tbuckley/cabot-search huggingface dataset:
No Causal Association Identified for Human Papillomavirus Infections in Lung Cancer
Authors: Devasena Anantharaman, Tarik Gheit, Tim Waterboer, Gordana Halec, Christine Carreira, Behnoush Abedi-Ardekani, Sandrine McKay-Chopin, David Zaridze, Anush Mukeria, Neonila Szeszenia-Dabrowska, Jolanta Lissowska, Dana Mates, Vladimir Janout, Lenka Foretova, Vladimir Bencko, Peter Rudnai, Eleonora Fabianova, Anne Tjønneland, Ruth C. Travis, Heiner Boeing, J. Ramón Quirós, Mikael Johansson, Vittorio Krogh, H. Bas Bueno-de-Mesquita, Anastasia Kotanidou, Françoise Clavel-Chapelon, Elisabete Weiderpass, Mattias Johansson, Michael Pawlita, Ghislaine Scelo, Massimo Tommasino, Paul Brennan
Journal: Cancer Research (2014)

Abstract Human papillomavirus (HPV) infections have been implicated in lung carcinogenesis, but causal associations remain uncertain. We evaluated a potential causal role for HPV infections in lung cancer through an analysis involving serology, tumor DNA, RNA, and p16 protein expression. Association between type-specific HPV antibodies and risk of lung cancer was examined among 3,083 cases and 4,328 controls in two case–control studies (retrospective) and one nested case–control study (prospective design). Three hundred and thirty-four available tumors were subjected to pathologic evaluation and subsequent HPV genotyping following stringent conditions to detect all high-risk and two low-risk HPV types. All HPV DNA-positive tumors were further tested for the expression of p16 protein and type-specific HPV mRNA. On the basis of the consistency of the results, although HPV11 and HPV31 E6 antibodies were associated with lung cancer risk in the retrospective study, no association was observed in the prospective design. Presence of type-specific antibodies correlated poorly with the presence of the corresponding HPV DNA in the tumor. Although nearly 10% of the lung tumors were positive for any HPV DNA (7% for HPV16 DNA), none expressed the viral oncogenes. No association was observed between HPV antibodies or DNA and lung cancer survival. In conclusion, we found no supportive evidence for the hypothesized causal association between HPV infections and lung cancer. Cancer Res; 74(13); 3525–34. ©2014 AACR.
Negative Diastolic Pressure in the Isolated Hypothermic Dog Heart
Authors: LARRY J. O'BRIEN, TOLGE BRUNO P.
Journal: Circulation Research (1960)

Pressure relationships in the left ventricle of the dog were studied under conditions in which left ventricular inflow was controlled by means of an artificial circuit. Hypothermia was used to slow the dynamics of the heart beat. When all inflow to the left ventricle was suddenly stopped, the succeeding beats showed negative diastolic pressures. The greatest drop in pressure occurred early in diastole; in most instances, end-diastolic pressures remained negative. Early diastolic pressures before occlusion average +2.6 mm. Hg; early diastolic pressures after occlusion of inflow averaged -4.7 mm. Hg. A physical model was proposed which could explain the occurrence and decay of the observed subatmospheric pressure. These experiments indicate that diastolic suction can be a factor that accomplishes ventricular filling during diastole in a heart following systolic discharge against a wide range of aortic pressures.
High or standard initial dose of budesonide to control mild-to-moderate asthma?
Authors: P. Chanez, R. Karlstrom, P. Godard
Journal: European Respiratory Journal (2001)

