tbuckley/cabot-search huggingface dataset:
Phospholipid composition of human gastric mucosa: a study of endoscopic biopsy specimens.
Authors: G Nardone, P Laccetti, C Civiletti, G Budillon
Journal: Gut (1993)

Gastric mucosal phospholipids, and in particular those of the surface layer, play an important part in mucosal barrier function. This study examined whether the phospholipid composition of the full thickness gastric mucosa is changed in peptic ulcer disease and gastritis. The phospholipid composition of gastric mucosa from endoscopic biopsy specimens in 28 subjects (eight healthy controls, 12 patients with duodenal ulcer, and eight with chronic atrophic gastritis) was studied. In addition, the phospholipid composition of gastric mucosa was compared with that of duodenal mucosa in 10 patients with duodenal ulcer. As expected phosphatidylcholine and phosphatidylethanolamine prevailed in all three groups. Lysolecithin was the smallest component in the duodenal ulcer and chronic atrophic gastritis groups. The phosphatidylethanolamine value was higher in duodenal ulcer and lower in chronic atrophic gastritis compared with the control group. In chronic atrophic gastritis there was an appreciable amount of phosphatidylglycerol that was not present in patients with duodenal ulcer or in the control group. There was no significant difference in phospholipid composition between antral and duodenal sites in duodenal ulcer patients. In conclusion, the phospholipid composition of gastric mucosa changes in human gastrointestinal diseases but its relation to cellular functions needs further study.
Transient Expression of FRNK Reveals Stage-Specific Requirement for Focal Adhesion Kinase Activity in Cardiac Growth
Authors: Laura A. DiMichele, Zeenat S. Hakim, Rebecca L. Sayers, Mauricio Rojas, Robert J. Schwartz, Christopher P. Mack, Joan M. Taylor
Journal: Circulation Research (2009)

Focal adhesion kinase (FAK) is strongly activated by integrins and growth factors and is essential for embryonic development. We previously showed that the C terminus of FAK is expressed as a separate protein termed FAK-related nonkinase (FRNK) in a smooth muscle cell-selective fashion and that FRNK functions to buffer FAK-dependent signals. We now show that FRNK is also transiently expressed in the neonatal myocardium, with peak levels occurring 5 to 7 days postnatal, just before cell cycle withdrawal. Using novel mouse models, we demonstrate that cardiac-selective expression of FRNK (leading to inhibition of FAK) starting at embryonic day 10.5 leads to a severe ventricular noncompaction defect associated with reduced cardiomyocyte proliferation. Remarkably, postnatal expression of nearly identical levels of FRNK is well tolerated and does not affect viability or anabolic cardiac growth. Nonetheless, FRNK expression in the adult heart does attenuate pathological cardiac hypertrophy following aortic banding, confirming and extending our previous data that this compensatory response is blunted in FAK null hearts. Our mechanistic studies in cultured neonatal cardiomyocytes reveal that FRNK expression induces p38/p27(kip)-dependent cell cycle withdrawal and attenuates extracellular signal-regulated kinase-dependent hypertrophic growth. These findings indicate that dynamic expression of FRNK in the neonatal heart may function to promote cardiomyocyte quiescence in an environment that is particularly rich in growth factors and growth promoting extracellular matrices.
Human lupus autoantibody–DNA complexes activate DCs through cooperation of CD32 and TLR9
Authors: Terry K. Means, Eicke Latz, Fumitaka Hayashi, Mandakolathur R. Murali, Douglas T. Golenbock, Andrew D. Luster
Journal: Journal of Clinical Investigation (2005)

