tbuckley/cabot-search huggingface dataset:
Clinical Relevance of the i(12p) Chromosome in Germ cell Tumors
Authors: G. J. Bosl, D. H. Ilson, E. Rodriguez, R. J. Motzer, V. E. Reuter, R. S.K. Chaganti
Journal: JNCI Journal of the National Cancer Institute (1994)

Journal Article Clinical Relevance of the i(12p) Chromosome in Germ cell Tumors Get access George J. Bosl, George J. Bosl * 1Gemtourinary Oncology Service, Division of Solid Tumor Oncology. Department of Medicine, Memorial Sloan-Kettering Cancer CenterNew York, N.Y. * George J. Bosl. M.D., Memorial Hospital, 1275 York Ave., New York, NY 10021. Search for other works by this author on: Oxford Academic PubMed Google Scholar David H. Ilson, David H. Ilson 1Gemtourinary Oncology Service, Division of Solid Tumor Oncology. Department of Medicine, Memorial Sloan-Kettering Cancer CenterNew York, N.Y. Search for other works by this author on: Oxford Academic PubMed Google Scholar Eduardo Rodriguez, Eduardo Rodriguez 2Department of Pathology and the Program in Cell Biology and Genetics. Memorial Sloan-Kettering Cancer Center Search for other works by this author on: Oxford Academic PubMed Google Scholar Robert J. Motzer, Robert J. Motzer 1Gemtourinary Oncology Service, Division of Solid Tumor Oncology. Department of Medicine, Memorial Sloan-Kettering Cancer CenterNew York, N.Y. Search for other works by this author on: Oxford Academic PubMed Google Scholar Victor E. Reuter, Victor E. Reuter 3Department of Pathology, Memorial Sloan-Kettering Cancer Center Search for other works by this author on: Oxford Academic PubMed Google Scholar Raju S.K. Chaganti Raju S.K. Chaganti 2Department of Pathology and the Program in Cell Biology and Genetics. Memorial Sloan-Kettering Cancer Center Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 5, 2 March 1994, Pages 349–355, https://doi.org/10.1093/jnci/86.5.349 Published: 02 March 1994 Article history Received: 24 August 1993 Revision received: 09 November 1993 Accepted: 17 November 1993 Published: 02 March 1994
Post-treatment, Long-term Clinical Efficacy Of A 300 IR Sublingual Tablet of 5-grass Pollen Allergen Extract In Adults With Grass Pollen-induced Allergic Rhinoconjunctivitis
Authors: H. Malling, A. Didier, F. Horak, M. Worm, O. de Beaumont, P. Rodriguez, A. Montagut, R.K. Zeldin
Journal: Journal of Allergy and Clinical Immunology (2012)
ATP Release From Activated Neutrophils Occurs via Connexin 43 and Modulates Adenosine-Dependent Endothelial Cell Function
Authors: Holger K. Eltzschig, Tobias Eckle, Alice Mager, Natalie Küper, Christian Karcher, Thomas Weissmüller, Kerstin Boengler, Rainer Schulz, Simon C. Robson, Sean P. Colgan
Journal: Circulation Research (2006)

Extracellular ATP liberated during hypoxia and inflammation can either signal directly on purinergic receptors or can activate adenosine receptors following phosphohydrolysis to adenosine. Given the association of polymorphonuclear leukocytes (PMNs) with adenine-nucleotide/nucleoside signaling in the inflammatory milieu, we hypothesized that PMNs are a source of extracellular ATP. Initial studies using high-performance liquid chromatography and luminometric ATP detection assays revealed that PMNs release ATP through activation-dependent pathways. In vitro models of endothelial barrier function and neutrophil/endothelial adhesion indicated that PMN-derived ATP signals through endothelial adenosine receptors, thereby promoting endothelial barrier function and attenuating PMN/endothelial adhesion. Metabolism of extracellular ATP to adenosine required PMNs, and studies addressing these metabolic steps revealed that PMN express surface ecto-apyrase (CD39). In fact, studies with PMNs derived from cd39 −/− mice showed significantly increased levels of extracellular ATP and lack of ATP dissipation from their supernatants. After excluding lytic ATP release, we used pharmacological strategies to reveal a potential mechanism involved in PMN-dependent ATP release (eg, verapamil, dipyridamole, brefeldin A, 18-α-glycyrrhetinic acid, connexin-mimetic peptides). These studies showed that PMN ATP release occurs through connexin 43 (Cx43) hemichannels in a protein/phosphatase-A–dependent manner. Findings in human PMNs were confirmed in PMNs derived from induced Cx43 −/− mice, whereby activated PMNs release less than 15% of ATP relative to littermate controls, whereas Cx43 heterozygote PMNs were intermediate in their capacity for ATP release ( P &lt;0.01). Taken together, our results identify a previously unappreciated role for Cx43 in activated PMN ATP release, therein contributing to the innate metabolic control of the inflammatory milieu.
F-box protein complex FBXL19 regulates TGFβ1-induced E-cadherin down-regulation by mediating Rac3 ubiquitination and degradation
Authors: Su Dong, Jing Zhao, Jianxin Wei, Rachel K Bowser, Andrew Khoo, Zhonghui Liu, James D Luketich, Arjun Pennathur, Haichun Ma, Yutong Zhao
Journal: Molecular Cancer (2014)

