tbuckley/cabot-search huggingface dataset:
Distinct Genomic Profiles in Hereditary Breast Tumors Identified by Array-Based Comparative Genomic Hybridization
Authors: Göran Jönsson, Tara L. Naylor, Johan Vallon-Christersson, Johan Staaf, Jia Huang, M. Renee Ward, Joel D. Greshock, Lena Luts, Håkan Olsson, Nazneen Rahman, Michael Stratton, Markus Ringnér, Åke Borg, Barbara L. Weber
Journal: Cancer Research (2005)

Abstract Mutations in BRCA1 and BRCA2 account for a significant proportion of hereditary breast cancers. Earlier studies have shown that inherited and sporadic tumors progress along different somatic genetic pathways and that global gene expression profiles distinguish between these groups. To determine whether genomic profiles similarly discriminate among BRCA1, BRCA2, and sporadic tumors, we established DNA copy number profiles using comparative genomic hybridization to BAC-clone microarrays providing &amp;lt;1 Mb resolution. Tumor DNA was obtained from BRCA1 (n = 14) and BRCA2 (n = 12) mutation carriers, as well as sporadic cases (n = 26). Overall, BRCA1 tumors had a higher frequency of copy number alterations than sporadic breast cancers (P = 0.00078). In particular, frequent losses on 4p, 4q, and 5q in BRCA1 tumors and frequent gains on 7p and 17q24 in BRCA2 tumors distinguish these from sporadic tumors. Distinct amplicons at 3q27.1-q27.3 were identified in BRCA1 tumors and at 17q23.3-q24.2 in BRCA2 tumors. A homozygous deletion on 5q12.1 was found in a BRCA1 tumor. Using a set of 169 BAC clones that detect significantly (P &amp;lt; 0.001) different frequencies of copy number changes in inherited and sporadic tumors, these could be discriminated into separate groups using hierarchical clustering. By comparing DNA copy number and RNA expression for genes in these regions, several candidate genes affected by up- or down-regulation were identified. Moreover, using support vector machines, we correctly classified BRCA1 and BRCA2 tumors (P &amp;lt; 0.0000004 and 0.00005, respectively). Further validation may prove this tumor classifier to be useful for selecting familial breast cancer cases for further mutation screening, particularly, as these data can be obtained using archival tissue.
Sequential two-line strategy for stage IV non-small-cell lung cancer: docetaxel–cisplatin versus vinorelbine–cisplatin followed by cross-over to single-agent docetaxel or vinorelbine at progression: final results of a randomised phase II study
Authors: J.-Y. Douillard, R. Gervais, G. Dabouis, A. Le Groumellec, M. D'Arlhac, D. Spaeth, B. Coudert, D. Caillaud, A. Monnier, C. Clary, B. Maury, M. Mornet, A. Rivière, P. Clouet, C. Couteau
Journal: Annals of Oncology (2004)
A hormonal effusion?
Authors: Charles Sharp, Mark Meller, Alison Moody, George Hands
Journal: Thorax (2012)

A 51-year-old woman presented to the chest clinic with history of progressive dyspnoea and dry cough for 8 weeks. Her past medical history was remarkable for sleeve gastrectomy 3 months ago, which resulted in loss of three stones. She also reported migraines for which she had an implanted occipital nerve stimulator and had undergone hysterectomy with bilateral salpingo-oophorectomy 18 months ago. Other history included hypothyroidism, hypertension and depression. Her medications were Hormone Replacement Therapy (HRT), Nifedipine, Losartan, Levothyroxine, Lansoprazole, Simvastatin and Fluoxetine. She had smoked for 3 years in her 20s, no more than 3–5 cigarettes per day and had no noteworthy occupational exposure. She had a family history of maternal myelodysplasia and paternal …
Vascular Endothelial Growth Factor-A and Platelet-Derived Growth Factor-B Combination Gene Therapy Prolongs Angiogenic Effects via Recruitment of Interstitial Mononuclear Cells and Paracrine Effects Rather Than Improved Pericyte Coverage of Angiogenic Vessels
Authors: Petra Korpisalo, Henna Karvinen, Tuomas T. Rissanen, Johanna Kilpijoki, Varpu Marjomäki, Peter Baluk, Donald M. McDonald, Yihai Cao, Ulf Eriksson, Kari Alitalo, Seppo Ylä-Herttuala
Journal: Circulation Research (2008)

