tbuckley/cabot-search huggingface dataset:
Abstract 563: Novel role of VEGF and neuropilin-1 in breast cancer tumor-stromal interactions
Authors: Zhican Qu, Anshu M. Roy, Yulia Y. Maxuitenko, Rongbao Li, Zhi Qiang Huang, Martin R. Johnson
Journal: Cancer Research (2010)

Abstract Human breast cancers contain high levels of fibroblastic stroma as a critical feature of desmoplasia. The complex interactions between tumor and stromal cells play important roles in tumor growth, metastasis and resistance to anticancer treatments. Our previous in vivo studies showed that increased levels of tumor-released VEGF were associated with increased desmoplastic responses and resulted in a hormonal resistance phenotype of ER+ breast tumor. Based on our findings, a clinical trial conducted at UAB with a new combinational treatment targeting both ER and VEGF signalings has achieved significant objective response in ER+ breast cancer patients. In our current studies, we further studied the role of VEGF in mediating tumor-stromal interactions and initiation of desmoplasia. Our results have shown that tumor released VEGF interacts with stromal fibroblasts which express VEGF receptors R1, R2 and Neuropilin-1 (NRP1), thereby stimulating their infiltration to promote desmoplastic response. Down regulation of NRP1 expression by siRNA significantly abolished the fibroblast chemo-attractive motility towards VEGF, while the VEGFR1 and VEGFR2 blocking antibodies had no effects on their migration mobility, suggesting that NRP1 expressed in fibroblast is involved in tumor-stroma cell interactions in breast cancer. Our studies using breast cancer xenograft mouse model with regulated tumor VEGF expression revealed that tumor VEGF expression was positively correlated with expression of NRP1 and alpha smooth muscle actin (α-SMA, a transformed/myo fibroblast marker) in the tumor stroma. In addition, levels of tumor VEGF, stromal NRP1 and α-SMA were all positively correlated with level of tumor stromal content and tumor growth. Blocking tumor VEGF with a neutralizing antibody (Avastin) as a treatment modality in xenograft mice reversed the VEGF increased desmoplasia. Our study results reveal a novel role of VEGF and NRP1 in tumor-stromal interactions and desmoplasia, indicating NRP1 can be a therapeutic target for breast cancer treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 563.
Combing Diabetes' Teratogenic 'Suspect List'
Authors: Chris Anne Raymond
Journal: JAMA (1988)

INFANTS of insulin-dependent diabetic mothers have a twofold to threefold higher rate of congenital malformations than infants of mothers without the disorder. In recent years, blood glucose has topped the list of teratogenic suspects, so much so that a recent controversial study suggested that slightly elevated levels even in nondiabetic mothers were associated with an increased incidence of congenital abnormalities in their offspring (<i>N Engl J Med</i>1986;315:989-992). However, the inclusion of anomalies not typically associated with diabetic pregnancies raised questions about the study's conclusions (<i>N Engl J Med</i>1987;316:1343-1346). Now, data from the Diabetes in Early Pregnancy Study, one of the largest ever to follow diabetic women throughout their pregnancies, suggest that while glucose control plays a role in malformations, investigators must redouble their search for other factors if they hope to prevent problems such as caudal regression (sacral dysgenesis and hypoplasia of the femora) and congenital heart defects
Acute generalized exanthematous pustulosis in cystic echinococcosis: immunological characterization
Authors: C. Cannistraci, I.L.LA Parola, R. RiganO, F. Bassetti, E. Ortona, B. Santucci, M. Picardo, S. Siracusano
Journal: British Journal of Dermatology (2003)

Summary We report the first case, to the best of our knowledge, of a woman suffering from cystic echinococcosis of the liver, who consequently developed urticaria and acute generalized exanthematous pustolosis (AGEP). Serum immunoglobulin (Ig)E and IgG4 specific to Echinococcus granulosus antigens were detected by immunoblotting. Furthermore, the intracellular cytokine analysis revealed a prevalent T‐helper 2 polarization. It can be reasoned that, while the presence of IgE specific to various E. granulosus allergens may be responsible for the chronic urticarial manifestations, the detection of IgG4 specific for E. granulosus antigens, forming immunocomplexes, may be related to the development of the AGEP.
Ribosomal deficiencies in Diamond-Blackfan anemia impair translation of transcripts essential for differentiation of murine and human erythroblasts
Authors: Rastislav Horos, Hanna IJspeert, Dagmar Pospisilova, Regine Sendtner, Charlotte Andrieu-Soler, Erdogan Taskesen, Andrzej Nieradka, Radek Cmejla, Michael Sendtner, Ivo P. Touw, Marieke von Lindern
Journal: Blood (2011)
Foundation trusts "will pressure regulator to allow changes to licence"
Authors: Z. Kmietowicz
Journal: BMJ (2003)

The debate over foundation hospitals was reignited this week when members of the House of Lords and delegates at the Trades Union Congress attacked the proposed legislation, claiming it spelt disaster for the NHS.

