tbuckley/cabot-search huggingface dataset:
Regulation of antigen-presenting cell function(s) in lung and airway tissues
Authors: PG Holt
Journal: European Respiratory Journal (1993)

A variety of cell populations present in respiratory tract tissues can express the function-associated molecules on their surface which are required for presentation of antigen to T-lymphocyte receptors. However, the potential role of individual cell populations in regulation of local T-lymphocyte-dependent immune reactions in the lung and airways depends on a variety of additional factors, including their precise localisation, migration characteristics, expression of T-cell "co-stimulatory" signals, responsiveness to inflammatory (in particular cytokine) stimuli, host immune status, and the nature of the antigen challenge. Recent evidence (reviewed below) suggests that the induction of primary immunity (viz. "sensitisation") to inhaled antigens is normally controlled by specialised populations of Dendritic Cells, which perform a surveillance role within the epithelia of the upper and lower respiratory tract; in the pre-sensitised host, a variety of other cell populations (both bone-marrow derived and mesenchymal) may participate in re-stimulation of "memory" T-lymphocytes.
Definition of organ involvement and treatment response in immunoglobulin light chain amyloidosis (AL): A consensus opinion from the 10th International Symposium on Amyloid and Amyloidosis
Authors: Morie A. Gertz, Ray Comenzo, Rodney H. Falk, Jean Paul Fermand, Bouke P. Hazenberg, Philip N. Hawkins, Giampaolo Merlini, Philippe Moreau, Pierre Ronco, Vaishali Sanchorawala, Orhan Sezer, Alan Solomon, Giles Grateau
Journal: American Journal of Hematology (2005)

We undertook this study to develop uniformly accepted criteria for the definition of organ involvement and response for patients on treatment protocols for immunoglobulin light-chain amyloidosis (AL). A consensus panel was convened comprising 13 specialists actively involved in the treatment of patients with amyloidosis. Institutional criteria were submitted from each, and a consensus was developed defining each organ involved and the criteria for response. Specific criteria have been developed with agreed on definitions of organ and hematologic response as a result of discussions at the 10th International Symposium on Amyloid and Amyloidosis held in Tours, France, April 2004. These criteria now form the working definition of involvement and response for the purposes of future data collection and reporting. We report criteria that centers can now use to define organ involvement and uniform response criteria for reporting outcomes in patients with light-chain AL. Am. J. Hematol. 79:319–328, 2005. © 2005 Wiley-Liss, Inc.
Translational bioinformatics applications in genome medicine
Authors: Atul J Butte
Journal: Genome Medicine (2009)

Although investigators using methodologies in bioinformatics have always been useful in genomic experimentation in analytic, engineering, and infrastructure support roles, only recently have bioinformaticians been able to have a primary scientific role in asking and answering questions on human health and disease. Here, I argue that this shift in role towards asking questions in medicine is now the next step needed for the field of bioinformatics. I outline four reasons why bioinformaticians are newly enabled to drive the questions in primary medical discovery: public availability of data, intersection of data across experiments, commoditization of methods, and streamlined validation. I also list four recommendations for bioinformaticians wishing to get more involved in translational research.
Nuclear Factor κB Downregulates the Transient Outward Potassium Current <i>I</i> <sub>to,f</sub> Through Control of KChIP2 Expression
Authors: Brian K. Panama, Desiree Latour-Villamil, Gerrie P. Farman, Dongling Zhao, Steffen-Sebastian Bolz, Lorrie A. Kirshenbaum, Peter H. Backx
Journal: Circulation Research (2011)

The fast transient outward K(+) current (I(to,f)) plays a critical role in early repolarization of the heart. I(to,f) is consistently downregulated in cardiac disease. Despite its importance, the regulation of I(to,f) in disease remains poorly understood.Because the transcription factor nuclear factor (NF)-κB is activated in cardiac hypertrophy and disease, we studied the role of NF-κB in mediating I(to,f) reductions induced by hypertrophy.Culturing neonatal rat ventricular myocytes in the presence of phenylephrine (PE) plus propranolol (Pro), to selectively activate α(1)-adrenergic receptors, caused reductions in I(to,f), as well as KChIP2 and Kv4.3 expression, while increasing Kv4.2 expression. Inhibition of NF-κB, via overexpression of a phosphorylation-deficient mutant of IκBα (IκBαSA) prevented PE/Pro-induced reductions in I(to,f) and KChIP2 mRNA, without affecting Kv4.2 or Kv4.3 expression, suggesting NF-κB mediates the I(to,f) reductions by repressing KChIP2. Indeed, overexpression of the NF-κB activator IκB kinase-β also decreased KChIP2 expression and I(to,f) (despite increasing Kv4.2), whereas IκBαSA overexpression elevated KChIP2 and decreased Kv4.2 levels. In addition, the classic NF-κB activator tumor necrosis factor α also induced NF-κB-dependent reductions of KChIP2 and I(to,f). Finally, inhibition of calcineurin did not prevent PE/Pro-induced reductions in KChIP2.NF-κB regulates KChIP2 and Kv4.2 expression. The reductions in I(to,f) observed following α-adrenergic receptor stimulation or tumor necrosis factor α application require NF-κB-dependent decreases in KChIP2 expression.
Five Years After: A Follow-Up of 50 Narcotic Addicts
Authors: BARRY S. LEVY
Journal: American Journal of Psychiatry (1972)

