tbuckley/cabot-search huggingface dataset:
Treatment of oral dryness related complaints (xerostomia) in Sjogren's syndrome
Authors: W. A van der Reijden, A. Vissink, E. C I Veerman, A. V N. Amerongen
Journal: Annals of the Rheumatic Diseases (1999)

Primary Sjogren’s syndrome (SS) is a systemic autoimmune disorder characterised by a chronic, progressive loss of salivary and lacrimal function resulting in symptoms of oral and ocular dryness. The involvement of exocrine glands is the result of a focal, periductal mononuclear cell infiltrate and the subsequent loss of secretory epithelial cells.1 As a consequence, major changes occur in both the salivary flow rate and salivary composition.2-9 In the case of secondary SS a second autoimmune disease is involved, mostly rheumatoid arthritis.

The role of saliva in maintaining oral health and even quality of life is obvious in people who are lacking sufficient saliva.10-12 The effects of the reduced salivary flow rate (xerostomia) and changed salivary composition in SS are apparent (table 1): there are problems in eating, speaking, and swallowing12-15 and frequently disturbances in taste perception.16 In addition, reduced clearance of food, changes in microbial ecology and a reduced buffer capacity have their effects on oral health: an increased susceptibility to dental caries and oral infections are important clinical manifestations of the oral component of SS.17 18 When the systemic disease advances, salivary secretion declines further.7

View this table:

Table 1 
Consequences of xerostomia



A reduction of the salivary flow rate below physiological values can be induced by several other causes as well.19 Dry mouth symptoms are known as a side effect of more than 400 drugs.20 21 In most of these cases the level of reduction of the salivary flow is slight and can be compensated for by mechanical or gustatory stimulation. Other common causes of prolonged hyposalivation include other autoimmune disorders such as systemic lupus erythematosus,22 23 uncontrolled diabetes mellitus24 25 and salivary gland injury as a result of radiotherapy in the head and neck region.26 

This review describes the current …
Id4 deficiency attenuates prostate development and promotes PIN-like lesions by regulating androgen receptor activity and expression of NKX3.1 and PTEN
Authors: Pankaj Sharma, Ashley Evans Knowell, Swathi Chinaranagari, Shravan Komaragiri, Peri Nagappan, Divya Patel, Mathew C Havrda, Jaideep Chaudhary
Journal: Molecular Cancer (2013)

Inhibitor of differentiation 4 (Id4), a member of the helix-loop-helix family of transcriptional regulators has emerged as a tumor suppressor in prostate cancer. Id4 is expressed in the normal prostate where its expression is also regulated by androgens. In this study we investigated the effect of loss of Id4 (Id4-/-) on adult prostate morphology.Histological analysis was performed on prostates from 6-8 weeks old Id4-/-, Id4+/- and Id4+/+ mice. Expression of Id1, Sox9, Myc, androgen receptor, Akt, p-Akt, Pten and Nkx3.1 was investigated by immunohistochemistry. Androgen receptor binding on NKX3.1 promoter was studied by chromatin immuno-precipitation. Id4 was either over-expressed or silenced in prostate cancer cell lines DU145 and LNCaP respectively followed by analysis of PTEN, NKX3.1 and Sox9 expression.Id4-/- mice had smaller prostates with fewer tubules, smaller tubule diameters and subtle mPIN like lesions. Levels of androgen receptor were similar between wild type and Id4-/- prostate. Decreased NKX3.1 expression was in part due to decreased androgen receptor binding on NKX3.1 promoter in Id4-/- mice. The increase in the expression of Myc, Sox9, Id1, Ki67 and decrease in the expression of PTEN, Akt and phospho-AKT was associated with subtle mPIN like lesions in Id4-/- prostates. Finally, prostate cancer cell line models in which Id4 was either silenced or over-expressed confirmed that Id4 regulates NKX3.1, Sox9 and PTEN.Our results suggest that loss of Id4 attenuates normal prostate development and promotes hyperplasia/dysplasia with subtle mPIN like lesions characterized by gain of Myc and Id1 and loss of Nkx3.1 and Pten expression. One of the mechanisms by which Id4 may regulate normal prostate development is through regulating androgen receptor binding to respective response elements such as those on NKX3.1 promoter. In spite of these complex alterations, large neoplastic lesions in Id4-/- prostates were not observed suggesting the possibility of mechanisms/pathways such as loss of Akt that could restrain the formation of significant pre-cancerous lesions.
Assessment of Left Atrial Appendage Function by 2-Dimensional Speckle-Tracking Imaging in Transesophageal Echocardiography
Authors: Erhan Saraçoğlu, Dilek Ural, Tayfun Şahin, Neslihan Özlem Al, Hakan Çakmak, Tayyar Akbulut, Kadriye Akay, Ertan Ural
Journal: Journal of the American College of Cardiology (2013)
Comparative outcome of nonmyeloablative and myeloablative allogeneic hematopoietic cell transplantation for patients older than 50 years of age
Authors: Edwin P. Alyea, Haesook T. Kim, Vincent Ho, Corey Cutler, John Gribben, Daniel J. DeAngelo, Stephanie J. Lee, Sarah Windawi, Jerome Ritz, Richard M. Stone, Joseph H. Antin, Robert J. Soiffer
Journal: Blood (2005)
Immune targeting of fibroblast activation protein triggers recognition of multipotent bone marrow stromal cells and cachexia
Authors: Eric Tran, Dhanalakshmi Chinnasamy, Zhiya Yu, Richard A. Morgan, Chyi-Chia Richard Lee, Nicholas P. Restifo, Steven A. Rosenberg
Journal: The Journal of Experimental Medicine (2013)

