tbuckley/cabot-search huggingface dataset:
T cell-dependent induction of NF-kappa B in B cells.
Authors: A C Lalmanach-Girard, T C Chiles, D C Parker, T L Rothstein
Journal: The Journal of Experimental Medicine (1993)

In comparison to B cell stimulation mediated by surface immunoglobulin (Ig) antigen receptor ligation, little is known about the intracellular events associated with T cell-dependent B cell responses. A model for the efferent phase of T cell-B cell interaction was used to examine the capacity of activated T cells to trigger nuclear expression of the trans-acting transcription factor, NF-kappa B, in B cells. Fixed, activated, but not fixed, resting Th2 cells were found to induce increased binding activity for a kappa B site-containing oligonucleotide in a time-dependent manner. This induction of NF-kappa B was eliminated by an antibody directed against a 39-kD cell interaction protein on activated T cells as well as by a soluble form of B cell CD40. Of particular relevance to intracellular signaling, NF-kappa B induction was not diminished by prior depletion of B cell protein kinase C (PKC) with phorbol myristate acetate. These results strongly suggest that T cell-dependent B cell stimulation is associated with NF-kappa B induction via p39-CD40 interaction and that this is brought about by non-PKC dependent signaling, in marked contrast to the previously documented requirement for PKC in sIg receptor-mediated stimulation. This suggest that NF-kappa B responds to more than one receptor-mediated intracellular signaling pathway in B cells and may be part of a "final common pathway" for B cell stimulation.
Prevention of ethanol and aspirin-induced gastric mucosal lesions by paracetamol and salicylate in rats: role of endogenous prostaglandins.
Authors: S J Konturek, T Brzozowski, I Piastucki, T Radecki
Journal: Gut (1982)

Paracetamol or sodium salicylate given intragastrically 30 minutes before the administration of absolute ethanol or acidified aspirin dose-dependently reduced the formation of mucosal lesions. The generation of gastric mucosal prostaglandin-like activity increased with ethanol and was completely suppressed by acidified aspirin. Paracetamol or sodium salicylate given alone increased the generation of mucosal prostaglandin-like material. Indomethacin, the prostaglandin synthesis inhibitor, suppressed this effect and inhibited the protective influence of paracetamol or sodium salicylate on the production of gastric lesions.
The RD1-encoded antigen Rv3872 of Mycobacterium tuberculosis as a potential candidate for serodiagnosis of tuberculosis
Authors: P. Mukherjee, M. Dutta, P. Datta, A. Dasgupta, R. Pradhan, M. Pradhan, M. Kundu, J. Basu, P. Chakrabarti
Journal: Clinical Microbiology and Infection (2006)
Oxidative stress status in elite female volleyball athletes with depleted iron stores
Authors: J Martinovic, V Dopsaj, J Kotur-Stevuljević, M Dopsaj, G Nesic
Journal: British Journal of Sports Medicine (2011)

Background Oxidative stress has been defined as a disturbance in the equilibrium status of pro-oxidant and antioxidant systems in favour of pro-oxidation. The elevated metabolic rate associated with exercise leads to increased mitochondrial oxygen consumption in tissues, free radical generation, metabolite oxidation and antioxidant depletion. Objective The aim of the present work was to examine the association of iron depletion and acute phase response with oxidative stress in female athletes. Setting and participants Based on serum ferritin values (cut-off 22 μg/L), 54 elite female volleyball athletes were divided into two groups: with iron depletion and with normal iron stores. Samples were taken from athletes who were members of the top two senior women volleyball teams in Serbia during the 2007/2008 competition season. Interventions The following parameters were measured: ferritin, C-reactive protein, interleukin-6, oxidative stress parameters (reactive oxygen metabolites – ROMs and lipid hydroperoxides – LOOH) and antioxidative defence parameters (biological antioxidative potential – BAP and superoxide-dismutase). Results A general linear model indicated significant differences between athletes (Wilks's λ=0.698, F=5.092, p=0.002) in reactive oxygen metabolites (278±57 vs 333±56; p=0.001) which were significantly higher in athletes with iron depletion and biological antioxidative potential (2547±257 vs 2366±297; p=0.026) which was significantly lower in this group. Besides iron depletion, multivariate analysis of covariance revealed C-reactive protein (p&lt;0.047) to be significant covariate with 18.2% proportion of variability for superoxide-dismutase activity. Iron depletion accounted for the largest proportion of variability for all oxidative stress parameters (30.2%). Conclusions Oxidative stress that occurs during exercise is related to acute phase response and iron depletion plays a significant role in processes that lead to free radical generation in professional athletes. Athletes with ferritin values below 22 μg/L had a decreased antioxidatve defence and were more susceptible to oxidative stress compared to those with adequate iron status.
Personalized Medicine in Non–Small-Cell Lung Cancer: Is <i>KRAS</i> a Useful Marker in Selecting Patients for Epidermal Growth Factor Receptor–Targeted Therapy?
Authors: Patrick J. Roberts, Thomas E. Stinchcombe, Channing J. Der, Mark A. Socinski
Journal: Journal of Clinical Oncology (2010)

