tbuckley/cabot-search huggingface dataset:
Altered TGF-β Signaling in a Subpopulation of Human Stromal Cells Promotes Prostatic Carcinogenesis
Authors: Omar E. Franco, Ming Jiang, Douglas W. Strand, James Peacock, Suzanne Fernandez, Roger S. Jackson, Monica P. Revelo, Neil A. Bhowmick, Simon W. Hayward
Journal: Cancer Research (2011)

Carcinoma-associated fibroblasts (CAF) play a critical role in malignant progression. Loss of TGF-β receptor II (TGFβR2) in the prostate stroma is correlated with prostatic tumorigenesis. To determine the mechanisms by which stromal heterogeneity because of loss of TGFβR2 might contribute to cancer progression, we attenuated transforming growth factor beta (TGF-β) signaling in a subpopulation of immortalized human prostate fibroblasts in a model of tumor progression. In a tissue recombination model, loss of TGFβR2 function in 50% of the stromal cell population resulted in malignant transformation of the nontumorigenic human prostate epithelial cell line BPH1. Mixing fibroblasts expressing the empty vector and dominant negative TGFβR2 increased the expression of markers of myofibroblast differentiation [coexpression of vimentin and alpha smooth muscle actin (αSMA)] through elevation of TGF-β1 and activation of the Akt pathway. In combination, these two populations of stromal cells recapitulated the tumor inductive activity of CAFs. TGFβR2 activity in mixed stromal cell populations cultured in vitro caused secretion of factors that are known to promote tumor progression, including TGF-β1, SDF1/CXCL12, and members of the fibroblast growth factor (FGF) and bone morphogenetic protein (BMP) families. In vivo, tissue recombination of fibroblasts overexpressing TGF-β1 and SDF1/CXCL12 not only induced transformation of BPH1 cells, but also promoted a robust growth of highly invasive cells, similar to effects produced by CAFs. While the precise nature and/or origin of the particular stromal cell populations in vivo remain unknown, these findings strongly link heterogeneity in TGF-β signaling to tumor promotion by tumor stromal cells.
As others see us: views from abroad: A rational bureaucracy in a civilised society
Authors: C. M Koeck
Journal: BMJ (1998)

Psychoanalysis is among the most important contributions to civilisation made by Austria. Sigmund Freud's theories about the structure of the human psyche and the unconscious have changed the way we look at ourselves and society. Among the most central concepts of his theory is the notion of ambivalence. This is probably the best word to use to describe how the NHS is viewed in Austria; the spectrum of opinion on the NHS ranges from praise to harsh rejection depending on whom you ask.

On one end of the spectrum are the average doctor, health policy maker, and professor in a medical faculty. Ask them about the NHS and you will most likely hear critical remarks—ranging from stories about poor care, long waiting lists, a lack of access to care, and a shortage of advanced technology to outright rejection of the NHS model, based on claims of inhumane rationing and the exclusion of the elderly and the very sick from the benefits of modern health care. The factual basis of these judgments is not entirely clear. It is most likely that stories such as those about child B (an 11 year old girl with myeloid leukaemia who was denied a second transplant operation by the local health authority) and about age limits for treatment options such as transplant operations and dialysis have left (independent of the actual facts and circumstances) a lasting impression among doctors and health policy makers. They have come to view the NHS as a system which is in desperate need …
Difficult asthma in children
Authors: S A McKenzie
Journal: Thorax (2002)

