tbuckley/cabot-search huggingface dataset:
Abstract 265: Mechanisms of Met-dependent tumorigenesis in models of triple negative breast cancer.
Authors: Vanessa Y.C. Sung, Jennifer F. Knight, Morag Park
Journal: Cancer Research (2013)

Abstract Human breast cancer is a heterogeneous disease encompassing multiple subtypes. The basal-like and claudin-low subtypes, collectively known as triple negative (TN) breast cancer, are predominantly negative for the expression of therapeutic targets (Her2 and estrogen receptors) and have poor prognosis. In human breast cancer, elevated levels of MET are correlated with TN subtypes and poor outcome, but the reasons for this are relatively unknown. The Met receptor tyrosine kinase (RTK) is a cell surface protein that is activated in response to the Hepatocyte Growth Factor (HGF). Upon stimulation, Met signaling pathways initiate a program of cell survival, migration, and invasive growth. To investigate the role of Met in tumourigenesis, we generated transgenic mice with mammary specific expression of an oncogenic variant of Met (MMTV-Metmut). These mice develop tumours with features of TN breast cancer. Tumour-initiating cells (TICs) have emerged as a key concept in prevailing models of tumour development. In breast and other solid tumours, where the bulk of the tumour mass consists of differentiated non-tumourigenic cells, TICs constitute a cell fraction of less differentiated tumourigenic cells, and have been shown to be highly resistant to radiation and chemotherapy. TICs are thus a key therapeutic target, yet little is known about TICs in TN breast cancer. Using tumoursphere assays, we have established the presence of TICs in tumours derived from MMTV-Metmut transgenic mice. MMTV-Metmut TICs have constitutively active Met. Interestingly, treatment with a small molecule inhibitor targeting Met can diminish both tumoursphere formation and proliferation. Thus, in TN breast cancers, elevated levels of Met signaling may promote TIC tumourigenicity. Here, mechanisms of Met-dependent TIC propagation and tumourigenicity will be addressed and supporting data presented. The molecular events that lead to human basal-like and claudin-low breast cancers are poorly understood. Validating a role for Met in TICs could identify key pathways involved in the pathogenesis of TN breast cancer, providing information for new therapeutic targets. Citation Format: Vanessa Y.C. Sung, Jennifer F. Knight, Morag Park. Mechanisms of Met-dependent tumorigenesis in models of triple negative breast cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 265. doi:10.1158/1538-7445.AM2013-265
Epidermal growth factor receptor distribution in burn wounds. Implications for growth factor-mediated repair.
Authors: B A Wenczak, J B Lynch, L B Nanney
Journal: Journal of Clinical Investigation (1992)

Epidermal growth factor (EGF) along with several related peptide growth factors has been shown both in vivo and in vitro to accelerate events associated with epidermal wound repair. EGF and transforming growth factor alpha act by binding to a common EGF receptor tyrosine kinase thereby initiating a series of events which ultimately regulate cell proliferation. This study examined the immunohistochemical localization of EGF receptor (EGF-R) in burn wound margins, adjacent proliferating epithelium, and closely associated sweat ducts, sebaceous glands, and hair follicles. Tissue specimens removed during surgical debridement were obtained from full and partial thickness burn wounds in 32 patients with total body surface area burns ranging from 2 to 88%. In the early postburn period (days 2-4), prominent staining for EGF-R was found in undifferentiated, marginal keratinocytes, adjacent proliferating, hypertrophic epithelium, and both marginal and nonmarginal hair follicles, sweat ducts, and sebaceous glands. During the late postburn period (days 5-16), EGF-R was depleted along leading epithelial margins; however, immunoreactive EGF-R remained intensely positive in the hypertrophic epithelium and all skin appendages. Increased detection of immunoreactive EGF-R and the presence of [125I]EGF binding in the hypertrophic epithelium correlated positively with proliferating cell nuclear antigen distributions. Thus, the presence of EGF-R in the appropriate keratinocyte populations suggests a functional role for this receptor during wound repair. Dynamic modulation in EGF receptor distribution during the temporal sequence of repair provides further evidence that an EGF/transforming growth factor alpha/EGF-R-mediated pathway is activated during human wound repair.
C9orf72 expansions in frontotemporal dementia and amyotrophic lateral sclerosis
Authors: Jonathan D Rohrer, Adrian M Isaacs, Sarah Mizielinska, Simon Mead, Tammaryn Lashley, Selina Wray, Katie Sidle, Pietro Fratta, Richard W Orrell, John Hardy, Janice Holton, Tamas Revesz, Martin N Rossor, Jason D Warren
Journal: The Lancet Neurology (2015)
Preventive and Therapeutic Effects of Polaprezinc Suspension on Oral Mucosal Injury
Authors: H. Ishihama, S. Sayo, T. Yokoyama, M. Ueno, N. Ebihara, Y. Doi, K. Asano, H. Kawamata, H. Imai, K. Ueki
Journal: Annals of Oncology (2013)
Glycosyl-phosphatidylinositol-anchored membrane proteins.
Authors: D Brown, G L Waneck
Journal: Journal of the American Society of Nephrology (1992)

