tbuckley/cabot-search huggingface dataset:
Methods for the Assessment of Endobronchial Biopsies in Clinical Research
Authors: Peter Jeffery, Stephen Holgate, Sally Wenzel
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

The capacity to sample directly the conducting airway tissue of subjects with asthma or chronic obstructive pulmonary disease (COPD) for comparison with tissue obtained from normal, healthy individuals has generated hypotheses and advanced our understanding of pathogenesis. Such studies in adults are now being extended, with informed consent and ethical approval, to include children. In adults, approval to obtain endobronchial biopsies on more than one occasion has also allowed us to begin to test whether or not therapeutic intervention will significantly reduce airway inflammation or restore altered tissue structure (i.e., remodeling) to normal. Endobronchial biopsy has been considered by some the standard by which to compare the validity and interpretation of results obtained by indirect, less invasive means, such as bronchoalveolar lavage (BAL) and induced sputum.
CD40-Mediated Activation of Chronic Lymphocytic Leukemia Cells Promotes Their CD44-Dependent Adhesion to Hyaluronan and Restricts CCL21-Induced Motility
Authors: Tamara Girbl, Elisabeth Hinterseer, Eva Melanie Grössinger, Daniela Asslaber, Karin Oberascher, Lukas Weiss, Cornelia Hauser-Kronberger, Daniel Neureiter, Hubert Kerschbaum, David Naor, Ronen Alon, Richard Greil, Tanja Nicole Hartmann
Journal: Cancer Research (2012)

Abstract Microenvironmental interactions are crucial for the survival and proliferation of chronic lymphocytic leukemia (CLL) cells. CD4+ T cells that express CD40 ligand (CD40L), along with other accessory immune and stromal cells within CLL lymph nodes, provide signals needed for activation and outgrowth of the tumor clone. Furthermore, correct positioning of CLL cells within lymphoid subcompartments is essential for the transmission of these supportive signals. Thereby, interstitial cell migration and adhesion events, influenced by activational stimuli, determine CLL cell localization. CD44 has been implicated in cell activation, migration, and tissue retention via binding to its extracellular matrix ligand hyaluronan (HA). In this study, we investigated the role of CD44–HA interactions for CLL positioning and interaction with supportive microenvironments in peripheral lymph nodes, focusing on its regulation via CD40L-dependent, T-cell–mediated activation of CLL cells. We found that hyaluronan triggered a robust CCL21-induced motility of resting CLL cells. However, CD40L stimulation promoted the firm, CD44-mediated adhesion of CLL cells to hyaluronan, antagonizing their motile behavior. N-linked glycosylations of CD44, particularly associated with the variant isoform CD44v6 after CD40L activation, seemed to facilitate hyaluronan recognition by CD44. We propose that the CD40L–CD40 signaling axis provides a stop signal to motile CLL cells within lymph node compartments by inducing high avidity CD44–HA adhesion. This might retain CLL cells close to T-cell stimuli and facilitate essential interactions with hyaluronan-bearing stromal cells, collectively promoting CLL cell proliferation and survival. Cancer Res; 73(2); 561–70. ©2012 AACR.
Discontinuation of Pneumocystis carinii pneumonia prophylaxis after start of highly active antiretroviral therapy in HIV-1 infection
Authors: Gerrit J Weverling, Amanda Mocroft, Bruno Ledergerber, Ole Kirk, Juan Gonzales-Lahoz, Antonella d'Arminio Monforte, Rui Proenca, Andrew N Phillips, Jens D Lundgren, Peter Reiss
Journal: The Lancet (1999)
Enterolith With Pseudogallstone Ileus
Authors: Guy J. Pieters
Journal: JAMA (1971)

<h3>To the Editor.—</h3> Gallstone ileus is a rare but well-defined entity that usually can be recognized easily at surgery. We report a case that closely resembled gallstone ileus but which was caused by a "pseudogallstone." <h3>Report of a Case.—</h3> A 55-year-old Tunisian farmer entered the hospital because of vomiting and abdominal pain. For several months he had noted vague diffuse abdominal pain. During the week before admission the pain became cramp-like and intense; there was bilious vomiting and obstipation. On examination the temperature was normal but he was hypotensive and oliguric. The abdomen was distended, tense, and tender throughout. The white blood cell count was 12,500/cu mm, red blood cell count was 3,900,000/ cu mm, and hemoglobin value was 42%. A plain film of the abdomen revealed an ovoid calculus in the pelvis. Small bowel distension was present. About three hours after admission the patient underwent laparotomy. Generalized peritonitis was
Effect of certirizine on histamine‐induced bronchoconstriction and bronchoalveolar cells
Authors: M. Söderberg, R. Lundgren, T. ÅNgström
Journal: Allergy (1991)