Vessel stabilization and the inhibition of side effects such as tissue edema are essential in angiogenic gene therapy. Thus, combination gene transfers stimulating both endothelial cell and pericyte proliferation have become of interest. However, there is currently little data to support combination gene transfer in large animal models. In this study, we evaluated the potential advantages of such a strategy by combining the transfer of adenoviral (Ad) vascular endothelial growth factor (VEGF)-A and platelet-derived growth factor (PDGF)-B into rabbit hindlimb skeletal muscle. AdLacZ alone or in combination with AdVEGF-A were used as controls. Contrast-enhanced ultrasound, modified Miles assay, and immunohistology were used to quantify perfusion, vascular permeability, and capillary size, respectively. Confocal microscopy was used in the assessment of pericyte-coverage. The transfer of AdPDGF-B alone and in combination with AdVEGF-A induced prominent proliferation of α-smooth muscle actin–, CD31-, RAM11-, HAM56-, and VEGF- positive cells. Although, pericyte recruitment to angiogenic vessels was not improved, combination gene transfer induced a longer-lasting increase in perfusion in both intact and ischemic muscles than AdVEGF-A gene transfer alone. In conclusion, intramuscular delivery of AdVEGF-A and AdPDGF-B, combined, resulted in a prolonged angiogenic response. However, the effects were most likely mediated via paracrine mechanisms rather than an increase in vascular pericyte coverage.
Measurement bias in different versions of the Dutch Health Assessment Questionnaire Disability Index
Authors: Martijn A H Oude Voshaar, Peter M ten Klooster, Harald E Vonkeman, Wietske Kievit, Piet L C M van Riel, Mart A F J van de Laar
Journal: Annals of the Rheumatic Diseases (2013)

Measurement bias in different versions of the Dutch Health Assessment Questionnaire Disability IndexThe Health Assessment Questionnaire (HAQ) Disability Index is the most frequently used and validated measure of physical function for patients with rheumatoid arthritis (RA). 1 Various translated versions of this questionnaire have been used in clinical research in the Netherlands.In 2007, a standardised translation, the Dutch consensus HAQ, was introduced and a letter detailing its development appeared in this journal. 2The Dutch DREAM registry, 3 a multicentre observational cohort study that monitors RA patients undergoing different treatment regimens, soon adopted the consensus HAQ.The consensus HAQ differs in a number of ways from the previously used version that was developed in Nijmegen. 4ifferences include the handling and number of aids and the translation of item 13: 'are you able to reach and get down a 5-pound object (such as a bag of sugar) from just above your head?'.In the Nijmegen version, the weight of the object had 2050
The rationale for the current boom in anti-TNFalpha treatment. Is there an effective means to define therapeutic targets for drugs that provide all the benefits of anti-TNFalpha and minimise hazards?
Authors: M. Feldmann, J. Bondeson, F. M Brennan, B. M J Foxwell, R. N Maini
Journal: Annals of the Rheumatic Diseases (1999)

