tbuckley/cabot-search huggingface dataset:
Nox1 transactivation of epidermal growth factor receptor promotes N-cadherin shedding and smooth muscle cell migration
Authors: Dammanahalli K. Jagadeesha, Maysam Takapoo, Botond Banfi, Ramesh C. Bhalla, Francis J. Miller
Journal: Cardiovascular Research (2011)

AimsIn atherosclerosis and restenosis, vascular smooth muscle cells (SMCs) migrate into the subendothelial space and proliferate, contributing to neointimal formation.The goal of this study was to define the signalling pathway by which Nox1 NAPDH oxidase mediates SMC migration. Methods and resultsSMCs were cultured from thoracic aorta from Nox1 2/y (Nox1 knockout, KO) and wild-type (WT) mice.In response to thrombin, WT but not Nox1 KO SMCs generated increased levels of reactive oxygen species (ROS).Deficiency of Nox1 prevented thrombin-induced phosphorylation of Src and the subsequent transactivation of the epidermal growth factor receptor (EGFR) at multiple tyrosine residues.Next, activation of extracellular signal-regulated kinase 1/2 (ERK1/2) and matrix metalloproteinase-9 (MMP-9) by thrombin was inhibited by the EGFR inhibitor AG1478 and in Nox1 KO SMCs.Thrombin-induced shedding of N-cadherin from the plasma membrane was dependent on the presence of Nox1 and was blocked by AG1478 and an inhibitor of metalloproteinases.Migration of SMCs to thrombin was impaired in the Nox1 KO SMCs and was restored by expression of Nox1.Finally, treatment of WT SMCs with AG1478 abrogated Nox1-dependent SMC migration. ConclusionsThe Nox1 NADPH oxidase signals through EGFR to activate MMP-9 and promote the shedding of N-cadherin, thereby contributing to SMC migration.
Postischemic recovery of mitochondrial adenine nucleotides in the heart.
Authors: G K Asimakis, J B Zwischenberger, K Inners-McBride, L A Sordahl, V R Conti
Journal: Circulation (1992)

BACKGROUND Adenine nucleotides (AdNs) are lost from the mitochondrial fraction of the heart cell during ischemia. It is unknown whether this pool of AdNs can be replenished after reperfusion. The purpose of this study was to evaluate the postischemic recovery of the mitochondrial AdN pool. METHODS AND RESULTS The left anterior descending coronary artery (LAD) of the canine heart was occluded for 30 minutes followed by either no reflow, 30-minute reflow, 1-day reflow, or 7-day reflow. Systolic shortening in the LAD-supplied region was absent during occlusion but recovered to approximately 30% of preocclusion values during early reperfusion. Mitochondrial and tissue AdNs (ATP, ADP, and AMP) were determined in the LAD-supplied and left circumflex-supplied (control) regions of the heart. The AdN content (expressed as percent of control values) of mitochondria from the LAD region was 55 +/- 10% (p less than 0.002), 64 +/- 7% (p less than 0.001), 81 +/- 6% (p less than 0.03), and 94 +/- 8% for the no-reflow, 30-minute-reflow, 1-day-reflow, and 7-day-reflow groups, respectively. The AdN content (expressed as percent of control values) of tissue samples from the LAD region was 52 +/- 9% (p less than 0.002), 48 +/- 12% (p less than 0.02), 68 +/- 5% (p less than 0.002), and 70 +/- 9% for the no-reflow, 30-minute-reflow, 1-day-reflow, and 7-day-reflow groups, respectively. There was a good correlation between mitochondrial and tissue AdN (r = 0.95). Using initial exchange rates, adenine nucleotide translocase activities of mitochondria from the LAD and control regions were not significantly different. State 3 respiration of LAD mitochondria was depressed (approximately 25%, p less than 0.05) only in the no-reflow group. Acceptor control ratios of the LAD mitochondria were not significantly different from control values in any group. CONCLUSIONS After 30 minutes of regional ischemia, postischemic restoration of the mitochondrial AdN pool occurs between 1 and 7 days; this restoration is preceded by recovery of respiratory and adenine nucleotide translocase functions. Although the abnormally low levels of AdN persist in the mitochondrial compartment during the early reperfusion period, postischemic contractile dysfunction cannot be explained by depressed mitochondrial respiratory activity.
Occupational photoallergic contact dermatitis in a pharmaceutical worker manufacturing carprofen, a canine nonsteroidal anti-inflammatory drug
Authors: S.L. Walker, R.D. Ead, M.H. Beck
Journal: British Journal of Dermatology (2006)