The effect of the histamine H1 receptor antagonist (cetirizine) on histamine‐induced bronchoconstriction and inflammatory cells in bronchoalveolar lavage fluid was studied in 12 healthy volunteers. In previous studies we have observed an increased number of inflammatory cells, albumin and hyaluronan in the bronchoalveolar lavage (BAL) fluid 24 h after an inhalation challenge test with histamine‐chloride. In the present study certirizine blocked the histamine‐induced bronchoconstriction but did not influence the cell counts in the bronchoalveolar lavage fluid. Our result suggests that the histamine‐induced bronchoconstriction but not the recruitment of inflammatory cells in the BAL fluid is mediated by histamine HI receptors.
Leaping for leptin: the 2010 Albert Lasker Basic Medical Research Award goes to Douglas Coleman and Jeffrey M. Friedman
Authors: Ushma S. Neill
Journal: Journal of Clinical Investigation (2010)

From Canada to Maine Douglas Coleman was raised in Ontario, Canada, the only child of English immigrant parents, who encouraged him to excel in school; he recalled, "Although my parents never had the luxury of completing high school, they always encouraged me to pursue a higher education, and in high school, I developed a keen interest in chemistry and biology."Coleman pursued his interest in chemistry at McMaster University.It was there he met his future wife, Beverly Benallick, "the only girl to graduate in Chemistry in the Class of 1954."During his time at McMaster University, Coleman began to focus on organic chemistry and had the fortune of working with, "a very dynamic professor, Sam Kirkwood, who not only taught me the rudiments of biochemistry, but also instilled an appreciation of the scientific method."Kirkwood encouraged Coleman to continue
Exaggerated phosphaturic response to circulating parathyroid hormone in patients with familial X-linked hypophosphatemic rickets.
Authors: E Short, R C Morris, A Sebastian, M Spencer
Journal: Journal of Clinical Investigation (1976)

To determine whether the phosphaturic response to circulating parathyroid hormone (PTH) is exaggerated in patients with familial x-linked hypophosphatemic vitamin D-resistant rickets (FHR), we examined the phosphaturic response to parathyroid extract (PTE) (administered intravenously in the posthypercalcemic state) in two unrelated adult hemizygotes with FHR. In these two patients whose plasma concentration of PTH was normal (determined by radioimmunoassay). neither vitamin D nor phosphate therapy had been given during the past 10 yr. Two normal men and a hypophosphatemic man with intestinal malabsorption, hypocalcemia, and osteomalacia served as control subjects. In all subjects, calcium gluconate was adminstered intravenously from 6 p.m. to 12 midnight at a rate that maintained the concentration of serum calcium at 13-15 mg/100 ml during the administration of calcium. When normocalcemia had recurred the next morning, and the plasma PTH concentration and urinary excretion of cyclic 3', 5'-AMP were reduced. PTE was administered intravenously at successively increasing rates of 0.1, 0.4, and 0.8 U/kg per h, each rate lasting 90 min. Minutes after the initiation of PTE in the affected hemizygotes, fractional excretion of filtered phosphate increased from negligible values to values strikingly greater than those of similarly studied control subjects and plateaued at strikingly greater values throughout further administration of PTE. This phenomenon of exaggerated phosphaturia could not be attributed to volume expansion, decreases in serum concentration of calcium during the study, differences in percent of administered calcium retained, or hemodynamic changes. Only the phosphaturic response to PTE appeared to be exaggerated. At any cumulative dose of PTE, urinary excretion of cyclic 3', 5'-AMP in the hemizogytes was indistinguishable from that of control subjects. The findings in this study suggest that in patients with FHR, circulating PTH is required for the genetically transmitted abnormality to be physiologically expressed as a reduction in net renal reabsorption of phosphate, and that this physiological expression of the genetic abnormality is expressed fully at normal or nearly normal circulating levels of PTH.
Amphiregulin and Epiregulin mRNA Expression in Primary Tumors Predicts Outcome in Metastatic Colorectal Cancer Treated With Cetuximab
Authors: Bart Jacobs, Wendy De Roock, Hubert Piessevaux, Robin Van Oirbeek, Bart Biesmans, Jef De Schutter, Steffen Fieuws, Jo Vandesompele, Marc Peeters, Jean-Luc Van Laethem, Yves Humblet, Frederique Pénault-Llorca, Gert De Hertogh, Pierre Laurent-Puig, Eric Van Cutsem, Sabine Tejpar
Journal: Journal of Clinical Oncology (2009)

