tbuckley/cabot-search huggingface dataset:
Comparative proteome analysis of lung tissue from patients with idiopathic pulmonary fibrosis (IPF) and non-specific interstitial pneumonia (NSIP)
Authors: Martina Korfei, Ingrid Henneke, Philipp Markart, Daniel Von Der Beck, Clemens Ruppert, Poornima Mahavadi, Walter Klepetko, Ludger Fink, Silke Meiners, Oliver Krämer, Werner Seeger, Carlo Vancheri, Andreas Guenther
Journal: European Respiratory Journal (2013)

Among the idiopathic interstitial pneumonias (IIP), the two entities IPF and NSIP seem to be clinically related, but NSIP has a better outcome. The proteomic signatures which distinguish NSIP from IPF remain still elusive. We therefore performed comparative proteomic analysis of subpleural lung tissue from patients with sporadic IPF (n=14) and fibrotic NSIP (fNSIP, n=8) and organ donors (Controls, n=10), by using the innovative Difference in Gel Electrophoresis (DIGE) technique and MALDI-TOF-MS. The study revealed that the proteomic profiles of IPF and fNSIP were quite similar. Among the upregulated proteins in IPF and fNSIP were stress-induced genes involved in the ER stress-pathway, whereas downregulated proteins in IPF and fNSIP included antiapoptotic factors and antifibrotic molecules, such as serum amyloid P component, an inhibitor of fibrocyte differentiation. The direct comparison fNSIP versus IPF indicated upregulation of subunits of the proteasome activator complex (PSME1) and antioxidant enzymes of the peroxiredoxin family. In line with this, immunohistochemical analysis revealed induction and upregulation of peroxiredoxin1 and PSME1 in alveolar type-II cells in fNSIP-, but not in IPF lungs. We conclude, that only few protein expression changes exist between IPF and fNSIP, and that epithelial ER- and oxidative stress play a major role in the pathogenesis of both diseases. In contrast to IPF, intracellular clearance of reactive oxygen species and misfolded protein carbonyls seem to be enhanced in fNSIP due to enhanced expression of antioxidant acting proteins, and may explain the better outcome/survival in patients with fNSIP.
Physiological, biochemical, and morphological characteristics of myocardial anoxia: the use of a semi-perfusion canine preparation
Authors: E. P. BORNET, J. M. WOOD, M. A. GOLDSTEIN, M. L. ENTMAN, R. M. LEWIS, F. A. DUNN, A. SCHWARTZ
Journal: Cardiovascular Research (1977)

Regional myocardial anoxia was produced in dogs by perfusion of the left circumflex artery (LCA) with deoxygenated blood. Isolated sarcoplasmic reticulum fragments (cardiac relaxing system) showed decreased Ca2+ binding and uptake. The ability of isolated mitochondria to utilise long-chain fatty acids was markedly reduced. This model has revealed inherent biochemical differences between ischaemia and anoxia.
Human herpesvirus 8 is not detectable in lesions of large plaque parapsoriasis, and in early-stage sporadic, familial, and juvenile cases of mycosis fungoides
Authors: Iris Amitay-Laish, Ronit Sarid, Dan Ben-Amitai, Inna Kalt, Shiri Rivka Masa, Michael David, Meora Feinmesser, Emmilia Hodak
Journal: Journal of the American Academy of Dermatology (2011)
Orthopaedic surgeons and thromboprophylaxis
Authors: B M Wroblewski
Journal: BMJ (1991)

300 ml (300 mg) per bottle.This may be a week's supply for a drug dependent adult, but 20-30 ml can be lethal to a small child.Methadone syrup tastes pleasant enough for children to consume 150-200 ml without complaint.Parents often delay bringing to hospital children who have taken methadone.Drug dependent adults who can tolerate large doses of the drug may assume that a child will "sleep it off," and parents may be deterred from taking a child to hospital because they know that their competence to look after the child will be questioned.We are not trying to imply that methadone users should not have the care of their small children, but some steps must be taken to protect these children.We strongly suggest that it should be a legal requirement that all methadone be prescribed in child resistant plastic bottles.Further, metha- done should be bitter to taste.Finally, very serious consideration should be given to limiting the quantity prescribed at any one time to methadone users who are responsible for small children.
Suppression of Prostate Cancer Nodal and Systemic Metastasis by Blockade of the Lymphangiogenic Axis
Authors: Jeremy B. Burton, Saul J. Priceman, James L. Sung, Ebba Brakenhielm, Dong Sung An, Bronislaw Pytowski, Kari Alitalo, Lily Wu
Journal: Cancer Research (2008)

