tbuckley/cabot-search huggingface dataset:
False-positive diagnosis of pulmonary hypertension by Doppler echocardiography
Authors: JL Vachiery, S Brimioulle, V Crasset, R Naeije
Journal: European Respiratory Journal (1998)

A 37-yr-old female presented with a history of several months of exertional dyspnoea. A diagnosis of primary pulmonary hypertension was suspected on the basis of a negative extensive cardiorespiratory work-up with a systolic pulmonary artery pressure of 41-46 mmHg calculated from repeated measurement of the maximum velocity of tricuspid regurgitation jets at 2.8-3 m x s(-1) by continuous-wave Doppler echocardiography. However, a right heart catheterization with a high-fidelity transducer-tipped catheter revealed pulmonary artery pressures of 22/8 mmHg at rest, which remained within normal limits at exercise. This case indicates a possible misleading overestimation of pulmonary artery pressures from Doppler echocardiographic studies of tricuspid regurgitation.
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Authors: Trevor Jackson
Journal: BMJ (2006)

Because abnormalities of mucosal immunity have been suggested in human IgA nephropathy, we examined the involvement of mucosal immunity in IgA deposition to the kidney in hyper IgA (HIGA) mice, which was established as a mouse model for human IgA nephropathy with hyperserum IgA. The number of surface IgA<sup>+</sup>B220<sup>−</sup> lymphocytes in the intestinal lamina propria (LP) of HIGA mice increased 2.7-fold at 30 wk of age as compared with those at 10 wk of age, whereas normal mice did not show such increase. The surface IgA<sup>+</sup>B220<sup>−</sup> LP lymphocytes spontaneously secreted IgA in culture. Morphological studies showed that the surface IgA<sup>+</sup>B220<sup>−</sup> lymphocytes of murine intestinal LP are identical with plasma cells (PCs). About 20% of IgA<sup>+</sup>B220<sup>−</sup> PC in LP expressed both Mac-1 and CD19, suggesting that they may derive from peritoneal B-1 cells. Cell cycle study on intestinal IgA-PCs using bromodeoxyuridine revealed no difference between HIGA mice and normal mice, suggesting that the high frequency of IgA-producing PCs in HIGA mice is not due to enhanced proliferation or prolonged survival of IgA-producing PCs in LP. In addition, IgA secretion into the gut lumen of HIGA mice decreased drastically (to one forth) with aging. These data suggest that the increased number of intestinal IgA-producing PCs and the down-regulation of IgA excretion into the intestinal lumen might synergistically contribute to the hyperserum IgA in HIGA mice and resultant IgA deposition to the kidney.
Hypersensitivity pneumonitis caused by occupational exposure to phytase
Authors: R. C. van Heemst, I. Sander, J. Rooyackers, L. de Jong, R. S. Djamin, J. G. Aerts, H. N. A. Belderbos
Journal: European Respiratory Journal (2009)

A 43-yr-old male presented with a 6-month history of episodes of coughing, shortness of breath and fever. He suffered from dyspnoea on minor exertion. The patient worked in a cattle feed factory and noticed that he had more complaints after his working hours. His symptoms could be ascribed to hypersensitivity pneumonitis due to contact with phytase, an enzyme added to cattle feed to strengthen bone and diminish phosphorus excretion. The diagnosis was supported by bibasal lung crackles on physical examination, restrictive ventilatory defect (with decreased diffusion capacity for carbon monoxide), typical radiographical findings, lymphocytosis in bronchoalveolar lavage fluid and a positive exposure test performed at the workplace. Blood examination showed high immunoglobulin G levels to phytase. After treatment and cessation of phytase contact the patient became symptom free and lung function normalised. Phytase should be considered as a cause of occupational hypersensitivity pneumonitis in the animal feed industry.
Comparing the Effect of Intranasal Fluticasone Furoate (FF) to Intraocular Olopatadine (OLO) on the Ocular Response to Nasal Allergen Challenge (NAC)
Authors: M. DeTineo, H. Logothetis, M. Bashir, J.M. Pinto, F.M. Baroody, R.M. Naclerio
Journal: Journal of Allergy and Clinical Immunology (2012)
The Extragenic Spacer Length Between the 5′ and 3′ Ends of the Transgene Expression Cassette Affects Transgene Silencing From Plasmid-based Vectors
Authors: Jiamiao Lu, Feijie Zhang, Siqun Xu, Andrew Z Fire, Mark A Kay
Journal: Molecular Therapy (2012)