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by pathogenic autoantibodies against nucleoproteins and DNA. Here we show that DNA-containing immune complexes (ICs) within lupus serum (SLE-ICs), but not protein-containing ICs from other autoimmune rheumatic diseases, stimulates plasmacytoid DCs (PDCs) to produce cytokines and chemokines via a cooperative interaction between Toll-like receptor 9 (TLR9) and FcγRIIa (CD32). SLE-ICs transiently colocalized to a subcellular compartment containing CD32 and TLR9, and CD32+, but not CD32–, PDCs internalized and responded to SLE-ICs. Our findings demonstrate a novel functional interaction between Fc receptors and TLRs, defining a pathway in which CD32 delivers SLE-ICs to intracellular lysosomes containing TLR9, inducing a signaling cascade leading to PDC activation. These data demonstrate that endogenous DNA-containing autoantibody complexes found in the serum of patients with SLE activate the innate immune system and suggest a novel mechanism whereby these ICs contribute to the pathogenesis of this autoimmune disease.
Recurrent respiratory distress associated with carbamazepine overdose
Authors: FA Wilschut, NA Cobben, FB Thunnissen, RJ Lamers, EF Wouters, M Drent
Journal: European Respiratory Journal (1997)

Acute interstitial pneumonia or diffuse alveolar damage is uncommon as an adverse reaction to carbamazepine therapy. We report the case of a 36 yr old woman, who developed respiratory failure after auto-intoxication with carbamazepine. Analysis, including bronchoalveolar lavage and lung tissue biopsy, suggested diffuse alveolar damage due to carbamazepine.
GABA Transporter-1 mRNA in the Prefrontal Cortex in Schizophrenia: Decreased Expression in a Subset of Neurons
Authors: David W. Volk, Mark C. Austin, Joseph N. Pierri, Allan R. Sampson, David A. Lewis
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: Within the prefrontal cortex of schizophrenic subjects, alterations in markers of γ-aminobutyric acid (GABA) neurotransmission, including decreased immunoreactivity for the GABA membrane transporter GAT-1, may be most prominent in a subset of inhibitory neurons. In the present study, the authors sought to determine whether the alterations in GAT-1 protein could be attributed to a reduction in GAT-1 mRNA expression. METHOD: Tissue sections containing prefrontal cortex area 9 from 10 matched pairs of schizophrenic and comparison subjects were processed for in situ hybridization histochemistry with 35S-oligonucleotide probes for GAT-1 mRNA. RESULTS: In the schizophrenic subjects, the relative density of labeled neurons was 21%–33% lower in layers 1–5 of the prefrontal cortex but was unchanged in layer 6. In contrast, cellular levels of GAT-1 mRNA expression, as reflected in grain density per labeled neuron, did not differ by more than 11% between subject groups in any layer. These findings indicate that GAT-1 mRNA expression is relatively unaltered in the majority of prefrontal cortex GABA neurons in schizophrenic subjects but is reduced below a detectable level in a subset of GABA neurons. Furthermore, the magnitude and laminar pattern of these results were strikingly similar to those found in a previous study of mRNA expression for the synthesizing enzyme of GABA, glutamic acid decarboxylase67, in the same subjects. CONCLUSIONS: Both GABA synthesis and reuptake appear to be altered at the level of gene expression in a subset of GABA neurons, and the resulting changes in GABA neurotransmission may contribute to prefrontal cortex dysfunction in schizophrenia.
Linkage of cytokine genes to rheumatoid arthritis. Evidence of genetic heterogeneity
Authors: S. John, A. Myerscough, A. Marlow, A. Hajeer, A. Silman, W. Ollier, J. Worthington
Journal: Annals of the Rheumatic Diseases (1998)

