tbuckley/cabot-search huggingface dataset:
Serum amyloid protein levels in south american children with rheumatoid arthritis: a co-operative study.
Authors: M A Scheinberg, O Hubscher, O G Morteo, M D Benson
Journal: Annals of the Rheumatic Diseases (1980)

Serum amyloid protein (SAA) levels were determined by radioimmunoassay in 90 children with juvenile rheumatoid arthritis (JRA). Significantly higher levels of SAA were present in children with the polyarticular and systemic forms of the disease. SAA levels correlate with disease activity, increasing during acute exacerbations, decreasing during remission and in patients having prednisone therapy. High serum SAA concentrations in children with JRA did not correlate with the presence of secondary amyloidosis and may be useful as a disease monitor.
Lack of Correlation between Rales and Arterial Oxygen Saturation in Patients with Pulmonary Congestion and Edema
Authors: ALBERT VITALE, PAUL R. DUMKE, J. H. COMROE
Journal: Circulation (1954)

It is generally believed that pulmonary edema impairs the diffusion of oxygen from alveoli to pulmonary capillary blood and produces anoxemia. However, some patients who apparently have widespread pulmonary edema, as judged by the extent of rales heard over the lung fields, still have normal arterial oxygen saturation. Explanations are advanced for the lack of correlation between extent of rales and arterial oxygen saturation.
Pirbuterol, an oral beta-adrenergic receptor agonist, in the treatment of chronic cardiac failure.
Authors: K T Weber, V Andrews, J S Janicki, M Likoff, N Reichek
Journal: Circulation (1982)

Pirbuterol (PB), an oral beta-adrenergic-receptor agonist, has the pharmacologic effects of vasodilation and positive inotropy. The present studies were undertaken to determine the value of PB in the long-term therapy of chronic cardiac failure. A double-blind, randomized, 7-week trial comparing PB (20 mg three times daily) with placebo in 12 patients was followed by 12 weeks of open PB therapy. Dose-dependent nervousness and tremulousness limited the unit PB dose to less than 20 mg in six patients. In all patients, clinical status, exercise tolerance and maximal oxygen uptake, left ventricular echocardiographic dimension and cardiothoracic ratio were unchanged from control after 7 weeks of placebo or PB or after 12--19 weeks of PB. To assess the adequacy of 20 mg of PB, the dose-response relations of cardiocirculatory effects to 10, 15, 20 and 30 mg of PB were compared in seven of the above patients and nine other patients. Cardiac output was significantly elevated and wedge pressure reduced after all four doses, but these changes were sustained from 6 hours after 20- and 30-mg doses only. Thus, the role of PB in the management of chronic cardiac failure appears limited; judgment of its utility must await the results of additional controlled trials.
LPA Receptors: Subtypes and Biological Actions
Authors: Ji Woong Choi, Deron R. Herr, Kyoko Noguchi, Yun C. Yung, Chang-Wook Lee, Tetsuji Mutoh, Mu-En Lin, Siew T. Teo, Kristine E. Park, Alycia N. Mosley, Jerold Chun
Journal: The Annual Review of Pharmacology and Toxicology (2010)

Lysophosphatidic acid (LPA) is a small, ubiquitous phospholipid that acts as an extracellular signaling molecule by binding to and activating at least five known G protein-coupled receptors (GPCRs): LPA(1)-LPA(5). They are encoded by distinct genes named LPAR1-LPAR5 in humans and Lpar1-Lpar5 in mice. The biological roles of LPA are diverse and include developmental, physiological, and pathophysiological effects. This diversity is mediated by broad and overlapping expression patterns and multiple downstream signaling pathways activated by cognate LPA receptors. Studies using cloned receptors and genetic knockout mice have been instrumental in uncovering the significance of this signaling system, notably involving basic cellular processes as well as multiple organ systems such as the nervous system. This has further provided valuable proof-of-concept data to support LPA receptors and LPA metabolic enzymes as targets for the treatment of medically important diseases that include neuropsychiatric disorders, neuropathic pain, infertility, cardiovascular disease, inflammation, fibrosis, and cancer.
DNA Damage and Repair in Translational Oncology: An Overview
Authors: Eddie Reed
Journal: Clinical Cancer Research (2010)