Allyson Pollock, professor of public health policy at University College London, said ahead of a debate at the TUC conference in Brighton on Tuesday, that MPs and Department of Health officials were only just waking up to the potential impact of the Health and Social Care Bill. The lack of safeguards in the bill to stop foundation hospitals doing exactly what they wanted is “devastating,” she said.

Professor Pollock has been examining the “arcane and technical” proposed legislation with Foundation Trust Concern, a coalition of more than 15 organisations including the Association of Community Health Councils for England and Wales, several trade unions, and …
Clinically Important Variants of Human Hemoglobin
Authors: Louis M. Sherwood, Edith E. Parris, Helen M. Ranney
Journal: New England Journal of Medicine (1970)

RECOGNITION of the role of human hemoglobin variants in the pathogenesis of disorders associated with sickling and with thalassemia constituted one of the most important advances in hematology during the last 20 years. More recent has been the realization that variants of human hemoglobin may be associated with other clinical syndromes: variants having altered oxygen equilibria, such as the M hemoglobins, may produce cyanosis or erythrocytosis, whereas unstable variants are associated with congenital Heinz-body anemias.In few fields of clinical investigation can one so clearly relate the clinical presentation of the patient to the molecular aspects of his disorder. However, . . .
Loss of Kindlin-3 in LAD-III eliminates LFA-1 but not VLA-4 adhesiveness developed under shear flow conditions
Authors: Eugenia Manevich-Mendelson, Sara W. Feigelson, Ronit Pasvolsky, Memet Aker, Valentin Grabovsky, Ziv Shulman, Sara Sebnem Kilic, Maria Alessandra Rosenthal-Allieri, Shifra Ben-Dor, Adi Mory, Alain Bernard, Markus Moser, Amos Etzioni, Ronen Alon
Journal: Blood (2009)
AN ALTERNATIVE MECHANISM FOR THE PROPERDIN SYSTEM
Authors: Robert A. Nelson
Journal: The Journal of Experimental Medicine (1958)

Evidence is presented that phenomena ascribed to the properdin system may be explained in terms of classical antibody (Ab) in combination with three of the components of complement (C'), i.e., C'(1), C'(4), and C'(2) respectively. The results suggest that the complex of properdin (P) with zymosan (Z) represents a mixture of Z.Ab, Z.Ab.C'(1, 4), Z.Ab-C'(1, 4, 2), and Z.Ab.C'(1, 4, 2) in a decayed state. The purported preferential reactivity of Z with the third component of C' (C'(3)) is not supported by the present experiments in which Z was reacted with C' in both guinea pig and human sera. Approximately the same number of reactive units of C'(1, 4) and of C'(3) were inactivated by Z, as well as by D. pneumoniae and a washed specific precipitate of bovine albumin-anti-albumin. The latter evidence that small amounts of antigen-antibody complex fix significant amounts of C'(3) stands in contrast with the classical concept that C'(3) is not fixed in ordinary complement fixation reaction. The observed reactivity of C'(3) is explained on the basis of the present use of essentially undiluted serum as a source of C'(3) and of 37 degrees as the temperature for fixation. Ancillary data indicate that purified properdin contains Ab. In the presence of a chelating agent and at 0 degrees properdin agglutinated Z granules. Measurements of nitrogen (N) uptake by Z suggest that 0.25 microg. N were contributed by solutions stated to contain 1 unit of properdin. The broad spectrum of reactivity or cross-reactivity of the Ab in normal serum is likely due to the wide distribution in nature of closely related polysaccharides. Further immunochemical studies are necessary to establish definitively the origin and mode of action in "natural resistance" of antibodies reactive with these polysaccharides.
Transgenic models in cardiac arrhythmias: how close can we get to the bedside?
Authors: C Napolitano
Journal: Cardiovascular Research (2004)

See article by Tian et al. [8] (pages 256–267) in this issue.