To document the long-term course of narcotic addicts, background and five-year follow-up data were obtained from records and interviews for 50 addicts who had first contact with a new treatment program in 1965. In mid-1970, 20 were either abstinent or were using drugs only occasionally. During the follow-up period these individuals spent less time in prison than the other 24 survivors and had more contact with treatment programs. The subjects' comments raise issues for further investigation.
Programmed cell death ligand 2 regulates TH9 differentiation and induction of chronic airway hyperreactivity
Authors: Jerome Kerzerho, Hadi Maazi, Anneliese O. Speak, Natacha Szely, Vincent Lombardi, Bryant Khoo, Stacey Geryak, Jonathan Lam, Pejman Soroosh, Jacques Van Snick, Omid Akbari
Journal: Journal of Allergy and Clinical Immunology (2012)
Attention sheds no light on the origin of phenomenal experience
Authors: Victor A. F. Lamme, Rogier Landman
Journal: Behavioral and Brain Sciences (2001)

In O'Regan &amp; Noë's (O&amp;N's) account for the phenomenal experience of seeing, awareness is equated to what is within the current focus of attention. They find no place for a distinction between phenomenal and access awareness. In doing so, they essentially present a dualistic solution to the mind-brain problem, and ignore that we do have phenomenal experience of what is outside the focus of attention.
Heparin desulfation modulates VEGF release and angiogenesis in diabetic wounds
Authors: Uwe Freudenberg, Andrea Zieris, Karolina Chwalek, Mikhail V. Tsurkan, Manfred F. Maitz, Passant Atallah, Kandice R. Levental, Sabine A. Eming, Carsten Werner
Journal: Journal of Controlled Release (2015)
Physical Activity, Biomarkers, and Disease Outcomes in Cancer Survivors: A Systematic Review
Authors: R. Ballard-Barbash, C. M. Friedenreich, K. S. Courneya, S. M. Siddiqi, A. McTiernan, C. M. Alfano
Journal: JNCI Journal of the National Cancer Institute (2012)

BackgroundCancer survivors often seek information about how lifestyle factors, such as physical activity, may influence their prognosis. We systematically reviewed studies that examined relationships between physical activity and mortality (cancer-specific and all-cause) and/or cancer biomarkers.
An Automated Particle Counting Immunoassay (PACIA) for Determination of Blocking Antibodies against Timothy Grass Pollen in Sera from Desensitized Allergies
Authors: R. Djurup, C. G. M. Magnusson, U. Minuva, I. Søndergaard, O. øSterballe, B. Weeke
Journal: Allergy (1983)

AN automated particle counting immunoassay (PACIA) for measurement of blocking antibodies (antigen neutralizing capacity) against timothy grass pollen extract in sera from desensitized allergies is described. Latex particles coated with E(ab') 2 ‐anti‐timothy are agglutinated by timothy. Serum containing anti‐timothy antibodies inhibits the agglutination. Non‐agglutinated particles are counted in a modified Auto Counter. Nineteen of 20 sera from timothy allergies who had undergone immunotherapy with purified timothy extract for 30 weeks, showed significant agglutination‐inhibition. None of 42 normal human sera gave significant inhibition. The inhibiting antibody could be removed by absorption with protein A and was thus of non‐ IgE nature, i.e. blocking antibody. The results obtained correlated statistically significantly with those found with a double‐antibody method (r S = 0.62, n = 20, t = 3.35, P &lt; 0.01) and with the cumulated dosage of timothy allergen extract administered to the individual patient (r S = 0.56, n = 20, t = 2.87, P &lt;0.02). Between‐assay coefficient of variation was from 6.4% to 18.3%. The capacity is 40 samples per hour. The method has also been applied to measurement of blocking antibodies to boney bee and wasp venom.
Growth Inhibition of Human Prostate Cancer Cells in Human Adult Bone Implanted into Nonobese Diabetic/Severe Combined Immunodeficient Mice by a Ligand-Specific Antibody to Human Insulin-Like Growth Factors
Authors: Masato Goya, Shin’ichi Miyamoto, Kanji Nagai, Yuji Ohki, Kazuyasu Nakamura, Kenya Shitara, Hiroyuki Maeda, Takafumi Sangai, Keiji Kodama, Yasushi Endoh, Genichiro Ishii, Takahiro Hasebe, Hiroyuki Yonou, Tadashi Hatano, Yoshihide Ogawa, Atsushi Ochiai
Journal: Cancer Research (2004)