In quiescent tissues, minicircle DNA vectors provide at least 10 times higher sustained levels of transgene expression compared to that achieved with a canonical plasmid containing the same expression cassette. It is not known if there is a specific DNA sequence or structure that is needed for DNA silencing. To directly address this question, we substituted the bacterial plasmid DNA with various lengths of extragenic spacer DNAs between the 5' and 3' ends of the transgene expression cassette and determined the expression profiles using two different reporter expression cassettes. Both the human alphoid repeat (AR) and randomly generated DNA sequences of ≥1 kb in length resulted in transgene silencing while shorter spacers, ≤500 bp exhibited similar transgene expression patterns to conventional minicircle DNA vectors. In contrast, when the ≥1 kb random DNA (RD) sequences were expressed as part of the 3'-untranslated region (UTR) transgene silencing was not observed. These data suggest that the length and not the sequence or origin of the extragenic DNA flanking the expression cassette is responsible for plasmid-mediated transgene silencing. This has implications for the design of nonviral vectors for gene transfer applications as well as providing insights into how genes are regulated.
Impact of the Addition of Carboplatin and/or Bevacizumab to Neoadjuvant Once-per-Week Paclitaxel Followed by Dose-Dense Doxorubicin and Cyclophosphamide on Pathologic Complete Response Rates in Stage II to III Triple-Negative Breast Cancer: CALGB 40603 (Alliance)
Authors: William M. Sikov, Donald A. Berry, Charles M. Perou, Baljit Singh, Constance T. Cirrincione, Sara M. Tolaney, Charles S. Kuzma, Timothy J. Pluard, George Somlo, Elisa R. Port, Mehra Golshan, Jennifer R. Bellon, Deborah Collyar, Olwen M. Hahn, Lisa A. Carey, Clifford A. Hudis, Eric P. Winer
Journal: Journal of Clinical Oncology (2014)

One third of patients with triple-negative breast cancer (TNBC) achieve pathologic complete response (pCR) with standard neoadjuvant chemotherapy (NACT). CALGB 40603 (Alliance), a 2 × 2 factorial, open-label, randomized phase II trial, evaluated the impact of adding carboplatin and/or bevacizumab.Patients (N = 443) with stage II to III TNBC received paclitaxel 80 mg/m(2) once per week (wP) for 12 weeks, followed by doxorubicin plus cyclophosphamide once every 2 weeks (ddAC) for four cycles, and were randomly assigned to concurrent carboplatin (area under curve 6) once every 3 weeks for four cycles and/or bevacizumab 10 mg/kg once every 2 weeks for nine cycles. Effects of adding these agents on pCR breast (ypT0/is), pCR breast/axilla (ypT0/isN0), treatment delivery, and toxicities were analyzed.Patients assigned to either carboplatin or bevacizumab were less likely to complete wP and ddAC without skipped doses, dose modification, or early discontinuation resulting from toxicity. Grade ≥ 3 neutropenia and thrombocytopenia were more common with carboplatin, as were hypertension, infection, thromboembolic events, bleeding, and postoperative complications with bevacizumab. Employing one-sided P values, addition of either carboplatin (60% v 44%; P = .0018) or bevacizumab (59% v 48%; P = .0089) significantly increased pCR breast, whereas only carboplatin (54% v 41%; P = .0029) significantly raised pCR breast/axilla. More-than-additive interactions between the two agents could not be demonstrated.In stage II to III TNBC, addition of either carboplatin or bevacizumab to NACT increased pCR rates, but whether this will improve relapse-free or overall survival is unknown. Given results from recently reported adjuvant trials, further investigation of bevacizumab in this setting is unlikely, but the role of carboplatin could be evaluated in definitive studies, ideally limited to biologically defined patient subsets most likely to benefit from this agent.
Outcome of acute ST-segment elevation myocardial infarction in diabetics treated with fibrinolytic or combination reduced fibrinolytic therapy and platelet glycoprotein IIb/IIIa inhibition
Authors: Hitinder S. Gurm, A.Michael Lincoff, David Lee, W.H.Wilson Tang, Gang Jia, Joan E. Booth, Robert M. Califf, E.M. Ohman, Frans Van de Werf, Paul W. Armstrong, Victor Guetta, Robert Wilcox, Eric J. Topol
Journal: Journal of the American College of Cardiology (2004)
Chemiluminescence of ischaemic and reperfused intestine in vivo.
Authors: E J Roldan, C R Pinus, J F Turrens, A Boveris
Journal: Gut (1989)

