tbuckley/cabot-search huggingface dataset:
Converting Enzyme Activity in Human Plasma
Authors: ANNETTE FITZ, GRAHAM W. BOYD, W. STANLEY PEART
Journal: Circulation Research (1971)

Human plasma converting enzyme activity was investigated by comparing biological with immunological activity of added or generated angiotensin after plasma incubation. Sodium citrate (2 x 10 -2 M ), 2:2'-dipyridyl (1 x 10 -4 and 1 x 10 -2 M ), chromotropic acid (3 x 10 -2 and 3 x 10 -3 M ) and desferrioxamine (10 and 100 mg/100 ml) did not interfere with converting enzyme. By contrast, EDTA (3 x 10 -3 M and 3 x 10 -2 M ), EGTA (3 x 10 -2 M ), 8-quinolinol (1 x 10 -2 M ), and oxalic acid (3 x 10 -2 M ) were shown to interfere with plasma converting enzyme activity. The EDTA inhibition of converting enzyme activity could be partially reversed by molar excess amounts of calcium, zinc and cobalt. The ability of these ions to restore converting enzyme activity to the plasma was quantitatively variable. Inhibition of converting enzyme activity by EDTA could not be reversed by the addition of iron, copper or manganese to the samples.
The combination of anti-B7 monoclonal antibody and cyclosporin A induces alloantigen-specific anergy during a primary mixed lymphocyte reaction.
Authors: S W Van Gool, M de Boer, J L Ceuppens
Journal: The Journal of Experimental Medicine (1994)

Interaction of CD28/CTLA-4 on T cells with B7 on antigen-presenting cells constitutes an important costimulatory signal for T cells and is responsible for cyclosporin A-resistant interleukin 2 (IL-2) gene expression and potentially also for prevention of anergy induction after T cell receptor triggering. In this paper, we demonstrate that addition of a monoclonal antibody to B7, which blocks B7-CD28/CTLA-4 interaction, and of cyclosporin A together, but not separately, to a primary mixed lymphocyte reaction of freshly isolated human T cells towards a human B cell line, induces nonresponsiveness of alloantigen-specific cytotoxic T lymphocyte precursors, whereas reactivity to a third party stimulator is intact. Nonresponsiveness could be reversed by culture in IL-2, indicating that anergy, and not clonal deletion, is responsible for this phenomenon. Our finding opens important perspectives for the development of new therapeutic strategies in transplantation.
P15 How important are blood cultures in the management of patients suspected to have Community Acquired Pneumonia?: Abstract P15 Table 1
Authors: W Kent, L Potter, S Roberts, R Shaw, K Vaudrey, P Deegan, J Folb
Journal: Thorax (2012)

<h3>Background</h3> It is acknowledged in the BTS guidelines that the routine use of blood cultures in community acquired pneumonia (CAP) has been questioned on the grounds of cost, low sensitivity and lack of impact on antimicrobial management.<sup>1</sup> In October 2011 the hospital policy for severe CAP (CURB 65 ≥ 3) at our trust changed to benzylpenicillin and clarithromycin. This combination is associated with decreased rates of <i>clostridium difficile</i>, however it has weak cover against <i>Haemophilus influenzae</i> and none against gramme negative bacilli. <h3>Aim</h3> To determine the positive yield from blood cultures in patients suspected as having CAP at presentation to hospital, their impact on management and, in particular, the outcomes associated with Gram negative bacteraemia. <h3>Method</h3> Patients were prospectively identified at a large University Hospital in whom CAP was suspected as their admitting diagnosis between November 2011 and January 2012. The patient demographics and outcomes were analysed at admission and revisited at 7 and 30 days. <h3>Results</h3> 151 patients were identified for inclusion. Age range was 22–97, median 75. The CXR was reported as showing infiltrates in 93/148 cases (62.8%). Blood cultures were sent in 41/88 patients (46.5%) with CURB score ≥ 2 and 21/37 patients (56.8%) with CURB score ≥ 3. There were 10 positive blood cultures (representing 14.5% of all blood cultures sent). 6 were positive for <i>streptococcus pneumoniae</i> and 4 yielding <i>E. Coli</i> or <i>Klebsiella</i> suggesting an alternative source of infection. There were no cases of severe CAP due to <i>Haemophilus influenzae.</i> 60/151 patients had a change in their antibiotics; 11 as a result of poor clinical progress, 11 due to positive microbiology results, 38 due to a new diagnosis or no evidence of infection. <h3>Conclusion</h3> Blood cultures can be of increased importance in the investigation of CAP when used in combination with a narrower spectrum of antibiotics, particularly when checking for the possibility of occult gram negative sepsis. <h3>References</h3> Lim WS et al. Pneumonia Guidelines Committee of the BTS Standards of Care Committee. BTS guidelines for the management of community acquired pneumonia in adults: update 2009. Thorax. 2009.Oct; 64 Suppl 3:iii 1–55.
Lenalidomide induced good clinical response in a patient with multiple relapsed and refractory Hodgkin's lymphoma
Authors: Inga Mandac, Slobodanka Ostojic Kolonic
Journal: Journal of Hematology & Oncology (2010)