Progress in understanding mechanisms of disease are necessary to usher in major changes in treatment. A new era in rheumatoid arthritis (RA) and related chronic autoimmune/inflammatory diseases is now beginning, with a variety of anti-TNFalpha treatments licensed for use in both RA and Crohn's disease. The rationale for this new treatment lies in an understanding that cytokines are critical, rate limiting molecules lying at the heart of the chronic autoimmune/inflammatory disease process. This understanding was developed from the critical evaluation of a hypothesis that was proposed linking cytokines, antigen presentation and autoimmunity in 1983. Detailed analysis focusing on the major site of the disease, the rheumatoid synovium was essential to developing indications that blockade of TNFalpha might be efficacious. This clue was validated using anti-TNFalpha treatment of an animal model of RA, murine collagen induced arthritis, and by immunohistochemical demonstration of upregulated TNF and TNF-R expression in the synovium. With this three pronged rationale, the authors were able to convince Centocor, Inc, which had developed a chimaeric anti-TNFalpha antibody for use in sepsis, to work with them to test the concept that TNFalpha blockade would be beneficial in RA. With the success of that first trial, other companies have subsequently tested their anti-TNF strategies successfully. Current interests extend to understanding the processes that regulate TNF production in the rheumatoid joint. Progress in this area is discussed, using adenoviruses to infect normal macrophages and rheumatoid synovium.
Risk and outcome of nosocomial Staphylococcus aureus bacteraemia in nasal carriers versus non-carriers
Authors: Heiman FL Wertheim, Margreet C Vos, Alewijn Ott, Alex van Belkum, Andreas Voss, Jan AJW Kluytmans, Peter HJ van Keulen, Christina MJE Vandenbroucke-Grauls, Marlene HM Meester, Henri A Verbrugh
Journal: The Lancet (2004)
Interstitial cells of the heart valves possess characteristics similar to smooth muscle cells.
Authors: D A Filip, A Radu, M Simionescu
Journal: Circulation Research (1986)

Interstitial cells of heart atrioventricular and sigmoid valves were examined in several laboratory animals (rabbit, hamster, rat, and mouse) and in humans. These cells constitute a large fraction of the total cell population of the valve; in mouse atrioventricular valves, they amount to approximately 30% of the volumetric density. By their ultrastructural features and functional properties, valvular interstitial cells are intermediate between fibroblasts and vascular smooth muscle cells. Like fibroblasts, valvular interstitial cells lack a basal lamina establishing direct and extensive contacts with collagen fibers, elastin microfibrils, and proteoglycans of the matrix. The cells have numerous slender and long processes, connected to one another, forming a complex cellular framework spanning the entire valve. Similar to smooth muscle cells, valvular interstitial cells are extensively coupled by communicating junctions as shown by thin sections, freeze-fracture, lanthanum staining, and carboxyfluorescein microinjection. The cells contain numerous bundles of actin filaments, which are decorated by the S1 fragment of heavy meromyosin. Valvular interstitial cells also express cyclic guanosine-monophosphate-dependent protein kinase, as detected by immunofluorescence and immunoperoxidase histochemistry. Motor nerve endings are located closely apposed to valvular interstitial cells: structurally most of them appear to be of the adrenergic type. Valvular interstitial cells contract on epinephrine or angiotensin II stimulation as shown both in culture and in situ (valvular strips). Taken together these observations suggest that VIC may have contractile properties, which can account for a controlled tonus, actively correlated with the cyclically changing forces acting on valves during diastole and systole.
Neuralgic amyotrophy and polyarthritis caused by parvovirus B19 infection
Authors: X. PUECHAL, P. HILLIQUIN, A. KAHAN, C. J MENKES
Journal: Annals of the Rheumatic Diseases (1998)

Infection with human parvovirus B19 causes a wide range of clinical manifestations, which may vary according to the immune status of the patient. They include erythema infectiosum (fifth disease), symmetrical polyarthritis, vasculitis, transient aplastic crisis in patients with low red cell production, and chronic infection in immunocompromised patients. We report a patient treated with immunosuppressive drugs in whom bilateral brachial plexitis and polyarthritis were associated with parvovirus B19 acute infection.