In patients with metastatic colorectal cancer, the predictive value of KRAS mutational status in the selection of patients for treatment with anti-epidermal growth factor (EGFR) monoclonal antibodies is established. In patients with non-small-cell lung cancer (NSCLC), the utility of determining KRAS mutational status to predict clinical benefit to anti-EGFR therapies remains unclear. This review will provide a brief description of Ras biology, provide an overview of aberrant Ras signaling in NSCLC, and summarize the clinical data for using KRAS mutational status as a negative predictive biomarker to anti-EGFR therapies. Retrospective investigations of KRAS mutational status as a negative predictor of clinical benefit from anti-EGFR therapies in NSCLC have been performed; however, small samples sizes as a result of low prevalence of KRAS mutations and the low rate of tumor sample collection have limited the strength of these analyses. Although an association between the presence of KRAS mutation and lack of response to EGFR tyrosine kinase inhibitors (TKIs) has been observed, it remains unclear whether there is an association between KRAS mutation and EGFR TKI progression-free and overall survival. Unlike colorectal cancer, KRAS mutations do not seem to identify patients who do not benefit from anti-EGFR monoclonal antibodies in NSCLC. The future value of testing for KRAS mutational status may be to exclude the possibility of an EGFR mutation or anaplastic lymphoma kinase translocation or to identify a molecular subset of patients with NSCLC in whom to pursue a drug development strategy that targets the KRAS pathway.
Identification, at the genomic level, of an HLA-DR restriction element for cloned antigen-specific T4 cells.
Authors: G Paulsen, E Qvigstad, G Gaudernack, L Rask, R Winchester, E Thorsby
Journal: The Journal of Experimental Medicine (1985)

Two T4 cell clones (TLC) specific for antigenic epitopes on Chlamydia trachomatis were studied. Using a panel of allogeneic antigen-presenting cells (APC), both TLC were found to be restricted by HLA class II elements closely associated with, but not identical to the DRw5S specificity, as determined by highly selected alloantisera, a monoclonal antibody (mAb), 109d6, and confirmed on the DNA level by determination of restriction fragment length polymorphisms (RFLP) with a DR beta probe. Furthermore, HLA-DR-specific mAb, including 109d6, but not other HLA class II- or class I-specific antibodies inhibited the two TLC, strongly suggesting that the restriction element is expressed by a DR molecule. Using digestion with Hind III restriction enzyme and a DR beta probe, we found a complete concordance between the appearance of a 9.3 kilobase band and the ability of allogeneic APC to restimulate the T cell clones. Thus, the restriction element for these T cell clones appear to be expressed by DR molecules, but can, at present, only be detected at the genomic level.
Marketing: Are you being duped?
Authors: T. Jackson
Journal: BMJ (2001)

How drug companies use opinion leaders

We all know that there is no such thing as a free drugs company lunch, but, what the hell, the food's good, those marketing people seem ever so nice, and, anyway, there doesn't really seem to be any catch. The catch, however, need no longer be a mystery. For the marketers have set out explicitly the methods they use to “educate” doctors into championing their products.

The May edition of Pharmaceutical Marketing magazine explains what it calls “the tricks of the trade.” These include developing “opinion leaders” (key doctors or other health professionals or even patient group representatives who are likely to be able to influence many others); building successful relationships with them (“how you can best get them to know and like you and your products”); and skills training (“ensuring your product champions communicate effectively on your behalf”).