Rac3 is a small GTPase multifunctional protein that regulates cell adhesion, migration, and differentiation. It has been considered as an oncogene in breast cancer; however, its role in esophageal cancer and the regulation of its stability have not been studied. F-box proteins are major subunits within the Skp1-Cullin-1-F-box (SCF) E3 ubiquitin ligases that recognize particular substrates for ubiquitination and proteasomal degradation. Recently, we have shown that SCFFBXL19 targets Rac1 and RhoA, thus regulating Rac1 and RhoA ubiquitination and degradation. Here, we demonstrate the role of FBXL19 in the regulation of Rac3 site-specific ubiquitination and stability. Expression of TGFβ1 is associated with poor prognosis of esophageal cancer. TGFβ1 reduces tumor suppressor, E-cadherin, expression in various epithelial-derived cancers. Here we investigate the role of FBXL19-mediated Rac3 degradation in TGFβ1-induced E-cadherin down-regulation in esophageal cancer cells. FBXL19-regulated endogenous and over-expressed Rac3 stability were determined by immunoblotting and co-immunoprecipitation. Esophageal cancer cells (OE19 and OE33) were used to investigate TGFβ1-induced E-cadherin down-regulation by Immunoblotting and Immunostaining. Overexpression of FBXL19 decreased endogenous and over-expressed Rac3 expression by interacting and polyubiquitinating Rac3, while down-regulation of FBXL19 suppressed Rac3 degradation. Lysine166 within Rac3 was identified as an ubiquitination acceptor site. The FBXL19 variant with truncation at the N-terminus resulted in an increase in Rac3 degradation; however, the FBXL19 variant with truncation at the C-terminus lost its ability to interact with Rac3 and ubiquitinate Rac3 protein. Further, we found that Rac3 plays a critical role in TGFβ1-induced E-cadherin down-regulation in esophageal cancer cells. Over-expression of FBXL19 attenuated TGFβ1-induced E-cadherin down-regulation and esophageal cancer cells elongation phenotype. Collectively these data unveil that FBXL19 functions as an antagonist of Rac3 by regulating its stability and regulates the TGFβ1-induced E-cadherin down-regulation. This study will provide a new potential therapeutic strategy to regulate TGFβ1 signaling, thus suppressing esophageal tumorigenesis.
Effects of acutely induced hypertension in cats on pial arteriolar caliber, local cerebral blood flow, and the blood-brain barrier.
Authors: E T MacKenzie, S Strandgaard, D I Graham, J V Jones, A M Harper, J K Farrar
Journal: Circulation Research (1976)

Acute hypertension was induced in 19 anesthetized cats by the intravenous administration of angiotensin. The caliber of pial arteries was measured by a television image-splitting technique and local cerebral blood flow by the hydrogen clearance technique. As the blood pressure was increased, pail arterioles constricted and cerebral blood flow remained relatively constant, showing that autoregulation of cerebral blood flow was intact. At mean arterial pressures of more than 170 mm Hg arteriolar dilation appeared. In smaller arterioles (initial diameter less than 100 mum) a segmental dilation (the "sausage'string" phenomenon) frequently preceded uniform dilation. This arteriolar dilation was associated with a marked increase in local cerebral blood flow indicating that the upper level of autoregulation had been breached. In no cat was vasospasm or a decrease in blood flow observed during induced hypertension. Hypertension also caused dysfunction of the bloodbrain barrier since, in 17 out of 19 of the cats examined, there was extravasation of protein-bound Evans blue into brain tissue. In only one of the 19 cats subjected to neuropathological analysis was ischemic brain damage identified and this was restricted to minimal ischemic cell change. The results indicate that severe, induced hypertension in cats produces cerebral arteriolar dilation, an increase of cerebral blood flow, and dysfunction of the blood-brain barrier. These observations may be of importance in understanding the pathogenesis of hypertensive encephalopathy.
Placebo-Controlled, Double-Blind, Prospective, Randomized Study on the Effect of Octreotide LAR in the Control of Tumor Growth in Patients With Metastatic Neuroendocrine Midgut Tumors: A Report From the PROMID Study Group
Authors: Anja Rinke, Hans-Helge Müller, Carmen Schade-Brittinger, Klaus-Jochen Klose, Peter Barth, Matthias Wied, Christina Mayer, Behnaz Aminossadati, Ulrich-Frank Pape, Michael Bläker, Jan Harder, Christian Arnold, Thomas Gress, Rudolf Arnold
Journal: Journal of Clinical Oncology (2009)