Advanced prostate cancer frequently involves the bone that has the largest content of insulin-like growth factors (IGFs). However, the role of bone-derived IGFs in bone metastasis of prostate cancer has not been studied extensively because of the lack of a reliable animal model. Therefore, we investigated whether a novel antibody directed against human IGF-I and IGF-II (KM1468) could inhibit the development of new bone tumors and the progression of established bone tumors in nonobese diabetic/severe combined immunodeficient mice implanted with human adult bone. We first confirmed that KM1468 bound specifically to human IGF-I, human IGF-II, and mouse IGF-II but not to insulin. It also blocked autophosphorylation of the type I IGF receptor induced by the binding of IGFs in human-type I IGF receptor-overexpressing BALB/c 3T3 cells, and it inhibited the IGF-stimulated growth of MDA PCa 2b cells in vitro. Then mice were injected intraperitoneally with KM1468 once weekly for 4 weeks either immediately or 4 weeks after inoculation of MDA PCa 2b cells. KM1468 markedly and dose-dependently suppressed the development of new bone tumors and the progression of established tumor foci, as determined by histomorphometry, and it also decreased serum prostate-specific antigen levels, compared with the control. This is the first report of an IGF ligand-specific inhibitory antibody that suppresses the growth of human prostate cancer cells in human adult bone. These results indicate that the IGF signaling axis is a potential target for prevention and treatment of bone metastases arising from prostate cancer.
Exemestane for Breast Cancer Prevention: A Feasible Strategy?
Authors: Per E. Lønning
Journal: Clinical Cancer Research (2005)

Third-generation aromatase inhibitors and inactivators have been successfully implemented in therapy of metastatic breast cancer, and three large phase III trials have revealed superiority compared with tamoxifen monotherapy in the adjuvant setting. Notably, each of these trials recorded a substantial reduction in contralateral breast cancer among patients exposed to the aromatase inhibitor/inactivator. A major concern in implementing use of these compounds in the preventive setting relates to potential detrimental effects of estrogen suppression on bone and lipid metabolism. Recent data from a placebo-controlled study now reveal 2 years of treatment with exemestane compared with placebo to have moderate effects on bone metabolism and plasma lipid profile, supporting further evaluation of exemestane as a potential preventive agent for breast cancer in postmenopausal women.
A Phase I Trial of Twice-Weekly 17-Allylamino-Demethoxy-Geldanamycin in Patients with Advanced Cancer
Authors: Grzegorz S. Nowakowski, Andrea K. McCollum, Matthew M. Ames, Sumithra J. Mandrekar, Joel M. Reid, Alex A. Adjei, David O. Toft, Stephanie L. Safgren, Charles Erlichman
Journal: Clinical Cancer Research (2006)

Abstract Purpose: To determine the maximum tolerated dose (MTD), dose-limiting toxicity, and pharmacokinetics of 17-allylamino-demethoxy-geldanamycin (17-AAG) administered on days 1, 4, 8, and 11 every 21 days and to examine the effect of 17-AAG on the levels of chaperone and client proteins. Experimental Design: A phase I dose escalating trial in patients with advanced solid tumors was done. Toxicity and tumor responses were evaluated by standard criteria. Pharmacokinetics were done and level of target proteins was measured at various points during cycle one. Results: Thirteen patients were enrolled in the study. MTD was defined as 220 mg/m2. Dose-limiting toxicities were as follows: dehydration, diarrhea, hyperglycemia, and liver toxicity. At the MTD, the mean clearance of 17-AAG was 18.7 L/h/m2. There was a significant decrease in integrin-linked kinase at 6 hours after infusion on day 1 but not at 25 hours in peripheral blood mononuclear cells. Treatment with 17-AAG on day 1 significantly increased pretreatment levels of heat shock protein (HSP) 70 on day 4, which is consistent with the induction of a stress response. In vitro induction of a stress response and up-regulation of HSP70 resulted in an increased resistance to HSP90-targeted therapy in A549 cells. Conclusions: The MTD of 17-AAG on a twice-weekly schedule was 220 mg/m2. Treatment at this dose level resulted in significant changes of target proteins and also resulted in a prolonged increase in HSP70. This raises the possibility that HSP70 induction as part of the stress response may contribute to resistance to 17-AAG.
Spontaneous Pneumoperitoneum After Scuba Diving
Authors: David M. Rose
Journal: JAMA (1978)