Low level chemiluminescence of exposed rat intestine was measured during occlusive ischaemia and reperfusion. Spontaneous emission of in vivo rat intestine (10 +/- 1 cps/cm2) decreased almost to zero in animals subjected to ischaemia and when the period of ischaemia lasted only two minutes, chemiluminescence increased beyond control levels (39%, three minutes after reperfusion) at intestine deligation. This overshoot did not occur when rats were pretreated with allopurinol (40 + 100 mg/kg bw). The ratio of xanthine dehydrogenase to xanthine oxidase activities was 3.46 in preischaemic intestine samples. The same ratio was changed to 0.35 in samples subjected to two minutes of ischaemia. As chemiluminescence appears to reflect the steady state level of singlet oxygen, which in turn derives from the steady state level of peroxy radicals, these results agree with the view that oxygen radicals derived from the xanthine oxidase reaction are involved in the cellular damage produced after ischaemia and reoxygenation in the intestine.
T cell growth and differentiation induced by interleukin-HP1/IL-6, the murine hybridoma/plasmacytoma growth factor.
Authors: C Uyttenhove, P G Coulie, J Van Snick
Journal: The Journal of Experimental Medicine (1988)

Interleukin-HP1 (HP1)/IL-6 is a 25-30-kD protein produced by macrophages, fibroblasts, and certain T cell lines. It was originally identified as a mouse growth factor for B cell hybridomas and plasmacytomas, and was recently shown to stimulate growth and differentiation of normal B cells. Here we demonstrate that, in the presence of lectins or anti-T cell receptor antibodies, HP1/IL-6 has a growth factor activity equivalent to that of IL-2 for mature thymic and peripheral T cells of both the L3T4+ and Lyt-2+ subsets. Contrary to IL-2 and IL-4, HP1/IL-6 was, however, not capable of supporting the growth of established T cell lines. In addition to its effects on T cell proliferation, HP1/IL-6 also enhanced the differentiation of mouse cytolytic T cell precursors in primary allogeneic mixed lymphocyte cultures. Fractionation of responding cell populations indicated that HP1/IL-6 was capable of restoring the response of accessory cell-depleted T cells to Con A. This observation suggests that the production of HP1/IL-6 by macrophages could, at least partly, explain their role in polyclonal T cell activation.
Early-Starting Conduct Problems: Intersection of Conduct Problems and Poverty
Authors: Daniel S. Shaw, Elizabeth C. Shelleby
Journal: Annual Review of Clinical Psychology (2014)

The current article reviews extant literature on the intersection between poverty and the development of conduct problems (CP) in early childhood. Associations between exposure to poverty and disruptive behavior are reviewed through the framework of models emphasizing how the stressors associated with poverty indirectly influence child CP by compromising parent psychological resources, investments in children's welfare, and/or caregiving quality. We expand on the best-studied model, the family stress model, by emphasizing the mediating contribution of parent psychological resources on children's risk for early CP, in addition to the mediating effects of parenting. Specifically, we focus on the contribution of maternal depression, in terms of both compromising parenting quality and exposing children to higher levels of stressful events and contexts. Implications of the adapted family stress model are then discussed in terms of its implications for the prevention and treatment of young children's emerging CP.
A Prospective Study of Telomere Length Measured by Monochrome Multiplex Quantitative PCR and Risk of Non-Hodgkin Lymphoma
Authors: Qing Lan, Richard Cawthon, Min Shen, Stephanie J. Weinstein, Jarmo Virtamo, Unhee Lim, H. Dean Hosgood, Demetrius Albanes, Nathaniel Rothman
Journal: Clinical Cancer Research (2009)

Telomere length plays an important role in the maintenance of chromosomal stability and in tumorigenesis. We hypothesized that telomere length in peripheral WBC DNA obtained from healthy individuals would be a predictor of future risk of developing non-Hodgkin lymphoma.Using a new assay to measure relative telomere length, monochrome multiplex quantitative PCR, which strongly correlates with telomere length measured by Southern blot (Spearman r = 0.91, P < 0.0001) and has high precision (coefficient of variation = 7%), we compared telomere length in peripheral WBC DNA in 107 incident male non-Hodgkin lymphoma cases and 107 matched controls within the prospective Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort.Median (10th, 90th percentile) telomere length was 1.10 (0.79, 1.43) in cases and 1.02 (0.78, 1.26) in controls (P = 0.0017, Wilcoxon sign test). There was a strong dose-response relationship between quartiles of telomere length and risk of non-Hodgkin lymphoma overall [odds ratios (95% confidence intervals) by quartile: 1.0; 1.1 (0.4-2.7); 1.8 (0.7-4.9); and 3.6 (1.4-8.9); P trend = 0.003], and this association was similar across the most common non-Hodgkin lymphoma subtypes present in this study.These results suggest that longer telomere length may be a potential predictor for future risk of non-Hodgkin lymphoma.
Genetic Deletion of Cell Division Autoantigen 1 Retards Diabetes-Associated Renal Injury
Authors: Zhonglin Chai, Aozhi Dai, Yugang Tu, Jiaze Li, Tieqiao Wu, Yu Wang, Lorna J. Hale, Frank Koentgen, Merlin C. Thomas, Mark E. Cooper
Journal: Journal of the American Society of Nephrology (2013)