Abstract Lymph node involvement denotes a poor outcome for patients with prostate cancer. Our group, along with others, has shown that initial tumor cell dissemination to regional lymph nodes via lymphatics also promotes systemic metastasis in mouse models. The aim of this study was to investigate the efficacy of suppressive therapies targeting either the angiogenic or lymphangiogenic axis in inhibiting regional lymph node and systemic metastasis in subcutaneous and orthotopic prostate tumor xenografts. Both androgen-dependent and more aggressive androgen-independent prostate tumors were used in our investigations. Interestingly, we observed that the threshold for dissemination is lower in the vascular-rich prostatic microenvironment compared with subcutaneously grafted tumors. Both vascular endothelial growth factor-C (VEGF-C) ligand trap (sVEGFR-3) and antibody directed against VEGFR-3 (mF4-31C1) significantly reduced tumor lymphangiogenesis and metastasis to regional lymph nodes and distal vital organs without influencing tumor growth. Conversely, angiogenic blockade by short hairpin RNA against VEGF or anti–VEGFR-2 antibody (DC101) reduced tumor blood vessel density, significantly delayed tumor growth, and reduced systemic metastasis, although it was ineffective in reducing lymphangiogenesis or nodal metastasis. Collectively, these data clarify the utility of vascular therapeutics in prostate tumor growth and metastasis, particularly in the context of the prostate microenvironment. Our findings highlight the importance of lymphangiogenic therapies in the control of regional lymph node and systemic metastasis. [Cancer Res 2008;68(19):7828–37] [Cancer Res 2008;68(19):7828–37]
Priorities in Colorectal Cancer Research: Recommendations From the Gastrointestinal Scientific Leadership Council of the Coalition of Cancer Cooperative Groups
Authors: Peter J. O'Dwyer, S. Gail Eckhardt, Daniel G. Haller, Joel Tepper, Dennis Ahnen, Stanley Hamilton, Al B. Benson, Mace Rothenberg, Nicholas Petrelli, Heinz-Joseph Lenz, Robert Diasio, Raymond DuBois, Daniel Sargent, Jeff Sloan, C. Daniel Johnson, Robert L. Comis, Michael J. O'Connell
Journal: Journal of Clinical Oncology (2007)

Emerging technologies have greatly expanded our ability to detect, characterize, and treat colorectal cancer. The Coalition of Cancer Cooperative Groups convened a multidisciplinary panel, the Scientific Leadership Council in GI cancer, to discuss and advise on the priorities and opportunities to advance current and future approaches into the clinical arena to impact most rapidly the morbidity and mortality from this disease. The Council's recommendations for research priorities are the result of engagement of community and academic oncologists, patient advocacy groups, and other stakeholders including the pharmaceutical industry and governmental agencies. We detail some key prospects for investigation in the areas of colon cancer detection, prevention, and surgical and medical management. Many are in early or definitive clinical trials, and a focus on rapid accrual is urged. The implementation of biology-directed laboratory investigations, both in association with ongoing clinical trials and as a separate developmental strategy for targeted therapies, is supported as the route to individualized therapy.
Wideband external pulse recording during cuff deflation: a new technique for evaluation of the arterial pressure pulse and measurement of blood pressure.
Authors: S G Blank, J E West, F B Müller, R J Cody, G A Harshfield, M S Pecker, J H Laragh, T G Pickering
Journal: Circulation (1988)