Fibroblast activation protein (FAP) is a candidate universal target antigen because it has been reported to be selectively expressed in nearly all solid tumors by a subset of immunosuppressive tumor stromal fibroblasts. We verified that 18/18 human tumors of various histologies contained pronounced stromal elements staining strongly for FAP, and hypothesized that targeting tumor stroma with FAP-reactive T cells would inhibit tumor growth in cancer-bearing hosts. T cells genetically engineered with FAP-reactive chimeric antigen receptors (CARs) specifically degranulated and produced effector cytokines upon stimulation with FAP or FAP-expressing cell lines. However, adoptive transfer of FAP-reactive T cells into mice bearing a variety of subcutaneous tumors mediated limited antitumor effects and induced significant cachexia and lethal bone toxicities in two mouse strains. We found that FAP was robustly expressed on PDGFR-α+, Sca-1+ multipotent bone marrow stromal cells (BMSCs) in mice, as well as on well-characterized, clinical-grade multipotent human BMSCs. Accordingly, both mouse and human multipotent BMSCs were recognized by FAP-reactive T cells. The lethal bone toxicity and cachexia observed after cell-based immunotherapy targeting FAP cautions against its use as a universal target. Moreover, the expression of FAP by multipotent BMSCs may point toward the cellular origins of tumor stromal fibroblasts.
The Treatment of Acidosis in Acute Lung Injury with Tris-Hydroxymethyl Aminomethane (THAM)
Authors: RICHARD H. KALLET, ROBERT M. JASMER, JOHN M. LUCE, LUDWIG H. LIN, JAMES D. MARKS
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Mechanical hyperventilation of acidemic patients with acute lung injury (ALI) requires the use of high volumes and pressures that may worsen lung injury. However, permissive hypercapnia in the presence of shock, metabolic acidosis, and multi-organ system dysfunction may compromise normal cellular function. Tris-hydroxymethyl aminomethane (THAM) may be an effective method to control acidosis in this circumstance. Protonated THAM is excreted by the kidneys, so that carbon dioxide production is not raised. In an uncontrolled study, we administered THAM to 10 patients with acidosis (mean pH = 7.14) and ALI (mean lung injury score = 3.28) in whom adequate control of arterial pH could not be maintained during either eucapnic ventilation or permissive hypercapnia ventilation. THAM was given at a mean dose of 0.55 mmol/kg/h. Administration of THAM was associated with significant improvements in arterial pH and base deficit, and a decrease in arterial carbon dioxide tension that could not be fully accounted for by ventilation. Although further studies are needed to confirm these observations, THAM appears to be an effective alternative to sodium bicarbonate for treating acidosis during ALI.
Sympathetic stimulation produces a greater increase in both transmural and spatial dispersion of repolarization in LQT1 than LQT2 forms of congenital long QT syndrome
Authors: Yasuko Tanabe, Masashi Inagaki, Takashi Kurita, Noritoshi Nagaya, Atsushi Taguchi, Kazuhiro Suyama, Naohiko Aihara, Shiro Kamakura, Kenji Sunagawa, Kazufumi Nakamura, Tohru Ohe, Jeffrey A Towbin, Silvia G Priori, Wataru Shimizu
Journal: Journal of the American College of Cardiology (2001)
Evolution of cellular immune responses to hepatitis C virus during antiretroviral therapy and its clinical implications
Authors: H. Diepolder, N. Gruener
Journal: Gut (2010)