The exponential growth of studies exploring the molecular bases of arrhythmogenesis is one of the most relevant trends recently taking place in the area of cardiovascular pathophysiology. The starting point of this line of research was the discovery of the DNA coding abnormalities causing Mendelian diseases (such as the Long QT syndrome (LQTS), the Brugada syndrome and catecholaminergic polymorphic ventricular tachycardia) that alter cardiac excitability and cause sudden cardiac death. This step constituted the inception of a novel type of research aimed at dissecting out the molecular pathways leading from a genetic defect to a clinical phenotype, the so-called “translational research”. Two major strategies have been undertaken: the first is “molecular epidemiology” that is aimed at linking the genotype (mutation) to the presentation of a disease; the second uses various cellular models in order to link the genotype to its cellular or sub-cellular functional counterpart at the protein level.

These strategies provided valuable information both for the understanding of the pathophysiology and about the ways … 

*Tel.: +39-382-592050; fax: +39-382-592094. cnapolitano{at}fsm.it
Epidemiology and clinical management of XDR-TB: a systematic review by TBNET
Authors: G. Sotgiu, G. Ferrara, A. Matteelli, M. D. Richardson, R. Centis, S. Ruesch-Gerdes, O. Toungoussova, J-P. Zellweger, A. Spanevello, D. Cirillo, C. Lange, G. B. Migliori
Journal: European Respiratory Journal (2009)

Extensively drug-resistant tuberculosis (XDR-TB) is present in all regions and poses serious challenges for public health and clinical management. Laboratory diagnosis is difficult and little evidence exists to guide clinicians in treating people with XDR-TB effectively. To summarise the available data on diagnosis and treatment, the current authors performed a systematic review on 13 recent studies of the epidemiology and clinical management of XDR-TB. Studies that met inclusion criteria were reviewed, in order to assess methodology, treatment regimens and treatment outcomes. Meta-analysis of currently available data is not possible because of inconsistent definitions and methodologies. Data show that XDR-TB can be successfully treated in up to 65% of patients, particularly those who are not co-infected with HIV. However, treatment duration is longer and outcomes are in general poorer than for non-XDR TB patients. To strengthen the evidence for extensively drug-resistant tuberculosis diagnosis, treatment and prevention, future studies should: 1) be prospective in design; 2) adopt standardised, internationally accepted definitions; 3) use quality-assured laboratory testing for all first- and second-line drugs; and 4) collect data on an agreed-upon set of standard variables, allowing for comparisons across studies. Early diagnosis and aggressive management of extensively drug-resistant tuberculosis provide the best chance of positive outcome, but prevention is still paramount.
HL-A8: a genetic link between dermatitis herpetiformis and gluten-sensitive enteropathy
Authors: Stephen I. Katz, Z. Myron Falchuk, Mark V. Dahl, G. Nicholas Rogentine, Warren Strober
Journal: Journal of Clinical Investigation (1972)

Histocompatibility antigen HL-A8 was found in 58% of 26 patients with dermatitis herpetiformis (DH) compared to 24% of a normal group. This difference in antigen frequency is significant at the P < 0.003 level. In a previous study, the frequency of this same genetic marker was found to be significantly increased in patients with gluten-sensitive enteropathy (GSE) (88% in patients vs. 22% in controls). The finding of an increased incidence of the HL-A8 antigen in both DH and GSE supports the concept that these diseases are related and provides a genetic basis for the association between the two.
Protein kinase CK2 enables regulatory T cells to suppress excessive TH2 responses in vivo
Authors: Alexander Ulges, Matthias Klein, Sebastian Reuter, Bastian Gerlitzki, Markus Hoffmann, Nadine Grebe, Valérie Staudt, Natascha Stergiou, Toszka Bohn, Till-Julius Brühl, Sabine Muth, Hajime Yurugi, Krishnaraj Rajalingam, Iris Bellinghausen, Andrea Tuettenberg, Susanne Hahn, Sonja Reißig, Irma Haben, Frauke Zipp, Ari Waisman, Hans-Christian Probst, Andreas Beilhack, Thierry Buchou, Odile Filhol-Cochet, Brigitte Boldyreff, Minka Breloer, Helmut Jonuleit, Hansjörg Schild, Edgar Schmitt, Tobias Bopp
Journal: Nature Immunology (2015)
Cutaneous adverse events in patients treated with BRAF inhibitor-based therapies for metastatic melanoma for longer than 52 weeks
Authors: R. Anforth, G. Carlos, A. Clements, R. Kefford, P. Fernandez-Peñas
Journal: British Journal of Dermatology (2014)