A 24-year-old female patient was diagnosed with classic Hodgkin's lymphoma in clinical stage II, and combination chemotherapy followed by radiotherapy was initiated. During the following 5 years, the disease progressed despite several standard therapeutic approaches, including autologous and allogeneic stem cell transplantation. Lenalidomide (25 mg daily) treatment was then initiated in a continuous dosing schedule. Positron emission tomography scans were performed before and during lenalidomide treatment. Hematologic and laboratory values, as well as physical condition were also assessed before and during lenalidomide treatment. Four months after continuous lenalidomide treatment, tumor load was significantly reduced, B symptoms had resolved, and the patient's physical condition had improved, allowing her to resume normal daily-living activities. Evaluations after 15 months of lenalidomide treatment indicated limited disease progression. Nevertheless, the patient was feeling well and maintaining a normal active life. Treatment was well tolerated, allowing the patient to remain on continuous dosing, which has now been maintained for 18 months. Daily, long-term lenalidomide treatment provided clinical benefit and was well tolerated in a patient with relapsed, advanced classic Hodgkin's lymphoma.
Molecular Pathogenesis of Ovarian Borderline Tumors: New Insights and Old Challenges
Authors: Ie-Ming Shih, Robert J. Kurman
Journal: Clinical Cancer Research (2005)

Abstract Ovarian borderline (low malignant potential) tumors are a puzzling group of neoplasms that do not fall neatly into benign or malignant categories. Their behavior is enigmatic, their pathogenesis unclear, and their clinical management controversial, especially for serous borderline tumors (SBT), the most common type of ovarian borderline tumor. Clarifying the nature of borderline tumors and their relationship to invasive carcinoma has puzzled investigators since the category was created over 30 years ago. Much of the confusion and controversy concerning these tumors is due to a lack of understanding of their pathogenesis and an absence of a model for the development of ovarian carcinoma. This review summarizes recent molecular studies of ovarian borderline tumors with special emphasis on the role of SBT in tumor progression and its relationship to ovarian serous carcinoma.
Explaining more by drawing on less
Authors: Ulrike Hahn
Journal: Behavioral and Brain Sciences (2009)

Abstract One of the most striking features of “Bayesian rationality” is the detail with which behavior on logical reasoning tasks can now be predicted and explained. This detail is surprising, given the state of the field 10 to 15 years ago, and it has been brought about by a theoretical program that largely ignores consideration of cognitive processes , that is, any kind of internal behavior that generates overt responding. It seems that an increase in explanatory power can be achieved by restricting a psychological theory.
Cis and Trans Regulatory Effects Contribute to Natural Variation in Transcriptome of Drosophila melanogaster
Authors: A. Genissel, L. M. McIntyre, M. L. Wayne, S. V. Nuzhdin
Journal: Molecular Biology and Evolution (2007)