A 33 year old woman presented with severe pain in the arms. She had a two year history of severe Crohn’s disease and was treated with azathioprine (125 …
THE ABSORPTIVE PROPERTY DF VARIOUS OINTMENTS
Authors: JOHN RAE
Journal: British Journal of Dermatology (1947)

Journal Article THE ABSORPTIVE PROPERTY DF VARIOUS OINTMENTS Get access JOHN RAE, M.P.S. JOHN RAE, M.P.S. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 59, Issue 10, 1 October 1947, Pages 338–339, https://doi.org/10.1111/j.1365-2133.1947.tb10872.x Published: 01 October 1947
Obstructive Sleep Apnea Syndrome Is Associated with Deficits in Verbal but Not Visual Memory
Authors: Gillian L. Twigg, Ioannis Papaioannou, Melinda Jackson, Ramesh Ghiassi, Zarrin Shaikh, Jay Jaye, Kim S. Graham, Anita K. Simonds, Mary J. Morrell
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Rationale: Although cognitive deficits are well documented in patients with sleep apnea, the impact on memory remains unclear.Objectives: To test the hypotheses that (1) patients with obstructive sleep apnea have memory impairment and (2) memory impairment is commensurate with disease severity.Methods: Patients with obstructive sleep apnea and healthy volunteers (apnea–hypopnea index <5 events/h) completed a test battery specially designed to differentiate between aspects of memory (semantic, episodic, and working) versus attention. Sleepiness was measured on the basis of the Epworth Sleepiness Scale and Oxford Sleep Resistance test. Memory performance in patients versus control subjects was compared (Mann-Whitney U test; P < 0.01, Bonferroni corrected for multiple comparisons) and relationships between performance and disease severity were analyzed by linear regression.Measurements and Main Results: Sixty patients and healthy control subjects matched for age (mean ± SD: patients, 51 ± 9 yr; control subjects, 50 ± 9 yr) and education (patients, 14 ± 3 yr; control subjects, 15 ± 3 yr) participated. Patients demonstrated impaired Logical Memory Test results (immediate recall: patients, median [range], 36 [9–69]; control subjects, 43 [19–64], P = 0.0004; and delayed recall: patients, 22 [6–42]; control subjects, 27 [10–46]; P = 0.0001). There were minimal differences in attention, visual episodic, semantic, or working memory; patients performed better than control subjects on Spatial Span forward and backward. Regression analysis revealed that Logical Memory Test performance was not significantly related to disease severity after controlling for age, education, and sleepiness.Conclusions: Obstructive sleep apnea is associated with impairment in verbal, but not visual, memory. The impairment was present across a range of disease severity and was not explained by reduced attention. Such verbal memory impairment may affect daytime functioning and performance.
Effect of Brain- and Tumor-Derived Connective Tissue Growth Factor on Glioma Invasion
Authors: Lincoln A. Edwards, Kevin Woolard, Myung Jin Son, Aiguo Li, Jeongwu Lee, Chibawanye Ene, Samuel A. Mantey, Dragan Maric, Hua Song, Galina Belova, Robert T. Jensen, Wei Zhang, Howard A. Fine
Journal: JNCI Journal of the National Cancer Institute (2011)