These “tricks” appear in a 24 page …
Self-administration of hospital-based narrowband ultraviolet B (TL-01) phototherapy: a feasibility study in an outpatient setting
Authors: S. Yule, S. Sanyal, S. Ibbotson, H. Moseley, R.S. Dawe
Journal: British Journal of Dermatology (2013)

Self-administration of narrowband (TL-01) ultraviolet (UV)B phototherapy by patients at home is a safe and effective mode of treatment. Could selected patients self-administer phototherapy in hospital?To assess the feasibility of outpatient self-administration of UVB phototherapy as a potential service development.A total of 20 patients with psoriasis (n = 15) and eczema (n = 5) (13 female, mean age 32 years, range 17-56 years) were included in this pilot project. Patients underwent a training programme over 2 days, which included a minimal erythemal dose test and supervised treatment, prior to commencing self-administration of phototherapy. Questionnaires were used to gather feedback from patients and staff.Treatment data were collected for 18 of the 20 patients. The mean number of exposures was 25 (range 3-45), and the mean cumulative dose was 16 J cm(-2) (range 0·23-41·27 J cm(-2) ). No unexpected adverse effects were noted. These results were similar to those of a sample group of outpatients who had nurse-administered UVB phototherapy, for whom the mean number of exposures was 24 (range 4-49) and the mean cumulative dose was 17 J cm(-2) (range 0·53-71·16 J cm(-2) ). Thirteen patients completed the questionnaires. All concluded that the training programme sufficiently prepared them for self-administering phototherapy, and 12 reported that they would be happy to self-administer treatment in the future.Self-administration of UVB phototherapy is practicable, safe and effective for most selected patients. This mode of treatment provides training and support for patients to gain more control over management of their skin disease, empowering them to take an active role in their treatment. Self-administration of UVB phototherapy by outpatients provides an intermediate level of care between nurse-administered hospital phototherapy and self-administered home phototherapy.
Relative increase in leukemia-specific DNA in peripheral blood plasma from patients with acute myeloid leukemia and myelodysplasia
Authors: Anna Rogers, Youngson Joe, Taghi Manshouri, Amanda Dey, Iman Jilani, Francis Giles, Elihu Estey, Emil Freireich, Michael Keating, Hagop Kantarjian, Maher Albitar
Journal: Blood (2003)
End Points in Advanced Colon Cancer Clinical Trials: A Review and Proposal
Authors: Carmen Allegra, Charles Blanke, Marc Buyse, Richard Goldberg, Axel Grothey, Neal J. Meropol, Leonard Saltz, Alan Venook, Greg Yothers, Daniel Sargent
Journal: Journal of Clinical Oncology (2007)

Colorectal cancer accounts for the death of more than 55,000 individuals in the United States each year. 1 The vast majority of these patients receive systemic chemotherapy with one or more of several agents presently approved for treatment in this setting. Given the relatively recent and rapid identification of new active therapeuticsforpatientswithadvancedcolorectalcancer,thealgorithm for patient management is undergoing a similarly rapid evolution. The traditional paradigm, dating from the initial use of fluorouracil in the 1960s, dictated that patients receive continuous systemic therapy until disease progression or unacceptable toxicity.Thistreatmentmodelhasgenerallybeenappliedtotherapeutic clinical trials and forms the foundation on which the currently accepted intermediate end points designed to assess the efficacy of new agents (eg, progression-free survival [PFS]) are based. The high level of activity of newer regimens and a particular element of treatment with the agent oxaliplatin are challenging these standard paradigms. Although highly effective when used in combination with fluorouracil, oxaliplatin is associated with a cumulative sensory neuropathy that occurs at clinically significant levels after approximately 5 months (approximately 850 mg/m 2 total dose) of therapy. 2 This adverse event generally precludes long-term continuous therapy with this agent. In other tumor types (eg, lung, ovary), the use of platinum therapy has resulted in preplanned, fixed therapeutic windows of 4 to 6 months. Similar approaches are beginning to be explored in colorectal cancer, driven primarily by the desire to obviate or at least mitigate neurotoxicity. In addition, as three-, four-, and five-drug regimens become more common and a majority of patients respond to treatment (or at least establish stable disease), in many cases, toxicityexceedstolerablelimitsbeforetheeffectivenessofaregimenis fully exploited. A recent study reported in abstract form may serve as an example of this phenomenon. 3 In this investigation, bevacizumab did not seem to improve the PFS of oxaliplatin-based regimens to the extent expected based on prior trials. 4 A possible
Absorption of antigens after oral immunisation and the simultaneous induction of specific systemic tolerance.
Authors: E T Swarbrick, C R Stokes, J F Soothill
Journal: Gut (1979)