The dissection of intraspecific variation in transcriptome is a central theme of many recent quantitative genomic analyses. Transcript level variation has been attributed to factors at the gene itself (cis) and elsewhere in the genome (trans). Previous analyses of Drosophila intraspecific transcriptome variation pointed toward a larger contribution of trans factors. However, data from other genera, and from interspecific comparisons within Drosophila, are more consistent with a major role for cis factors. We investigated the relative amount of cis and trans variation in Drosophila melanogaster, using whole-genome expression from an oligonucleotide microarray in the 2 extensively studied genotypes Ore and 2b3, and 6 recombinant inbred (RI) lines derived from these parents. We examined 2 types of models to decompose cis and trans contributions to genetic variation in transcript level: 1) an infinitesimal model assuming that the transcription variation is highly polygenic and due to many small effects and 2) contrast models assuming that a few large effects contribute to the transcriptional variation. We explicitly fitted cis-by-trans interactions and extended our analyses to consider regulation of alternatively spliced transcripts. We estimated that approximately 10% of the transcriptome was differentially regulated among the lines. We were able to identify cis and trans effects that contribute to this differential regulation for 1,340 genes. Our analyses revealed numerous cis effects (90%) but much fewer trans effects, perhaps due to reduced power of detection for trans effects. In addition, we identified 15 genes that have alternative splice variants differentially regulated in cis.
Effect of Improving Depression Care on Pain and Functional Outcomes Among Older Adults With Arthritis
Authors: Elizabeth H. B. Lin, Wayne Katon, Michael Von Korff, Lingqi Tang, John W. Williams, Jr, Kurt Kroenke, Enid Hunkeler, Linda Harpole, Mark Hegel, Patricia Arean, Marc Hoffing, Richard Della Penna, Chris Langston, Jürgen Unützer, None for the IMPACT Investigators
Journal: JAMA (2003)

Depression and arthritis are disabling and common health problems in late life. Depression is also a risk factor for poor health outcomes among arthritis patients.To determine whether enhancing care for depression improves pain and functional outcomes in older adults with depression and arthritis.Preplanned subgroup analyses of Improving Mood-Promoting Access to Collaborative Treatment (IMPACT), a randomized controlled trial of 1801 depressed older adults (> or =60 years), which was performed at 18 primary care clinics from 8 health care organizations in 5 states across the United States from July 1999 to August 2001. A total of 1001 (56%) reported coexisting arthritis at baseline.Antidepressant medications and/or 6 to 8 sessions of psychotherapy (Problem-Solving Treatment in Primary Care).Depression, pain intensity (scale of 0 to 10), interference with daily activities due to arthritis (scale of 0 to 10), general health status, and overall quality-of-life outcomes assessed at baseline, 3, 6, and 12 months.In addition to reduction in depressive symptoms, the intervention group compared with the usual care group at 12 months had lower mean (SE) scores for pain intensity (5.62 [0.16] vs 6.15 [0.16]; between-group difference, -0.53; 95% confidence interval [CI], -0.92 to -0.14; P =.009), interference with daily activities due to arthritis (4.40 [0.18] vs 4.99 [0.17]; between-group difference, -0.59; 95% CI, -1.00 to -0.19; P =.004), and interference with daily activities due to pain (2.92 [0.07] vs 3.17 [0.07]; between-group difference, -0.26; 95% CI, -0.41 to -0.10; P =.002). Overall health and quality of life were also enhanced among intervention patients relative to control patients at 12 months.In a large and diverse population of older adults with arthritis (mostly osteoarthritis) and comorbid depression, benefits of improved depression care extended beyond reduced depressive symptoms and included decreased pain as well as improved functional status and quality of life.
Inhibition of mesangial cell proliferation by platelet factor 4.
Authors: J L Barnes, K A Woodruff, S P Levine, H E Abboud
Journal: Journal of the American Society of Nephrology (1996)