Guidelines on the use of inhaled steroids in asthma advocate that the daily dose should be chosen according to the severity of the disease. However, the question of the optimal starting dose remains to be properly addressed, as does the issue of the adjustment in dose required for a given patient. Whether a high initial dose of budesonide (800 µg b.i.d ) was more efficacious than a standard dose (200 µg b.i.d ) in controlling mild-to-moderate asthma was investigated, and whether the dose could be decreased, based on peak expiratory flow (PEF), symptom-score, β 2 -agonist use in a double-blind, randomized, parallel-group 18-week study. One-hundred and sixty-nine patients (mean age 38 yrs, mean forced expiratory volume in one second 74% predicted) were enrolled. No difference was detected between the two groups in improvement in morning PEF (+61 L·min −1 in the high-dose group, +60 L·min −1 in the standard-dose group by 16 weeks). Morning and evening PEF values stabilized before the end of the first 4 weeks. No difference between groups was observed in symptom score, β 2 -agonist use, number of exacerbation per interval and the best forced expiratory volume in one second achieved. The proportion of subjects being able to decrease the doses of budesonide was similar in both treatment strategies. It is concluded that both high and standard initial doses are equally effective in controlling symptoms and improving lung function in mild-to-moderate asthma.
Phase 1 and pharmacodynamic studies of G3139, a Bcl-2 antisense oligonucleotide, in combination with chemotherapy in refractory or relapsed acute leukemia
Authors: Guido Marcucci, John C. Byrd, Guowei Dai, Marko I. Klisovic, Peter J. Kourlas, Donn C. Young, Spero R. Cataland, Diane B. Fisher, David Lucas, Kenneth K. Chan, Pierluigi Porcu, Zhong-Pin Lin, Sherif F. Farag, Stanley R. Frankel, James A. Zwiebel, Eric H. Kraut, Stanley P. Balcerzak, Clara D. Bloomfield, Michael R. Grever, Michael A. Caligiuri
Journal: Blood (2002)
New Reagents on the Horizon for Immune Tolerance
Authors: E. William St. Clair, Larry A. Turka, Andrew Saxon, Jeffrey B. Matthews, Mohamed H. Sayegh, George S. Eisenbarth, Jeffrey Bluestone
Journal: Annual Review of Medicine (2006)

Recent advances in immunology and a growing arsenal of new drugs are bringing the focus of tolerance research from animal models into the clinical setting. The conceptual framework for therapeutic tolerance induction has shifted from a "sledgehammer" approach that relies solely on cellular depletion and cytokine targeting, to a strategy directed toward restoring a functional balance across the immune system, namely the different populations of naive cells, effector and memory cells, and regulatory cells. Unlocking the key to tolerance induction in the future will likely depend on our ability to harness the functions of T regulatory cells. Also, dendritic cells are strategically positioned at the interface between innate and adaptive immunity and may be subject to deliberate medical intervention in a way that can control a chronic inflammatory response. Many reagents with tolerance-inducing potential are currently undergoing clinical testing in transplantation, autoimmune diseases, and allergic diseases, and even more that are on the horizon promise to offer enormous benefits to human health.
Albumin Regulates the Na+/H+ Exchanger 3 in OKP Cells
Authors: Jelena Klisic, Jianning Zhang, Vera Nief, Livia Reyes, Orson W. Moe, Patrice M. Ambühl
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Albumin filtered by the glomerulus is reabsorbed in the proximal tubule. We have shown previously that proteinuria stimulates the proximal tubular Na+/H+ exchanger 3 (NHE3) in rats. Activation of NHE3 may be a pathophysiologically important factor in the development of renal salt and water retention observed in the nephrotic syndrome. For examining whether albumin is a specific inducer of proximal tubular Na+/H+ exchange and to determine the molecular mechanisms by which it regulates Na+/H+ exchange, the effect of albumin on NHE3 in opossum kidney cells was studied. Albumin activated Na+/H+ exchange in a time- and dose-dependent manner up to 100% in 48 h. In the early phase of stimulation (2 to 12 h), NHE3 activity was increased without changes in NHE3 protein and mRNA. At 24 h, increased NHE3 activity was accompanied by increase in cell surface NHE3 protein. The increase in surface NHE3 was associated with increased bidirectional trafficking of NHE3 protein between intracellular compartments and the cell surface. At 48 h, total cell NHE3 protein abundance and mRNA were increased as well. Whereas NHE3 translation was increased, NHE3 protein half-life remained unchanged. The effects of albumin on NHE3 protein abundance were modified by hydrocortisone in a complicated pattern. These results indicate that albumin directly regulates proximal tubular NHE3 at multiple levels.
Noninvasive imaging of myocardial angiogenesis following experimental myocardial infarction
Authors: David F. Meoli, Mehran M. Sadeghi, Svetlana Krassilnikova, Brian N. Bourke, Frank J. Giordano, Donald P. Dione, Haili Su, D. Scott Edwards, Shuang Liu, Thomas D. Harris, Joseph A. Madri, Barry L. Zaret, Albert J. Sinusas
Journal: Journal of Clinical Investigation (2004)