Asthmatic children on high dose corticosteroids need to be fully assessed to ensure that such dosages are really necessary. Further work needs to be undertaken to find the best approach to poor treatment adherence and false claims for financial support. The benefits of particular components of specialist assessment need to be evaluated prospectively and multicentre collaboration is needed to evaluate phenotype specific treatment and new treatments for truly difficult asthma.
cDNA Cloning, Functional Characterization, and Tissue Distribution of an Alternatively Spliced Variant of Organic Cation Transporter hOCT2 Predominantly Expressed in the Human Kidney
Authors: Yumiko Urakami, Maiko Akazawa, Hideyuki Saito, Masahiro Okuda, Ken-ichi Inui
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. A cDNA coding a novel organic cation transporter, hOCT2-A, was isolated from human kidney. The hOCT2-A cDNA is an alternatively spliced variant of hOCT2 with an insertion of 1169 bp. The open reading frame encodes a 483-amino acid protein that has 81% amino acid identity with hOCT2. From hydropathy analysis, hOCT2-A is predicted to have nine transmembrane domains. hOCT2-A mRNA is expressed mainly in kidney and weakly in brain, liver, colon, skeletal muscle, bone marrow, spinal cord, testis, and placenta. When expressed in HEK293 cells, hOCT2-A stimulated the uptake of tetraethylammonium (TEA) in an electrogenic manner. The transport of TEA by hOCT2-A–transfected cells was saturable with the apparent Km value of 63 μM. hOCT2-A stimulated the uptake of TEA, 1-methyl-4-phenylpyridinium, and cimetidine as well as did hOCT2. The uptake of guanidine and choline by hOCT2-transfected cells also increased markedly but not that by hOCT2-A–transfected cells. The uptake of TEA mediated by hOCT2-A but not by hOCT2 was inhibited significantly by organic cations such as procainamide, N-acetylprocainamide, and levofloxacin, indicating that hOCT2-A differs from hOCT2 in its affinity for several compounds. These findings suggested that hOCT2-A contributes to the renal clearance of endogenous and exogenous organic cations.
Changes in Bronchoalveolar Lavage Indices Associated with Radiographic Classification in Coal Miners
Authors: VAL VALLYATHAN, MICHEAL GOINS, LEROY N. LAPP, DONNA PACK, STEPHEN LEONARD, XIANGLIN SHI, VINCENT CASTRANOVA
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Previous studies on symptomatic coal miners have shown that alveolar macrophages, recovered by bronchoalveolar lavage (BAL), release excessive amounts of reactive oxygen species (ROS) and inflammatory cytokines. It has been proposed that these secretions may mediate cell injury and initiate the disease process. We hypothesized that acellular bronchoalveolar lavage fluid (BALF) indices in coal miners chronically exposed to coal dust may reflect the status of important homeostatic modulations in the lung that lead to the development of coal workers' pneumoconiosis (CWP). To test this hypothesis, we measured inflammatory status, oxidant burden, antioxidant defenses, cytokines, growth factors, fibronectin, and alpha(1)-antitrypsin (alpha(1)-AT) in the BALF of healthy never-smoker control subjects, never-smoker underground coal miners with negative radiographs (ILO 0/0-1/0), and two miners with moderate changes in the chest radiographs (ILO 2/2). Interestingly, indices of injury and inflammation increased with the progression of disease in coal miners. Antioxidant enzymes, such as catalase, glutathione peroxidase, and superoxide dismutase, showed a 19-fold, 22-fold, and 6-fold increase above control, respectively, in coal miners with category 2/2 CWP. Significant increases in the secretion of IL-1, IL-6, TNF-alpha, TGF-beta, fibronectin, and alpha(1)-AT also were evident in coal miners with disease. This up-regulation of antioxidant defenses and cytokines was not evident in coal miners in the absence of clinically evident radiographic disease. In addition, the concentration of lipid peroxidation by products in the BALF of coal miners without evidence of radiographic disease showed a moderate 3-fold increase, whereas, in coal miners with category 2/2 CWP it showed a 59-fold increase compared to control subjects. These results are in good agreement with our hypothesis that development of CWP and its progression may be correlated with an oxidative stress and up-regulation of cytokines and mediators of growth.
Chloroquine resistance in the malarial parasite, <i>Plasmodium falciparum</i>
Authors: Lyann M.B. Ursos, Paul D. Roepe
Journal: Medicinal Research Reviews (2002)

Abstract Malarial parasites remain a health problem of staggering proportions. Worldwide, they infect about 500 million, incapacitate tens of millions, and kill approximately 2.5 million (mostly children) annually. Four species infect humans, but most deaths are caused by one particular species, Plasmodium falciparum . The rising number of malarial deaths is due in part to increased drug resistance in P. falciparum . There are many varieties of antimalarial drug resistance, and there may very well be several molecular level contributions to each variety. This is because there are a number of different drugs with different mechanisms of action in use, and more than one molecular event may sometimes be relevant for resistance to any one class of drugs. Thus, “multidrug” resistance in a clinical setting likely entails complex combinations of overlapping resistance pathways, each specific for one class of drug, that then add together to confer the particular multidrug resistance phenotype. Nonetheless, rapid progress has been made in recent years in elucidating mechanisms of resistance to specific classes of antimalarial drugs. As one example, resistance to the antimalarial drug chloroquine, which has been the mainstay therapy for decades, is becoming well understood. This article focuses on recent advances in determining the molecular mechanism of chloroquine resistance, with particular attention to the biochemistry and biophysics of the P. falciparum digestive vacuole, wherein changes in pH have recently been found to be associated with chloroquine resistance. © 2002 Wiley Periodicals, Inc. Med Res Rev, 22, No. 5, 465–491, 2002; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/med.10016
Relationship of sitting time and physical activity with non-alcoholic fatty liver disease
Authors: Seungho Ryu, Yoosoo Chang, Hyun-Suk Jung, Kyung Eun Yun, Min-Jung Kwon, Yuni Choi, Chan-Won Kim, Juhee Cho, Byung-Seong Suh, Yong Kyun Cho, Eun Chul Chung, Hocheol Shin, Yeon Soo Kim
Journal: Journal of Hepatology (2015)
Prospective, Randomized, Multicenter Trial on the Antiproliferative Effect of Lanreotide, Interferon Alfa, and Their Combination for Therapy of Metastatic Neuroendocrine Gastroenteropancreatic Tumors—The International Lanreotide and Interferon Alfa Study Group
Authors: Siegbert Faiss, Ulrich-Frank Pape, Michael Böhmig, Yvonne Dörffel, Ulrich Mansmann, Werner Golder, Ernst Otto Riecken, Bertram Wiedenmann
Journal: Journal of Clinical Oncology (2003)

