified. Cases with co-existent liver disease or medication that would result in hepatic steatosis were excluded. Pathology and case notes were then reviewed. <h3>Results</h3> <i>Demographics</i>: 59 patients were included: 56% male; mean age 47 years. 39% had insulin resistance (IR) and 20% diabetes. On biopsy, 9 (15%) patients had microvesicular, 30 (51%) macrovesicular and 18 (30%) mixed steatosis. <i>Steatosis</i>: Microvesicular steatosis was associated with a reduced incidence of IR and diabetes (p=0.016). There was a significant difference in GGT between micro and macrovesicular steatosis (278 vs 107 U/l; p=0.05). However, there was no correlation between droplet size and disease activity (either by ALT or NAFLD activity score). There was a trend to a correlation between microvesicular droplets and less fibrosis (p=0.066) and lower amounts of total steatosis (p=0.053). Total amount of steatosis on biopsy did not show any further significant correlations. <i>Fibrosis Scores</i>: There was a significant correlation between HA and fibrosis (p=0.003). Post-test analysis demonstrated a significant trend between increasing fibrosis scores and increasing HA levels (p=0.001). AUC for fibrosis grade 3 or 4 was 0.89 (95% CI &gt;0.75 to 1.03). A ROC curve indicated as a cut off value of 85 ng/ml would indicate severe fibrosis (sensitivity of 86%; specificity 89%). <h3>Conclusion</h3> Microvesicular steatosis represented 15% of cases and was associated with less insulin resistance and a higher GGT. It is possible that different stages of NAFLD severity are associated with different size of fat droplet but not significant change in the quantity of fat in the liver. HA is sensitive at assessing fibrosis of NAFLD irrespective of inflammation or amount of fat on biopsy.
ASK1 Regulates Cardiomyocyte Death but Not Hypertrophy in Transgenic Mice
Authors: Qinghang Liu, Michelle A. Sargent, Allen J. York, Jeffery D. Molkentin
Journal: Circulation Research (2009)

Apoptosis signal-regulating kinase (ASK)1 is a central upstream kinase in the greater mitogen-activated protein kinase cascade that mediates growth and death decisions in cardiac myocytes in response to diverse pathological stimuli.However, the role that ASK1 plays in regulating the cardiac hypertrophic response in vivo remains controversial.Here, we generated mice with cardiac-specific and inducible overexpression of ASK1 in the heart to assess its gain-of-function effect. ASK1 transgenic mice exhibited no induction of cardiac hypertrophy or pathology at 3 and 12 months of age, and these mice showed an identical hypertrophic response to controls following 2 weeks of pressure-overload stimulation or isoproterenol infusion. Although ASK1 overexpression did not alter the cardiac hypertrophic response, it promoted cardiomyopathy and greater TUNEL following pressure-overload stimulation and myocardial infarction. Indeed, ASK1 transgenic mice showed a greater than 2-fold increase in ischemia reperfusion-induced injury to the heart compared with controls. Examination of downstream signaling showed a prominent activation of mitogen-activated protein kinase kinase 4/6 and c-Jun NH(2)-terminal kinase (JNK)1/2 (but not p38 or extracellular signal-regulated kinases [ERKs]), inhibition of calcineurin-NFAT (nuclear factor of activated T cells), and induction of Bax in the hearts of ASK1 transgenic mice following 1 and 8 weeks of pressure-overload stimulation. Mechanistically, cardiomyopathy associated with ASK1 overexpression after 8 weeks of pressure overload was significantly reduced in the calcineurin Abeta-null (CnAbeta(-/-)) background.These results indicate that ASK1 does not directly regulate the cardiac hypertrophic response in vivo, but it does alter cell death and propensity to cardiomyopathy, in part, through a calcineurin-dependent mechanism.
Messenger RNA Expression of Leptin and Leptin Receptors and their Prognostic Value in 322 Human Primary Breast Cancers
Authors: Françoise Révillion, Madia Charlier, Valérie Lhotellier, Louis Hornez, Sylvia Giard, Marie-Christine Baranzelli, Jean Djiane, Jean-Philippe Peyrat
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Leptin and obesity are clearly related, and obesity is associated with an increased risk of breast cancer. We therefore measured the expression of leptin and its two main receptor isoforms, OBR-L and OBR-S, in 322 breast cancers. We analyzed their relations with the classical prognostic factors and with survival to establish their links with breast cancer. Experimental Design: The expression of leptin and its receptors was quantified by real-time reverse transcription-PCR, using TaqMan fluorogenic probes and an ABI PRISM 7700 sequence detector system (Applied Biosystems, Courtaboeuf, France). TATA box binding protein was used to normalize expression. The human breast cancer cell, SK-BR-3, expressing the three targets, was chosen as the calibrator sample (i.e., target expression = 1). Results: All the tumors expressed both receptors, and 318 of 322 expressed leptin. These three variables correlated positively with each other and with estradiol and progesterone receptors, whereas they correlated negatively with histoprognostic grading and tumor diameter. OBR-L/OBR-S expression was inversely correlated with progesterone receptors. Patients with elevated OBR-S expression had longer relapse-free survival (P = 0.008), whereas high OBR-L/OBR-S was associated with a shorter relapse-free survival (P = 0.05). In Cox multivariate analyses, OBR-S maintained its prognostic value (P = 0.02; relative risk, 0.51). Conclusions: This study shows that (a) almost all of the breast cancers coexpress leptin and its two main isoforms of receptors, suggesting that the human epithelial breast cancer cells respond to leptin acting via an autocrine pathway; (b) high expression levels of leptin and leptin receptors are biological markers of a more differentiated phenotype; and that (c) OBR-S is an independent prognostic factor.
Comprehensive Outpatient Care in Rheumatoid Arthritis
Authors: Sidney Katz
Journal: JAMA (1968)