SPONTANEOUS pneumoperitoneum is an unusual condition that, to our knowledge, has not been reported as a consequence of scuba diving. <h3>Report of a Case</h3> A 29-year-old man, who was underwater cave diving at a depth of 30 m for 1 1/2 hours, was forced to make an emergency ascent without taking the recommended decompression stops. Within one hour of surfacing, he began to experience pain in his right elbow, left shoulder, and left hip; he also had a bilateral frontal headache. In the hospital emergency room, the patient reported having no visual symptoms, weakness, sensory loss, chest pain, dyspnea, or abdominal pain. Decompression sickness was diagnosed, and he submitted to a recompression regimen. Postero-anterior and lateral chest roentgenograms showed the presence of pneumoperitoneum without pneumothorax, pneumomediastinum, or subcutaneous air. A left lateral decubitus film confirmed the presence of free air in the abdomen as well as emphysematous bullae in the
Magnetic Resonance Visualization of Tumor Angiogenesis by Targeting Neural Cell Adhesion Molecules with the Highly Sensitive Gadolinium-Loaded Apoferritin Probe
Authors: Simonetta Geninatti Crich, Benedetta Bussolati, Lorenzo Tei, Cristina Grange, Giovanna Esposito, Stefania Lanzardo, Giovanni Camussi, Silvio Aime
Journal: Cancer Research (2006)

Abstract Tumor vessel imaging could be useful in identifying angiogenic blood vessels as well as being a potential predictive marker of antiangiogenic treatment response. We recently reported the expression of the neural cell adhesion molecule (NCAM) in the immature and tumor endothelial cell (TEC) lining vessels of human carcinomas. Exploiting an in vivo model of human tumor angiogenesis obtained by implantation of TEC in Matrigel in severe combined immunodeficiency mice, we aimed to image angiogenesis by detecting the expression of NCAM with magnetic resonance imaging. The imaging procedure consisted of (a) targeting NCAMs with a biotinylated derivative of C3d peptide that is known to have high affinity for these epitopes and (b) delivery of a streptavidin/gadolinium (Gd)-loaded apoferritin 1:1 adduct at the biotinylated target sites. The remarkable relaxation enhancement ability of the Gd-loaded apoferritin system allowed the visualization of TEC both in vitro and in vivo when organized in microvessels connected to the mouse vasculature. Gd-loaded apoferritin displayed good in vivo stability and tolerability. The procedure reported herein may be easily extended to the magnetic resonance visualization of other epitopes suitably targeted by proper biotinylated vectors. (Cancer Res 2006; 66(18): 9196-201)
Myosin transitions in the bovine and human heart. A developmental and anatomical study of heavy and light chain subunits in the atrium and ventricle.
Authors: P Cummins, S J Lambert
Journal: Circulation Research (1986)

Transitions in cardiac myosin isotypes occur in response to a variety of stimuli. These are well documented in small, but less so in larger, mammals where data on quantitative isotype composition of normal atria and ventricles are scarce. In this study, heavy and light chain isotypes were examined in fetal, neonatal, and adult bovine and human hearts. Defined anatomical areas of chambers were studied, and detailed mapping of isotypes was conducted on bovine atria. Heavy chain isotype quantification was carried out electrophoretically either after peptide mapping or by a new technique for separating whole cardiac alpha- and beta-heavy chains capable of detecting 5% of either isotope. Atrial and ventricular light chains were resolved electrophoretically, and all isotypes were quantified densitometrically. Beta-Heavy chain was almost exclusively expressed (greater than 95%) in the ventricles at all ages except in the bovine neonate. Ventricular light chains predominated in the adult ventricle, but atrial light chain 1 was present at mid-gestation. This was replaced by ventricular light chain 1 in the neonate with no transitions in light chain 2 isotypes. Transitions were more marked in the atria. Only alpha-heavy chains were detected at mid-gestation, but beta-heavy chain increased toward birth. After a decline in the neonatal period, beta-heavy chain levels usually increased in the adult. Atrial light chains were the main isotypes in the atria, but ventricular light chain 2 was the major adult bovine atrial isotype. Transitions in isotypes were significant at birth as in smaller mammals. No close relationship existed between heavy and light chain transitions. Significant anatomical variation in bovine atrial isotype expression was present, and may reflect functional demand in each area.
Abuse and Neglect of Elderly Persons
Authors: Mark S. Lachs, Karl Pillemer
Journal: New England Journal of Medicine (1995)