Somatostatin analogs and interferon alfa control hormone-active/functional neuroendocrine gastroenteropancreatic tumors. In addition to hormonal control, variable degrees of antiproliferative effects for both agents have been reported. Until now, however, no prospective, randomized studies in therapy-naive patients have compared somatostatin analogs or interferon alfa alone with a combination of the two.Eighty therapy-naive patients with histologically verified neuroendocrine tumor disease (primary localization: foregut, n = 36; midgut, n = 30; hindgut, n = 3; unknown, n = 11; functional, n = 29; nonfunctional, n = 51) were randomly treated either with lanreotide (1 mg three times a day administered subcutaneously [SC]) or interferon alfa (5 x 106 U three times a week SC) or both. All patients had disease progression in the 3 months before study entry, verified with imaging procedures.Twenty-five patients were treated with lanreotide, 27 patients were treated with interferon alfa, and 28 patients were treated with the combination. Partial tumor remission was seen in four patients (one patient who received lanreotide, one patient who received interferon alfa, and two patients who received the combination). During the 12 months of therapy, stable disease was observed in 19 patients (seven patients who received lanreotide, seven patients who received interferon alfa, and five patients who received the combination), whereas tumor progression occurred in 14 of 25 patients (lanreotide), 15 of 27 patients (interferon alfa), and 14 of 28 patients (combination). Side effects leading to an interruption of therapy were more frequent in the combination group than in the monotherapy arms.This prospective, randomized, multicenter study shows for the first time that somatostatin analogs, interferon alfa, or the combination of the two had comparable antiproliferative effects in the treatment of metastatic neuroendocrine gastroenteropancreatic tumors. Response rates were lower compared with those published in previous, nonrandomized studies. The antiproliferative effect of the tested substances was similar for functional and nonfunctional neuroendocrine tumors.
Ambrisentan Therapy for Pulmonary Arterial Hypertension
Authors: Nazzareno Galié, David Badesch, Ronald Oudiz, Gérald Simonneau, Michael D. McGoon, Anne M. Keogh, Adaani E. Frost, Diane Zwicke, Robert Naeije, Shelley Shapiro, Horst Olschewski, Lewis J. Rubin
Journal: Journal of the American College of Cardiology (2005)
Both structural damage and inflammation of the spine contribute to impairment of spinal mobility in patients with ankylosing spondylitis
Authors: P. Machado, R. Landewe, J. Braun, K.-G. A. Hermann, D. Baker, D. van der Heijde
Journal: Annals of the Rheumatic Diseases (2010)