To investigate linkage of candidate disease susceptibility genes to rheumatoid arthritis (RA) in affected sibling pair families stratified for specific clinical features.Two hundred RA affected sibling pair families were genotyped for informative microsatellite markers mapping within or less than 3cM from: INF alpha, INF gamma, INF beta, IL1 alpha, IL1 beta, IL1R, IL2, IL6, IL5R, IL8R, BCL2, CD40L, NOS3, NRAMP, alpha 1 anti-trypsin, and alpha 1 anti-chymotrypsin, using fluorescence based automated technology. Linkage was examined by defining allele sharing sibling pairs. This was assessed by maximum likelihood-inheritance by descent methods.An increase in allele sharing was seen for IL5R in female sibling pairs (LOD 0.91, p = 0.03), for INF gamma in sibling pairs with an affected male (LOD 0.96, p = 0.03) and most significantly for IL2 in sibling pairs where one or both were persistently seronegative (LOD 1.05, p = 0.02).Weak evidence of linkage of RA to IL5R, IFN gamma, and IL2 has been detected in clinical subsets of sibling pairs suggesting that RA is a genetically heterogeneous disease.
Pericyte Depletion Results in Hypoxia-Associated Epithelial-to-Mesenchymal Transition and Metastasis Mediated by Met Signaling Pathway
Authors: Vesselina G. Cooke, Valerie S. LeBleu, Doruk Keskin, Zainab Khan, Joyce T. O'Connell, Yingqi Teng, Michael B. Duncan, Liang Xie, Genta Maeda, Sylvia Vong, Hikaru Sugimoto, Rafael M. Rocha, Aline Damascena, Ricardo R. Brentani, Raghu Kalluri
Journal: Cancer Cell (2012)
Bayesian Methods Affirm the Use of Percutaneous Coronary Intervention to Improve Survival in Patients With Unprotected Left Main Coronary Artery Disease
Authors: John A. Bittl, Yulei He, Alice K. Jacobs, Clyde W. Yancy, Sharon-Lise T. Normand
Journal: Circulation (2013)

Background— Several randomized clinical trials support the use of coronary artery bypass grafting (CABG) for patients with unprotected left main coronary artery disease. Studies suggesting the equivalence of percutaneous coronary intervention (PCI) with CABG for this indication indirectly support the 2011 American College of Cardiology Foundation/American Heart Association Class IIa recommendation for PCI to improve survival in patients with unprotected left main coronary artery disease. We tested whether bayesian approaches uphold the new recommendation. Methods and Results— We performed a bayesian cross-design and network meta-analysis of 12 studies (4 randomized clinical trials and 8 observational studies) comparing CABG with PCI (n=4574 patients) and of 7 studies (2 randomized clinical trials and 5 observational studies) comparing CABG with medical therapy (n=3224 patients). The odds ratios of 1-year mortality after PCI compared with CABG using bayesian cross-design meta-analysis were not different among randomized clinical trials (odds ratio, 0.99; 95% bayesian credible interval, 0.67–1.43), matched cohort studies (odds ratio, 1.10; 95% bayesian credible interval, 0.76–1.73), and other types of cohort studies (odds ratio, 0.93; 95% bayesian credible interval, 0.58–1.35). A network meta-analysis suggested that medical therapy is associated with higher 1-year mortality than the use of PCI for patients with unprotected left main coronary artery disease (odds ratio, 3.22; 95% bayesian credible interval, 1.96–5.30). Conclusions— Bayesian methods support the current guidelines, which were based on traditional statistical methods and have proposed that PCI, like CABG, improves survival for patients with unprotected left main coronary artery disease compared with medical therapy. An integrated approach using both direct and indirect evidence may yield new insights to enhance the translation of clinical trial data into practice.
A Comparison of Medical Management with Misoprostol and Surgical Management for Early Pregnancy Failure
Authors: Jun Zhang, Jerry M. Gilles, Kurt Barnhart, Mitchell D. Creinin, Carolyn Westhoff, Margaret M. Frederick
Journal: New England Journal of Medicine (2005)