Somatostatin analogs are indicated for symptom control in patients with gastroenteropancreatic neuroendocrine tumors (NETs). The ability of somatostatin analogs to control the growth of well-differentiated metastatic NETs is a matter of debate. We performed a placebo-controlled, double-blind, phase IIIB study in patients with well-differentiated metastatic midgut NETs. The hypothesis was that octreotide LAR prolongs time to tumor progression and survival.Treatment-naive patients were randomly assigned to either placebo or octreotide LAR 30 mg intramuscularly in monthly intervals until tumor progression or death. The primary efficacy end point was time to tumor progression. Secondary end points were survival time and tumor response. This report is based on 67 tumor progressions and 16 observed deaths in 85 patients at the time of the planned interim analysis.Median time to tumor progression in the octreotide LAR and placebo groups was 14.3 and 6 months, respectively (hazard ratio [HR] = 0.34; 95% CI, 0.20 to 0.59; P = .000072). After 6 months of treatment, stable disease was observed in 66.7% of patients in the octreotide LAR group and 37.2% of patients in the placebo group. Functionally active and inactive tumors responded similarly. The most favorable effect was observed in patients with low hepatic tumor load and resected primary tumor. Seven and nine deaths were observed in the octreotide LAR and placebo groups, respectively. The HR for overall survival was 0.81 (95% CI, 0.30 to 2.18).Octreotide LAR significantly lengthens time to tumor progression compared with placebo in patients with functionally active and inactive metastatic midgut NETs. Because of the low number of observed deaths, survival analysis was not confirmatory.
Repair of erosions occurs almost exclusively in damaged joints without swelling
Authors: C. Lukas, D. van der Heijde, S. Fatenajad, R. Landewe
Journal: Annals of the Rheumatic Diseases (2009)

<h3>Background</h3> Negative radiographic change scores obtained under blinded time-sequence conditions suggest that repair of joints may indeed occur. It is likely that, if repair truly exists, it would be preferentially seen in clinically inactive joints from patients treated with drugs with well-known structural efficacy. <h3>Objective</h3> To determine whether repair is associated with both the absence or improvement of swelling and with treatment. <h3>Patients and methods</h3> Radiographs from patients of the TEMPO trial were scored twice by two readers according to the Sharp–van der Heijde score, blinded to both treatment and true time sequence. Single-joint change scores in erosions were coupled with single-joint swelling scores obtained from clinical examination. Consistency of observed improvement across readers and repeat reads was described, and factors expected to increase the likelihood of occurrence of both worsening and improvement of erosion were tested by generalised estimating equations (GEE) modelling. <h3>Results</h3> In all of the four independent reads, the mean change in erosion score was statistically significantly negative only in the subgroup of joints with absent or improved swelling, when erosions were present at baseline. Multivariate analysis showed that worsening of the erosion score in a joint was significantly increased if that joint was already damaged at study entry, clinical swelling persisted and methotrexate was used instead of etanercept. Repair was associated with improvement of swelling and use of etanercept (p≤0.007 for all associations). <h3>Conclusion</h3> Repair of erosions almost exclusively occurs in joints with improvement or absence of swelling, in patients treated with etanercept. Progression is seen more frequently in joints with persistent swelling, in patients receiving methotrexate monotherapy, primarily if damage is already present.
Transcriptional Repression of Epithelial Cell Adhesion Molecule Contributes to p53 Control of Breast Cancer Invasion
Authors: Narendra V. Sankpal, Michael W. Willman, Timothy P. Fleming, John D. Mayfield, William E. Gillanders
Journal: Cancer Research (2009)