Many proteins of eukaryotic cells are anchored to membranes by covalent linkage to glycosyl-phosphatidylinositol (GPI). These proteins lack a transmembrane domain, have no cytoplasmic tail, and are, therefore, located exclusively on the extracellular side of the plasma membrane. GPI-anchored proteins form a diverse family of molecules that includes membrane-associated enzymes, adhesion molecules, activation antigens, differentiation markers, protozoan coat components, and other miscellaneous glycoproteins. In the kidney, several GPI-anchored proteins have been identified, including uromodulin (Tamm-Horsfall glycoprotein), carbonic anhydrase type IV, alkaline phosphatase, Thy-1, BP-3, aminopeptidase P, and dipeptidylpeptidase. GPI-anchored proteins can be released from membranes with specific phospholipases and can be recovered from the detergent-insoluble pellet after Triton X-114 treatment of membranes. All GPI-anchored proteins are initially synthesized with a transmembrane anchor, but after translocation across the membrane of the endoplasmic reticulum, the ecto-domain of the protein is cleaved and covalently linked to a preformed GPI anchor by a specific transamidase enzyme. Although it remains obscure why so many proteins are endowed with a GPI anchor, the presence of a GPI anchor does confer some functional characteristics to proteins: (1) it is a strong apical targeting signal in polarized epithelial cells; (2) GPI-anchored proteins do not cluster into clathrin-coated pits but instead are concentrated into specialized lipid domains in the membrane, including so-called smooth pinocytotic vesicles, or caveoli; (3) GPI-anchored proteins can act as activation antigens in the immune system; (4) when the GPI anchor is cleaved by PI-phospholipase C or PI-phospholipase D, second messengers for signal transduction may be generated; (5) the GPI anchor can modulate antigen presentation by major histocompatibility complex molecules. Finally, at least one human disease, paroxysmal nocturnal hemoglobinuria, is a result of defective GPI anchor addition to plasma membrane proteins.
CONGENITAL INFECTIONS WITH REOVIRUS
Authors: Ali Hashimi, Mary M. Carruthers, Paul Wolf, A. Martin Lerner
Journal: The Journal of Experimental Medicine (1966)