Combination antiretroviral therapy (cART) has dramatically decreased the progression to acquired immune deficiency syndrome (AIDS) and thus the human immunodeficiency virus (HIV)-related mortality in HIV-infected patients. Consequently, hepatitis C virus (HCV) has emerged as a leading cause of death in HIV/HCV co-infected patients. Pre-existing HIV infection increases the rate of chronicity in acute HCV infection1 and is associated with higher HCV viraemia.2 Most importantly, HIV/HCV co-infected patients show more rapid progression to cirrhosis and its complications.3 This particular observation is still incompletely understood and seems to contradict the assumptions that HCV by itself is not cytopathic, that the level of viraemia does not correlate with the risk of fibrosis and cirrhosis in HIV-negative patients and that liver inflammation is immune mediated.

The clinical outcome of acute hepatitis C in HIV-negative patients is associated with a strong and maintained HCV-specific CD4+ T-cell response against both structural and non-structural proteins,4 which is typically weak in patients with chronic hepatitis C. The role of HCV-specific CD4+ T-cell responses in treatment-induced viral clearance has been examined in several studies, yielding divergent results: while some studies found a moderate but significant increase in the HCV-specific CD4+ T-cell response during antiviral treatment with a peak late in the course of …
A quagmire for clinicians: when technological advances exceed clinical knowledge
Authors: S. REDLINE, M. SANDERS
Journal: Thorax (1999)

During the past few years findings from two studies-the International Study of Asthma and Allergies in Childhood (ISAAC) 1 and the European Community Respiratory Health Survey (ECRHS) 2 -seem to have dominated much of the thinking about the geographical variations in the prevalence of asthma.These studies suggest important variations by geographical site in diVerent countries and, to a lesser extent, in study centres within countries.However, these studies only raise new questions as to how geographical factors contribute to the aetiology of asthma.For example, are the geographical variations in the prevalence of asthma caused by unique exposures to disease causing agents found only in local environments?Do diVerences in geographical location in some way alter host susceptibility?Do local environmental conditions, either physical or sociocultural, alter the host/agent interactions in ways that are critical to the expression of this condition?In this issue of Thorax Duran-Tauleria and Rona 3 further elucidate how social and physical environmental factors may explain some of the geographical expression of asthma prevalence.Their study focuses on the diVerences in asthma and respiratory symptoms among three populations-two nationally representative samples of English and Scottish children and a third sample of children living within the inner cities of England.The authors found a higher prevalence of children with persistent (as opposed to occasional) wheeze within the inner city population than in the other two sampled populations.They also found that the prevalence of asthma attacks was higher in the non-inner city sample of English children than in the other two groups.Social and physical environmental factors-mainly social deprivation (as measured by the Townsend score)-seemed to explain much of the geographical variation in children with persistent wheezing.This finding held even after adjusting the analysis for many of the well known risk factors that might otherwise have explained these diVerences such as age, sex, parental atopy, and maternal smoking.The importance of social and physical environmental factors in disease expression is well known and has been studied extensively for many health conditions, including asthma.A number of studies suggest an association between higher asthma morbidity/mortality rates and geographical areas of lower socioeconomic standing.The literature on the eVects of social environmental factors on the prevalence of asthma is less definitive, but there have been several studies that suggest findings similar to those of Duran-Tauleria and Rona.Yet this current study also provides new insights into the possible mechanisms by which poverty may influence the development of asthma based on its impact on communities independent of its eVect on individuals.
Adrenomedullin Blockade Suppresses Growth of Human Hormone–Independent Prostate Tumor Xenograft in Mice
Authors: Caroline Berenguer-Daizé, Françoise Boudouresque, Cyrille Bastide, Asma Tounsi, Zohra Benyahia, Julie Acunzo, Nadège Dussault, Christine Delfino, Nathalie Baeza, Laurent Daniel, Mylène Cayol, Dominique Rossi, Assou El Battari, Denis Bertin, Kamel Mabrouk, Pierre-Marie Martin, L'Houcine Ouafik
Journal: Clinical Cancer Research (2013)

