tbuckley/cabot-search huggingface dataset:
Effect of Angiotensin on the Pressor Response to Tyramine in Normotensive Subjects and Hypertensive Patients
Authors: YOSHIHIRO KANEKO, TADANAO TAKEDA, KOUJI NAKAJIMA, HIDEO UEDA
Journal: Circulation Research (1966)

Arterial blood pressure was recorded directly in 11 normotensive subjects, in 11 patients with essential hypertension and in 10 patients with renovascular hypertension. The pressor response to intravenous injections of norepinephrine, tyramine, angiotensin and ephedrine was compared in these three groups. An infusion of angiotensin was then given and the pressor response to injections of norepinephrine, tyramine, and ephedrine was again measured; in some cases, a comparison of the effects of the cold pressor test was made. In normotensive subjects, angiotensin infusion caused a significant increase in the responses to tyramine and ephedrine but not to norepinephrine; this occurred with subpressor doses and was unrelated to the level of blood pressure. In patients with renovascular hypertension, the mean pressor responses to injections of tyramine and ephedrine and the ratio of response to tyramine to that to norepinephrine were significantly increased, and the infusion of angiotensin failed to cause any further increase in these responses. In contrast, in patients with essential hypertension, the average response to injections of tyramine was not significantly increased, but during angiotensin infusion the response to tyramine increased as in normotensive subjects. It is proposed that increased response to tyramine, and lack of the potentiating effect of angiotensin demonstrated in renovascular hypertension, may be caused by increased formation of endogenous angiotensin due to renin secretion in this disease.
The Public Health Workforce
Authors: Hugh Tilson, Kristine M. Gebbie
Journal: Annual Review of Public Health (2004)

The development of a fully-competent public health workforce as a key component of the nation's public health infrastructure has become the focus of increasing attention. The subject is included in one, and is the major topic of a second, report from the Institute of Medicine published late in 2002. Workforce issues have stimulated the convening of the majority of public health–related associations in a range of collaborations on the subjects of defining, enumerating, credentialing, educating, and studying the workforce. The authors review the major questions confronting the field and introduce key components of current thinking about approaches to improvement.
Phenotypic and genotypic characterization of Neisseria gonorrhoeae in parts of Italy: detection of a multiresistant cluster circulating in a heterosexual network
Authors: I. Dal Conte, B Fianchino, S Delmonte, F Robbiano, A. D'Antuono, E Mirone, A Matteelli, M.A. De Francesco, M Cusini, L Scioccati, A. Di Carlo, G. Prignano, M.C. Salfa, S Starnino, B Suligoi, V Regine, N Bilek, P Stefanelli
Journal: Clinical Microbiology and Infection (2008)
Deletion of peroxiredoxin 6 potentiates OVA-induced asthma epithelial-mesenchymal transition through EGFR pathway
Authors: Dong Yang, Yan Mou, Chunling Dong, Meiling Jin, Chunxue Bai
Journal: European Respiratory Journal (2013)

Background: Epithelial-mesenchymal transition(EMT) has been proposed as an important mechanism for airway remodeling in asthma. Reactive oxygen species have been demonstrated to induce EMT. We aim to investigate the role and signaling pathway of peroxiredoxin 6, a newly identified peroxidase, in ovalbumin(OVA) induced asthma airway remodeling in mice.  Methods and results: Prdx6(-/-) and wild-type(WT) mice were immunized on day 1, 8, 15 with OVA 20ug/200uL intraperitoneally(ip) and challenged on day 25-28 with 0.4% OVA 50uL intranasally. Another group of WT mice were treated ip with 10mg/kg AG1478, inhibitor of EGFR tyrosine kinase, 1hr before each challenging. Twenty-four hours after the last OVA challenge, bronchoalveolar lavage fluid(BALF) and lungs were collected. After OVA exposure, leukocyte influx including eosinophils into BALF, IL-4 and IL-13 protein levels in BALF were significantly greater in Prdx6(-/-) mice compared with WT mice, which showed more severe asthma in Prdx6(-/-) mice. Hydrogen peroxide(H2O2) and malondialdehyde levels, matrix metalloproteinase (MMP)-9 mRNA and activity, E-cadherin, and phospho-EGFR expression were markedly increased in lungs of Prdx6(-/-) mice compared with WT mice, which showed more oxidative stress and mesenchymal production in Prdx6(-/-) mice. AG1478 treatment markedly suppressed OVA induced release of cytokines, production of H2O2, MMP-9 and E-cadherin, and phosphorylation of EGFR in WT mice.  Conclusions: Deletion of prdx 6 exaggerates OVA-induced asthma and airway remodelling with increased oxidative stress, inflammatory responses and mesenchymal transition, all of which were partially dependent on EGFR pathway.
Rare diseases bullet 4: Hereditary haemorrhagic telangiectasia and pulmonary arteriovenous malformations: issues in clinical management and review of pathogenic mechanisms
Authors: C. L Shovlin, M. Letarte
Journal: Thorax (1999)