Unknown to early investigators, DNA damage and repair has been a major focus of anticancer therapy from the beginning of clinical oncology. From the early days of using x-irradiation, to the development of nitrogen mustard analogs, to today's more sophisticated approaches, DNA damage and repair has strongly impacted our ability to successfully treat human malignancy. This area of basic, translational, and clinical science is very broad. The traditional focus of DNA damage and repair has been on diseases such as Xeroderma pigmentosum, and attempting to understand the basic molecular mechanisms of DNA repair processes. It is only recently that we have begun to appreciate how we might modulate these processes to improve our ability to advance cancer care. No fewer than 10 separate DNA repair processes are operative in higher organisms, and the total number of separable processes could be substantially higher. Some of our most useful clinical agents depend on causing DNA damage that is repaired by nucleotide excision repair. X-irradiation induces damage that is mostly repaired by base excision repair and double-strand break repair. We are now learning how to modulate select DNA repair pathways to benefit patients with breast cancer and other malignancies.
PTH-052 Microscopic Colitis Is Expensive To Diagnose: An Analysis Of The Utility Of Random Colonic Biopsies: Abstract PTH-052 Table 1
Authors: S Pannick, S Chaggar, A Dehn Lunn, I Beveridge, K Monahan, K Sundaram, C Collins, J Mawdsley
Journal: Gut (2013)

<h3>Introduction</h3> Microscopic colitis is reported in up to 9.5% of patients with watery diarrhoea, and in almost 20% of those older than 70<sup>1</sup>. The Joint Advisory Group on GI Endoscopy mandates diagnostic colorectal biopsies in patients with persistent diarrhoea. However, the Royal College of Pathologists advises that biopsies be taken only in the “correct clinical setting… usually in a middle-aged or elderly (often female) patient”<sup>2</sup>. We examined our local incidence of microscopic colitis and the cost of universal biopsies, and sought to identify factors that could be used to reduce the number of biopsies required. <h3>Methods</h3> We performed a retrospective analysis of patients investigated for diarrhoea at West Middlesex University Hospital between 1/1/2011 and 31/12/2012, where colonic biopsies were taken to exclude microscopic colitis. The patient cohort, and their endoscopic and histological findings, were drawn from the hospital’s electronic medical records. Patients whose biopsies were taken for inflammatory bowel disease assessment were excluded. Those patients with a new diagnosis of microscopic colitis were identified. The estimated cost of processing 4 colonic biopsies was £55. <h3>Results</h3> 616 patients were identified who underwent biopsies to exclude microscopic colitis during the study period. The mean number of biopsies per patient was 3.1. A total of 2056 diagnostic colonoscopies were performed in our unit during this interval; biopsies for this indication were therefore required in 30% of cases. The cost of these biopsies was around £26,700. 9 cases of microscopic colitis were identified (median age 58; interquartile range 47.5–76.5; 3 males and 6 females), with an overall incidence of 1.5%. Incidence increased with age (see table). There were no significant differences between the patients with microscopic colitis and those with other diagnoses in terms of sex or number of biopsies. <h3>Conclusion</h3> Biopsies for this indication are required in a high percentage of diagnostic colonoscopies, with significant resultant costs (£13,300 per annum). Our local incidence of microscopic colitis is far lower than that published in the literature, suggesting we may be over-biopsying. We could not justify restricting biopsies to female patients, but a minimum age criterion might be appropriate. <h3>Disclosure of Interest</h3> None Declared. <h3>References</h3> Olesen<i> et al. Microscopic colitis: a common diarrhoeal disease.</i> Gut 2004; 53:346–350. Howat<i> et al. Histopathology and cytopathology of limited or no clinical value</i>. Royal College of Pathologists. Report number: 2, 2005.
Estrogen Enhances whereas Tamoxifen Retards Development of Tsc Mouse Liver Hemangioma: A Tumor Related to Renal Angiomyolipoma and Pulmonary Lymphangioleiomyomatosis
Authors: Nisreen El-Hashemite, Victoria Walker, David J. Kwiatkowski
Journal: Cancer Research (2005)