To study the role of the adrenomedullin system [adrenomedullin and its receptors (AMR), CLR, RAMP2, and RAMP3] in prostate cancer androgen-independent growth.Androgen-dependent and -independent prostate cancer models were used to investigate the role and mechanisms of adrenomedullin in prostate cancer hormone-independent growth and tumor-associated angiogenesis and lymphangiogenesis.Adrenomedullin and AMR were immunohistochemically localized in the carcinomatous epithelial compartment of prostate cancer specimens of high grade (Gleason score >7), suggesting a role of the adrenomedullin system in prostate cancer growth. We used the androgen-independent Du145 cells, for which we demonstrate that adrenomedullin stimulated cell proliferation in vitro through the cAMP/CRAF/MEK/ERK pathway. The proliferation of Du145 and PC3 cells is decreased by anti-adrenomedullin antibody (αAM), supporting the fact that adrenomedullin may function as a potent autocrine/paracrine growth factor for prostate cancer androgen-independent cells. In vivo, αAM therapy inhibits the growth of Du145 androgen-independent xenografts and interestingly of LNCaP androgen-dependent xenografts only in castrated animals, suggesting strongly that adrenomedullin might play an important role in tumor regrowth following androgen ablation. Histologic examination of αAM-treated tumors showed evidence of disruption of tumor vascularity, with depletion of vascular as well as lymphatic endothelial cells and pericytes, and increased lymphatic endothelial cell apoptosis. Importantly, αAM potently blocks tumor-associated lymphangiogenesis, but does not affect established vasculature and lymphatic vessels in normal adult mice.We conclude that expression of adrenomedullin upon androgen ablation in prostate cancer plays an important role in hormone-independent tumor growth and in neovascularization by supplying/amplifying signals essential for pathologic neoangiogenesis and lymphangiogenesis. Clin Cancer Res; 19(22); 6138-50. ©2013 AACR.
Indian cardiologists plan campaign to reduce unnecessary investigations
Authors: C. Travasso
Journal: BMJ (2014)

Some of India’s best known cardiologists are planning an initiative called the Society for Less Investigative Medicine to help reduce the number of unnecessary investigations that patients undergo, beginning with cardiology.

Balram Bhargava, professor of cardiology at the All India Institute of Medical Sciences in New Delhi and executive director at the Stanford-India Biodesign Centre, is helping to spearhead the effort. He told The BMJ that modern medicine was practised with an increasing emphasis on investigative …
Gene Expression Profiling of Lymphoid Malignancies
Authors: Louis M. Staudt
Journal: Annual Review of Medicine (2002)

▪ Abstract Comprehensive gene expression profiling using DNA microarrays is providing a molecular classification of cancer into disease categories that are homogeneous with respect to pathogenesis and clinical behavior. Gene expression profiling revealed that diffuse large B cell lymphoma (DLBCL) consists of at least two molecularly distinct diseases that are derived from distinct stages of B cell differentiation and have strikingly different clinical outcomes. By contrast, chronic lymphocytic leukemia (CLL) was found to be a single disease defined by a characteristic gene expression signature. Nonetheless, gene expression profiling distinguished two clinically divergent CLL subtypes and provided evidence that signaling through the B cell antigen receptor may play a role in the clinically aggressive subtype. Gene expression analysis also illuminated the mechanism of lymphomagenesis caused by BCL-6 translocations and provided evidence that the NF-κB signaling pathway is a new molecular therapeutic target in DLBCL.
Cell-free fetal nucleic acids in amniotic fluid
Authors: L. Hui, D.W. Bianchi
Journal: Human Reproduction Update (2010)

BACKGROUNDResearch into cell-free fetal (cff) nucleic acids has primarily focused on maternal plasma; however, cff DNA and RNA are also detectable in other body fluids such as amniotic fluid (AF). In AF, cff DNA is present in much greater concentrations than in maternal plasma and represents a pure fetal sample uncontaminated by maternal- and trophoblast-derived nucleic acids. The aim of this review was to summarize the current knowledge on cff nucleic acids in AF and to outline future research directions.
T cell-mediated eradication of murine metastatic melanoma induced by targeted interleukin 2 therapy.
Authors: J C Becker, J D Pancook, S D Gillies, K Furukawa, R A Reisfeld
Journal: The Journal of Experimental Medicine (1996)