Journal Article Occupational photoallergic contact dermatitis in a pharmaceutical worker manufacturing carprofen, a canine nonsteroidal anti‐inflammatory drug Get access S.L. Walker, S.L. Walker Contact Dermatitis Investigation Unit, Hope Hospital, Manchester M6 8HD, U.K. E‐mail: drstevewalker@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar R.D. Ead, R.D. Ead Contact Dermatitis Investigation Unit, Hope Hospital, Manchester M6 8HD, U.K. E‐mail: drstevewalker@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar M.H. Beck M.H. Beck Contact Dermatitis Investigation Unit, Hope Hospital, Manchester M6 8HD, U.K. E‐mail: drstevewalker@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 154, Issue 3, 1 March 2006, Pages 569–570, https://doi.org/10.1111/j.1365-2133.2005.07096.x Published: 01 March 2006
Plasma <i>AR</i> and abiraterone-resistant prostate cancer
Authors: Alessandro Romanel, Delila Gasi Tandefelt, Vincenza Conteduca, Anuradha Jayaram, Nicola Casiraghi, Daniel Wetterskog, Samanta Salvi, Dino Amadori, Zafeiris Zafeiriou, Pasquale Rescigno, Diletta Bianchini, Giorgia Gurioli, Valentina Casadio, Suzanne Carreira, Jane Goodall, Anna Wingate, Roberta Ferraldeschi, Nina Tunariu, Penny Flohr, Ugo De Giorgi, Johann S. de Bono, Francesca Demichelis, Gerhardt Attard
Journal: Science Translational Medicine (2015)

Androgen receptor mutations and amplifications in circulating tumor DNA provide clues to prostate cancer drug resistance.
Zoledronic Acid Inhibits Adjuvant Letrozole–Induced Bone Loss in Postmenopausal Women With Early Breast Cancer
Authors: Adam Brufsky, W. Graydon Harker, J. Thaddeus Beck, Robert Carroll, Elizabeth Tan-Chiu, Christopher Seidler, John Hohneker, Leo Lacerna, Stephanie Petrone, Edith A. Perez
Journal: Journal of Clinical Oncology (2006)

Purpose Treatment with aromatase inhibitors decreases bone mineral density (BMD) and may increase the risk of fractures in postmenopausal women with early-stage breast cancer. The addition of zoledronic acid to adjuvant letrozole therapy may protect against bone loss. Patients and Methods Patients receiving adjuvant letrozole were randomly assigned to receive either upfront or delayed-start zoledronic acid (4 mg intravenously every 6 months). The delayed group received zoledronic acid when lumbar spine (LS) or total hip (TH) T score decreased to less than −2.0 or when a nontraumatic fracture occurred. The primary end point of this study was to compare the change in LS BMD at month 12 between the groups. Secondary end points included change in TH BMD and changes in serum bone turnover markers at month 12. Results The upfront and delayed groups each included 301 patients. At month 12, LS BMD was 4.4% higher in the upfront group than in the delayed group (95% CI, 3.7% to 5.0%; P &lt; .0001), and TH BMD was 3.3% higher (95% CI, 2.8% to 3.8%; P &lt; .0001). In the upfront group, mean serum N-telopeptide and bone-specific alkaline phosphatase concentrations decreased by 15.1% (P &lt; .0001) and 8.8% (P = .0006), respectively, at month 12, whereas concentrations increased significantly in the delayed group by 19.9% (P = .013) and 24.3% (P &lt; .0001), respectively. Conclusion With 1 year of follow-up, results of the primary end point of the Zometa-Femara Adjuvant Synergy Trial (Z-FAST) indicate that upfront zoledronic acid therapy prevents bone loss in the LS in postmenopausal women receiving adjuvant letrozole for early-stage breast cancer.
RRR-α-Vitamin E Succinate Potentiates the Antitumor Effect of Calcitriol in Prostate Cancer without Overt Side Effects
Authors: Yi Yin, Jing Ni, Ming Chen, Yinglu Guo, Shuyuan Yeh
Journal: Clinical Cancer Research (2008)