Analysis of the external brachial pulse recorded during standard blood pressure cuff deflation with use of a transducer with a wide frequency response has revealed a reproducible pattern with three distinct components that we have labeled K1, K2, and K3. K1 is a low-amplitude, low-frequency signal that is present with cuff pressures above systolic pressure. K2 is a triphasic signal appearing at systolic pressure and disappearing at diastolic pressure, which approximately corresponds to the audible Korotkoff sound. K3 appears with cuff pressure between systolic and diastolic pressure and continues to be present below diastolic pressure. Intra-arterial pressure recordings made with a high-fidelity Millar catheter-tip manometer revealed K2 and K3 analogs. K3 resembles the intra-arterial pressure waveform and when calibrated according to the pulse pressure, noninvasive dK3/dt determinations correlated well with intra-arterial dP/dt measurements. The appearance/disappearance property of K2 was designated as the "K2 algorithm" and represents a new, objective noninvasive method for measurement of blood pressure. The K2 algorithm compares favorably with intra-arterial measurements, is more accurate than the auscultatory technique, and may be especially useful in clinical situations in which the auscultatory technique does not work well.
Comparison of Queen-Specific Gene Expression in Related Lower Termite Species
Authors: T. Weil, J. Korb, M. Rehli
Journal: Molecular Biology and Evolution (2009)

The molecular mechanisms regulating caste determination and reproductive division of labor, the hallmarks of insect societies, are poorly defined. The identification of key genes involved in these developmentally important processes will be essential to gain a better understanding of the mechanisms controlling one of the most impressive examples of polyphenism, the caste structure of eusocial species. Here, we applied representational difference analysis of cDNAs, to study differential gene expression between queens (female neotenics) and workers in the dry wood termite Cryptotermes cynocephalus and identified 13 genes that were highly expressed in queens. In addition, we partially cloned several homologous genes of the related termite species Cryptotermes secundus and compared the expression profiles of 10 homologous genes. In most cases, the preferential expression in female neotenics was not conserved between species, despite the close phylogenetic relationship of both Cryptotermes species. It is possible that these genes are associated with known species-specific differences in caste development modes. Only three genes (Neofem1, 2, and 3) showed a conserved and highly preferential expression in female neotenics, suggesting that their products may play important roles in female reproductives, in particular in controlling caste determination and reproductive division of labor.
Active Surveillance in Young Patients With Prostate Cancer: The Unanswered Question
Authors: Fabio Campodonico, Massimo Maffezzini
Journal: Journal of Clinical Oncology (2010)

In their long-term follow-up study on a cohort of 450 patients with low-risk prostate cancer managed with active surveillance, Klotz et al 1 reclassified 30% of patients as higher risk, thus requiring definitive therapy (radical prostatectomy or radiotherapy).The critical decision to offer deferred treatment is based on prostate-specific antigen kinetics and histology at rebiopsy.Notwithstanding no difference noted in overall survival between patients who remained on surveillance and those who underwent radical treatment, at a median follow-up of 6.8 years, some doubts remain for long-term outcomes in men reclassified as progressed who were referred to delayed treatment as noted by the authors.An uncertainty immediately arises, considering the median patient age was 70.3 years, and ongoing studies on prostate cancer, such as the European Prostate Cancer Research International: Active Surveillance (PRIAS) project, 2 offer active surveillance that include all patients.The Canadian study reported that patients received an initial biopsy according to the Vienna nomogram scheme of eight to 14 core biopsies, depending on patient age and gland volume.However, the study began in November 1995 and the Vienna nomogram 3 was published in 2005.Before 1998, no studies reported an extended prostate biopsy scheme, which is at least eight cores (sextant plus two lateral biopsies). 4Thus, it is likely that the cohort was not homogeneous in its accuracy of cancer risk definition among patients recruited at the beginning of the study and afterward.We think a more accurate initial biopsy schedule (the Vienna nomogram should be optimal) may enhance detection accuracy of patients at higher cancer risk in terms of the number of positive cores and reliability of the Gleason score, and, most importantly, identify the true low-risk patients suitable for surveillance.
Slow decision making by trusts impedes progress in practice based commissioning
Authors: A. O'Dowd
Journal: BMJ (2010)

Primary care trusts are still too slow to make decisions on proposals made by doctor led practice based commissioning groups, despite improved cooperation between them, a survey has shown.

Figures from the survey published by the Department of Health show that only 29% of people leading commissioning groups rated the speed of trusts’ decisions on proposals they put forward as being good, and more than one quarter considered that the quality of feedback was poor.

The BMA has described the statistics as “lamentable” and “disappointing” given that practice based commissioning has been in place since 2005.