Tumor cell invasion is the principal cause of treatment failure and death among patients with malignant gliomas. Connective tissue growth factor (CTGF) has been previously implicated in cancer metastasis and invasion in various tumors. We explored the mechanism of CTGF-mediated glioma cell infiltration and examined potential therapeutic targets. Highly infiltrative patient-derived glioma tumor–initiating or tumor stem cells (TIC/TSCs) were harvested and used to explore a CTGF-induced signal transduction pathway via luciferase reporter assays, chromatin immunoprecipitation (ChIP), real-time polymerase chain reaction, and immunoblotting. Treatment of TIC/TSCs with small-molecule inhibitors targeting integrin β1 (ITGB1) and the tyrosine kinase receptor type A (TrkA), and short hairpin RNAs targeting CTGF directly were used to reduce the levels of key protein components of CTGF-induced cancer infiltration. TIC/TSC infiltration was examined in real-time cell migration and invasion assays in vitro and by immunohistochemistry and in situ hybridization in TIC/TSC orthotopic xenograft mouse models (n = 30; six mice per group). All statistical tests were two-sided. Treatment of TIC/TSCs with CTGF resulted in CTGF binding to ITGB1–TrkA receptor complexes and nuclear factor kappa B (NF-κB) transcriptional activation as measured by luciferase reporter assays (mean relative luciferase activity, untreated vs CTGF 200 ng/mL : 0.53 vs 1.87, difference = 1.34, 95% confidence interval [CI] = 0.69 to 2, P < .001). NF-κB activation resulted in binding of ZEB-1 to the E-cadherin promoter as demonstrated by ChIP analysis with subsequent E-cadherin suppression (fold increase in ZEB-1 binding to the E-cadherin promoter region: untreated + ZEB-1 antibody vs CTGF 200 ng/mL + ZEB-1 antibody: 1.5 vs 6.4, difference = 4.9, 95% CI = 4.8 to 5.0, P < .001). Immunohistochemistry and in situ hybridization revealed that TrkA is selectively expressed in the most infiltrative glioma cells in situ and that the surrounding reactive astrocytes secrete CTGF. A CTGF-rich microenvironment facilitates CTGF–ITGB1–TrkA complex activation in TIC/TSCs, thereby increasing the invasiveness of malignant gliomas.
EP 80317, a selective CD36 ligand, shows cardioprotective effects against post-ischaemic myocardial damage in mice
Authors: Valérie L. Bessi, Sébastien M. Labbé, David N. Huynh, Liliane Ménard, Christian Jossart, Maria Febbraio, Brigitte Guérin, M'Hamed Bentourkia, Roger Lecomte, André C. Carpentier, Huy Ong, Sylvie Marleau
Journal: Cardiovascular Research (2012)

The CD36 receptor plays an important role in facilitating fatty acid transport to the heart. The present study aimed to assess whether EP 80317, a selective synthetic peptide ligand of CD36, is cardioprotective in a murine model of myocardial ischaemia and reperfusion (MI/R) injury. Mice were pretreated with daily subcutaneous injections of EP 80317 for 14 days before being subjected to a 30 min ligation of the left anterior descending coronary artery. The treatment reduced the infarct area and improved myocardial haemodynamics and function, as shown by an increase in cardiac output, ejection fraction and stroke work, and a reduced total peripheral resistance. In contrast, administration of EP 51389, a tripeptide analogue devoid of binding affinity to CD36, did not protect against myocardial injury. Six hours after myocardial reperfusion, EP 80317-treated mice showed reduced myocardial fatty acid uptake, as assessed by micro-positron emission tomography, in agreement with reduced levels of circulating non-esterified fatty acids. Studies using [14C]-palmitate infusion revealed reduced lipolysis, although no significant change in insulin or catecholamine plasma levels were observed. Increased expression levels of adipogenic and anti-lipolytic genes further supported an effect of EP 80317 in preventing fatty acid mobilization from adipose tissue. No effect of the treatment was observed in CD36−/− mice. Our results show that pretreatment with EP 80317 protected the heart against damage and dysfunction elicited by MI/R, along with a transient reduction in peripheral lipolysis. Our findings support CD36 as a novel target for the treatment of ischaemic cardiopathy.
Nitric Oxide Inhibits Dystrophin Proteolysis by Coxsackieviral Protease 2A Through <i>S</i> -Nitrosylation
Authors: Cornel Badorff, Birgit Fichtlscherer, Robert E. Rhoads, Andreas M. Zeiher, Alexander Muelsch, Stefanie Dimmeler, Kirk U. Knowlton
Journal: Circulation (2000)