Platelet factor 4(PF4), an abundant platelet secretory product, is a strong candidate for modulating glomerular pathology. Because PF4 might be released from platelets and influence intrinsic cell growth during glomerular injury, the effect of PF4 on fetal calf serum- and platelet-derived growth factor (PDGF)-induced mesangial cell mitogenesis was examined. Mitogenesis was measured as the amount of 3H-thymidine incorporated into acid-precipitable material as well as by autoradiography. The effect of PF4 on mesangial cell expression of mRNA for PDGF A chain and transforming growth factor-beta (TGF-beta 1) was also examined. Fetal calf serum (10%)- and PDGF (10 ng/mL)-stimulated increases in mesangial cell 3H-thymidine incorporation were inhibited by incremental concentrations of PF4 (1 to 25 micrograms/mL) showing a maximum reduction of approximately 80% at 25 micrograms/mL of PF4. PF4 was effective when added 24 h before and 1, 4, and 8 h, but not 16 h after the addition of PDGF, indicating that inhibition occurred at delayed events in cell-cycle regulation. PF4 inhibited PDGF-induced increments in mRNA encoding PDGF A chain and TGF-beta 1. Also, PF4 did not interfere with PDGF receptor binding. The results of this study show that PF4 is a negative regulator of mesangial cell proliferation and suggest an interference in cell growth by pathways associated with modulation of the autocrine growth factors PDGF and TGF-beta 1.
Tim-3 expression defines a novel population of dysfunctional T cells with highly elevated frequencies in progressive HIV-1 infection
Authors: R. Brad Jones, Lishomwa C. Ndhlovu, Jason D. Barbour, Prameet M. Sheth, Aashish R. Jha, Brian R. Long, Jessica C. Wong, Malathy Satkunarajah, Marc Schweneker, Joan M. Chapman, Gabor Gyenes, Bahareh Vali, Martin D. Hyrcza, Feng Yun Yue, Colin Kovacs, Aref Sassi, Mona Loutfy, Roberta Halpenny, Desmond Persad, Gerald Spotts, Frederick M. Hecht, Tae-Wook Chun, Joseph M. McCune, Rupert Kaul, James M. Rini, Douglas F. Nixon, Mario A. Ostrowski
Journal: The Journal of Experimental Medicine (2008)

Progressive loss of T cell functionality is a hallmark of chronic infection with human immunodeficiency virus 1 (HIV-1). We have identified a novel population of dysfunctional T cells marked by surface expression of the glycoprotein Tim-3. The frequency of this population was increased in HIV-1-infected individuals to a mean of 49.4 +/- SD 12.9% of CD8(+) T cells expressing Tim-3 in HIV-1-infected chronic progressors versus 28.5 +/- 6.8% in HIV-1-uninfected individuals. Levels of Tim-3 expression on T cells from HIV-1-infected inviduals correlated positively with HIV-1 viral load and CD38 expression and inversely with CD4(+) T cell count. In progressive HIV-1 infection, Tim-3 expression was up-regulated on HIV-1-specific CD8(+) T cells. Tim-3-expressing T cells failed to produce cytokine or proliferate in response to antigen and exhibited impaired Stat5, Erk1/2, and p38 signaling. Blocking the Tim-3 signaling pathway restored proliferation and enhanced cytokine production in HIV-1-specific T cells. Thus, Tim-3 represents a novel target for the therapeutic reversal of HIV-1-associated T cell dysfunction.
Aeroallergen analyses and their clinical relevance
Authors: C. R. Johnsen, E.R. Weeke, J. Nielsen, J. Jensen, H. Mosbech, L. Frølund, F. Madsen, L. K. Poulsen
Journal: Allergy (1992)