Noninvasive imaging strategies will be critical for defining the temporal characteristics of angiogenesis and assessing efficacy of angiogenic therapies. The αvβ3 integrin is expressed in angiogenic vessels and represents a potential novel target for imaging myocardial angiogenesis. We demonstrated the localization of an indium-111–labeled (111In-labeled) αvβ3-targeted agent in the region of injury-induced angiogenesis in a chronic rat model of infarction. The specificity of the targeted αvβ3-imaging agent for angiogenesis was established using a nonspecific control agent. The potential of this radiolabeled αvβ3-targeted agent for in vivo imaging was then confirmed in a canine model of postinfarction angiogenesis. Serial in vivo dual-isotope single-photon emission–computed tomographic (SPECT) imaging with the 111In-labeled αvβ3-targeted agent demonstrated focal radiotracer uptake in hypoperfused regions where angiogenesis was stimulated. There was a fourfold increase in myocardial radiotracer uptake in the infarct region associated with histological evidence of angiogenesis and increased expression of the αvβ3 integrin. Thus, angiogenesis in the heart can be imaged noninvasively with an 111In-labeled αvβ3-targeted agent. The noninvasive evaluation of angiogenesis may have important implications for risk stratification of patients following myocardial infarction. This approach may also have significant clinical utility for noninvasively tracking therapeutic myocardial angiogenesis.
Excellent Outcome With Reduced Treatment for Infants With Disseminated Neuroblastoma Without <i>MYCN</i> Gene Amplification
Authors: Bruno De Bernardi, Mary Gerrard, Luca Boni, Hervé Rubie, Adela Cañete, Andrea Di Cataldo, Victoria Castel, Ana Forjaz de Lacerda, Ruth Ladenstein, Ellen Ruud, Benédicte Brichard, Jerome Couturier, Caroline Ellershaw, Caroline Munzer, Paolo Bruzzi, Jean Michon, Andrew D.J. Pearson
Journal: Journal of Clinical Oncology (2009)

Purpose On the assumption that most infants with disseminated neuroblastoma without MYCN amplification (MYCNA) have a favorable prognosis, two concomitant prospective trials were started in which chemotherapy was limited to patients presenting life- or organ-threatening symptoms or overt metastases to skeleton, lung, or CNS. Surgery was to be performed only in the absence of surgical risk factors. Patients and Methods One hundred seventy infants with disseminated neuroblastoma without MYCNA, diagnosed between June 1999 and June 2004 in nine European countries were eligible for either of the two studies. Trial 99.2 included all stage 4S infants and those with stage 4 with a primary tumor infiltrating across the midline or positive skeletal scintigraphy who were to be observed in absence of symptoms. Trial 99.3 included infants with overt metastases to the skeleton, lung, and CNS to be treated with a minimum of four chemotherapy courses. Results The 125 infants treated on trial 99.2 had a 2-year overall survival (OS) of 97.6% with no difference between asymptomatic and symptomatic patients (97.7% v 97.3%), patients without or with unresectable primary tumors (96.8% v 100%), and patients without or with positive skeletal scintigraphy without radiologic abnormalities (97.2% v 100%). The 45 infants treated on trial 99.3 had a 2-year OS of 95.6%. No patients died of surgery- or chemotherapy-related complications. Conclusion Infants with disseminated disease without MYCNA have excellent survival with minimal or no treatment. Asymptomatic infants with an unresectable primary tumor or positive skeletal scintigraphy without radiologic abnormalities may undergo observation alone.
Clinical and Biological Significance of <i>CDK4</i> Amplification in Well-Differentiated and Dedifferentiated Liposarcomas
Authors: Antoine Italiano, Laurence Bianchini, Elisabet Gjernes, Frédérique Keslair, Dominique Ranchere-Vince, Jean-Marc Dumollard, Juliette Haudebourg, Agnès Leroux, Claire Mainguené, Philippe Terrier, Frédéric Chibon, Jean-Michel Coindre, Florence Pedeutour
Journal: Clinical Cancer Research (2009)