Congenital reovirus, type 2 infections were produced after intraperitoneal inoculations of brood mothers on the 1st, 3rd, 6th, 10th, and 15th day of gestation. The offspring presented with a varied syndrome. About a quarter of a total of over 200 mice showed symptoms within the first 14 days of life; namely, lassitude, retarded growth, and roughening of fur. Some died, apparently of respiratory or renal failure. Post mortem examination showed marked interstitial pneumonia and subcortical renal tubular necrosis. Reovirus was isolated in high titer from the kidney and lungs as well as from blood, hearts, hind limbs, and brains in lesser titer. At 3 wk of age over 50 apparently well mice were sacrificed, and virologic, serologic, and pathologic study was done. High titers of virus were again found in the kidney, lung, blood, brain, heart, and skeletal muscle, but all tissues appeared normal histologically. Type-specific serum antibody titers in these mice were approximately those of their mothers. Another half of these mice showed decreased spontaneous activity and growth retardation which appeared between the 15th and 36th days of life. Three of these mice with late illnesses had marked proptosis and conjunctivitis. A subepidermal conjunctival and extraocular muscle lymphocytic infiltrate was observed on section, and reovirus was isolated from these eyes in tissue culture. Again blood, brain, kidney, liver, spleen, myocardium, and skeletal muscle were studied, and were found to be normal histologically and not to contain reovirus. Finally, the rest of the mice remain well to date. At 3 months of age, 10 of them were sacrificed. All had lost their maternal antibody and contained no reovirus, type 2 hemagglutinating inhibiting antibodies. No developmental abnormalities were observed. These data suggest that prolonged reovirus infections may be established by means of congenital inoculation of the developing fetus. Tolerant infection with immune paralysis seems to have been established.
Approximate Entropy of Respiratory Patterns in Panic Disorder
Authors: Daniela Caldirola, Laura Bellodi, Andrea Caumo, Giovanni Migliarese, Giampaolo Perna
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: Considerable evidence suggests a connection between panic disorder and respiration, but the nature of the respiratory abnormalities in panic disorder remains unclear. The authors investigated the breath-by-breath complexity of respiration dynamics in panic disorder. METHOD: Respiratory physiology was assessed in 40 patients with panic disorder and 31 healthy comparison subjects by using a breath-by-breath stationary system for testing cardiorespiratory function. Irregularity in the breathing pattern was determined by applying the approximate entropy index, which is an indicator of the irregularity and the "disorder" of the measure. RESULTS: The patients with panic disorder showed significantly higher approximate entropy indexes than the healthy subjects for the measured respiratory parameters. Sighs contributed to the irregularity of breathing patterns but did not account for all the differences in approximate entropy between the patients with panic disorder and the comparison subjects. Anxiety state, severity of illness, and somatic and individual variables such as participation in sports and cigarette smoking did not seem to influence the results. CONCLUSIONS: Patients with panic disorder showed greater entropy in baseline respiratory patterns, indicating higher levels of irregularity and complexity in their respiratory function. Greater respiratory entropy could be a factor in vulnerability to panic attacks.
Diaphragm and quadriceps muscle fatigue in self-paced cycling exercise of different durations
Authors: Elisabeth C. Eberle, Thomas Wüthrich, Christina M. Spengler
Journal: European Respiratory Journal (2011)

Introduction:  Individuals are believed to pace cycling intensity in a time trial (TT) such that the level of quadriceps muscle fatigue (QF) attained is similar independent of cycling conditions. We aimed to assess whether diaphragm fatigue (DF), known to affect leg muscle fatigue, would also reach similar levels between different tests.   Methods:  12 healthy, young athletes (67.1±6.3 ml min -1  kg -1 ) performed 15 and 30min cycling time trials (15TT, 30TT; randomised), on two different days. DF and QF were assessed by measuring reductions in esophageal and gastric (transdiaphragmatic) pressure/quadriceps force during magnetic phrenic/femoral nerve stimulation after exercise relative to before (ΔP di,tw ; ΔQ tw ).   Results:  The average degree of ΔP di,tw  did not differ -21.2±12.8% (15TT) vs. -17.6±9.3% (30TT; p=0.228) while ΔQ tw  of the shorter and more intensive test -34.0±5.7% (15TT) was significantly larger than that of the longer test -29.5±6.9% (30TT; p=0.044). Individual between-test differences of ΔP di,tw  did not correlate with those of ΔQ tw . However, individual ΔP di,tw  of both TTs taken together significantly correlated with the workload of the finish (last 30 s) relative to the maximal workload (R 2 =0.30; p=0.005).   Conclusion:  The present work does not support the notion that the level of QF is the same, independent of cycling TT conditions. Knowing that DF develops early during exercise, these findings may indicate that DF possibly affected finish intensity via afferent feedback from the fatigued diaphragm, attenuating central motor output to working limb muscles.
Nicotine Dependence in Schizophrenia: Clinical Phenomena and Laboratory Findings
Authors: G W Dalack, D J Healy, J H Meador-Woodruff
Journal: American Journal of Psychiatry (1998)