BRAF inhibitor-based therapies have been shown to induce cutaneous toxicities, with onset generally in the first 8-26 weeks of therapy.To determine whether cutaneous toxicities persist in patients who have remained on BRAF inhibitor-based therapies for longer than 52 weeks, and therefore whether ongoing dermatology assessment is required.All patients treated with the BRAF inhibitors vemurafenib or dabrafenib or combination BRAF inhibitor and mitogen-activated protein kinase kinase (MEK) inhibitor therapy at Westmead Hospital, Sydney, Australia underwent regular dermatological assessments for the duration of therapy. All patients enrolled in a clinical trial, and 18% of patients in the compassionate access scheme underwent a baseline assessment prior to commencement of therapy and every 4-8 weeks thereafter. Patients' adverse events were recorded in a specific database.Patients continued to develop cutaneous adverse events after 52 weeks of continuous therapy. Patients on single-agent BRAF inhibitor therapy suffered from Grover disease (45%), plantar hyperkeratosis (45%), verrucal keratosis (18%) and even cutaneous squamous cell carcinoma (16%). The most frequent adverse event seen in patients in the combination BRAF and MEK inhibitor group was an acneiform eruption (40%).Patients on BRAF inhibitor-based therapies need to continue to have regular dermatological follow-up independent of the duration of their therapy.
Babies born in a district general hospital to mothers taking heroin.
Authors: H M Klenka
Journal: BMJ (1986)

The effect of maternal abuse of heroin on newborn babies was studied in 25 babies born during 1982-6 to 23 heroin users, most of whom smoked the drug. Nineteen of the babies developed withdrawal symptoms, which in 12 were severe enough to require treatment. Five babies were born prematurely; 17 were adequately grown for their gestational age. Four mothers successfully established breast feeding. Twenty two infants were discharged from the hospital into their mother9s care with support from the family and community services; at the end of the study only six were living in families in which the parents were married or had a stable relationship. Withdrawal symptoms were short lasting and often self limiting, and no evidence of adverse effect on postnatal growth and development was found. Unstable social circumstances with changes in family dynamics made follow up difficult. Further assessment needs to be carried out to investigate the long term effect of maternal heroin abuse on children.
Early Diagnosis of Glaucoma
Authors: D. K. Ray
Journal: BMJ (1961)

<h3>BACKGROUND</h3> Strains of <i>Helicobacter pylori</i> that express the cytotoxin associated gene product A (CagA) may be more strongly associated with serious gastric diseases, such as gastric cancer and peptic ulceration, than other strains. Data, however, are sparse on the prevalence, risk factors, and other correlates of these strains in the general popu- lation. <h3>AIM</h3> To characterise aspects of the seroepidemiology of CagA<sup>+</sup> strains of<i>H pylori</i> in the general British population. <h3>METHODS</h3> We measured serum IgG antibodies to mixed <i>H pylori</i>antigens and separately to CagA in 1025 men aged 40–59 years who were randomly selected from a larger group of participants in a community based survey conducted in 18 different British towns. <h3>RESULTS</h3> Overall, 44% (95% confidence interval 41–47%) of the men were seropositive to CagA antibodies, representing about 61% (57–65%) of the men seropositive to mixed antigen <i>H pylori</i>. The risk factors for seropositivity to CagA antibodies were similar to those for seropositivity to mixed antigen <i>H pylori</i>, apart from an increased prevalence of reported bedroom sharing in childhood (p&lt;0.01). <h3>CONCLUSION</h3> In a nationwide study of potentially virulent <i>H pylori</i> strains, there was a high prevalence of the infection, with some evidence that acquisition of such strains might occur earlier in life than other strains.
Hematology: A Pathophysiological Approach
Authors: O'Neill Barrett
Journal: JAMA (1990)