The MDM2 and HMGA2 genes are consistently amplified in well-differentiated/dedifferentiated liposarcomas (WDLPS/DDLPS) whereas CDK4 is frequently but not always amplified in these tumors. Our goal was to determine whether the absence of CDK4 amplification was (a) correlated to a specific clinico-histopathologic profile; and (b) compensated by another genomic anomaly involving the CCND1/CDK4/P16INK4a/RB1/E2F pathway.We compared the clinical characteristics of a series of 143 WDLPS/DDLPS with amplification of both MDM2 and CDK4 (MDM2+/CDK4+) to a series of 45 WDLPS/DDLPS with MDM2 amplification and no CDK4 amplification (MDM2+/CDK4-). We used fluorescence in situ hybridization, real time quantitative reverse transcription PCR, and immunohistochemistry to explore the status of CCND1, P16INK4a, P14ARF, and RB1.We found that MDM2+/CDK4- WDLPS/DDLPS represent a distinct clinical subgroup with favorable prognostic features, including low-grade lipoma-like histology, peripheral location, and lower rate of recurrence. By using fluorescence in situ hybridization, we found that genomic aberrations expected to be alternative mechanisms for compensating the lack of CDK4 amplification, such as RB1 and CDKN2A deletions or CCND1 amplification, were very uncommon. In contrast, by using real time quantitative reverse transcription PCR and immunohistochemistry, we observed that overexpression of P16INK4a (and P14ARF) and CCND1 and reduced expression of RB1 were very frequent, independently of the CDK4 status.Our results underscore the complex coordinated regulation of the RB and p53 growth-control pathways in WDLPS/DDLPS. Because the absence of CDK4 amplification is not specifically counterbalanced by a genomic alteration of the CCND1/CDK4/P16INK4a/RB1/E2F pathway, CDK4 amplification may only represent a "MDM2-HMGA2-helper" in WDLPS/DDLPS tumorigenesis.
Hysteria (Briquet's Syndrome) in a Psychiatric Hospital: The Significance of Secondary Depression
Authors: RICHARD C. BIBB, SAMUEL B. GUZE
Journal: American Journal of Psychiatry (1972)

Hysteria (Briquet's syndrome) is a frequent disorder among psychiatric inpatients. Depressed mood, often complicated by alcohol or drug abuse or suicidal behavior, is the usual reason for admission. Cross-sectionally, the depressive symptoms of these patients resemble those of patients with primary depressions, although the two groups differ markedly in past medical history. Patients with hysteria are less likely to receive ECT, however. The authors discuss the significance of this form of secondary affective disorder.
THE CRYSTAL STRUCTURE OF THE HUMAN HIGH-AFFINITY IgE RECEPTOR (FcεRIα)
Authors: Scott C. Garman, Jean-Pierre Kinet, Theodore S. Jardetzky
Journal: Annual Review of Immunology (1999)

Exhausted CD8 T (Tex) cells are a distinct cell lineage that arise during chronic infections and cancers in animal models and humans. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, ...Read More
Airway response of children with primary ciliary dyskinesia to exercise and beta2-agonist challenge
Authors: GE Phillips, S Thomas, S Heather, A Bush
Journal: European Respiratory Journal (1998)

In primary ciliary dyskinesia (PCD), chest physiotherapy for airway clearance is essential. Exercise and inhaled beta2-agonists can produce bronchodilation thereby augmenting physiotherapy. However, both can also cause bronchoconstriction, and the effects of these stimuli in PCD are not known. In a preliminary study, the mean coefficients of variation for forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and peak expiratory flow rate (PEFR) in children with PCD were determined. They were 5.4%, 4.4% and 8.4%, respectively. Twelve children with PCD and 12 normal children performed pulmonary functions under resting conditions; during and after a validated treadmill exercise test; and before and 15 min after 200 microg of inhaled salbutamol. At baseline, FEV1, FVC, forced mid-expiratory flow (FEF25-75%) and PEFR were significantly reduced in the PCD group compared with the control group. Exercise produced a significant increase in PEFR in the PCD group. There was no significant difference between the groups in response to salbutamol. Within the PCD group, exercise produced a significantly greater increase in PEFR than beta2-agonist therapy. In conclusion, in children with primary ciliary dyskinesia there is evidence of obstructive pulmonary disease. In these children, exercise is a more potent stimulus for bronchodilation than by inhaled beta2-agonists. Enhancement of airway clearance may best be achieved by encouraging patients to exercise before physiotherapy rather than by inhaling beta2-agonists, but the effects of each should be assessed for each individual before instigating treatment.
Suppression of active Arthus reaction by colchicine
Authors: YOSHIKI MIYACHI, KIICHIRO DANNO, SADAO IMAMURA
Journal: British Journal of Dermatology (1981)