Objective:The goal of this report is to examine the potential implications of the high prevalence of smoking in schizophrenia for our understanding of this illness.Method:A selective review of the relevant clinical and preclinical literature was conducted. The authors present a review of the clinical observations about smoking in schizophrenia, summarize the preclinical data about the complexity of the CNS nicotinic receptor family, and examine the modulatory effects of nicotine on neurotransmitter systems implicated in schizophrenia.Results:Clinical data suggest that smoking in schizophrenia may represent an attempt to self-medicate symptoms of the illness. Preclinical findings support a potential role of nicotine in medicating negative symptoms in particular. Recent preclinical and clinical data suggest that schizophrenic patients have a primary defect in the CNS nicotinergic system that leads to abnormal sensory gating. The complexity of the neuromodulatory effects of CNS nicotinic systems on other neurotransmitter systems underscores both the scope and potential importance of continued advancement of research in this area.Conclusions:Despite increasing clinical research focused on the extremely high prevalence of smoking in schizophrenia, linkages to the prodigious preclinical data about nicotine and nicotinic receptors are largely unexplored. These linkages are likely to be very important. Integrating nicotine use into our clinical and basic models of schizophrenia leads to a more complex but more realistic representation of brain dysfunction in this illness. Understanding how and why schizophrenic individuals use nicotine may lead to the development of new treatments for both schizophrenia and nicotine dependence. Am J Psychiatry 1998; 155: 1490-1501
Socioeconomic inequality in neonatal mortality in countries of low and middle income: a multicountry analysis
Authors: Britt McKinnon, Sam Harper, Jay S Kaufman, Yves Bergevin
Journal: The Lancet Global Health (2014)

Neonatal mortality rates (NMRs) in countries of low and middle income have been only slowly decreasing; coverage of essential maternal and newborn health services needs to increase, particularly for disadvantaged populations. Our aim was to produce comparable estimates of changes in socioeconomic inequalities in NMR in the past two decades across these countries.We used data from Demographic and Health Surveys (DHS) for countries in which a survey was done in 2008 or later and one about 10 years previously. We measured absolute inequalities with the slope index of inequality and relative inequalities with the relative index of inequality. We used an asset-based wealth index and maternal education as measures of socioeconomic position and summarised inequality estimates for all included countries with random-effects meta-analysis.24 low-income and middle-income countries were eligible for inclusion. In most countries, absolute and relative wealth-related and educational inequalities in NMR decreased between survey 1 and survey 2. In five countries (Cameroon, Nigeria, Malawi, Mozambique, and Uganda), the difference in NMR between the top and bottom of the wealth distribution was reduced by more than two neonatal deaths per 1000 livebirths per year. By contrast, wealth-related inequality increased by more than 1·5 neonatal deaths per 1000 livebirths per year in Ethiopia and Cambodia. Patterns of change in absolute and relative educational inequalities in NMR were similar to those of wealth-related NMR inequalities, although the size of educational inequalities tended to be slightly larger.Socioeconomic inequality in NMR seems to have decreased in the past two decades in most countries of low and middle income. However, a substantial survival advantage remains for babies born into wealthier households with a high educational level, which should be considered in global efforts to further reduce NMR.Canadian Institutes of Health Research.
Establishing Comparable Requirements and Treatment Groups Before Applying Statistical Comparison—Reply
Authors: Saurav Chatterjee, Partha Sardar, Giuseppe Biondi-Zoccai, Dharam J. Kumbhani
Journal: JAMA Neurology (2014)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
Distinct Renin Isoforms Generated by Tissue-Specific Transcription Initiation and Alternative Splicing
Authors: Min Ae Lee-Kirsch, Francois Gaudet, M. Cristina Cardoso, Klaus Lindpaintner
Journal: Circulation Research (1999)