Induction of a T-cell mediated antitumor response is the ultimate goal for tumor immunotherapy. We demonstrate here that antibody-targeted IL2 therapy is effective against established pulmonary and hepatic melanoma metastases in a syngeneic murine tumor model. The effector mechanisms involved in this tumor eradication are not dependent on NK cells, since the therapeutic effect of antibody-IL2 fusion protein was not altered in NK cell-deficient mice. In contrast, T cells are essential for the observed antitumor effect, since therapy with antibody IL2 fusion proteins is unable to induce tumor eradication in T cell-deficient SCID mice. In vivo depletion studies characterized the essential effector cell population further as CD8 + T cells. Such CD8 + T cells, isolated from tumor bearing mice after antibody-directed IL2 therapy, exerted a MHC class I-restricted cytotoxicity against the same tumor in vitro. These data demonstrate the ability of antibody-targeted IL2 delivery to induce a T cell-dependent host immune response that is capable of eradicating established melanoma metastases in clinically relevant organs.
Effect of roflumilast N-oxide on non-typable haemophilus influenzae (NTHi) interaction with human airway epithelial A549 cells
Authors: Victoria Cano, Pau Morey, Junkal Garmendia, José Bengoechea
Journal: European Respiratory Journal (2011)

Background/Aim:  NTHi is associated with lung colonisation and exacerbations in COPD. Previously we found that NTHi invasion of airway epithelial cells is PI3-kinase (PI3K)-dependent. Furthermore NTHi survives intracellularly in vacuoles with late endosome features, explaining airway colonisation despite NTHi-negative sputum. Here we explored whether the PDE4 inhibitor roflumilast N-oxide (RNO), the active metabolite of roflumilast (approved in EU for severe COPD), dexamethasone (DEX) and salmeterol (SAL) affect NTHi invasion of A549 cells and NTHi-induced IL-8 release.   Methods:  For invasion, cells were infected with NTHi (100 bacteria/cell, 2h), incubated with gentamycin (1h) to kill extracellular bacteria, and lysed to determine intracellular bacteria by plating. Intracellular lifestyle was monitored by immunofluorescence with antibodies to late endosome markers (lamp1, CD63). PI3K-dependent Akt phosphorylation was assessed by Western. IL-8 was measured by ELISA.   Results:  RNO (1μM) reduced NTHi invasion by 50% (c.f.u./well; Control: 5000±100, RNO: 2439±122; n=3, p   Conclusions:  PDE4 inhibition (1μM RNO) reduced NTHi internalisation in A549 cells by interfering with PI3K signalling. RNO inhibited IL-8 release. DEX, while reducing NTHI-induced IL-8, did not affect internalisation.
Human Interferon-γ–inducible Protein 10 (IP-10) Inhibits Constitutive Signaling of Kaposi's Sarcoma–associated Herpesvirus G Protein–coupled Receptor
Authors: Elizabeth Geras-Raaka, Anjali Varma, Hao Ho, Ian Clark-Lewis, Marvin C. Gershengorn
Journal: The Journal of Experimental Medicine (1998)

A G protein–coupled receptor (GPCR) is encoded within the genome of Kaposi's sarcoma– associated herpesvirus (KSHV)/human herpesvirus 8, a virus that may be involved in the pathogenesis of Kaposi's sarcoma and primary effusion lymphomas. KSHV-GPCR exhibits constitutive signaling activity that causes oncogenic transformation. We report that human interferon (IFN)-γ–inducible protein 10 (HuIP-10), a C-X-C chemokine, specifically inhibits signaling of KSHV-GPCR. In contrast, monokine induced by IFN-γ (HuMig), which like HuIP-10 is an agonist of C-X-C chemokine receptor 3, does not inhibit KSHV-GPCR signaling. Moreover, HuIP-10, but not HuMig, inhibits KSHV-GPCR–induced proliferation of NIH 3T3 cells. These results show that HuIP-10 is an inverse agonist that converts KSHV-GPCR from an active to an inactive state. Thus, a human chemokine inhibits constitutive signaling and cellular proliferation that is mediated by a receptor encoded by a human disease-associated herpesvirus.
Comparison of one-tube multiplex PCR, automated ribotyping and intergenic spacer (ITS) sequencing for rapid identification of Acinetobacter baumannii
Authors: T.-L. Chen, L.-K. Sin, R.C.-C. Wu, M.-F. Shaio, L.-Y. Huang, C.-P. Fung, C.-M. Lee, W.-L. Cho
Journal: Clinical Microbiology and Infection (2007)