p53 is a tumor suppressor gene with well-characterized roles in cell cycle regulation, apoptosis, and maintenance of genome stability. Recent evidence suggests that p53 may also contribute to the regulation of migration and invasion. Epithelial cell adhesion molecule (EpCAM) is a transmembrane glycoprotein that is overexpressed in the majority of human epithelial carcinomas, including breast and colorectal carcinomas. We show by chromatin immunoprecipitation assays that p53 interacts with a candidate p53 binding site within the EpCAM gene. p53-mediated transcriptional repression of EpCAM was confirmed in gain-of-function and loss-of-function experimental systems. Induction of wild-type p53 was associated with a significant dose-dependent decrease in EpCAM expression; conversely, specific ablation of p53 was associated with a significant increase in EpCAM expression. At the functional level, specific ablation of p53 expression is associated with increased breast cancer invasion, and this effect is abrogated by concomitant specific ablation of EpCAM expression. Taken together, these biochemical and functional data are the first demonstration that (a) wild-type p53 protein binds to a response element within the EpCAM gene and negatively regulates EpCAM expression, and (b) transcriptional repression of EpCAM contributes to p53 control of breast cancer invasion.
Natural Resistance to Infection with Intracellular Pathogens: The <i>Nramp1</i> Protein Is Recruited to the Membrane of the Phagosome
Authors: Samantha Gruenheid, Elhanan Pinner, Michel Desjardins, Philippe Gros
Journal: The Journal of Experimental Medicine (1997)

The Nramp1 (natural-resistance-associated macrophage protein 1) locus (Bcg, Ity, Lsh) controls the innate resistance or susceptibility of mice to infection with a group of unrelated intracellular parasites which includes Salmonella, Leishmania, and Mycobacterium. Nramp1 is expressed exclusively in professional phagocytes and encodes an integral membrane protein that shares structural characteristics with ion channels and transporters. Its function and mechanism of action remain unknown. The intracellular localization of the Nramp1 protein was analyzed in control 129/sv and mutant Nramp1−/− macrophages by immunofluorescence and confocal microscopy and by biochemical fractionation. In colocalization studies with a specific anti-Nramp1 antiserum and a panel of control antibodies directed against known cellular structures, Nramp1 was found not to be expressed at the plasma membrane but rather localized to the late endocytic compartments (late endosome/lysosome) of resting macrophages in a Lamp1 (lysosomal-associated membrane protein 1)-positive compartment. Double immunofluorescence studies and direct purification of latex bead–containing phagosomes demonstrated that upon phagocytosis, Nramp1 is recruited to the membrane of the phagosome and remains associated with this structure during its maturation to phagolysosome. After phagocytosis, Nramp1 is acquired by the phagosomal membrane with time kinetics similar to Lamp1, but clearly distinct from those of the early endosomal marker Rab5. The targeting of Nramp1 from endocytic vesicles to the phagosomal membrane supports the hypothesis that Nramp1 controls the replication of intracellular parasites by altering the intravacuolar environment of the microbe-containing phagosome.
ACQUIRED IMMUNODEFICIENCY SYNDROME WITH SEVERE GASTROINTESTINAL MANIFESTATIONS IN HAITI
Authors: R Malebranche, J.M Guérin, A.C Laroche, R Elie, T Spira, P Drotman, E Arnoux, G.D Pierre, C Pean-Guichard, P.H Morisset, R Mandeville, T Seemayer, J.-M Dupuy
Journal: The Lancet (1983)
PSYCHOTIC VISITORS TO THE WHITE HOUSE
Authors: JOSEPH A. SEBASTIANI, JAMES L. FOY
Journal: American Journal of Psychiatry (1965)

This study described a group of patients who, with few exceptions, were hospitalized after attempting to see the President at his official residence, the White House. In 1943, Dr. Jay L. Hoffman reported his survey of psychotic visitors to government offices which included 55 cases in the years 1927 and 1937, but only 28 of these were visitors to the White House. Most came to Washington to seek relief from persecution (21 cases). Dr. Hoffman suggested that the personality of the presidential incumbent and the current problems of the government influenced the type of patient and the number of patients hospitalized. He also considered them "the most potentially dangerous of all patients." To test these hypotheses, the charts of the 40 White House cases admitted to D.C. General Hospital in 1960 and 1961 were reviewed. In 1960, when Mr. Eisenhower was President, only nine patients were admitted, but 32 were hospitalized in 1961, Mr. Kennedy's inaugural year. This would suggest that some personal characteristic of the President was important. Finally, ten White House cases were seen in psychiatric interviews between October 1, 1963 and January 1, 1964, and all ten cases were briefly summarized. In general, the more recent White House cases were quite similar to the patients of 20 years ago. Based on the preceding data, the factors affecting the admission rate were discussed. The person of the President was important in some way. The surprisingly high number of foreign-born patients suggested a cultural determinant, although this could have been a function of the screening procedures by the Secret Service. To persist in trying to see the President, to give a history of previous mental illness and to be foreign-born were factors consistently found in the data. Finally, "centrality," "need for validation" and "pseudo-community"—concepts which have been proposed in recent publications about paranoid states—were discussed in relation to this specialized group of patients. In the opinion of the authors, none of these hospitalized patients represented a special threat to the life of the President, whom they incorporated as a benevolent and necessary agent in a paranoid pseudo-community.
ADVANTAGES OF THE USE OF MINUS CYLINDERS IN ROUTINE REFRACTIONS
Authors: JOSEPH D. HEITGER
Journal: JAMA (1922)