Hereditary haemorrhagic telangiectasia (HHT, Rendu-Osler-Weber syndrome) exemplifies an important group of diseases which have catalysed advances in the understanding of fundamental pathophysiological mechanisms. In this paper areas of clinical management of HHT are discussed and the molecular pathogenesis is reviewed. The first section is aimed at all clinicians and concentrates on the recognition of a disorder in which silent cerebral and pulmonary involvement may be life threatening if left untreated. Recent data concerning the diagnostic and treatment modalities for pulmonary arteriovenous malformations (PAVMs) are also reviewed, and the growing concern that many patients with HHT may have small or residual PAVMs is highlighted. The paucity of good longitudinal data on these patients and others with different forms of HHT highlights the need for further clinical studies. In the second section the results of molecular research which suggests a role for receptors and ligands of the transforming growth factor (TGF)-β superfamily in the pathogenesis of this vascular disease are discussed. The means by which such information may relate to the clinical heterogeneity observed in HHT are specifically addressed, and more fundamental questions such as how reduced cell surface expression of endoglin predisposes a patient to develop PAVMs are also discussed.

The classical patient with the vascular disorder hereditary haemorrhagic telangiectasia (HHT) has nose bleeds, dilated blood vessels over the lips and finger tips, and gastrointestinal bleeding in later life. However, this clinical scenario represents only one of the presentation patterns of HHT.1 2 It is now recognised that, in addition to microscopic mucocutaneous telangiectases derived from post capillary venules (fig 1A),3 HHT leads to the development of larger abnormal vascular structures at other sites. Arteriovenous malformations in the pulmonary, cerebral, and hepatic circulations account for some of the most devastating clinical complications of the disease.



Figure 1 
Hereditary haemorrhagic telangiectasia …
Adiponectin and leptin increase IL-8 production in human chondrocytes
Authors: R. Gomez, M. Scotece, J. Conde, J. J. Gomez-Reino, F. Lago, O. Gualillo
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Abstract</h3> The Lake Baikal ecosystem is unique. The largest, oldest and deepest lake in the world presents a variety of rare evolutionary opportunities and ecological niches to the species that inhabit it, and as a result the lake is a biodiversity hotspot. More than 80% of the animals found there are endemic, and they often exhibit unusual traits. The freshwater sponge <i>Lubomirskia baicalensis</i> and its relatives are good examples of these idiosyncratic organisms. Lake Baikal sponges are unusually large for freshwater sponges, and possess particular symbiotic microorganisms which aid their survival and growth. As sponges are the most abundant benthic organisms in Lake Baikal, with 13 extant species (and 2 subspecies), they play a variety of key roles in the maintenance of this unusual ecosystem. In recent years the flora and fauna of Lake Baikal have been challenged by human activity in the region. Pollution, invasive species, temperature increases, eutrophication and falling water levels have all had deleterious effects. Sponges have suffered in particular from bleaching events, where their symbiotes are no longer retained, with knock-on effects to their survival and that of the ecosystem as a whole. To better understand the unique biology of these sponges we have established here a variety of resources for understanding these sponges at a molecular level. We have sequenced transcriptomes from three species of Lubomirskiidae. We have also assembled a draft genome resource for <i>L. baicalensis</i>. With these resources in place, a sizable addition to our knowledge of freshwater sponge genetics, we have investigated the adaptations of these and other freshwater sponge species to their environment, investigated their symbioses, and established a range of molecular tools for understanding the molecular and population-level biology of these key species across their habitat in Lake Baikal.
The Role of Complement in the Development of Systemic Lupus Erythematosus
Authors: Anthony P. Manderson, Marina Botto, Mark J. Walport
Journal: Annual Review of Immunology (2004)