Abstract Purpose: To determine the antitumor efficacy of using calcitriol combined with RRR-α-vitamin E succinate (VES) on prostate cancer. Experimental Design: The effects of VES or VES in combination with calcitriol on the calcitriol target genes were evaluated by Western blot and real-time PCR. The antiproliferation effect of the combination in prostate cancer cells was evaluated by the combination index method. The role of the vitamin D3 receptor (VDR) in the enhanced antitumor effects of the combination was confirmed by small interfering RNA knockdown strategy. Xenograft-bearing mice were used to reaffirm the antitumor efficacy of this combination. Pathohistology analyses and expressions of VDR and its target genes were analyzed in untreated and treated tumors. Results: VES selectively increased VDR protein in different prostate cancer cells. Low doses of calcitriol combined with VES were significantly superior to the additive effect of individual treatments against prostate cancer cell proliferation. The expression of VDR target genes involved in antiproliferation were further sensitized in the presence of VES. Knockdown of VDR expression abolished the combination benefits in LNCaP and PC3 cells. Consistently, in prostate cancer xenograft models, VES enhanced the therapeutic efficacy of a tolerated dose of calcitriol yet without overt evidence of systemic toxicity and hypercalcemia. This notable in vivo effect was also accompanied by up-regulation of VDR target genes. Conclusions: Low-dose calcitriol combined with vitamin E analogue could be a solution to the calcemic side effect. The demonstration of superior antitumor activity of low-dose calcitriol plus VES provides the preclinical basis for developing a useful therapeutic strategy for prostate cancer.
Impact of Folic Acid Fortification of the US Food Supply on the Occurrence of Neural Tube Defects
Authors: Margaret A. Honein
Journal: JAMA (2001)

Daily consumption of 400 microg of folic acid before conception and during early pregnancy dramatically reduces the occurrence of neural tube defects (NTDs). Before food fortification, however, only an estimated 29% of US reproductive-aged women were taking a supplement containing 400 microg of folic acid daily. The US Food and Drug Administration authorized addition of folic acid to enriched grain products in March 1996, with compliance mandatory by January 1998.To evaluate the impact of food fortification with folic acid on NTD birth prevalence.National study of birth certificate data for live births to women in 45 US states and Washington, DC, between January 1990 and December 1999.Birth certificate reports of spina bifida and anencephaly before fortification (October 1995 through December 1996) compared with after mandatory fortification (October 1998 through December 1999).The birth prevalence of NTDs reported on birth certificates decreased from 37.8 per 100 000 live births before fortification to 30.5 per 100 000 live births conceived after mandatory folic acid fortification, representing a 19% decline (prevalence ratio [PR], 0.81; 95% confidence interval [CI], 0.75-0.87). During the same period, NTD birth prevalence declined from 53.4 per 100 000 to 46.5 per 100 000 (PR, 0.87; 95% CI, 0.64-1.18) for women who received only third-trimester or no prenatal care.A 19% reduction in NTD birth prevalence occurred following folic acid fortification of the US food supply. However, factors other than fortification may have contributed to this decline.
Conservative win in Spain's general election will boost role of private sector in healthcare
Authors: A. Garcia Rada
Journal: BMJ (2011)

The private sector involvement in the management of Spain’s public health system is set to rise sharply if—as widely predicted—the conservative Popular Party wins the general election on 19 November. 

The Popular Party electoral manifesto states that the party “will promote PPP [public private partnerships] for the management of infrastructures and public services.”

Although all regional health systems contract out some 15-20% of provision to private providers for waiting list management, public private partnership is so far only being developed in regions governed by the Popular Party and in Catalonia, which is governed by Catalan nationalists.

Spending on public private partnerships in the community of Madrid, which serves 6.5 million people and is governed by the conservative Popular …
SYNTAX SCORE AND TYPE OF STENT CAN PREDICT THE MID TERM OUTCOME AFTER PRIMARY PERCUTANEOUS CORONARY INTERVENTION IN ACUTE ST-ELEVATION MYOCARDIAL INFARCTION
Authors: Andreas Synetos, Konstantinos Toutouzas, Ourania Boutziona, Haralampia Nikolaou, Eleftherios Tsiamis, Dimitrios Tousoulis, Christodoulos Stefanadis
Journal: Journal of the American College of Cardiology (2011)
A Comparative Analysis of Prognostic Factor Models for Follicular Lymphoma Based on a Phase III Trial of CHOP–Rituximab versus CHOP + 131Iodine—Tositumomab
Authors: Oliver W. Press, Joseph M. Unger, Lisa M. Rimsza, Jonathan W. Friedberg, Michael LeBlanc, Myron S. Czuczman, Mark Kaminski, Rita M. Braziel, Catherine Spier, Ajay K. Gopal, David G. Maloney, Bruce D. Cheson, Shaker R. Dakhil, Thomas P. Miller, Richard I. Fisher
Journal: Clinical Cancer Research (2013)

