tbuckley/cabot-search huggingface dataset:
Inhibition of ACE/kininase-II after myocardial infarction - addendum
Authors: S. G Ball, A. Hall, L.-B. Tan
Journal: Cardiovascular Research (1994)

Journal Article Inhibition of ACE/kininase-II after myocardial infarction - addendum Get access Stephen G Ball, Stephen G Ball Cardiovascular Studies Unit, University of Leeds, Leeds LS2 9JT, United Kingdom: S G Ball, A S Hall, L-B Tan. Corrrespondence to Professor Ball. Search for other works by this author on: Oxford Academic PubMed Google Scholar Alistair Hall, Alistair Hall Cardiovascular Studies Unit, University of Leeds, Leeds LS2 9JT, United Kingdom: S G Ball, A S Hall, L-B Tan. Corrrespondence to Professor Ball. Search for other works by this author on: Oxford Academic PubMed Google Scholar Lip-Bun Tan Lip-Bun Tan Cardiovascular Studies Unit, University of Leeds, Leeds LS2 9JT, United Kingdom: S G Ball, A S Hall, L-B Tan. Corrrespondence to Professor Ball. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 28, Issue 2, February 1994, Pages 199–200, https://doi.org/10.1093/cvr/28.2.199 Published: 01 February 1994
CARD15/NOD2 polymorphisms are associated with severe pulmonary sarcoidosis
Authors: H. Sato, H. R. T. Williams, P. Spagnolo, A. Abdallah, T. Ahmad, T. R. Orchard, S. J. Copley, S. R. Desai, A. U. Wells, R. M. du Bois, K. I. Welsh
Journal: European Respiratory Journal (2009)

Sarcoidosis and Crohn's disease are heterogeneous systemic diseases characterised by granulomatous inflammation. Caspase recruitment domain (CARD)15 is a major susceptibility gene for Crohn's disease, and specifically for ileal and fibrostenotic subtypes. The C-C chemokine receptor (CCR)5 gene has been associated with both parenchymal pulmonary sarcoidosis and perianal Crohn's disease. This study explored associations between CARD15 polymorphisms, CCR5 haplotype and distinct pulmonary sarcoidosis subtypes. 185 Caucasian sarcoidosis patients were genotyped for CARD15 and CCR5 polymorphisms. The genetic data were compared with 347 healthy controls and were examined for associations with serial pulmonary function tests and chest radiographs. CARD15 genotypes did not differ between the unselected sarcoidosis cohort and controls. However, patients carrying the functional 2104T (702W) polymorphism were more likely to have radiographic stage IV disease at 4-yr follow-up. All patients possessing both CARD15 2104T and CCR5 HHC haplotype had stage IV disease at presentation. Carriage of 2104T was associated with worse forced expiratory volume in 1 s, whereas carriage of the CARD15 1761G (587R) polymorphism was associated with better lung function. For the first time, an association between two CARD15 polymorphisms and specific sarcoidosis phenotypes has been demonstrated, as well as an additive effect of possessing CARD15 2104T and CCR5 HHC haplotype.
Increased plasma concentration of ribavirin as a result of renal dysfunction in hepatitis C virus patients treated with telaprevir
Authors: Massimo Tempestilli, Raffaella Lionetti, Gianpiero D'Offizi, Marzia Montalbano, Andrea Giaffreda, Simone Fazio, Leopoldo P. Pucillo
Journal: Hepatology (2013)