▪ Abstract Complement has both beneficial and deleterious roles in the pathogenesis of systemic lupus erythematosus (SLE). On the one hand, patients with SLE present with decreased complement levels and with complement deposition in inflammed tissues, suggestive of a harmful role of complement in the effector phase of disease. On the other hand, homozygous deficiency of any of the classical pathway proteins is strongly associated with the development of SLE. There are two main hypotheses to explain these observations. The first invokes an important role for complement in the physiological waste-disposal mechanisms of dying cells and immune complexes. The second hypothesis is based around the role of complement in determining the activation thresholds of B and T lymphocytes, with the proposal that complement deficiency causes incomplete maintenance of peripheral tolerance. These two hypotheses are not mutually exclusive. In addition, there is evidence for a contribution from other genetic factors in determining the phenotype of disease in the absence of complement.
MSF calls for urgent help for war torn Yemen
Authors: Anne Gulland
Journal: BMJ (2015)

The aid charity Medecins Sans Frontieres has called for donors worldwide to respond urgently to the unfolding humanitarian crisis in Yemen.

Violence between warring factions has increased since March, with fighting taking place in civilian areas, and a blockade on goods, including drugs and food, leading to a worsening humanitarian crisis, the charity said. The naval blockade on Yemen, which relies heavily on foreign imports, has been imposed by Saudi Arabia, which supports Yemen’s exiled president, Abdrabbuh Mansour Hadi.1 Hadi’s supporters are fighting rebels whom the Saudis and other countries in the region believe are backed by Iran.

Speaking at a press conference in New York, Teresa Sancristόval, head of MSF’s emergency unit, said …
Patterns of molecular evolution in avian microsatellites
Authors: C. R. Primmer, H. Ellegren
Journal: Molecular Biology and Evolution (1998)

In order to develop models which appropriately reflect microsatellite evolution, more knowledge is required about the processes by which these simple sequences evolve. In this study, historical mutation events in three avian microsatellite loci belonging to distinct classes of repeat types (one perfect di-, one compound di-, and one perfect tetranucleotide repeat) were examined by sequence analysis of 76 alleles in 39 species spanning the avian phylogeny. The mode and tempo of evolution varied greatly between loci. For the perfect dinucleotide repeat, intraspecific length polymorphism was detected when alleles contained as few as six or seven repeat units, and size expansion over evolutionary timescales was demonstrated for repeats as short as (AG)2. A remarkable level of fragment stability was found for the compound dinucleotide repeat, even in species thought to have diverged over 60 MYA, coinciding with a high level of primer sequence conservation at this locus. In contrast, a hypervariable (AAAG)n locus revealed extraordinary instability and structural heterogeneity in the repeat region, including long arrays of derivative repeat motifs such as (AG)n, (AAGG)n, (AAAAG)n, and even (AAAGAGAG)n. Often, several motifs could be found within the same allele. A large number of cases of allele size homoplasy were detected for all three loci. These findings reinforce the fact that greater attention should be paid to the repeat type and the mutational characteristics of a marker before use in phylogenetic studies.
Development and Validation of a New Measure to Evaluate Psychological Resistance to Insulin Treatment
Authors: Frank Petrak, Elmar Stridde, Friedhelm Leverkus, Alexander A. Crispin, Thomas Forst, Andreas Pfützner
Journal: Diabetes Care (2007)

To develop a psychometric questionnaire to measure psychological barriers to insulin treatment in patients with type 2 diabetes.Scale development was based on principal component analyses in two cross-sectional studies of insulin-naïve patients with type 2 diabetes. The structure of the questionnaire was developed in the first sample of 448 patients and subsequently cross-validated in an independent sample of 449 patients.Analyses in the first sample yielded five components that accounted for 74.5% of the variance based on 14 items and led to the following subscales: fear of injection and self-testing, expectations regarding positive insulin-related outcomes, expected hardship from insulin treatment, stigmatization by insulin injections, and fear of hypoglycemia. In addition, an overall sum score of all values was calculated. The structure of the questionnaire was cross-validated in the second sample, with almost identical component loadings and an explained variance of 69.4%. An additional confirmatory factor analysis also indicated an acceptable to good model fit with root mean square error of approximation equal to 0.04 and comparative fit index equal to 0.97. Coefficients of reliability (Cronbach's alpha 0.62-0.85 and 0.78 for overall sum score) were acceptable, considering the very small number of items for each scale.The Barriers to Insulin Treatment Questionnaire appears to be a reliable and valid measure of psychological insulin resistance in patients with type 2 diabetes. This short instrument is easy to administer and may be used by both clinicians and researchers to assess the psychological barriers to insulin treatment.
Titin Isoform Switch in Ischemic Human Heart Disease
Authors: Ciprian Neagoe, Michael Kulke, Federica del Monte, Judith K. Gwathmey, Pieter P. de Tombe, Roger J. Hajjar, Wolfgang A. Linke
Journal: Circulation (2002)