Cell division autoantigen 1 (CDA1) enhances TGF-β signaling in renal and vascular cells, and renal expression of CDA1 is elevated in animal models of diabetes. In this study, we investigated the genetic deletion of Tspyl2, the gene encoding CDA1, in C57BL6 and ApoE knockout mice. The increased renal expression of TGF-β1, TGF-β type I and II receptors, and phosphorylated Smad3 associated with diabetes in wild-type mice was attenuated in diabetic CDA1 knockout mice. Notably, CDA1 deletion significantly reduced diabetes-associated renal matrix accumulation and immunohistochemical staining for collagens III and IV and attenuated glomerular and tubulointerstitial injury indices, despite the presence of persistent hyperglycemia, polyuria, renal hypertrophy, and hyperfiltration. Furthermore, CDA1 deletion reduced gene expression of TGF-β1 receptors in the kidney, resulting in a functionally attenuated response to exogenous TGF-β, including reduced levels of phosphorylated Smad3 and ERK1/2, in primary kidney cells from CDA1 knockout animals. Taken together, these data suggest that CDA1 deletion reduces but does not block renal TGF-β signaling. Because direct antagonism of TGF-β or its receptors has unwanted effects, CDA1 may be a potential therapeutic target for retarding DN and perhaps, other kidney diseases associated with TGF-β-mediated fibrogenesis.
The Fatty Acid Biosynthesis Enzyme FabI Plays a Key Role in the Development of Liver-Stage Malarial Parasites
Authors: Min Yu, T.R. Santha Kumar, Louis J. Nkrumah, Alida Coppi, Silke Retzlaff, Celeste D. Li, Brendan J. Kelly, Pedro A. Moura, Viswanathan Lakshmanan, Joel S. Freundlich, Juan-Carlos Valderramos, Catherine Vilcheze, Mark Siedner, Jennifer H.-C. Tsai, Brie Falkard, Amar bir Singh Sidhu, Lisa A. Purcell, Paul Gratraud, Laurent Kremer, Andrew P. Waters, Guy Schiehser, David P. Jacobus, Chris J. Janse, Arba Ager, William R. Jacobs, James C. Sacchettini, Volker Heussler, Photini Sinnis, David A. Fidock
Journal: Cell Host & Microbe (2008)
Differential Induction of Apoptosis by Fas–Fas Ligand Interactions in Human Monocytes and Macrophages
Authors: Peter A. Kiener, Patricia M. Davis, Gary C. Starling, Christopher Mehlin, Seymour J. Klebanoff, Jeffrey A. Ledbetter, W. Conrad Liles
Journal: The Journal of Experimental Medicine (1997)

Human monocytes undergo spontaneous apoptosis upon culture in vitro; removal of serum from the media dramatically increases the rate of this process. Monocyte apoptosis can be significantly abrogated by the addition of growth factors or proinflammatory mediators. We have evaluated the role of the endogenous Fas–Fas ligand (FasL) interaction in the induction of this spontaneous apoptosis and found that a Fas–immunoglobulin (Ig) fusion protein, an antagonistic anti-Fas monoclonal antibody and a rabbit anti-FasL antibody all greatly reduced the onset of apoptosis. The results indicate that spontaneous death of monocytes is mediated via an autocrine or paracrine pathway. Treatment of the cells with growth factors or cytokines that prevented spontaneous apoptosis had no major effects on the expression of Fas or FasL. Additionally, monocyte-derived macrophages were found to express both Fas and FasL but did not undergo spontaneous apoptosis and were not sensitive to stimulation by an agonistic anti-Fas IgM. These results indicate that protective mechanisms in these cells exist at a site downstream of the receptor–ligand interaction.
Cost Containment and Changing Physicians' Practice Behavior
Authors: John M. Eisenberg
Journal: JAMA (1981)