Antigenic proteins may be absorbed intact. We report here results from in vivo experiments in mice showing that the prior feeding of protein antigen may reduce the subsequent absorption of that antigen without altering its elimination from the circulation. This may be a function of local immunity. We have also shown that the same feeding regime can paradoxically induce a state of systemic tolerance and suggest that the two phenomena contribute to the safe handling of these antigens.
Adherence to topical dermatological therapy: lessons from oral drug treatment
Authors: G. Gupta, P. Mallefet, D.W. Kress, A. Sergeant
Journal: British Journal of Dermatology (2009)

Patients are remarkably nonadherent to medical treatment regimens across all diseases and classes of therapy, and it has been estimated that nonadherence to drug treatment is responsible for as many as 10% of all hospital admissions. Nonadherence to treatment also has significant negative effects on treatment outcomes across a wide range of diseases. Patient-related factors such as age, ethnicity, literacy (including health literacy), health beliefs, and socioeconomic conditions have been shown to influence adherence to oral therapy. Medication-related factors, such as regimen complexity and duration of treatment, also impact on adherence. Variables that significantly influence adherence to oral drugs have similar effects on adherence to topical therapy. Both educational and psychological interventions along with simplification of dosing regimens can significantly improve adherence to oral therapy and limited evidence indicates that these approaches are also effective in patients receiving topical therapy. There is very little information about the effects of dosing regimens on adherence to topical medical therapy. The advent of new drug formulations that permit once-daily or single-dose drug application will, however, permit evaluation of different topical treatment regimens on adherence and treatment outcomes in patients with dermatological disease.
Impact of different descriptions of the Kellgren and Lawrence classification criteria on the diagnosis of knee osteoarthritis
Authors: D. Schiphof, B. de Klerk, H. Kerkhof, A. Hofman, B. Koes, M. Boers, S. Bierma-Zeinstra
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Objectives</h3> Although the Kellgren and Lawrence (K&amp;L) criteria for defining radiological osteoarthritis are widely used in epidemiological and clinical studies, the authors previously documented the existence of five different versions of these criteria. This study identifies the impact of the use of alternative versions of the K&amp;L criteria and evaluates which description has the highest association with knee complaints. <h3>Methods</h3> Two readers scored most radiographs of the knees of participants of the Rotterdam Study with the original K&amp;L description (90%). In addition, each alternative description was used in a random part (20%) of the radiographs. The authors calculated reproducibility of all descriptions, and compared sensitivity and specificity of the alternative descriptions for three cut-off points with the original description as reference standard (K&amp;L≥1, K&amp;L≥2 and K&amp;L≥3). The authors calculated κ statistics to compare agreement between the original and alternative descriptions, and evaluated the association with knee complaints. <h3>Results</h3> The dataset comprises radiographs of knees of 3071 people. For cut-off K&amp;L≥1 all four alternatives classified more people as having osteoarthritis than the original description; κ was low, and sensitivity and specificity were moderate to good. For cut-offs K&amp;L≥2 and K&amp;L≥3 there was little difference in the number of cases and κ, sensitivity and specificity were good to perfect. The original description and alternative 3 showed the strongest association with knee complaints. <h3>Conclusions</h3> The different descriptions of the K&amp;L criteria have impact on the classification of osteoarthritis in the lowest grade (K&amp;L≥1). All descriptions have strengths and weaknesses. It depends on the purpose which is the best description.
Lung diseases directly associated with rheumatoid arthritis and their relationship to outcome
Authors: Y. Tsuchiya, N. Takayanagi, H. Sugiura, Y. Miyahara, D. Tokunaga, Y. Kawabata, Y. Sugita
Journal: European Respiratory Journal (2010)

The outcome and cause of death of each lung disease directly associated with rheumatoid arthritis (RA-LD) have been poorly investigated. A retrospective study was conducted of 144 patients with RA-LD, in whom the median follow-up period after the initial visit for a respiratory examination was 4.5 yrs. A total of 57 patients were identified with usual interstitial pneumonia (UIP), 31 with bronchiectasis, 16 with nonspecific interstitial pneumonia (NSIP), 11 with bronchiolitis, five with organising pneumonia (OP), five with diffuse alveolar damage (DAD) and 19 with combined disease. The 5-yr survival rates were 36.6% in the UIP group, 87.1% in the bronchiectasis group, 93.8% in the NSIP group, 88.9% in the bronchiolitis group, 60.0% in the OP group and 20.0% in the DAD group. Survival of patients with DAD was worse than that of patients with UIP. Overall, survival of patients with UIP was worse than that of patients with bronchiectasis, NSIP or bronchiolitis. Of the 144 patients, 71 (49.3%) died, of whom 58 (81.7%) died due to respiratory lesions. Of patients with RA-LD, patients with DAD experienced the highest mortality, and the survival of patients with UIP was worse than that of patients with NSIP.
Intra-articular pressure changes in rheumatoid and normal peripheral joints.
Authors: K Gaffney, R B Williams, V A Jolliffe, D R Blake
Journal: Annals of the Rheumatic Diseases (1995)