Background— Ischemia-induced cardiomyopathy usually is accompanied by elevated left ventricular end-diastolic pressure, which follows from increased myocardial stiffness resulting from upregulated collagen expression. In addition to collagen, a main determinant of stiffness is titin, whose role in ischemia-induced left ventricular stiffening was studied here. Human heart sarcomeres coexpress 2 principal titin isoforms, a more compliant N2BA isoform and a stiffer N2B isoform. In comparison, normal rat hearts express almost no N2BA titin. Methods and Results— Gel electrophoresis and immunoblotting were used to determine the N2BA-to-N2B titin isoform ratio in nonischemic human hearts and nonnecrotic left ventricle of coronary artery disease (CAD) patients. The average N2BA-to-N2B ratio was 47:53 in severely diseased CAD transplanted hearts and 32:68 in nonischemic transplants. In normal donor hearts and donor hearts with CAD background, relative N2BA titin content was ≈30%. The titin isoform shift in CAD transplant hearts coincided with a high degree of modifications of cardiac troponin I, probably indicating increased preload. Immunofluorescence microscopy on CAD transplant specimens showed a regular cross-striated arrangement of titin and increased expression of collagen and desmin. Force measurements on isolated myofibrils revealed reduced passive-tension levels in sarcomeres of CAD hearts with high left ventricular end-diastolic pressure compared with sarcomeres of normal hearts. In a rat model of ischemia-induced myocardial infarction (left anterior descending coronary artery ligature), 43% of animals, but only 14% of sham-operated animals, showed a distinct N2BA titin band on gels. Conclusions— A titin isoform switch was observed in chronically ischemic human hearts showing extensive remodeling, which necessitated cardiac transplantation. The shift, also confirmed in rat hearts, caused reduced titin-derived myofibrillar stiffness. Titin modifications in long-term ischemic myocardium could impair the ability of the heart to use the Frank-Starling mechanism.
Postmastectomy Radiotherapy: Clinical Practice Guidelines of the American Society of Clinical Oncology*
Authors: Abram Recht, Stephen B. Edge, Lawrence J. Solin, David S. Robinson, Alison Estabrook, Richard E. Fine, Gini F. Fleming, Silvia Formenti, Clifford Hudis, Jeffrey J. Kirshner, David A. Krause, Robert R. Kuske, Amy S. Langer, George W. Sledge, Timothy J. Whelan, David G. Pfister
Journal: Journal of Clinical Oncology (2001)

OBJECTIVE: To determine indications for the use of postmastectomy radiotherapy (PMRT) for patients with invasive breast cancer with involved axil-lary lymph nodes or locally advanced disease who receive systemic therapy. These guidelines are intended for use in the care of patients outside of clinical trials. POTENTIAL INTERVENTION: The benefits and risks of PMRT in such patients, as well as subgroups of these patients, were considered. The details of the PMRT technique were also evaluated. OUTCOMES: The outcomes considered included freedom from local-regional recurrence, survival (disease-free and overall), and long-term toxicity. EVIDENCE: An expert multidisciplinary panel reviewed pertinent information from the published literature through July 2000; certain investigators were contacted for more recent and, in some cases, unpublished information. A computerized search was performed of MEDLINE data; directed searches based on the bibliographies of primary articles were also performed. VALUES: Levels of evidence and guideline grades were assigned by the Panel using standard criteria. A “recommendation” was made when level I or II evidence was available and there was consensus as to its meaning. A “suggestion” was made based on level III, IV, or V evidence and there was consensus as to its meaning. Areas of clinical importance were pointed out where guidelines could not be formulated due to insufficient evidence or lack of consensus. RECOMMENDATIONS: The recommendations, suggestions, and expert opinions of the Panel are described in this article. VALIDATION: Seven outside reviewers, the American Society of Clinical Oncology (ASCO) Health Services Research Committee members, and the ASCO Board of Directors reviewed this document.
Overexpression of RRM2 decreases thrombspondin-1 and increases VEGF production in human cancer cells in vitro and in vivo: implication of RRM2 in angiogenesis
Authors: Keqiang Zhang, Shuya Hu, Jun Wu, Linling Chen, Jianming Lu, Xiaochen Wang, Xiyong Liu, Bingsen Zhou, Yun Yen
Journal: Molecular Cancer (2009)