Misoprostol is increasingly used to treat women who have a failed pregnancy in the first trimester. We assessed the efficacy, safety, and acceptability of this treatment in a large, randomized trial.A total of 652 women with a first-trimester pregnancy failure (anembryonic gestation, embryonic or fetal death, or incomplete or inevitable spontaneous abortion) were randomly assigned to receive 800 microg of misoprostol vaginally or to undergo vacuum aspiration (standard of care) in a 3:1 ratio. The misoprostol group received treatment on day 1, a second dose on day 3 if expulsion was incomplete, and vacuum aspiration on day 8 if expulsion was still incomplete. Surgical treatment (for the misoprostol group) or repeated aspiration (for the vacuum-aspiration group) within 30 days after the initial treatment constituted treatment failure.Of the 491 women assigned to receive misoprostol, 71 percent had complete expulsion by day 3 and 84 percent by day 8 (95 percent confidence interval, 81 to 87 percent). Treatment failed in 16 percent of the misoprostol group and 3 percent of the surgical group (absolute difference, 12 percent; 95 percent confidence interval, 9 to 16 percent) by day 30. Hemorrhage or endometritis requiring hospitalization was rare (1 percent or less in each group), with no significant differences between the groups. In the misoprostol group, 78 percent of the women stated that they would use misoprostol again if the need arose and 83 percent stated that they would recommend it to others.Treatment of early pregnancy failure with 800 microg of misoprostol vaginally is a safe and acceptable approach, with a success rate of approximately 84 percent.
Nodal Stage Classification for Breast Carcinoma: Improving Interobserver Reproducibility Through Standardized Histologic Criteria and Image-Based Training
Authors: Roderick R. Turner, Donald L. Weaver, Gabor Cserni, Susan C. Lester, Karen Hirsch, David A. Elashoff, Patrick L. Fitzgibbons, Giuseppe Viale, Giovanni Mazzarol, Julio A. Ibarra, Stuart J. Schnitt, Armando E. Giuliano
Journal: Journal of Clinical Oncology (2008)

Purpose Reliable pathologic stage classification of axillary lymph nodes is an important determinant of prognosis and therapeutic decision making for patients with invasive breast cancer. Pathologists' distinction between micrometastasis (pN1mi) and isolated tumor cells [ITC; pN0(i+)] is variable using the American Joint Committee on Cancer (AJCC) Staging Manual (Sixth Edition). We sought to determine whether a set of clearly defined histologic criteria could lead to reproducible nodal classification by pathologists. Patients and Methods Digital images of sentinel lymph node biopsies from 56 patients with small-volume nodal metastases were examined by six experienced breast pathologists (MDs), first as a pre-test, and again as a post-test after studying a training program that outlined and illustrated the classification criteria. Results Post-test results, after study of the training program, were significantly improved. Compared with the reference MD, agreement improved from 76.2% (pre-test κ = 0.575; standard deviation [SD], 0.25) to 97.3% (post-test κ = 0.947; SD, 0.049). Multirater analysis of agreement among the six MDs improved from 71.5% (pre-test κ = 0.487; ASE, 0.039) to 95.7% (post-test κ = 0.915; ASE, 0.037). Agreement on lobular carcinoma metastasis classification improved from 55% (23 of 42; pre-test) to 100% (42 of 42; post-test) (P &lt; .001), and agreement on ITC classification in nodal parenchyma improved from 67.6% (69 of 102; pre-test) to 98.0% (100 of 102; post-test; P &lt; .001). Conclusion Application of current definitions for classification of small-volume nodal metastases are inconsistent, leading to variable classification of ITC and micrometastases. Reproducibility of pathologic nodal stage classification is achievable through study of a training set to clarify the AJCC criteria.
Extended lamivudine treatment in patients with chronic hepatitis B enhances hepatitis B e antigen seroconversion rates: Results after 3 years of therapy
Authors: Nancy W.Y. Leung, Ching-Lung Lai, Ting-Tsung Chang, Richard Guan, Chuan-Mo Lee, Keng-Yeen Ng, Seng-Gee Lim, Pui-Chee Wu, Julie C. Dent, Sally Edmundson, Lynn D. Condreay, Rong-Nan Chien
Journal: Hepatology (2001)