The important role of physicians in the generation of medical care costs is evident, but methods of inducing physicians to participate in cost-containment efforts are not well developed. Efforts to change physicians' use of medical services have included education, peer review and feedback, administrative changes, participation, penalties, and rewards. Although educational programs have had mixed success, those using individualized instruction have been most effective. Several feedback and peer-review programs have demonstrated reductions in costs, as have administrative interventions. While penalties and direct rewards may be effective, alterations in the current reimbursement system could offer financial incentives to physicians who practice in a cost-effective manner.
Dietary Soy Isoflavones Inhibit Estrogen Effects in the Postmenopausal Breast
Authors: Charles E. Wood, Thomas C. Register, Adrian A. Franke, Mary S. Anthony, J. Mark Cline
Journal: Cancer Research (2006)

Soy isoflavones are promising dietary agents for prevention of breast cancer. Isoflavones bind estrogen receptors (ER) and may variably act as either estrogen agonists or antagonists depending on the estrogen environment. In this study, we used a postmenopausal primate model to evaluate interactive effects of dietary soy isoflavones and estrogen on risk markers for breast cancer. The experiment followed a randomized factorial design in which 31 ovariectomized adult female cynomolgus monkeys were divided into social groups of three to four animals each and rotated through eight different diets containing the human equivalent of 0, 60, 120, or 240 mg/d soy isoflavones with a dose of oral micronized 17beta-estradiol (E(2)) corresponding to either a low (0.09 mg/d) or a high (0.5 mg/d) postmenopausal estrogen environment. Treatment periods lasted 4 months with a 1-month washout period between diets. The highest isoflavone dose resulted in significantly lower breast proliferation and uterine size in the high-estrogen environment. These effects were accompanied by divergent changes in breast markers of ER activation in which pS2 expression was significantly lower and progesterone receptor expression was significantly higher following the 240 mg isoflavone dose. All isoflavone doses resulted in lower serum estrone and E(2) concentrations in the high-estrogen environment. In contrast, isoflavone treatment had no significant estrogen agonist effects and minimal antagonistic effects in the lower-estrogen environment. These findings show that in the presence of estrogen higher doses of dietary soy isoflavones may alter ER signaling and induce selective antagonistic effects in the breast.
2-Chlorodeoxyadenosine produces a high rate of complete hematologic remission in relapsed acute myeloid leukemia.
Authors: V M Santana, J Mirro, C Kearns, M J Schell, W Crom, R L Blakley
Journal: Journal of Clinical Oncology (1992)

PURPOSE The purine analog 2-chlorodeoxyadenosine (2-CDA) was well tolerated and showed promising anti-leukemic activity in a phase I trial conducted at St Jude Children's Research Hospital. To substantiate and extend this result, we performed a phase II trial in a representative group of children and young adults with relapsed acute leukemia. PATIENTS AND METHODS Twenty-four patients (median age, 11 years) with acute myeloid or lymphoid leukemia in first or later relapse (acute myeloid leukemia [AML], 17; acute lymphoid leukemia [ALL], seven) were given continuous infusion 2-CDA for 5 days at 8.9 mg/m2/d. Patients with residual blast cells 10 days after treatment received a second course of 2-CDA that was identical to the first. Detailed pharmacokinetic studies were performed on plasma collected from five patients. RESULTS Eight (47%) of the 17 patients with AML had complete hematologic remissions (four after the initial course of 2-CDA), and two (12%) had partial remissions, for a total response rate of 59%. Only one child with ALL achieved remission. Seven of the responding patients underwent allogeneic or autologous bone marrow transplantation, with six remaining free of leukemia for a median of 7 months (range, 1 to 11 months). The major form of drug-induced toxicity was hematologic, with severe neutropenia and thrombocytopenia (National Cancer Institute [NCI] grade 3 or 4) developing in 34 of the 36 courses of 2-CDA. In responding patients, the median times to recovery of neutrophil counts greater than 0.5 x 10(9)/L and platelet counts greater than 50 x 10(9)/L were 18 and 21 days, respectively. There were no deaths due to toxicity. The mean steady-state plasma concentration of 2-CDA was 34.6 nmol/L (range, 20 to 54 nmol/L). CONCLUSION 2-CDA given by prolonged continuous infusion has clinically significant activity against AML and merits further testing in multidrug regimens for this disease.