An effect of colchicine on the active Arthus reaction in rabbits was investigated in vivo with simultaneous evaluation of in vitro chemotactic activity of polymorphonuclear leukocytes. Arthus reactions were induced by intracutaneous injection of ovalbumin into rabbits preimmunized with ovalbumin. Colchicine, 1 mg/kg or 2 mg/kg, injected intraperitoneally one hour prior to the induction of the Arthus reaction, suppressed erythema and induration at 12 h, when histology showed decreased numbers of C3, suggestive of the presence of immune complexes, persisted to 24 h. In vitro chemotaxis of polymorphonuclear leukocytes using Boyden chamber techniques revealed suppression of the activity in the colchicine-treated animals at 6 and 12 h. These findings suggest that colchicine inhibits vascular injury by interfering with directional chemotaxis of polymorphonuclear leukocytes to the lesional sites.
Responder cells in the human autologous mixed lymphocyte reaction.
Authors: J S Smolen, T A Luger, T M Chused, A D Steinberg
Journal: Journal of Clinical Investigation (1981)

Isolated human T4+ cells proliferate in the autologous mixed lymphocyte reaction (AMLR), whereas isolated T8+ cells do not. However, in the presence of Interleukin 2 or T4+ cells, the T8+ cells demonstrated substantial proliferation. These studies suggest that T8+ cells recognize signals from autologous non-T cells, but require an additional factor for the subsequent proliferative response. Since this stimulus can be provided by T4+ cells, the AMLR appears to constitute an inducer circuit. Different defects in this circuit may be responsible for the common abnormality of the AMLR in different diseases.
Characterisation of uveitis in patients with psoriatic arthritis
Authors: Eduardo S Paiva, Damien C Macaluso, Albert Edwards, James T Rosenbaum
Journal: Annals of the Rheumatic Diseases (2000)

<h3>OBJECTIVE</h3> The purpose of this study is to describe the clinical characteristics of uveitis related to psoriatic arthritis (PsA), and also to compare the uveitis in PsA to the uveitis in spondyloarthropathy (SA). <h3>METHODS</h3> Sixteen patients with uveitis and PsA were evaluated in a tertiary care uveitis clinic. These patients were compared retrospectively to a series of 89 patients with uveitis and SA. <h3>RESULTS</h3> Eight (50%) of the 16 patients with uveitis had strictly peripheral arthritis, while two (12.5%) had axial only, and six (37.5%) had axial and peripheral arthritis. Patients with uveitis and axial disease were more likely to be male (100% <i>v</i> 38%) and HLA-B27 positive (6 of 6 typed positive <i>v</i> 0 of 3 typed positive) when compared with those with uveitis and peripheral arthritis only. Compared with patients with SA, those with PsA were more likely to have insidious onset (19% <i>v</i>3%), simultaneously bilateral (37.5% <i>v</i>7%), chronic duration (31% <i>v</i> 6%), or posterior (44% <i>v</i> 17%) uveitis. Complications of uveitis were similar in the SA and PsA groups. <h3>CONCLUSION</h3> Uveitis in patients with PsA was more likely to be insidious in onset, continuous, posterior, and active bilaterally compared with uveitis in patients with SA. Patients with uveitis and axial involvement were more likely to be male and HLA-B27 positive compared with patients with uveitis and peripheral arthritis alone. Patients with seronegative arthritis and uveitis that begins insidiously, lasts longer than six months, is bilateral, or is posterior, should be carefully questioned about the presence of either psoriasis or inflammatory bowel disease.
Neutrophil–DC close encounters
Authors: Heather L. Van Epps
Journal: The Journal of Experimental Medicine (2005)

![Graphic][1] 

The dendritic cell lectin DC-SIGN (red) binds to carbohydrate structures on the neutrophil integrin Mac-1 (green).On 

[page 1281][2], van Gisbergen and colleagues describe for the first time a direct interaction between neutrophils and dendritic cells (DCs). The event
Assessment of the Harmful Psychiatric and Behavioral Effects of Different Forms of Child Maltreatment
Authors: David D. Vachon, Robert F. Krueger, Fred A. Rogosch, Dante Cicchetti
Journal: JAMA Psychiatry (2015)

Several widely held beliefs about child abuse and neglect may be incorrect. It is most commonly assumed that some forms of abuse (eg, physical and sexual abuse) are more harmful than others (eg, emotional abuse and neglect); other assumptions are that each form of abuse has specific consequences and that the effects of abuse differ across sex and race.