The metaphor of domestic violence as chronic disease is a useful one for clinicians. Studies of domestic violence over the life span suggest that, like many ongoing illnesses that are typified by periods of quiescence and exacerbation, abuse is more often episodic and recurrent than an isolated event.13 This metaphor may also help to remind physicians that elderly patients are at risk; a report from the House Select Committee on Aging has suggested that between 1 million and 2 million older Americans experience mistreatment each year.4 Given the scope of this clinical and public health problem, what has been . . .
Inflammation impairs eNOS activation by HDL in patients with acute coronary syndrome
Authors: Monica Gomaraschi, Alice Ossoli, Elda Favari, Maria Pia Adorni, Gianfranco Sinagra, Luigi Cattin, Fabrizio Veglia, Franco Bernini, Guido Franceschini, Laura Calabresi
Journal: Cardiovascular Research (2013)

The aim of the present study was to evaluate the high-density lipoprotein (HDL) structure and endothelial NO synthase (eNOS) activation capacity in ST-elevation myocardial infarction (STEMI) patients with different acute-phase inflammatory response (APR).Forty-five STEMI patients were stratified in quartiles according to the delta CRP level, calculated by subtracting the CRP value at admission from the CRP peak value (APR peak). The HDL structure and HDL capacity to stimulate NO production were evaluated at admission and at APR peak. STEMI patients with a low APR had a completely preserved HDL structure and HDL ability to activate eNOS and promote NO production, which did not change during STEMI. On the contrary, HDL from STEMI patients developing a significant APR had compromised ability to stimulate eNOS and promote NO production, and underwent a significant particle remodelling during STEMI. The defective capacity to stimulate NO production of HDL isolated from STEMI patients with high APR was explained, at least in part, by the reduced PON-1 and S1P content. The HDL ability to promote cell cholesterol efflux through different pathways was preserved in ACS patients independently of the inflammatory response.The present results extend previous studies reporting an impaired eNOS-activating capacity of HDL from ACS patients, showing that only a subset of patients undergoing STEMI, and in particular those developing an important inflammatory response, have circulating HDL defective in stimulating endothelial eNOS and NO production.
A phase I stndy of a fixed dose of cisplatin with increasing doses of raltitrexed (Tomudex®) in the treatment of patients with locally advanced or metastatic squamous cell carcinoma of the head and neck.
Authors: D. Ten Bokkel Huinink, M.E.T. Tesselaar, R.J. Baatenburg de Jong, H.P. Verschuur, H.J. Keizer
Journal: Annals of Oncology (2001)
Physical impairments and activity limitations in people with femoroacetabular impingement: a systematic review
Authors: Laura E Diamond, Fiona L Dobson, Kim L Bennell, Tim V Wrigley, Paul W Hodges, Rana S Hinman
Journal: British Journal of Sports Medicine (2014)

Femoroacetabular impingement (FAI) is a morphological hip condition that can cause hip and/or groin pain in younger active adults. Understanding the nature of physical impairments and activity limitations associated with symptomatic FAI is important to evaluate outcomes and guide development of rehabilitation strategies. The purpose of this systematic review was to establish: (1) whether people with symptomatic FAI demonstrate physical impairments and/or activity limitations compared with people without FAI; and (2) whether treatment affects these parameters.Four databases (Pubmed, CINAHL, SportDISCUS and Cochrane Library) were searched until the 21 June 2013. Studies evaluated measures of physical impairment and/or activity limitations in people with symptomatic FAI and included either: (1) a comparison control group; or (2) a pretreatment and post-treatment comparison. Methodological quality was assessed using the Newcastle-Ottawa Scale.16 studies were included. The most commonly reported physical impairment was decreased range of motion (ROM) into directions of hip joint impingement. Other impairments included altered sagittal and frontal plane hip ROM during gait, altered sagittal plane hip ROM during stair climbing, and decreased hip adductor and flexor muscle strength. Effects of surgery on physical impairments are inconsistent but suggest improved hip ROM during gait, but not during stair climbing. Squatting depth improves following surgical intervention for symptomatic FAI.People with symptomatic FAI demonstrate physical impairments and activity limitations. Surgical intervention may restore some deficiencies, but not all. Further studies of physical impairment and activity limitation are needed to evaluate outcomes from surgical and conservative interventions and to inform rehabilitation programmes.