Patients with classical or definite rheumatoid arthritis by American Rheumatism Association (ARA) criteria (peripheral type, functional classes 2 and 3 and anatomical stages 2 and 4), were randomly assigned to treatment and control groups in a study of effectiveness of multidisciplinary clinic and home care. Comprehensive care was supplied by staff of the Arthritis Outpatient Clinic of University Hospitals of Cleveland and by staff of the Visiting Nurse Association of Cleveland. Services were coordinated through regularly held staff conferences. An independent clinical investigation team evaluated changes in function and disease activity. Treatment was beneficial in the following terms: fewer deteriorations in activities of daily living, more numerous improvements and fewer deteriorations in economic dependence, and more improvements and fewer deteriorations in clinical manifestations of disease activity. Of methodologic importance was the demonstration of the feasibility of controlled testing of long-term program effectiveness.
Analysis of the Mechanisms Mediating Tumor-Specific Changes in Gene Expression in Human Liver Tumors
Authors: Luis G. Acevedo, Mark Bieda, Roland Green, Peggy J. Farnham
Journal: Cancer Research (2008)

There is widespread interest in efficient characterization of differences between tumor and normal samples. Here, we show an effective methodology for genome-scale characterization of tumors. Using matched normal and tumor samples from liver cancer patients, as well as non-cancer-related normal liver tissue, we first determined changes in gene expression as monitored on RNA expression arrays. We identified several hundred mRNAs that were consistently changed in the tumor samples. To characterize the mechanisms responsible for creation of the tumor-specific transcriptome, we performed chromatin immunoprecipitation on microarray experiments to assay binding of RNA polymerase II, H3me3K27, and H3me3K9 and DNA methylation in 25,000 promoter regions. These experiments identified changes in active and silenced regions of the genome in the tumor cells. Finally, we used a "virtual comparative genomic hybridization" method to identify copy number alterations in the tumor samples. Through comparison of RNA polymerase II binding, chromatin structure, DNA methylation, and copy number changes, we suggest that the major contributor to creation of the liver tumor transcriptome was changes in gene copy number.
Proteomic profiling reveals the prognostic value of adenomatous polyposis coli-end-binding protein 1 in hepatocellular carcinoma
Authors: Tatsuya Orimo, Hidenori Ojima, Nobuyoshi Hiraoka, Shigeru Saito, Tomoo Kosuge, Tatsuhiko Kakisaka, Hideki Yokoo, Kazuaki Nakanishi, Toshiya Kamiyama, Satoru Todo, Setsuo Hirohashi, Tadashi Kondo
Journal: Hepatology (2008)