A study in Chinese patients with chronic hepatitis B showed that treatment with lamivudine for 1 year significantly improves liver histology and enhances hepatitis B e antigen (HBeAg) seroconversion compared with placebo. Fifty–eight patients from this 1–year study have received long–term treatment with lamivudine 100 mg; the outcome of 3 years of lamivudine is reported here. Before treatment, all patients had detectable HBeAg. HBeAg seroconversion (HBeAg–negative, anti–HBe-positive), hepatitis B virus (HBV)–DNA suppression, alanine transaminase (ALT) normalization, emergence of YMDD variant HBV, liver histology, and long–term safety were assessed. After 3 years of continuous treatment with lamivudine 100 mg daily, 40% (23 of 58) of patients achieved HBeAg seroconversion. In patients with baseline serum ALT &gt;2× upper limit of normal (ULN), the rate of HBeAg seroconversion was 65% (17 of 26). Median serum HBV–DNA concentrations were below the level of detection, and median ALT concentrations were within the normal range throughout 3 years of treatment. YMDD variant HBV emerged in 33 of 58 (57%) patients during the 3 years, of whom 9 (27%) achieved HBeAg seroconversion (6 after emergence of YMDD variant HBV). ALT levels and histologic scores after emergence of YMDD variant HBV did not show major deterioration. Lamivudine was well tolerated during 3 years of therapy. In conclusion, these data in Chinese patients with chronic hepatitis B show enhanced seroconversion rates with extended lamivudine treatment. Up to two thirds of patients with moderately elevated pretreatment ALT achieved HBeAg seroconversion after 3 years of therapy.
P59An epigenetic signature regulates gene expression in cardiac hypertrophy
Authors: P Kunderfranco, P Cattaneo, CM Greco, P Carullo, GG Stirparo, F Rusconi, G Hasenfuss, J Chen, G Condorelli, R Papait
Journal: Cardiovascular Research (2014)

The epigenetic signature for transcription regulation is poorly understood in cardiac hypertrophy. Here, we investigate the genome-wide distribution of several histone modifications and the correlated transcriptome in adult mouse cardiomyocytes subjected to a pro-hypertrophy stimulus in vivo. We demonstrate that the epigenetic profile dynamic of cardiac genes changes in response to the stimulus, and that distinct epigenetic signatures at promoters regulate the gene re-programming occurring with cardiac hypertrophy. Moreover, we identify 9,207 enhancers that impact transcription in normal and hypertrophic cardiomyocytes and whose activity is governed by unique epigenetic signatures. In fact, combinations of H3K27ac, H3K9ac, and H3K4me3 marks define new subclasses of highly active and dynamic enhancers in cardiac myocytes. We also analyzed the transcriptional network within which these genetic elements act to orchestrate hypertrophy gene expression, finding a role for myocyte enhancer factor (MEF)2C and MEF2A in regulating enhancers. The association of cardiac hypertrophy with a specific epigenetic profile provides a new basis for understanding the molecular mechanisms underlying hear failure, and opens up the possibility of developing new therapies based on the control of the epigenetic profile of cardiomyocytes.
Randomized Trial of Autologous Cellular Immunotherapy with Sipuleucel-T in Androgen-Dependent Prostate Cancer
Authors: Tomasz M. Beer, Guy T. Bernstein, John M. Corman, L. Michael Glode, Simon J. Hall, Wayne L. Poll, Paul F. Schellhammer, Lori A. Jones, Yi Xu, Jelle W. Kylstra, Mark W. Frohlich
Journal: Clinical Cancer Research (2011)