Abstract Pulmonary lymphangioleiomyomatosis and abdominal angiomyolipoma are related lesions for which there is no authentic animal model. Both of these proliferative lesions occur in sporadic patients, and at much higher frequency in patients with tuberous sclerosis, which is due to mutations in the TSC1 and TSC2 genes. Tsc1+/− and Tsc2+/− mice frequently develop liver hemangioma. We found that the Tsc mouse liver hemangioma are composed predominantly of endothelial cells but with a smooth muscle component, and express HMB45 antigen, estrogen receptor, and progesterone receptor, similar to lymphangioleiomyomatosis and angiomyolipoma. Estrogen treatment significantly accelerated the development of liver hemangioma in Tsc1+/− female mice, with 91% having liver hemangioma and 55% having severe lesions by 7 months of age. Similarly, an increased frequency and severity of liver hemangiomas was seen in Tsc1+/− males treated with estrogen. In contrast, tamoxifen treatment for 9 months significantly reduced the frequency and severity of hemangiomas in Tsc1+/− female mice. In addition, estrogen treatment significantly increased serum vascular endothelial growth factor levels in Tsc1+/− mice, whereas tamoxifen reduced vascular endothelial growth factor levels. These mouse model observations indicate the importance of estrogen signaling in vivo for the growth of tuberous sclerosis lesions, suggesting the possible benefits of tamoxifen therapy for the treatment of angiomyolipoma and lymphangioleiomyomatosis.
The SUMO E3-ligase PIAS1 Regulates the Tumor Suppressor PML and Its Oncogenic Counterpart PML-RARA
Authors: Andrea Rabellino, Brandon Carter, Georgia Konstantinidou, Shwu-Yuan Wu, Alessandro Rimessi, Lauren A. Byers, John V. Heymach, Luc Girard, Cheng-Ming Chiang, Julie Teruya-Feldstein, Pier Paolo Scaglioni
Journal: Cancer Research (2012)

Abstract The ubiquitin-like SUMO proteins covalently modify protein substrates and regulate their functional properties. In a broad spectrum of cancers, the tumor suppressor PML undergoes ubiquitin-mediated degradation primed by CK2 phosphorylation. Here, we report that the SUMO E3-ligase inhibitor PIAS1 regulates oncogenic signaling through its ability to sumoylate PML and the PML-RARA oncoprotein of acute promyelocytic leukemia (APL). PIAS1-mediated SUMOylation of PML promoted CK2 interaction and ubiquitin/proteasome-mediated degradation of PML, attenuating its tumor suppressor functions. In addition, PIAS1-mediated SUMOylation of PML-RARA was essential for induction of its degradation by arsenic trioxide, an effective APL treatment. Moreover, PIAS1 suppression abrogated the ability of arsenic trioxide to trigger apoptosis in APL cells. Lastly, PIAS1 was also essential for PML degradation in non–small cell lung carcinoma (NSCLC) cells, and PML and PIAS1 were inversely correlated in NSCLC cell lines and primary specimens. Together, our findings reveal novel roles for PIAS1 and the SUMOylation machinery in regulating oncogenic networks and the response to leukemia therapy. Cancer Res; 72(9); 2275–84. ©2012 AACR.
J chain is encoded by a single gene unlinked to other immunoglobulin structural genes.
Authors: M Yagi, P D'Eustachio, F H Ruddle, M E Koshland
Journal: The Journal of Experimental Medicine (1982)

Immunoglobulin J chain mediates the polymerization of both IgM and IgA immunoglobulins. Its synthesis is closely regulated in B lymphocytes, apparently at the level of RNA transcription. To define the genetic bases of this regulation, we have determined the location and number of J chain genes in the mouse. Analysis of DNA from a group of somatic cell hybrids containing various mouse chromosomes on a constant background of Chinese hamster chromosomes indicated that this gene is located on mouse chromosome 5, unlinked to immunoglobulin heavy and light chain structural genes. Restriction mapping experiments further suggested the existence of a single J chain gene per haploid genome. This result was confirmed by quantitative analyses of band intensities yielded by Southern blots of mouse genomic DNA and J gene-containing plasmid DNA.
Meniscal tear and extrusion are strongly associated with progression of symptomatic knee osteoarthritis as assessed by quantitative magnetic resonance imaging
Authors: M-J Berthiaume, J-P Raynauld, J Martel-Pelletier, F Labonté, G Beaudoin, D A Bloch, D Choquette, B Haraoui, R D Altman, M Hochberg, J M Meyer, G A Cline, J-P Pelletier
Journal: Annals of the Rheumatic Diseases (2004)