Abstract Histological differentiation is a major pathological parameter associated with poor prognosis in patients with hepatocellular carcinoma (HCC) and the molecular signature underlying HCC differentiation may involve key proteins potentially affecting the malignant characters of HCC. To develop prognostic biomarkers for HCC, we examined the global protein expression profiles of 45 surgically resected tissues, including 27 HCCs with different degree of histological differentiation, 11 adjacent nontumor tissues, and seven normal liver tissues. Unsupervised classification grouped the 45 samples according to their histological classification based on the protein expression profiles created by laser microdissection and two-dimensional difference gel electrophoresis (2D-DIGE). Statistical analysis and mass spectrometry identified 26 proteins with differential expression, of which 14 were functionally linked to c-Myc, AP-1, HIF1A, hepatocyte nuclear factor 4 alpha, or the Ras superfamily (RhoA, CDC42, and Rac1). Among the proteins identified, we focused on APC-binding protein EB1 (EB1) because it was dominantly expressed in poorly differentiated HCCs, which generally correlate with the poor prognosis in patients with HCC. In addition, EB1 is controlled by c-Myc, RhoA, and CDC42, which have all been linked to HCC malignancy. Immunohistochemistry in a further 145 HCC cases revealed that EB1 significantly correlated with the degree of histological differentiation ( P &lt; 0.001), and univariate and multivariate analyses indicated that EB1 is an independent prognostic factor for recurrence (hazard ratio, 2.740; 95% confidence interval, 1.771–4.239; P &lt; 0.001) and survival (hazard ratio, 2.256; 95% confidence interval, 1.337–3.807; P = 0.002) of patients with HCC after curative surgery. Conclusion : Proteomic profiling revealed the molecular signature behind the progression of HCC, and the prognostic value of EB1 in HCC. (Hepatology 2008;48:1851-1863.)
Alternative Splicing and Gene Duplication in the Evolution of the FoxP Gene Subfamily
Authors: M. E. Santos, A. Athanasiadis, A. B. Leitao, L. DuPasquier, E. Sucena
Journal: Molecular Biology and Evolution (2010)

The FoxP gene subfamily of transcription factors is defined by its characteristic 110 amino acid long DNA-binding forkhead domain and plays essential roles in vertebrate biology.Its four members, FoxP1-P4, have been extensively characterized functionally.FoxP1, FoxP2, and FoxP4 are involved in lung, heart, gut, and central nervous system (CNS) development.FoxP3 is necessary and sufficient for the specification of regulatory T cells (Tregs) of the adaptive immune system.In Drosophila melanogaster, in silico predictions identify one unique FoxP subfamily gene member (CG16899) with no described function.We characterized this gene and established that it generates by alternative splicing two isoforms that differ in the forkhead DNA-binding domain.In D. melanogaster, both isoforms are expressed in the embryonic CNS, but in hemocytes, only isoform A is expressed, hinting to a putative modulation through alternative splicing of FoxP1 function in immunity and/or other hemocyte-dependent processes.Furthermore, we show that in vertebrates, this novel alternative splicing pattern is conserved for FoxP1.In mice, this new FoxP1 isoform is expressed in brain, liver, heart, testes, thymus, and macrophages (equivalent in function to hemocytes).This alternative splicing pattern has arisen at the base of the Bilateria, probably through exon tandem duplication.Moreover, our phylogenetic analysis suggests that in vertebrates, FoxP1 is more related to the FoxP gene ancestral form and the other three paralogues, originated through serial duplications, which only retained one of the alternative exons.Also, the newly described isoform differs from the other in amino acids critical for DNA-binding specificity.The integrity of its fold is maintained, but the molecule has lost the direct hydrogen bonding to DNA bases leading to a putatively lower specificity and possibly affinity toward DNA.With the present comparative study, through the integration of experimental and in silico studies of the FoxP gene subfamily across the animal kingdom, we establish a new model for the FoxP gene in invertebrates and for the vertebrate FoxP1 paralogue.Furthermore, we present a scenario for the structural evolution of this gene class and reveal new previously unsuspected levels of regulation for FoxP1 in the vertebrate system.