Though I may not be able to inform men more than they know, yet I may be able to give them occasion to consider.—<i>Sir W. Temple</i>. In the last decade, from conversations with various persons at our special meetings, I have been impressed by the general diversity of opinion regarding the use of minus cylinders in routine refractions. From what I have been able to deduce, this difference of view is largely due to a failure to employ the principles of physiologic optics involved in the geometrical figure of the conoid of Sturm, coupled with the faulty use of astigmatic charts or the use of charts which were at fault in proper construction or, when astigmatic charts were not used, failure to grasp one of the first fundamental rules of refraction: "As much plus or as little minus spherical power as the patient will accept, combined with the weakest
Preferential linkage of bcl-2 to immunoglobulin light chain gene in chronic lymphocytic leukemia.
Authors: M Adachi, A Tefferi, P R Greipp, T J Kipps, Y Tsujimoto
Journal: The Journal of Experimental Medicine (1990)

Most of human follicular lymphomas possess the t(14;18) chromosome translocation that juxtaposes the IgH gene to the 3' region of bcl-2 in a head-to-tail configuration. Here we show that the rearrangement of the bcl-2 gene occurs in a significant fraction (approximately of 10%) of B cell CLL. In all cases analyzed, breakpoints on chromosome 18 clustered at the 5' flanking region of the bcl-2 gene, and no rearrangements were found at the major or minor breakpoint clustering region (3' region of bcl-2 gene) typical of the t(14;18) chromosome translocation. All of the rearranged bcl-2 genes were juxtaposed with the Ig lambda or K genes in a head-to-head configuration. These results imply that the bcl-2 gene is preferentially linked to the IgL genes in CLL and could function in leukemogenesis.
Labour induction with prostaglandins: a systematic review and network meta-analysis
Authors: Zarko Alfirevic, Edna Keeney, Therese Dowswell, Nicky J Welton, Sofia Dias, Leanne V Jones, Kate Navaratnam, Deborah M Caldwell
Journal: BMJ (2015)

<b>Objectives</b> To assess the effectiveness and safety of prostaglandins used for labour induction. <b>Design</b> Systematic review with Bayesian network meta-analysis <b>Data sources</b> The Cochrane Pregnancy and Childbirth Group’s Database of Trials (which incorporates the results of a broad generic search for all pregnancy and postpartum trials). Sources included are CENTRAL, Medline, Embase, NHS Economic Evaluation Database, CINAHL, relevant journals, conference proceedings, and registries of ongoing trials. <b>Eligibility criteria for selecting studies</b> Randomised clinical trials of prostaglandin or prostaglandin analogues used for third trimester cervical ripening or labour induction versus placebo or no treatment, alternative prostaglandin dose or administration, or a different type of prostaglandin. We included studies recruiting women with a viable fetus, but had no other restrictions relating to indication for labour induction or language of publication. Outcomes assessed were serious neonatal morbidity (trialist defined) or perinatal death; serious maternal morbidity (trialist defined) or death; vaginal delivery not achieved within 24 hours, caesarean section, and uterine hyperstimulation with fetal heart rate changes. <b>Results</b> 280 randomised clinical trials were included (48&nbsp;068 women) in the review. Maternal and neonatal mortality and serious morbidity were rarely reported and are summarized narratively. Unresolved inconsistency was observed for the hyperstimulation outcome. Relative to placebo, the odds of failing to achieve a vaginal delivery were lowest for vaginal misoprostol (≥50 µg) (odds ratio 0.06 (95% credible interval 0.02 to 0.12)), with a 39% absolute probability of event (95% credible interval 1% to 94%). Compared with placebo, odds of caesarean section were lowest for titrated oral misoprostol solution (&lt;50 µg) (odds ratio 0.65 (0.49 to 0.83)), with an absolute probability of event of 15% (3% to 40%). <b>Conclusions</b> Low dose(&lt;50 µg) titrated oral misoprostol solution had the lowest probability of caesarean section, whereas vaginal misprostol (≥50 µg) had the highest probability of achieving a vaginal delivery within 24 hours. These findings have important implications for a series of current national and international guidelines for induction of labour and future research in this area. <b>Systematic review registration</b> PROSPERO 2013:CRD42013005116