<b>Background:</b> The relation between knee meniscal structural damage and cartilage degradation is plausible but not yet clearly proven. <b>Objectives:</b> To quantitate the cartilage volume changes in knee osteoarthritis using magnetic resonance imaging (MRI), and determine whether meniscal alteration predicts cartilage volume loss over time. <b>Methods:</b> 32 patients meeting ACR criteria for symptomatic knee osteoarthritis were studied. MRI knee acquisitions were done every six months for two years. The cartilage volumes of different knee regions were measured. Three indices of structural change in the medial and lateral menisci were evaluated—degeneration, tear, and extrusion—using a semiquantitative scale. <b>Results:</b> 24 patients (75%) had mild to moderate or severe meniscal damage (tear or extrusion) at baseline. A highly significant difference in global cartilage volume loss was observed between severe medial meniscal tear and absence of tear (mean (SD), −10.1 (2.1)% <i>v</i> −5.1 (2.4)%, p = 0.002). An even greater difference was found between the medial meniscal changes and medial compartment cartilage volume loss (−14.3 (3.0)% in the presence of severe tear <i>v</i> −6.3 (2.7)% in the absence of tear; p&lt;0.0001). Similarly, a major difference was found between the presence of a medial meniscal extrusion and loss of medial compartment cartilage volume (−15.4 (4.1)% in the presence of extrusion <i>v</i> −4.5 (1.7)% with no extrusion; p&lt;0.001). <b>Conclusions:</b> Meniscal tear and extrusion appear to be associated with progression of symptomatic knee osteoarthritis.
Hunter′s syndrome and associated sleep apnoea cured by CPAP and surgery
Authors: O. Orliaguet, J.L. Pépin, D Veale, E Kelkel, N Pinel, P. Lévy
Journal: European Respiratory Journal (1999)

A 42-yr-old male with Hunter9s syndrome presented with severe obstructive sleep apnoea syndrome (OSAS) and daytime respiratory failure. Continuous positive airway pressure (CPAP) therapy was initially ineffective and produced acute respiratory distress. Extensive Hunter9s disease infiltration of the upper airway with a myxoma was confirmed. Following surgery to remove the myxoma at the level of the vocal cords, CPAP therapy was highly effective and well tolerated. This report demonstrates the necessity of evaluating fully the upper airway in patients with unusual variants of OSAS, particularly where the disease is not adequately controlled by CPAP.
The Potential Role of Curcumin in Patients with Monoclonal Gammopathy of Undefined Significance—Its Effect on Paraproteinemia and the Urinary N-Telopeptide of Type I Collagen Bone Turnover Marker
Authors: Terry Golombick, Terrence H. Diamond, Vladimir Badmaev, Arumugam Manoharan, Rajeev Ramakrishna
Journal: Clinical Cancer Research (2009)

Abstract Purpose: To determine the effect of curcumin on plasma cells and osteoclasts in patients with MGUS. Experimental Design: Twenty-six patients with MGUS were recruited into the study and administered 4 grams/day oral curcumin. Blood and urine samples were collected at specified visits after initiating therapy. Full blood count, B2 microglobulin, serum paraprotein, and immunoglobulin electrophoresis (IEPG and EPG) were determined for all patients at each visit. Serum calcium, 25 hydroxyvitamin D3, and bone-specific alkaline phosphatase were determined at baseline only. Urine, as a morning second-void sample, was collected at each visit for urinary N-telopeptide of type I collagen. Results: Our results show that oral curcumin is able to decrease paraprotein load in a select group (i.e., those having a paraprotein level of &amp;gt;20 g/L) of patients with MGUS. Fifty percent (5 of 10) of these patients had a 12% to 30% reduction in their paraprotein levels, while on curcumin therapy. In addition, 27% of patients on curcumin had a &amp;gt;25% decrease in urinary N-telopeptide of type I collagen. Conclusion: Due to the possible progression of MGUS to multiple myeloma, the potential role of curcumin as a therapeutic intervention for MGUS patients warrants further investigation. (Clin Cancer Res 2009;15(18):5917–22)
Health-related quality of life and unmet needs in patients with primary ciliary dyskinesia
Authors: M. Pifferi, A. Bush, M. Di Cicco, U. Pradal, V. Ragazzo, P. Macchia, A. L. Boner
Journal: European Respiratory Journal (2009)

Few studies have evaluated the quality of life of patients with primary ciliary dyskinesia (PCD). We sought to determine the health impact of the disease as well as the unmet needs in a large group of patients. Questionnaires were either posted or e-mailed to known patients with PCD and published online. Questionnaires included the St George's Respiratory Questionnaire, the Medical Outcomes Study Short Form-36 and a questionnaire that we produced to obtain information on age of diagnosis, symptoms and likely PCD-specific problems of these patients. 78 subjects (96% of those invited) answered all the questionnaires. Patients were diagnosed at a mean age of 9.4 yrs. Progressive worsening of the disease was observed and adherence to physiotherapy was found to be poor, particularly in adolescents and adults. Patients with the highest treatment burden had a worse quality of life. Over time patients become progressively less interested in treating their disease and adherence to treatment modalities decreases. PCD is associated with a progressive and continuous impact on the physical and mental health of the patients. Earlier identification of the patients and better strategies aimed at improving compliance with care are urgently needed.
Breast cancer mortality trends in England and the assessment of the effectiveness of mammography screening: population-based study
Authors: Toqir K Mukhtar, David RG Yeates, Michael J Goldacre
Journal: Journal of the Royal Society of Medicine (2013)