To study the power of the epidermal growth factor receptor (EGFR) epiregulin (EREG) and amphiregulin (AREG) ligands' expression in primary tumors to predict the outcome in patients with chemorefractory metastatic colorectal cancer (cmCRC) treated with the combination of cetuximab and irinotecan.Gene expression measurements and KRAS mutation analysis were performed on archival formalin-fixed paraffin-embedded primary tumors of 220 cmCRC patients. Response was measured using RECIST (Response Evaluation Criteria in Solid Tumors) criteria. The relation between ligand expression levels and outcome was evaluated using logistic regression for response and Cox regression for survival data. Receiver operating characteristics analysis was performed for response and survival data. CIs for the performance indices were obtained with a nonparametric bootstrap procedure. Findings were externally validated on a series of 67 samples treated in a similar setting.In KRAS wild type (WT) patients, there was a significant association between log-transformed ligand expression and response for EREG (odds ratio for objective response, 1.90; 95% CI, 1.27 to 2.83; P = .0005; concordance index [c-index], 0.681) and for AREG (odds ratio for objective response, 1.862; 95% CI, 1.22 to 2.72; P = .0017; c-index, 0.673). In a Cox regression model, dichotomized ligand expression was significantly associated with progression-free survival (PFS) and overall survival (OS). EREG PFS hazard ratio (HR) was 0.41 (95% CI, 0.274 to 0.609; P < .001; time-dependent c-index [Ctau index], 0.640), and AREG PFS HR was 0.43 (95% CI, 0.29 to 0.64; P < .001; Ctau index, 0.627). EREG OS HR was 0.42 (95% CI, 0.28 to 0.63; P < .0001; Ctau index, 0.639), and AREG OS HR was 0.40 (95% CI, 0.27 to 0.64; P < .0001; Ctau index, 0.625). There was no predictive power of ligand expression in patients with KRAS mutation.Expression of EGFR ligands in primary tumors significantly predicts outcome in KRAS WT cmCRC treated with cetuximab and irinotecan.
Dobutamine potentiates amrinone's beneficial effects in moderate but not in advanced heart failure. 31P-MRS in isolated hamster hearts.
Authors: P T Buser, W Auffermann, S T Wu, G Jasmin, W W Parmley, J Wikman-Coffelt
Journal: Circulation Research (1990)

There is controversy as to whether potent inotropic agents are beneficial or detrimental in moderate to severe heart failure. Accordingly, we studied the effects of amrinone, amrinone plus dobutamine, and dobutamine alone on mechanical performance, myocardial oxygen consumption, and high energy phosphate metabolism in different stages of congestive heart failure in the cardiomyopathic Syrian hamster. In hearts with moderate heart failure, administration of amrinone, amrinone plus dobutamine, and dobutamine alone increased developed pressure significantly, whereas the phosphorylation potential increased significantly only with amrinone and amrinone plus dobutamine. In hearts with advanced heart failure, administration of amrinone and amrinone plus dobutamine increased developed pressure significantly, whereas dobutamine alone had no effect. The phosphorylation potential improved significantly only with amrinone. Thus, amrinone improved mechanical performance and mitochondrial activity in both heart failure states. Dobutamine potentiated amrinone's beneficial effects in moderate heart failure, but negated the positive inotropic effect of amrinone in advanced heart failure. Therefore, hearts responded differently to potent inotropic agents depending on the severity of heart failure.
Why Physicians Participate in Executions
Authors: Bruce E Ellerin
Journal: New England Journal of Medicine (2006)

Gawande makes contradictory and thus unpersuasive statements. Although he believes that “some human beings . . . do such evil as to deserve to die,” he still would like “a legal ban on the participation of physicians . . . in executions.” His reason, that “the medical assistance provided primarily serves the government’s purposes,” overlooks the reality that in the United States, “the government” is us and prisoners are execut-ed by “we the people.” I do not personally favor, nor do I participate in, executions, but until the law changes, I believe we owe it to the condemned to ensure that they die quickly and painlessly; do-ing so serves the interests of both the prisoner and society.Gawande also says “the government actively subverts core ethical principles of medical prac-tice.” How so? Government merely asks physicians to make an independent decision to help; there is no coercion whatsoever.Finally, the guidelines of the American Medi-cal Association (AMA) are equally illogical. Their policy that pronouncing death is unethical but certifying it is ethical seems a rationalized dis-tinction without a difference.Lawrence I. Bonchek, M.D.
Intrapleural urokinase in the treatment of complicated parapneumonic pleural effusions and empyema
Authors: D Bouros, S Schiza, N Tzanakis, J Drositis, N Siafakas
Journal: European Respiratory Journal (1996)