There is currently no consensus on optimal frontline therapy for patients with follicular lymphoma. We analyzed a phase III randomized intergroup trial comparing six cycles of CHOP-R (cyclophosphamide-Adriamycin-vincristine-prednisone (Oncovin)-rituximab) with six cycles of CHOP followed by iodine-131 tositumomab radioimmunotherapy (RIT) to assess whether any subsets benefited more from one treatment or the other, and to compare three prognostic models.
Proprietary hydrocortisone creams
Authors: B.W. BARRY, R. WOODFORD
Journal: British Journal of Dermatology (1976)

Six proprietary hydrocortisone creams were evaluated for vasoconstrictor activities and bio‐availabilities using an occluded blanching test. Statistical analysis showed a significant difference between the formulations. Dioderm, containing 0.1% hydrocortisone, was significantly more active than the 1% hydrocortisone creams—Alphaderm, Calmurid HC, Efcortelan and Vioform‐Hydrocortisone. There was no significant difference between Dioderm and Dioderm C. Unlike creams containing more potent corticosteroids the hydrocortisone formulations apparently failed to produce steroid reservoirs in the stratum corneum as assessed by the blanching response.
Altered cytokine regulation in the lungs of cigarette smokers.
Authors: K A McCrea, J E Ensor, K Nall, E R Bleecker, J D Hasday
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

Cigarette smoking is the major factor responsible for chronic obstructive lung disease, but it occurs in only a minority of smokers. Smoking is associated with increased susceptibility to pulmonary infections and with a neutrophil- and macrophage-rich inflammation of the small airways. We compared concentrations of tumor necrosis factor (TNF), interleukin (IL)-6, and IL-8 in bronchoalveolar lavage fluid (BALF) and measured the capacity of BALF macrophages to release TNF and IL-6 in vitro in nine smokers (19.1 +/- 4.2 pack-years; mean +/- SE) and nine nonsmokers. Compared with nonsmokers, BALF from smokers contained more cells (65.3 +/- 13.2 versus 27.2 +/- 4.8 x 10(6); p < 0.02), but much lower concentrations of IL-6 (1.8 +/- 1.0 versus 15.9 +/- 5.8 pg/ml; p < 0.05). The two smokers with the highest number of BALF cells had increased BALF concentrations of interleukin-8 (IL-8), but there was no difference in BALF IL-8 concentrations between the two groups (p = 0.08). Compared with BALF macrophages from nonsmokers, cells from smokers released less TNF (211 +/- 77 versus 1,406 +/- 348 units per 10(8) cells; p < 0.01) and IL-6 (5.8 +/- 2.6 versus 64.9 +/- 23.3 hybridoma units per ml; p < 0.02) during a 6-h incubation with lipopolysaccharide (LPS). We conclude that even in young, healthy smokers the pulmonary microenvironment is markedly abnormal, characterized by depressed levels of IL-6, macrophages that have a markedly depressed capacity for LPS-induced cytokine release and, in some smokers, increased concentrations of IL-8.
ABC of breast diseases: Breast cancer
Authors: J R C Sainsbury
Journal: BMJ (2000)

Breast cancers are derived from the epithelial cells that line the terminal duct lobular unit.Cancer cells that remain within the basement membrane of the elements of the terminal duct lobular unit and the draining duct are classified as in situ or non-invasive.An invasive breast cancer is one in which there is dissemination of cancer cells outside the basement membrane of the ducts and lobules into the surrounding adjacent normal tissue.Both in situ and invasive cancers have characteristic patterns by which they can be classified.
Very small size proteoliposomes abrogate cross-presentation of tumor antigens by myeloid-derived suppressor cells and induce their differentiation to dendritic cells
Authors: Audry Fernández, Liliana Oliver, Rydell Alvarez, Arletty Hernández, Judith Raymond, Luis E Fernández, Circe Mesa
Journal: Journal for ImmunoTherapy of Cancer (2014)