Background —Infection with enteroviruses like coxsackievirus B3 (CVB3) as well as genetic dystrophin deficiency can cause dilated cardiomyopathy. We recently identified cleavage and functional impairment of dystrophin by the viral protease 2A during CVB3-infection as a molecular mechanism that may contribute to the pathogenesis of enterovirus-induced cardiomyopathy. Nitric oxide (NO) is elevated in human dilated cardiomyopathy, but the relevance of this finding is unknown. In mice, NO inhibits CVB3 myocarditis. Therefore, we investigated the effects of NO on the coxsackieviral protease 2A. Methods and Results —In vitro, NO donors like PAPA-NONOate inhibited the cleavage of human and mouse dystrophin by recombinant coxsackievirus B protease 2A in a dose-dependent manner (IC 50 , 51 μmol/L). In CVB3-infected HeLa cells, addition of the NO donor SNAP inhibited protease 2A catalytic activity on dystrophin. Because this inhibitory effect was reversed by the thiol-protecting agent DTT, we investigated whether NO S -nitrosylates the protease 2A. In vitro, NO nitrosylated the active-site cysteine (C110) of the coxsackieviral protease 2A, as demonstrated by site-directed mutagenesis. Within living COS-7 cells, SNAP-induced S -nitrosylation of this site was confirmed with electron spin resonance spectroscopy. Conclusions —These data demonstrate inactivation of a coxsackieviral protease 2A by NO through active-cysteine S -nitrosylation in vitro and intracellularly. Given that the enteroviral protease 2A cleaves mouse and human dystrophin, NO may be protective in human heart failure with an underlying enteroviral pathogenesis through inhibition of dystrophin proteolysis.
Hot Line to the Heart
Authors: G. Douglas Talbott
Journal: JAMA (1966)

Familiarity with current medical literature is generally agreed to be a vital factor in the growth and development of a physician; yet the vast number of current biomedical publications (5,500 in 1962, according to the director of the National Library of Medicine<sup>1</sup>) makes the task of selecting, let alone reading, pertinent material an increasingly difficult problem. It is the purpose of this paper to describe a new automated specific-inquiry and information-retrieval system devised to help solve this problem. The prototype system was developed, and recently tested, at Cox Coronary Heart Institute, where it is being used to extract from current periodicals (1) immediate answers to specific questions and (2) bibliographies, abstracts, and/or original papers on a given subject, all within the circumscribed area of coronary heart disease. Preliminary tests of the system were made by running a series of more than 25 duplicate searches, with both manual methods and
Molecular Mechanisms of Acid-Base Sensing by the Kidney
Authors: Dennis Brown, Carsten A. Wagner
Journal: Journal of the American Society of Nephrology (2012)

A major function of the kidney is to collaborate with the respiratory system to maintain systemic acid-base status within limits compatible with normal cell and organ function. It achieves this by regulating the excretion and recovery of bicarbonate (mainly in the proximal tubule) and the secretion of buffered protons (mainly in the distal tubule and collecting duct). How proximal tubular cells and distal professional proton transporting (intercalated) cells sense and respond to changes in pH, bicarbonate, and CO(2) status is a question that has intrigued many generations of renal physiologists. Over the past few years, however, some candidate molecular pH sensors have been identified, including acid/alkali-sensing receptors (GPR4, InsR-RR), kinases (Pyk2, ErbB1/2), pH-sensitive ion channels (ASICs, TASK, ROMK), and the bicarbonate-stimulated adenylyl cyclase (sAC). Some acid-sensing mechanisms in other tissues, such as CAII-PDK2L1 in taste buds, might also have similar roles to play in the kidney. Finally, the function of a variety of additional membrane channels and transporters is altered by pH variations both within and outside the cell, and the expression of several metabolic enzymes are altered by acid-base status in parts of the nephron. Thus, it is possible that a master pH sensor will never be identified. Rather, the kidney seems equipped with a battery of molecules that scan the epithelial cell environment to mount a coordinated physiologic response that maintains acid-base homeostasis. This review collates current knowledge on renal acid-base sensing in the context of a whole organ sensing and response process.