This is the second edition of the hematology text by Babior and Stossel. It is a splendid book and differs from more traditional works on hematology in several ways. The authors emphasize that their approach has been to emphasize pathophysiological mechanisms, and they do this very well. They also point out that to be effective, they have changed some of the traditional classification systems; this approach is interesting and, for the most part, successful. For example, autoimmune thrombocytopenia is classified under the section on "Immune Destruction of Blood Cells," which deals with not only platelets, but red and white blood cells as well. On the other hand, one cannot find a discussion of the general topic of thrombocytopenia, especially those conditions causing decreased platelet formation. Likewise, thrombocytosis is dismissed with a one-paragraph comment about the ineffectiveness of antiplatelet drugs in this condition. In general, the book is well organized and
Bilateral atrial ganglionated plexus involvement in atrial responses to left-sided plexus stimulation in canines
Authors: Emmanuel Moss, René Cardinal, Yalin Yin, Pierre Pagé
Journal: Cardiovascular Research (2013)

Given the clinical interest concerning ‘reflex vagal’ responses to identify left atrial (LA) targets for ablative therapy of atrial fibrillation, we investigated whether vagal and bilateral atrial neural pathways may be involved in chronotropic and atrial repolarization responses to LA ganglionated plexus (GP) stimulation. Unipolar electrograms were recorded from 191 right atrial (RA) and LA sites in anaesthetized canines prior to and during electrical stimulation of the right vagus nerve (VgN), left VgN, or LAGP at baseline and following (i) bilateral VgN decentralization, and radiofrequency ablation of (ii) periaortic/superior vena cava (Ao/SVC) and (iii) RAGP in 14 animals (anterograde group), and in the reverse order in 7 (retrograde). Repolarization changes were also measured in similar preparations during Ao/SVC (n = 8) and RAGP stimulation (n = 23). Sinus cycle length (SCL) prolongation, and RA and LA repolarization changes (affected atrial surface area) were induced during LAGP stimulation. SCL prolongation and RA repolarization changes were unaffected by VgN decentralization but reduced following Ao/SVC and RAGP ablation in the anterograde group. In the retrograde group, chronotropic and RA repolarization changes were reduced following RAGP and abolished following Ao/SVC ablation. In contrast, LA repolarization responses to LAGP stimulation were reduced following VgN decentralization and each subsequent ablation step, with small residual responses after completing the anterograde protocol. Ao/SVC and RAGP stimulation exerted predominant influences in adjacent regions as well as demonstrating LA extensions. Vagal as well as bilateral atrial neural pathways are involved in mediating chronotropic and LA repolarization responses to LAGP stimulation.
MEDICAL TREATMENT OF EXOPHTHALMIC GOITER.
Authors: ROBERT B. PREBLE
Journal: JAMA (1907)

A correct estimation of the value of any plan of treatment of a given disease is easy or difficult, possible or impossible, in direct proportion to the closeness with which the disease follows a type. If the disease is acute andtypical, the therapeutic value of any measure is readily determined; but if, on the contrary, the course of the disease is chronic and subject to the many spontaneous remissions and exacerbations, it is nearly impossible to reach a just estimate of the value of any plan of treatment. When, in addition to these characteristics, the pathologic phenomena are not sharply separated from physiologic processes, the difficulties opposed to correct judgment are further increased. There is perhaps no disease, the history of which better demonstrates the truth of these principles, than does exophthalmic goiter. An almost unending list of plans of treatment might be prepared and in regard to each the
Organization of an Inhalation Therapy Service
Authors: Vincent J. Collins
Journal: JAMA (1963)

A WORKING DEFINITION of inhalation therapy is essential as a background to organizational problems. Such a definition was prepared by the Joint Committee on Inhalation Therapy of the American Society of Anesthesiologists and American College of Chest Physicians and is quoted from their memorandum of 1957. 1   Inhalation therapy is that therapy designed to restore toward normal pathophysiologic alterations of gas exchange in the cardiopulmonary system. It aims at adequate oxygenation as well as proper elimination of carbon dioxide.  Such therapy is accomplished by means of the proper application of therapeutic gases, including oxygen, helium-oxygen, and carbon dioxide mixtures; the use of pressure breathing devices, resuscitators and respirators to promote artificial ventilation and respiration; the administration of aerosols to improve the airway of the pulmonary system by relieving bronchospasm, liquefying secretions and combating infections; and the use of artificial airways to relieve obstruction.  Prior to 1950, inhalation therapy was generally