The Practice based commissioning—group and independent leads survey: wave 3 results were based on 483 responses from lead individuals in commissioning …
ESE3/EHF Controls Epithelial Cell Differentiation and Its Loss Leads to Prostate Tumors with Mesenchymal and Stem-like Features
Authors: Domenico Albino, Nicole Longoni, Laura Curti, Maurizia Mello-Grand, Sandra Pinton, Gianluca Civenni, George Thalmann, Gioacchino D'Ambrosio, Manuela Sarti, Fausto Sessa, Giovanna Chiorino, Carlo V. Catapano, Giuseppina M. Carbone
Journal: Cancer Research (2012)

Cancer stem cells (CSC) play a significant role in tumor progression, disease recurrence, and treatment failure. Here, we show that the endogenously expressed ETS transcription factor ESE3/EHF controls prostate epithelial cell differentiation and stem-like potential. We found that loss of ESE3/EHF induced epithelial-to-mesenchymal transition (EMT), stem-like features, and tumor-initiating and metastatic properties in prostate epithelial cells, and reexpression of ESE3/EHF inhibited the stem-like properties and tumorigenic potential of prostate cancer cells. Mechanistically, ESE3/EHF repressed the expression of key EMT and CSC genes, including TWIST1, ZEB2, BMI1, and POU5F1. Analysis of human tissue microarrays showed that reduced ESE3/EHF expression is an early event in tumorigenesis, frequently occurring independently of other ETS gene alterations. Additional analyses linked loss of ESE3/EHF expression to a distinct group of prostate tumors with distinctive molecular and biologic characteristics, including increased expression of EMT and CSC genes. Low ESE3/EHF expression was also associated with increased biochemical recurrence of prostate cancer and reduced overall survival after prostatectomy. Collectively, our findings define a key role for ESE3/EHF in the development of a subset of prostate tumors and highlight the clinical importance of identifying molecularly defined tumor subgroups.
Endogenous Glutathione Conjugates: Occurrence and Biological Functions
Authors: W Wang, N Ballatori
Journal: Pharmacological Reviews (1998)

Glutathione (GSH)b performs a variety of important physiological and metabolic functions in all mammalian cells, including the detoxification of free radicals, metals, and other electrophilic compounds. One important detoxification mechanism involves the binding of GSH to electrophilic chemicals and
Isolated Loss of PMS2 Expression in Colorectal Cancers: Frequency, Patient Age, and Familial Aggregation
Authors: Sharlene Gill, Noralane M. Lindor, Lawrence J. Burgart, Regenia Smalley, Olga Leontovich, Amy J. French, Richard M. Goldberg, Daniel J. Sargent, Jeremy R. Jass, John L. Hopper, Mark A. Jenkins, Joanne Young, Melissa A. Barker, Michael D. Walsh, Andrew R. Ruszkiewicz, Stephen N. Thibodeau
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Most colorectal cancers that have high levels of microsatellite instability (MSI-H) show loss of immunohistochemical expression of proteins that participate in the DNA mismatch repair process, most often involving MLH1 and MSH2. Less commonly, a third DNA mismatch repair protein, MSH6, may also be lost as the primary event. Rarely, tumors with MSI-H show normal expression of these three proteins. The genetic deficiency leading to the MSI-H phenotype in such cases is unknown. PMS2 is another member of the DNA mismatch repair complex. Its expression is generally lost in tumors with MLH1 loss of expression. Rarely, there is selective loss of PMS2 expression. We sought to describe the frequency and clinical correlates of selective loss of expression of PMS2 with the MSI-H tumor phenotype. Experimental Design: Two thousand seven hundred nineteen colorectal cancers from both clinic- and research-based ascertainment were studied. Tumor MSI testing and immunohistochemistry for MLH1, MSH2, MSH6, and PMS2 were conducted. Medical records were abstracted for age at diagnosis, gender, colorectal cancer site, and family history. Results: Five hundred thirty-five of the 2,719 tumors were MSI-H. Of these, 93% showed loss of expression of MLH1, MSH2, and/or MSH6. Thirty-eight showed normal expression for these proteins. PMS2 immunohistochemical staining was successful in 32 of 38 of these tumors. Of the 32, 23 showed selective loss of expression of PMS2. This was associated with young age of diagnosis and right-sided location but not with a striking family history of cancer. Conclusions: Overall, 97% of the MSI-H tumors showed loss of expression for one or more of these four mismatch repair proteins. Selective loss of expression of PMS2 was present in 72% of cases in which colorectal cancers had an MSI-H phenotype but no alteration of expression of MLH1, MSH2, and MSH6. The underlying mechanism involved cannot be determined from this study but could involve point mutations in other DNA mismatch repair genes with retention of immunohistochemical expression, somatic inactivation of PMS2, or germ line mutation of PMS2.
Potential Liability for Transfusion-Associated AIDS-Reply
Authors: Patti J. Miller
Journal: JAMA (1986)