<h3>Objective</h3> To study the relationship between spinal mobility, radiographic damage of the spine and spinal inflammation as assessed by MRI in patients with ankylosing spondylitis (AS). <h3>Methods</h3> In this subanalysis of the Ankylosing Spondylitis Study for the Evaluation of Recombinant Infliximab Therapy cohort, 214 patients, representing an 80% random sample, were investigated. Only baseline data were used. MRI inflammation was assessed by the AS spinal MRI activity (ASspiMRI-a) score, structural damage by the modified Stoke AS Spine Score (mSASSS) and spinal mobility by the linear definition of the Bath Ankylosing Spondylitis Metrology Index (BASMI). Univariate correlations were calculated on baseline values using Spearman rank correlation. Independent associations between the variables of interest were investigated by multivariate linear regression analysis. Associations with clinical disease activity, C-reactive protein, disease duration, age, gender, body mass index and HLA-B27 status were also investigated. Subanalyses were performed according to disease duration. <h3>Results</h3> BASMI correlated moderately well with mSASSS (Spearman9s ρ=0.6) and weakly with ASspiMRI-a (ρ=0.3). A best-fit model for BASMI included both mSASSS (regression coefficient (B)=0.865, p&lt;0.001) and ASspiMRI-a (B=0.236, p=0.018). In patients with a disease duration ≤3 years, B was greater for ASspiMRI-a than for mSASSS (0.595 vs 0.380), while in patients with a disease duration &gt;3 years B was greater for mSASSS than for ASspiMRI-a (0.924 vs 0.156). <h3>Conclusion</h3> Spinal mobility impairment in AS is independently determined both by irreversible spinal damage and by reversible spinal inflammation. Spinal mobility impairment is more influenced by spinal inflammation in early disease, and by structural damage in later disease.
IMMUNIZATION WITH MIXTURES OF POLIOMYELITIS VIRUS AND ALUMINUM HYDROXIDE
Authors: C. P. Rhoads
Journal: The Journal of Experimental Medicine (1931)

Preliminary experiments are presented which indicate that poliomyelitis virus can be inactivated by a certain preparation of aluminum hydroxide. This effect is seen at neutrality and at a pH of 5.5, but not at a pH of 8.8. Monkeys treated by repeated subcutaneous injections of poliomyelitis virus so inactivated evince immunity as shown by resistance to intranasal instillation and intracerebral inoculation as well as by the neutralizing power of their sera. The treatments which give rise to the immunity produce no symptoms of disease.
Achievements and Assignments of Regional Medical Corporation and Palliative Care Corporation in Our Hospital
Authors: K. Kamei, M. Isogai, T. Harada, Y. Kaneoka, A. Maeda, Y. Takayama, S. Otsuka, S. Kawakatsu, H. Mori, Y. Yonekawa
Journal: Annals of Oncology (2013)
Rational Use of New and Existing Disease-Modifying Agents in Rheumatoid Arthritis
Authors: Joel M. Kremer
Journal: Annals of Internal Medicine (2001)

Because of radiographic evidence of progressive bone loss and the inability to eliminate synovial proliferation with methotrexate, it became apparent that therapy for rheumatoid arthritis needed further advancement. Methotrexate is not a remission-inducing drug and may have dose-limiting toxicity. In the past 2 years, three new disease-modifying antirheumatic drugs (DMARDs) have been approved: leflunomide, etanercept, and infliximab. Each of these agents has demonstrated efficacy compared with placebo in randomized, controlled studies. Because methotrexate had a dominant therapeutic role, the new drugs were also studied in combination with it. Other established DMARDs, such as sulfasalazine and hydroxychloroquine, have also demonstrated efficacy when used together with methotrexate. The results of these combination studies clearly demonstrate that clinical responses can be meaningfully improved when new and existing DMARDs are added to methotrexate. Although toxicity remains a serious concern when powerful immune modulators and antimetabolites are used in combination, relatively few serious adverse events have been reported during 2-year treatment periods. It has also become apparent that combinations of new DMARDs and methotrexate virtually halt radiographic progression over 2 years. The new agents are expensive, but annual costs must be weighed against the personal and societal expense of joint arthroplasty, hospitalizations, disability, and diminished quality of life that accompanies poorly controlled rheumatoid arthritis. The ultimate value of combination DMARD therapy with methotrexate will be determined by long-term data on safety, efficacy, and effects on radiographic deterioration of bone. Additional long-term observational data on the incidence of joint arthroplasty and disability will help to place the issue of societal costs in a better perspective. This will allow the value of aggressive treatment to be established with certainty.
Dynamics of double strand breaks and chromosomal translocations
Authors: Olga V Iarovaia, Mikhail Rubtsov, Elena Ioudinkova, Tatiana Tsfasman, Sergey V Razin, Yegor S Vassetzky
Journal: Molecular Cancer (2014)

Chromosomal translocations are a major cause of cancer. At the same time, the mechanisms that lead to specific chromosomal translocations that associate different gene regions remain largely unknown. Translocations are induced by double strand breaks (DSBs) in DNA. Here we review recent data on the mechanisms of generation, mobility and repair of DSBs and stress the importance of the nuclear organization in this process.
Suspected Acute Coronary Syndrome Patients With Diabetes and Normal Troponin-I Levels Are at Risk for Early and Late Death
Authors: Steven P. Marso, David M. Safley, John A. House, Todd Tessendorf, Kimberly J. Reid, John A. Spertus
Journal: Diabetes Care (2006)

Clinicians use a variety of methods (1,2) to risk stratify patients with acute coronary syndromes (ACSs). Based on elevated risk, patients are often triaged to an aggressive strategy, including early angiography (3,4) and upstream use of intravenous glycoprotein IIb/IIIa inhibitors (5–7). The current American College of Cardiology (ACC)/American Heart Association (AHA) Guidelines for the Management of Patients with Unstable Angina and Non-ST-segment Elevation Myocardial Infarction do not recognize diabetes as a high-risk ACS indicator. Therefore, we sought to clarify the relative risk of diabetes in early and late death in suspected ACS patients.