Abstract Background In addition to its essential role in ribonucleotide reduction, ribonucleotide reductase (RNR) small subunit, RRM2, has been known to play a critical role in determining tumor malignancy. Overexpression of RRM2 significantly enhances the invasive and metastatic potential of tumor. Angiogenesis is critical to tumor malignancy; it plays an essential role in tumor growth and metastasis. It is important to investigate whether the angiogenic potential of tumor is affected by RRM2. Results We examined the expression of antiangiogenic thrombospondin-1 (TSP-1) and proangiogenic vascular endothelial growth factor (VEGF) in two RRM2-overexpressing KB cells: KB-M2-D and KB-HURs. We found that TSP-1 was significantly decreased in both KB-M2-D and KB-HURs cells compared to the parental KB and mock transfected KB-V. Simultaneously, RRM2-overexpressing KB cells showed increased production of VEGF mRNA and protein. In contrast, attenuating RRM2 expression via siRNA resulted in a significant increased TSP-1 expression in both KB and LNCaP cells; while the expression of VEGF by the two cells was significantly decreased under both normoxia and hypoxia. In comparison with KB-V, overexpression of RRM2 had no significant effect on proliferation in vitro, but it dramatically accelerated in vivo subcutaneous growth of KB-M2-D. KB-M2-D possessed more angiogenic potential than KB-V, as shown in vitro by its increased chemotaxis for endothelial cells and in vivo by the generation of more vascularized tumor xenografts. Conclusion These findings suggest a positive role of RRM2 in tumor angiogenesis and growth through regulation of the expression of TSP-1 and VEGF.
Prospective Phase II Study on 5-Days Azacitidine for Treatment of Symptomatic and/or Erythropoietin Unresponsive Patients with Low/INT-1–Risk Myelodysplastic Syndromes
Authors: Carla Filì, Michele Malagola, Matilde Y. Follo, Carlo Finelli, Ilaria Iacobucci, Giovanni Martinelli, Federica Cattina, Cristina Clissa, Anna Candoni, Renato Fanin, Marco Gobbi, Monica Bocchia, Marzia Defina, Pierangelo Spedini, Cristina Skert, Lucia Manzoli, Lucio Cocco, Domenico Russo
Journal: Clinical Cancer Research (2013)

Abstract Purpose: This phase II prospective study aimed to evaluate the efficacy and safety of 5-days azacytidine (5d-AZA) in patients with low-risk myelodysplastic syndromes (MDS). Second, single-nucleotide polymorphism (SNP) genetic profile and phosphoinositide-phospholipase C (PI-PLC) β1 levels were studied to evaluate possible biologic markers able to predict the hematologic response. Experimental Design: The study tested a lower intensity schedule of azacytidine. The treatment plan consisted of 75 mg/sqm/d subcutaneous administered for 5 days every 28 days, for a total of 8 cycles. Results: Thirty-two patients were enrolled in the study. The overall response rate was 47% (15 of 32) on intention-to-treat and 58% (15 of 26) for patients completing the treatment program. In this latter group, 5 (19%) achieved complete remission (CR) and 10 (38%) had hematologic improvement, according to the International Working Group (IWG) criteria. Three patients have maintained their hematologic improvement after 37, 34, and 33 months without other treatments. Moreover, 21 and 2 of 26 cases completing 8 cycles were transfusion-dependent for red blood cells and platelets at baseline, respectively. Of these, 7 (33%) and 2 (100%) became transfusion-independent at the end of the treatment program, respectively. Grade 3–4 neutropenia occurred in 28% of patients and 4 patients died early due to infections or hemorrhage. SNP results were not significantly correlated to the clinical outcome, whereas PI-PLCβ1 level anticipated either positive or negative clinical responses. Conclusions: 5d-AZA is safe and effective in a proportion of patients with low-risk MDS. PI-PLCβ1 gene expression is a reliable and dynamic marker of response that can be useful to optimize azacytidine therapy. Clin Cancer Res; 19(12); 3297–308. ©2013 AACR.
What about seeding during prostate biopsy?
Authors: G. D. Stainsby
Journal: BMJ (2012)

Neither the study of the short term outcomes of prostate biopsy nor the accompanying editorial covers the potential of transrectal ultrasound guided (TRUS) prostate biopsy to cause needle track seeding and extracapsular extension of tumour.1 2

This was identified in 1991 and acknowledged in a 1997 Health Technology Assessment report.3 4 It noted that diagnosis of …