Myeloid-derived suppressor cells (MDSCs) are among the major obstacles that adjuvants for cancer vaccines have to overcome. These cells cross-present tumor-associated antigens (TAA) to naive T lymphocytes with a tolerogenic outcome. Very Small Size Proteoliposomes (VSSP) is used as adjuvant by four therapeutic cancer vaccines currently in Phase I and II clinical trials. We previously found that VSSP reduces the suppressive function of MDSCs, then activating antigen-specific CTL responses in tumor-bearing (TB) mice, with the consequent reduction of tumor growth. However the mechanistic explanation for the immunomodulatory effect of this adjuvant in TB hosts has not been addressed before.TB mice were inoculated with VSSP and MDSCs isolated and characterized by their expression of Arg1 and Nos2 genes by RT-PCR. The effect of VSSP on antigen cross-presentation by MDSCs, regulatory T cells (Tregs) expansion and MDSCs differentiation towards dendritic cells (DCs) was analyzed by FACS. Student's t test or ANOVA and Tukey's tests were used for statistical analyses.After inoculating VSSP into TB mice, a significant reduction of Arg1 and Nos2 gene expression was observed in recovered MDSCs. Concurrently the ability of these cells to induce down-regulation of CD3ζ chain on T cells was lost. Likewise in mice inoculated with the adjuvant lower percentages of Tregs were detected. In vitro, VSSP treatment was enough to differentiate MDSCs into phenotypically mature DCs, eliminating the former suppressive effect. Noteworthy, in vivo administration of VSSP to OVA-expressing (EG.7) TB mice abrogated this model antigen cross-presentation by splenic MDSCs. Similar results were obtained even when OVA antigen was administered into these TB mice formulated in VSSP. On the contrary, immunization with the same protein in polyI:C did not change the percentage of MDSCs expressing SIINFEKL/H-2K(b) complexes, whereas a concomitant injection of VSSP aborted the limitations of polyI:C in this setting.Altogether, these results indicate that VSSP has the peculiar capacity of inhibiting TAA cross-presentation and certain suppressive mechanisms on MDSCs which in turn, combined with the ability to induce differentiation of these cells into antigen-presenting cells (APCs), sustains this adjuvant as an ideal immunomodulator for cancer immunotherapy.
New approaches to enhance the accuracy of the diagnosis of reflux disease
Authors: P Moayyedi
Journal: Gut (2004)

The accuracy of symptoms in diagnosing gastro-oesophageal reflux disease (GORD) is complicated by the lack of a gold standard test. Statistical techniques such as latent class and Bayesian analyses can estimate accuracy of symptoms without a gold standard. Both techniques require three independent diagnostic tests. Latent class analysis makes no assumptions about the performance of the tests. Bayesian analysis is useful when the accuracy of the other tests is known. These statistical techniques should be used in the future to validate GORD symptom questionnaires comparing them with endoscopy, oesophageal pH monitoring, and response to proton pump inhibitor therapy. Studies that evaluate GORD symptoms are usually done in secondary care. The prevalence of GORD in primary care will be lower and this reduces the positive predictive value of symptoms. There will be some bias in the type of patient referred for diagnosis and this usually decreases the specificity of symptom diagnosis.
Identification and Characterization of Two Genes (MIP-1β, VE-CADHERIN) Implicated in Acute Rejection in Human Heart Transplantation
Authors: A.L.S. Roussoulières, O. Raisky, L. Chalabreysse, G. Dureau, C. Cerutti, C. Thieblemont, P. Boissonnat, L. Sebbag, J.-F. Obadia, J. Ninet, O. Bastien, F. Thivolet-Bejui, J.L. McGregor
Journal: Circulation (2005)

Genes and mechanisms of action involved in human acute rejection after allogeneic heart transplantation remain to be elucidated. The use of a murine allograft model in tandem with cDNA arrays and quantitative real-time polymerase chain reaction (Q-PCR) can greatly help in identifying key genes implicated in human heart acute rejection.Hearts from Balb/c mice were either not transplanted or transplanted heterotopically in the abdomen of Balb/c (isografts) and C57BL/6 (allografts) mice. Histological analysis showed acute rejection only in allografts. Total RNA was extracted from isografts (n=3), allografts (n=4), and not transplanted hearts (n=4); reverse transcribed; and labeled with P32. Each probe was hybridized to cDNA macroarrays. Eight genes were overexpressed and 7 genes were underexpressed in allografts compared with isografts. Macrophage inflammatory protein-1beta (MIP-1beta), an overexpressed gene, and VE-cadherin, an underexpressed gene, were validated by immunohistochemistry and Q-PCR in the murine models. Genes of interest, validated in the 3 murine groups, were then investigated in human heart tissues. Immunohistochemistry and Q-PCR performed on endomyocardial biopsies after heart transplantation showing no rejection (n=10) or grade IB (n=10) or IIIA (n=10) rejection, according to International Society of Heart and Lung Transplantation criteria, confirmed the results obtained from the murine model.We have demonstrated that the upregulation of MIP-1beta and downregulation of VE-cadherin may strongly participate in human acute heart rejection.