In this study, a prospective registry of consecutive ACS patients with and without diabetes ( n = 864) was used. ACS was diagnosed as either myocardial infarction (8) or unstable angina (9) using standard definitions. Patients with ST-segment elevation myocardial infarction were excluded. All potential unstable angina patients who had a diagnostic angiographic, nuclear, or echocardiographic stress test that excluded obstructive coronary disease or who had an additional diagnostic study confirming an alternative explanation for presentation were excluded. Diabetes was defined by reported history or new antidiabetic therapy initiated during …
A role for CCR4 in development of mature circulating cutaneous T helper memory cell populations
Authors: Espen S. Baekkevold, Marc-André Wurbel, Pia Kivisäkk, Clare M. Wain, Christine A. Power, Guttorm Haraldsen, James J. Campbell
Journal: The Journal of Experimental Medicine (2005)

Expression of the chemokine receptor CCR4 is strongly associated with trafficking of specialized cutaneous memory T helper (Th) lymphocytes to the skin. However, it is unknown whether CCR4 itself participates in the development of cutaneous Th populations. We have addressed this issue via competitive bone marrow (BM) reconstitution assays; equal numbers of BM cells from CCR4+/+ and CCR4−/− donors were allowed to develop side-by-side within RAG-1−/− hosts. Cells from both donor types developed equally well into B cells, naive CD8 T cells, naive CD4 T cells, interferon-γ+ Th1 cells, and interleukin-4+ Th2 cells. In marked contrast, circulating cutaneous memory Th cells (i.e., E-selectin ligand+ [E-lig+]) were more than fourfold more likely to be derived from CCR4+/+ donors than from CCR4−/− donors. Most of this effect resides within the CD103+ subset of the E-lig+ Th population, in which donor CCR4+/+ cells can outnumber CCR4−/− cells by &amp;gt;12-fold. No similar effect was observed for α4β7+ intestinal memory Th cells or CD103+/E-lig− Th cells. We conclude that CCR4 expression provides a competitive advantage to cutaneous Th cells, either by participating in their development from naive Th cells, or by preferentially maintaining them within the memory population over time.
Epidemiology of sarcoidosis in Japan
Authors: T. Morimoto, A. Azuma, S. Abe, J. Usuki, S. Kudoh, K. Sugisaki, M. Oritsu, T. Nukiwa
Journal: European Respiratory Journal (2007)

The present study was designed to identify recent clinical phenotypes using the National Epidemiological Survey and to compare findings with those of previous surveys in Japan. Pathologically confirmed sarcoidosis cases newly diagnosed in 2004 were eligible for the present study. Disease parameters were recorded and compared. A total of 1,027 patients were enrolled from a cluster encompassing 79.4% of the entire Japanese population. The study participants consisted of 364 males and 663 females, providing an average incidence rate of 1.01 per 100,000 inhabitants (0.73 for males and 1.28 for females). The age-specific incidence rate displayed a biphasic pattern in the whole patient population and in the females. The male incidence rates peaked in the 20-34-yr-old group. A second peak for 50-60-yr-old females showed a higher incidence than the first younger peak. Patients with abnormalities in eyes, skin and cardiac laboratory findings accounted for 54.8, 35.4 and 23.0% of cases, respectively. The female/male incidence ratio was increased, and the frequency of eye and skin involvement and cardiac abnormality was higher than in previous surveys conducted in Japan. In conclusion, the data obtained in the present study differ from those of other countries and showed changes in sarcoidosis clinical phenotypes compared with previous studies in Japan.
Phase I trial of a murine antibody to MUC1 in patients with metastatic cancer: evidence for the activation of humoral and cellular antitumor immunity
Authors: J.S. de Bono, S.Y. Rha, J. Stephenson, B.C. Schultes, P. Monroe, G.S. Eckhardt, L.A. Hammond, T.L. Whiteside, C.F. Nicodemus, J.M. Cermak, E.K. Rowinsky, A.W. Tolcher
Journal: Annals of Oncology (2004)