<h3>In Reply.—</h3> We are pleased to respond to the comments of Drs Menitove, Bove, and Westphal and are in total agreement with the assessment that our article presented exclusively the legal perspective. This caveat was stated in our article, while we also underscored the importance of medical, ethical, and political considerations. The following is in response to their specific comments. We seriously question Dr Westphal's statement that the safest blood comes from volunteer donors, not designated donors. To our knowledge, there are no prospective, controlled studies that have demonstrated that volunteer blood is safer. Likewise, we did not state that directed donations are safer. Our intent was to encourage the medical community to explore the legal implications of following established blood banking guidelines. We emphasize that designated donor blood should be subjected to routine screening procedures. The blood banking community's opposition to directed donations does not necessarily protect potential defendants
Suppression of Colorectal Oncogenesis by Selenium-Enriched Milk Proteins: Apoptosis and <i>K-ras</i> Mutations
Authors: Ying Hu, Graeme H. McIntosh, Richard K. Le Leu, Richard Woodman, Graeme P. Young
Journal: Cancer Research (2008)

Abstract The chemical form and bioavailability of dietary selenium may influence its protectiveness against colorectal cancer. Selenium is readily incorporated into milk proteins by feeding cows with selenized-yeast. This study examined whether a dairy source of organic selenium (as milk proteins) is more effective than a yeast source at inhibiting oncogenesis in carcinogen-treated mice and whether it regulates the homeostatic response to carcinogen-induced DNA damage. Dietary interventions are as follows: selenium-enriched milk protein isolate (Tatura-Bio Se; 0.5 or 1 ppm selenium) or milk protein control and selenized-yeast (Sel-Plex; 1 or 4 ppm selenium) with casein or casein alone as control. After 4 weeks on diet, mice received a single azoxymethane (10 mg/kg) injection to induce mutations and were killed 6 hours later. Measures were as follows: plasma selenium, cell proliferation, and acute apoptotic response to azoxymethane (AARGC). Separate groups of mice on the same diets were given 4 weekly azoxymethane (15 mg/kg) injections to induce oncogenesis. Mice were killed 6 or 30 weeks after the last azoxymethane injection. Measures were as follows: aberrant crypt foci (ACF), cancers, and K-ras mutations. Dairy-selenium at 1 ppm significantly suppressed ACF and cancers, whereas yeast-selenium at an equivalent selenium intake had no effect. Dairy-selenium significantly increased plasma selenium levels and AARGC, and reduced cell proliferation and frequency of K-ras mutations in ACF relative to an equivalent dose of selenium from yeast. Selenium-enriched milk protein isolate is superior to selenized-yeast in terms of its bioavailability and capacity to suppress oncogenesis. Suppression may be a consequence of enhanced apoptotic deletion of azoxymethane-induced DNA lesions and the subsequent reduction in frequency of K-ras mutations. [Cancer Res 2008;68(12):4936–44]
International Union of Pharmacology. LXXI. Free Fatty Acid Receptors FFA1, -2, and -3: Pharmacology and Pathophysiological Functions
Authors: Leigh A. Stoddart, Nicola J. Smith, Graeme Milligan
Journal: Pharmacological Reviews (2008)

Identification of G protein-coupled receptors that are activated by free fatty acids has led to considerable interest in their pharmacology and function because of the wide range of normal physiology and disease states in which fatty acids have been implicated. Free fatty acid receptor (FFA) 1 is activated by medium- to long-chain fatty acids and is expressed in the insulin-producing β-cells of the pancreas. Activation of FFA1 has been proposed to mediate fatty acid augmentation of glucose-stimulated insulin secretion although it is unclear whether the known long-term detrimental effects of β-cell exposure to high levels of fatty acids are also mediated through this receptor. The related receptors FFA2 and FFA3 are both activated by short-chain fatty acids although they have key differences in the signaling pathways they activate and tissue expression pattern. The aim of this review is to provide a comprehensive overview of the current understanding of the pharmacology and physiological role of these fatty acid receptors.