OBJECTIVE--To investigate the intraarticular pressure (IAP) dynamics of a spectrum of joints in rheumatoid and normal subjects in order to determine whether a reperfusion event is likely to occur at these sites. METHODS--IAP was measured in the metacarpophalangeal (MCP) (n = 8), wrist (n = 8), ankle (n = 4), and elbow joints (n = 4) of rheumatoid subjects, in addition to the MCP (n = 8), wrist (n = 6), and ankle joints (n = 1) of normal healthy controls, using the hand held portable 295-1 Intra-Compartmental Pressure Monitor System (Stryker, UK). RESULTS--Resting IAP was positive in all rheumatoid joints, and subatmospheric or weakly atmospheric in normal subjects (p &lt; 0.01). Exercise produced an increase in IAP in rheumatoid subjects only (p &lt; 0.01). The addition of saline to normal joints mimicked the IAP changes seen in the rheumatoid group. CONCLUSION--These observations suggest that increased resting IAP is a marker for chronic joint inflammation. The IAP increase seen in the rheumatoid group during exercise supports the concept of hypoxic reperfusion mediated joint injury.
Optoacoustic Imaging and Staging of Inflammation in a Murine Model of Arthritis
Authors: N. Beziere, C. von Schacky, Y. Kosanke, M. Kimm, A. Nunes, K. Licha, M. Aichler, A. Walch, E. J. Rummeny, V. Ntziachristos, R. Meier
Journal: Arthritis & Rheumatology (2014)

Objective Rheumatoid arthritis (RA) is one of the most frequent inflammatory diseases, causing pain and disability in the affected joints. Early diagnosis is essential for the efficiency of symptom‐targeting treatments, but its diagnosis requires careful clinical, serologic, and imaging examinations, such as magnetic resonance imaging (MRI), which is both expensive and time consuming. In an effort to provide the biomedical community with a more accessible way to assess the advancement of arthritis, this study sought to investigate the use of multispectral optoacoustic tomography (MSOT) in a murine arthritis model, to visualize the extent of inflammation in vivo through an L‐selectin/P‐selectin–targeting contrast agent. Methods Mice with collagen‐induced arthritis were studied as a model of RA. MSOT was performed using an L‐selectin/P‐selectin–targeting contrast agent, polyanionic dendritic polyglycerol sulfate (dPGS) labeled with a near‐infrared (NIR) fluorophore, to increase the contrast of the arthritic joint. The signal intensity ratios between healthy legs and arthritic legs were calculated. Findings on contrast‐enhanced MRI, clinical observations, the lymphocyte:granulocyte ratio, and histologic findings served as referents for comparison. Results MSOT using an inflammation‐targeting contrast agent, dPGS‐NIR, allowed for accurate diagnosis of inflammation in the mouse joints. In addition, use of this technique resulted in significant differentiation of the inflamed joints from the healthy joints ( P = 0.023). The observed advancement of arthritis on the MSOT images was confirmed by clinical observation, blood analysis, contrast‐enhanced MRI, and ex vivo histologic examinations. Conclusion This study demonstrates that the combination of an inflammation‐targeting contrast agent and optoacoustic tomographic imaging presents a promising means for the diagnosis of RA and the staging of arthritis‐related inflammation.
Impaired receptor editing and heterozygous RAG2 mutation in a patient with systemic lupus erythematosus and erosive arthritis
Authors: Jolan E. Walter, Mindy S. Lo, Katalin Kis-Toth, Irit Tirosh, Francesco Frugoni, Yu Nee Lee, Krisztian Csomos, Karin Chen, Shiv Pillai, Jonathan Dunham, George C. Tsokos, Eline T. Luning Prak, Luigi D. Notarangelo
Journal: Journal of Allergy and Clinical Immunology (2014)