Intrapleural urokinase has not been evaluated systemically in terms of efficacy, safety, and cost of treatment in a large series of patients with complicated (parapneumonic) pleural effusions (CPE) and pleural empyemas (PE). Furthermore, the optimal dose and duration of treatment is not known. Twenty consecutive patients with multiloculated parapneumonic effusions (13 with CPE and 7 with PE), in whom a single chest tube failed to drain the fluid, were studied prospectively. The age of the patients ranged 15-92 yrs (median 51 yrs). Urokinase was administered intrapleurally, in a low single daily dose of 50,000 U in 100 mL normal saline via the chest tube. Previous intrapleural instillation of 100 mL normal saline failed to promote drainage in all patients. Urokinase enhanced drainage in all patients. Clinical and radiological improvement was noted in all but one patient. The mean (SD) volume of fluid significantly increased in the first 24 h post-urokinase (p&lt;0.001). The number of urokinase instillations ranged 3-7 (median 5). Radiological evaluation showed excellent improvement in 13 of the 20 (65%) patients. Urokinase was well-tolerated in all patients. The clinical course of patients was uneventful at a mean follow-up of 15 months (range 6-30 months) later. Mean total cost of treatment was $530 +/- 34.6. Our results show that intrapleural instillation of small doses of urokinase is a cost-effective and safe mode of treatment of complicated pleural effusions and pleural empyema and could be the fibrinolytic of choice.
Cytochrome P4502E1 is present in rat pancreas and is induced by chronic ethanol administration
Authors: I D Norton, M V Apte, P S Haber, G W McCaughan, R C Pirola, J S Wilson
Journal: Gut (1998)

The mechanisms responsible for the initiation of alcoholic pancreatitis remain elusive. However, there is an increasing body of evidence that reactive oxygen species play a role in both acute and chronic pancreatitis. In the liver, cytochrome P4502E1 (CYP2E1, the inducible ethanol metabolising enzyme) is one of the proposed pathways by which ethanol induces oxidative stress.To determine whether CYP2E1 is present in the pancreas and, if so, whether it is inducible by chronic ethanol feeding.Eighteen male Sprague-Dawley rats were pair fed liquid diets with or without ethanol as 36% of energy for four weeks. CYP2E1 levels were determined by western blotting of microsomal protein from both pancreas and liver. Messenger RNA (mRNA) levels for CYP2E1 were quantified using dot blots of total pancreatic RNA.CYP2E1 was found in the pancreas. Furthermore, the amount of CYP2E1 was greater in the pancreas of rats fed ethanol compared with controls (mean increase over controls 5.1-fold, 95% confidence intervals 2.4 to 7.7, p < 0.02). In the liver, induction by ethanol of CYP2E1 was similar (mean increase over controls 7.9-fold, 95% confidence intervals 5.2 to 10.6, p < 0.005). Pancreatic mRNA levels for CYP2E1 were similar in ethanol fed and control rats.CYP2E1 is present in the rat pancreas and is inducible by chronic ethanol administration. Induction of pancreatic CYP2E1 is not regulated at the mRNA level. The metabolism of ethanol via CYP2E1 may contribute to oxidative stress in the pancreas during chronic ethanol consumption.
E2F3a Is Critically Involved in Epidermal Growth Factor Receptor–Directed Proliferation in Ovarian Cancer
Authors: Daniel Reimer, Michael Hubalek, Svenja Riedle, Sergej Skvortsov, Martin Erdel, Nicole Concin, Heidi Fiegl, Elisabeth Müller-Holzner, Christian Marth, Karl Illmensee, Peter Altevogt, Alain G. Zeimet
Journal: Cancer Research (2010)