Objective To investigate whether mortality statistics show an effect of mammographic screening on population-based breast cancer mortality in England. Design Joinpoint regression analyses, and other analyses, of population-based mortality data. Setting Analysis of mortality rates in the Oxford region, UK (1979–2009) because, unlike the rest of England, all causes of death mentioned on each death certificate for its residents (not just the underlying cause) are available prior to commencement of the English National Breast Screening Programme (NHSBSP). In addition, analysis of English national breast cancer mortality rates (1971–2009). Participants Women who died from breast cancer in the Oxford region (1979--2009) and England (1971--2009) Main outcome measures Age-specific mortality rates, and age-standardized mortality rates. Joinpoint regression analysis was used to estimate years (‘joinpoints’) in which trends changed, and annual percentage change between joinpoints, with confidence intervals. Results In the Oxford region, trends for breast cancer mortality based on underlying cause and on mentions were very similar. For all ages combined, mortality rates peaked for both underlying cause and mentions in 1985 and then started to decline, prior to the introduction of the NHSBSP in 1988. Between 1979 and 2009, for mortality measured as underlying cause, rates declined by −2.1% (95% CI −2.7 to −1.4) per year for women aged 40–49 years (unscreened), and by the same percentage per year (−2.1% [−2.4 to −1.7]) for women aged 50–64 years (screened). In England, the first estimated changes in trend occurred prior to the introduction of screening, or before screening was likely to have had an effect (between 1982 and 1989). Thereafter, the downward trend was greatest in women aged under 40 years: −2.0% per year (−2.8 to −1.2) in 1988–2001 and −5.0% per year (−6.7 to −3.3) in 2001–2009. There was no evidence that declines in mortality rates were consistently greater in women in age groups and cohorts that had been screened at all, or screened several times, than in other (unscreened) women, in the same time periods. Conclusions Mortality statistics do not show an effect of mammographic screening on population-based breast cancer mortality in England.
c-Jun NH2-Terminal Kinase 2 Is Required for Ras Transformation Independently of Activator Protein 1
Authors: Christina Nielsen, Jacob Thastrup, Trine Bøttzauw, Marja Jäättelä, Tuula Kallunki
Journal: Cancer Research (2007)

Abstract Active Ras oncogene is expressed in ∼30% of human cancers. Yet, very little is known about the molecular mechanisms responsible for its transforming potential. Here, we show that H-Ras-mediated transformation requires isoform 2 of the c-Jun-NH2-terminal kinase (JNK). H-Ras-transduced JNK2-deficient (Jnk2−/−) murine embryonic fibroblasts (MEFs) were severely inhibited in colony formation and growth in soft agar in vitro as well as in tumor formation in immunodeficient mice as compared with corresponding Jnk1−/− and wild-type MEFs. Accordingly, the RNA interference–based depletion of JNK2 form wild-type MEFs also resulted in defective Ras transformation. The extra barrier against H-Ras transformation in Jnk2−/− MEFs was not due to their inability to inactivate p53 signaling because all JNK2-deficient MEF lines had lost p19Arf. Furthermore, expression of the E6 protein of the human papilloma virus failed to overcome the transformation defect. It could, however, be overcome by coexpression of H-Ras with the SV40 large T antigen or c-Myc. Surprisingly, the H-Ras-transduced JNK2-deficient MEFs exhibited higher activity of activator protein-1 and higher levels of c-Jun expression compared with H-Ras-transduced JNK1-deficient or wild-type cells, indicating that the key target of JNK2 during Ras transformation was divergent from activator protein-1. These results clearly show that a single kinase, JNK2, could control Ras transformation and thus point out a vulnerable control point that may prove important for the tumor development in general. [Cancer Res 2007;67(1):178–85]
Use of Thyroid Supplements in Relation to the Risk of Breast Cancer
Authors: Samuel Shapiro
Journal: JAMA (1980)

We conducted a case-control study to determine whether the use of thyroid supplements increases the risk of breast cancer. We compared 659 women with breast cancer and 1,719 control subjects. The rates of use of thyroid supplements were 9.1% and 8.7%, respectively (age-standardized rate ratio, 1.0; 95% confidence interval, 0.7 to 1.3). There was no evidence of an association when women known to be at increased risk for breast cancer (eg, nulliparae) were examined, even when thyroid supplements were taken for more than 15 years. Overall, there were no grounds to suggest that the long-term use of thyroid supplements increases the risk of breast cancer.