A comparison was made between the amount of airborne pollen collected by Burkard airsampler and the allergenic activity of particles trapped on glass fibre filters in an Accu‐Vol high‐volume airsampler. The comparison was made throughout the pollen seasons 1986 to 1989. Both airsamplers were operated 24 h a day. They were placed less than 5 m apart, and estimation of the pollen amount was made on a day‐to‐day basis during the pollen seasons, and on a weekly basis outside the seasons. The occurrence of the 3 clinically most important allergenic types of pollen, birch, grass, and mugwort, was analysed, and close correlations between the 2 sampling techniques were found (r s 0.5–0.8, p&lt; 0.001). The detected range of counted pollens/m 3 was: birch 0–1075, grass 0–156, and mugwort 0–44. By immunochemical analysis we found the corresponding amounts to be 0–80, 0–8, and 0–1 SQ‐U/m 3 respectively. Pollen counts and immunochemical estimation were compared with the symptom score recordings of allergic persons for birch season 1989 and for grass seasons 1986, 1988, and 1989. A close correlation was found for both sampling techniques for the grass seasons in 1986 and 1989 (r s 0.51–0.61, p&lt; 0.001–0.0001), but a less significant correlation was found for the 1988 grass season, and for birch in 1989 (r s 0.24–0.34, p&lt;0.001–0.05).
A preliminary algorithm introducing immunogenicity assessment in the management of patients with RA receiving tumour necrosis factor inhibitor therapies
Authors: Sandra Garcês, Marília Antunes, Elizabeth Benito-Garcia, José Canas da Silva, Lucien Aarden, Jocelyne Demengeot
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Introduction</h3> Clinical remission is today the treatment goal for rheumatoid arthritis (RA), which requires fast and assertive therapeutic decisions for a tight control of disease activity. Few objective parameters are available to guide clinical decisions, particularly in switcher patients. We designed a preliminary algorithm introducing immunogenicity assessment in the current approach to patients with RA receiving tumour necrosis factor inhibitors (TNFi). <h3>Objective</h3> To evaluate the concordance between the new algorithm and current clinical practice, comparing the effectiveness of 'immunogenicity-based' versus 'empirical-based' switches in a cohort of patients with established RA receiving biologics. <h3>Methods</h3> EULAR therapeutic response was evaluated in 105 patients with RA (naive or switchers) over one year, through generalised estimation equation (GEE) analyses. Serum drug trough levels were assessed by ELISA and antidrug antibodies (ADAb) by Bridging ELISA. <h3>Results</h3> During follow-up, 48.6% of patients had therapeutic decisions concordant with the proposed algorithm (Group A), and 51.4% had discordant decisions (Group B). One year after the therapeutic decision, patients from Group A had a higher probability of achieving response (OR=7.91, p&lt;0.001, 95% CI 3.27 to 19.13) and low disease activity (OR=9.77, p&lt;0.001, 95% CI 4.69 to 20.37) than patients in Group B. <h3>Conclusions</h3> Immunogenicity assessment might help to optimise therapeutic decisions, leading to a better control of disease activity with significantly better clinical outcomes in patients with RA receiving TNFi.
Activity of the Dual Kinase Inhibitor Lapatinib (GW572016) against HER-2-Overexpressing and Trastuzumab-Treated Breast Cancer Cells
Authors: Gottfried E. Konecny, Mark D. Pegram, Natarajan Venkatesan, Richard Finn, Guorong Yang, Martina Rahmeh, Michael Untch, David W. Rusnak, Glenn Spehar, Robert J. Mullin, Barry R. Keith, Tona M. Gilmer, Mark Berger, Karl C. Podratz, Dennis J. Slamon
Journal: Cancer Research (2006)

Lapatinib (GW572016) is a selective inhibitor of both epidermal growth factor receptor (EGFR) and HER-2 tyrosine kinases. Here, we explore the therapeutic potential of lapatinib by testing its effect on tumor cell growth in a panel of 31 characterized human breast cancer cell lines, including trastuzumab-conditioned HER-2-positive cell lines. We further characterize its activity in combination with trastuzumab and analyze whether EGFR and HER-2 expression or changes induced in the activation of EGFR, HER-2, Raf, AKT, or extracellular signal-regulated kinase (ERK) are markers of drug activity. We report that concentration-dependent antiproliferative effects of lapatinib were seen in all breast cancer cell lines tested but varied significantly between individual cell lines with up to 1,000-fold difference in the IC(50)s (range, 0.010-18.6 micromol/L). Response to lapatinib was significantly correlated with HER-2 expression and its ability to inhibit HER-2, Raf, AKT, and ERK phosphorylation. Long-term in vivo lapatinib studies were conducted with human breast cancer xenografts in athymic mice. Treatment over 77 days resulted in a sustained and significant reduction in xenograft volume compared with untreated controls. For the combination of lapatinib plus trastuzumab, synergistic drug interactions were observed in four different HER-2-overexpressing cell lines. Moreover, lapatinib retained significant in vitro activity against cell lines selected for long-term outgrowth (>9 months) in trastuzumab-containing (100 microg/mL) culture medium. These observations provide a clear biological rationale to test lapatinib as a single agent or in combination with trastuzumab in HER-2-overexpressing breast cancer and in patients with clinical resistance to trastuzumab.
A "respiratory" cause of abdominal pain
Authors: D. Gupta, R. Agarwal, A. Singh, K. Joshi
Journal: European Respiratory Journal (2006)

A 52-yr-old female presented with complaints of upper abdominal pain, nausea and vomiting.There was no history of prior abdominal pain, abdominal distension and constipation.In June 2003, the patient had presented to her general practitioner with pain and swelling in multiple joints, both small and large.She was diagnosed to have seronegative rheumatoid arthritis and had received diclofenac, vitamin D, calcium supplements and methotrexate (7.5 mg p.o.?week -1 ) for the same.She had partial response, and methotrexate was stopped for the last 6 months of treatment up until June 2005; however she was continued on diclofenac and calcium supplements.