We describe for the first time a new integral molecular pathway, linking transcription factor E2F3a to epidermal growth factor receptor (EGFR) activation in ovarian cancer cells. Investigations on the role of E2F family members in EGFR-mediated mitogenic signaling revealed that E2F3a was selectively upregulated following EGFR activation, whereas all other E2F family members remained unaffected. In contrast, EGF treatment of healthy ovarian surface epithelial and mesothelial cells yielded a selective upregulation of proliferation-promoting E2F1 and E2F2 without influencing E2F3a expression. In ovarian cancer cell lines, the extent of EGF-induced proliferative stimulus was closely related to the magnitude of E2F3a increase, and proliferation inhibition by E2F3a knockdown was not overcome by EGF exposure. Furthermore, the EGFR-E2F3a axis was found to be signal transducer and activator of transcription 1/3 dependent and the ratio of IFN-regulatory factor (IRF)-1 to IRF-2 was shown to be determinative for E2F3a control. In a pilot study on 32 primary ovarian cancer specimens, a highly significant correlation between activated EGFR and E2F3a expression was disclosed. This new integral pathway in the EGFR-driven mitogenic cell response, which through its key player E2F3a was found to be essential in triggering proliferation in ovarian cancer cells, provides new insights into EGFR signaling and could represent the basis for appealing new therapeutic approaches in ovarian cancer.
Prevalence and risk factors of the metabolic syndrome in adult survivors of childhood leukemia
Authors: Claire Oudin, Marie-Claude Simeoni, Nicolas Sirvent, Audrey Contet, Audrey Begu-Le Coroller, Pierre Bordigoni, Catherine Curtillet, Maryline Poirée, Isabelle Thuret, Barbara Play, Mara Carazza Massot, Pascal Chastagner, Hervé Chambost, Pascal Auquier, Gérard Michel
Journal: Blood (2011)
Endothelial protein C receptor is overexpressed in rheumatoid arthritic (RA) synovium and mediates the anti-inflammatory effects of activated protein C in RA monocytes
Authors: M. Xue, L. March, P. N Sambrook, K. Fukudome, C. J Jackson
Journal: Annals of the Rheumatic Diseases (2007)

<h3>Objectives:</h3> (1) To investigate whether inflammatory synovial tissues from patients with rheumatoid arthritis (RA) express endothelial protein C receptor (EPCR) and (2) to determine the major cell type(s) that EPCR is associated with and whether EPCR functions to mediate the effects of activated protein C (APC) on these cells. <h3>Methods:</h3> EPCR, CD68 and PC/APC in synovial tissues were detected by immunostaining and in situ PCR. Monocytes were isolated from peripheral blood of patients with RA and treated with APC, lipopolysaccharide (LPS), and/or EPCR blocking antibody RCR252. Cells and supernatants were collected for RT-PCR, western blotting, enzyme-linked immuosorbent assay and chemotaxis assay. Results: EPCR was expressed by both OA and RA synovial tissues but was markedly increased in RA synovium. EPCR was colocalised with PC/APC mostly on CD68 positive cells in synovium. In RA monocytes, APC upregulated EPCR expression and reduced monocyte chemoattractant protein-1-induced chemotaxis of monocytes by approximately 50%. APC also completely suppressed LPS-stimulated NF-κB activation and attenuated TNF-α protein by more than 40% in RA monocytes. The inhibitory effects of APC were reversed by RCR252, indicating that EPCR is required. <h3>Conclusions:</h3> Our results demonstrate for the first time that EPCR is expressed by synovial tissues, particularly in RA, where it co-localises with PC/APC on monocytes/macrophages. In addition, APC inhibits the migration and activation of RA monocytes via EPCR. These inhibitory effects on RA monocytes suggest that PC pathway may have a beneficial therapeutic effect in RA.
Rheumatology beyond 2000: wither or whither?
Authors: W W Buchanan, P M Brooks
Journal: Annals of the Rheumatic Diseases (1989)

Still thou art blest, compar'd wi' me The present only toucheth thee: But och!I backward cast my e'e, On prospects drear!An' forward, tho' I canna see, I guess an', fear!ROBERT BURNS (1759-1796) 'To a mouse Many of the rheumatology societies in the Western World have now celebrated their first half-century anniversary and have rightly congratulated them- selves on their achievements.Achievements there certainly have been-the unravelling of the path- ways of purine biochemistry with control of gouty arthritis, the applications of advances in immunolo- gy to the diagnosis and management of connective tissue diseases, the treatment of septic arthritis and prevention of recurrent attacks of rheumatic fever with antibiotic therapy, and the replacement of severely damaged joints by artificial prostheses.1 2In addition, much basic information has been gathered on the biochemistry of connective tissues, the mechanics of joint lubrication and movement, the pharmacology of inflammation, the genetics of the HLA system, and the modes of action of antirheumatic drugs.Simultaneously and equally with these advances there has been an increase in membership of rheumatology societies world wide, associated with increasing numbers of abstracts and papers submitted to the ever burgeoning number of international meetings and journals.