Sipuleucel-T, an autologous cellular immunotherapy, was investigated in a randomized, double-blind, controlled trial to determine its biologic activity in androgen-dependent prostate cancer (ADPC).Patients with prostate cancer detectable by serum prostate-specific antigen (PSA) following radical prostatectomy received 3 to 4 months of androgen suppression therapy, and were then randomized (2:1) to receive sipuleucel-T (n = 117) or control (n = 59). The primary endpoint was time to biochemical failure (BF) defined as serum PSA ≥ 3.0 ng/mL. PSA doubling time (PSADT), time to distant failure, immune response, and safety were also evaluated.Median time to BF was 18.0 months for sipuleucel-T and 15.4 months for control (HR = 0.936, P = 0.737). Sipuleucel-T patients had a 48% increase in PSADT following testosterone recovery (155 vs. 105 days, P = 0.038). With only 16% of patients having developed distant failure, the treatment effect favored sipuleucel-T (HR = 0.728, P = 0.421). The most frequent adverse events in sipuleucel-T patients were fatigue, chills, and pyrexia. Immune responses to the immunizing antigen were greater in sipuleucel-T patients at Weeks 4 and 13 (P < 0.001, all) and were sustained prior to boosting as measured in a subset of patients a median of 22.6 months (range: 14.3-67.3 months) following randomization.No significant difference in time to BF could be shown. The finding of increased PSADT in the sipuleucel-T arm is consistent with its biologic activity in ADPC. Long-term follow-up will be necessary to determine if clinically important events, such as distant failure, are affected by therapy. Treatment was generally well tolerated.
Phase III Open-Label Randomized Study of Eribulin Mesylate Versus Capecitabine in Patients With Locally Advanced or Metastatic Breast Cancer Previously Treated With an Anthracycline and a Taxane
Authors: Peter A. Kaufman, Ahmad Awada, Chris Twelves, Louise Yelle, Edith A. Perez, Galina Velikova, Martin S. Olivo, Yi He, Corina E. Dutcus, Javier Cortes
Journal: Journal of Clinical Oncology (2015)

Purpose This phase III randomized trial (ClinicalTrials.gov identifier: NCT00337103) compared eribulin with capecitabine in patients with locally advanced or metastatic breast cancer (MBC). Patients and Methods Women with MBC who had received prior anthracycline- and taxane-based therapy were randomly assigned to receive eribulin or capecitabine as their first-, second-, or third-line chemotherapy for advanced/metastatic disease. Stratification factors were human epidermal growth factor receptor-2 (HER2) status and geographic region. Coprimary end points were overall survival (OS) and progression-free survival (PFS). Results Median OS times for eribulin (n = 554) and capecitabine (n = 548) were 15.9 and 14.5 months, respectively (hazard ratio [HR], 0.88; 95% CI, 0.77 to 1.00; P = .056). Median PFS times for eribulin and capecitabine were 4.1 and 4.2 months, respectively (HR, 1.08; 95% CI, 0.93 to 1.25; P = .30). Objective response rates were 11.0% for eribulin and 11.5% for capecitabine. Global health status and overall quality-of-life scores over time were similar in the treatment arms. Both treatments had manageable safety profiles consistent with their known adverse effects; most adverse events were grade 1 or 2. Conclusion In this phase III study, eribulin was not shown to be superior to capecitabine with regard to OS or PFS.
Reduced MIC Gene Repertoire Variation in West African Chimpanzees as Compared to Humans
Authors: Natasja G. de Groot, Christian A. Garcia, Ernst J. Verschoor, Gaby G. M. Doxiadis, Steven G. E. Marsh, Nel Otting, Ronald E. Bontrop
Journal: Molecular Biology and Evolution (2005)

The human major histocompatibility complex class I chain-related (MIC) genes are members of a multicopy family showing similarity to the classical HLA-A, HLA-B, and HLA-C genes. Only the MICA and MICB genes produce functional transcripts. In chimpanzees, however, only one MIC gene is expressed, showing an intermediate character, resulting from a deletion fusing the MICA and MICB gene segments together. The present population study illustrates that all chimpanzee haplotypes sampled possess the hybrid MICA/B gene. In contrast to the human situation this gene displays reduced allelic variation. The observed repertoire reduction of the chimpanzee MICA/B gene is in conformity with the severe repertoire condensation documented for Patr-B locus lineages, probably due to the close proximity of both genes.