Abstract —The aspartyl protease renin catalyzes the initial and rate-limiting step in the formation of the biologically active peptide angiotensin II. It is mainly synthesized in the kidney as a preprohormone and secreted via constitutive and regulated pathways. We identified a novel transcript of the rat renin gene, renin b, characterized by the presence of an alternative first exon (exon 1b) that is spliced to exon 2 of the known transcript, termed renin a. We demonstrated that renin b is exclusively expressed in the brain. In contrast, renin a was not expressed in the brain. Using primer extension assays, we mapped the transcriptional start site of this novel mRNA within intron 1 of the rat genomic sequence, suggesting the presence of a brain-specific promoter within intron 1. The presence of a brain-specific renin isoform is evolutionally conserved, as demonstrated by the finding of renin b isoforms in mice and humans. The predicted protein renin b lacks the prefragment as well as a significant portion of the profragment and is therefore predicted not to be a secreted protein, unlike the classically described isoform renin a. As shown by in vitro translation of full-length renin b mRNA in the presence of microsomal membranes, renin b was not targeted into the endoplasmatic reticulum and remained intracellularly in transiently transfected AtT-20 cells. These findings provide evidence for a novel pathway of intracellular angiotensin generation that occurs exclusively in the brain.
Remarks on ESSENTIAL VASCULAR HYPERTENSION
Authors: S. H. Rolleston
Journal: BMJ (1933)

The term " essential hypertension" is now widely used ON to describe persistent high blood pressure not obviously ESSENTIAL VASCULAR HYPERTENSION * secondary to renal or other disease, the accurate recognition of which has beeni facilitated and-become general as a BY result of the routine use of the sphygmomanometer and of SIR UMPHYRLL ,BART.the elaboration of tests for renal efficiency which help to SIR .V.O., HUMPHRY ROL, eliminate the nephritic cases.WV.H. Broadbent in 1890 G.C.V
Tofacitinib in Combination With Nonbiologic Disease-Modifying Antirheumatic Drugs in Patients With Active Rheumatoid Arthritis
Authors: Joel Kremer, Zhan-Guo Li, Stephen Hall, Roy Fleischmann, Mark Genovese, Emilio Martin-Mola, John D. Isaacs, David Gruben, Gene Wallenstein, Sriram Krishnaswami, Samuel H. Zwillich, Tamas Koncz, Richard Riese, John Bradley
Journal: Annals of Internal Medicine (2013)

Chinese translation Background: Many patients with rheumatoid arthritis (RA) do not achieve adequate and safe responses with disease-modifying antirheumatic drugs (DMARDs). Tofacitinib is a novel, oral, Janus kinase inhibitor that treats RA. Objective: To evaluate the efficacy and safety of tofacitinib in combination with nonbiologic DMARDs. Design: 1-year, double-blind, randomized trial (ClinicalTrials.gov: NCT00856544). Setting: 114 centers in 19 countries. Patients: 792 patients with active RA despite nonbiologic DMARD therapy. Intervention: Patients were randomly assigned 4:4:1:1 to oral tofacitinib, 5 mg or 10 mg twice daily, or placebo advanced to tofacitinib, 5 mg or 10 mg twice daily. Measurements: Primary end points were 20% improvement in American College of Rheumatology (ACR20) criteria; Disease Activity Score for 28-joint counts based on the erythrocyte sedimentation rate (DAS28-4[ESR]) of less than 2.6; DAS28-4(ESR)–defined remission, change in Health Assessment Questionnaire Disability Index (HAQ-DI) score, and safety assessments. Results: Mean treatment differences for ACR20 response rates (month 6) for the 5-mg and 10-mg tofacitinib groups compared with the combined placebo groups were 21.2% (95% CI, 12.2% to 30.3%; P < 0.001) and 25.8% (CI, 16.8% to 34.8%; P < 0.001), respectively. The HAQ-DI scores (month 3) and DAS28-4(ESR) less than 2.6 response rates (month 6) were also superior in the tofacitinib groups versus placebo. The incidence rates of serious adverse events for patients receiving 5-mg tofacitinib, 10-mg tofacitinib, or placebo were 6.9, 7.3, or 10.9 events per 100 patient-years of exposure, respectively. In the tofacitinib groups, 2 cases of tuberculosis, 2 cases of other opportunistic infections, 3 cardiovascular events, and 4 deaths occurred. Neutrophil counts decreased, hemoglobin and low- and high-density lipoprotein cholesterol levels increased, and serum creatinine levels had small increases in the tofacitinib groups. Limitations: Placebo groups were smaller and of shorter duration. Patients received primarily methotrexate. The ability to assess drug combinations other than tofacitinib plus methotrexate was limited. Conclusion: Tofacitinib improved disease control in patients with active RA despite treatment with nonbiologic DMARDs, primarily methotrexate. Primary Funding Source: Pfizer.