Pronounced anemia is observed in hepatitis C virus (HCV) patients treated with a triple therapy containing ribavirin (RBV), pegylated interferon (Peg-IFN), and telaprevir (TLV), when compared to patients treated with the dual therapy (RBV and Peg-IFN).1 Mauss et al.2 recently suggested, in Hepatology, that this could be a result of accumulation of RBV consequent to impaired renal drug elimination. To confirm this hypothesis, the estimated glomerular filtration rate (eGFR),3 hemoglobin (Hb), and RBV plasma concentration in 23 HCV genotype 1–infected patients treated with fixed doses of the triple therapy for 12 weeks and, successively, with the dual therapy until 48 weeks, were evaluated at weeks 4, 8, 12, 24, and 48. eGFR decreased during the period of triple therapy from 100.8 ± 23.6 mL/min pretherapy to 88.5 ± 16.9, 75.7 ± 19.7, 83.4 ± 20.7 mL/min at weeks 4, 8, and 12, respectively (P < 0.001). When TLV was discontinued, eGFR returned to pretherapy levels (99.8 ± 24.6 and 104.9 ± 20.2 mL/min at weeks 24 and 48, respectively). Hb levels positively correlated with eGFR (r = 0.191; P = 0.02), showing a similar trend. In contrast, RBV plasma concentrations increased when TLV was administered at 8 and 12 weeks (2,777 ± 1,093 and 3,175 ± 737 ng/mL, respectively) and decreased (P < 0.01) at 24 and 48 weeks (2,255 ± 587 and 1,872 ± 622 ng/mL, respectively) when TLV was suspended (see Fig. 1). Moreover, significant inverse correlations were found between eGFR and Hb versus RBV (P = 0.02 and P < 0.0001 respectively). These results are in agreement with those presented by Karino et al.,4 who studied 68 patients during 8 weeks in triple therapy. Our study, which expanded therapy to 48 weeks using both the triple and dual regimens in sequence, concludes that plasma concentration of RBV and Hb levels are influenced by the decrease in renal function induced by TLV. We can thus confirm the hypothesis of Mauss et al. and suggest use of eGFR, therapeutic drug monitoring, and dose adjustment of RBV to prevent onset of anemia induced by the triple therapy containing TLV. Massimo Tempestilli, M.Sc.* Raffaella Lionetti, M.D.* Gianpiero D'Offizi, M.D. Marzia Montalbano, M.D. Andrea Giaffreda, M.Sc. Simone Fazio, M.Sc. Leopoldo P. Pucillo, M.D. National Institute for Infectious Diseases "L. Spallanzani" I.R.C.C.S. Rome, Italy
Obstructive Sleep Apnea and Risk of Cardiovascular Events and All-Cause Mortality: A Decade-Long Historical Cohort Study
Authors: Tetyana Kendzerska, Andrea S. Gershon, Gillian Hawker, Richard S. Leung, George Tomlinson
Journal: PLoS Medicine (2014)

Tetyana Kendzerska and colleagues explore the association between physiological measures of obstructive sleep apnea other than the apnea-hypopnea index and the risk of cardiovascular events. Please see later in the article for the Editors' Summary
Effects of high-affinity nerve growth factor receptor inhibitors on symptoms in the NC/Nga mouse atopic dermatitis model
Authors: N. Takano, T. Sakurai, Y. Ohashi, M. Kurachi
Journal: British Journal of Dermatology (2006)

Nerve growth factor (NGF) is an important substance in the skin, where it modulates nerve maintenance and repair. However, the direct link between NGF and pruritic diseases such as atopic dermatitis is not yet fully understood. Our previous study showed that NGF plays an important role in the pathogenesis of atopic dermatitis-like skin lesions in NC/Nga mice. NGF mediates its effects by binding to two classes of transmembrane receptors, a high-affinity receptor (tropomyosin-related kinase A, TrkA) and a low-affinity receptor (p75).To determine the significance of NGF receptors in the pathogenesis of atopic dermatitis, the effects of TrkA inhibitors AG879 and K252a on the symptoms of NC/Nga mice were evaluated.Male NC/Nga mice with severe skin lesions were used. AG879 or K252a was applied to the rostral part of the back of mice five times a week. The dermatitis score for the rostral back was assessed once a week. The scratching behaviour was measured using an apparatus, MicroAct (Neuroscience, Tokyo, Japan). Immunofluorescence examinations were made in the rostral back skin for nerve fibres, NGF and TrkA receptor.Repeated applications of AG879 or K252a significantly improved the established dermatitis and scratching behaviour, and decreased nerve fibres in the epidermis. NGF was observed more weakly in keratinocytes, and a lower expression of TrkA was observed in stratum germinativum of the epidermis of mice treated with AG879 or K252a compared with those treated with vehicle.We suggest that NGF plays an important role in the pathogenesis of atopic dermatitis-like skin lesions via the high-affinity NGF receptor. These findings provide a new potential therapeutic approach for the amelioration of symptoms of atopic dermatitis.
WNT Signaling Pathway and Stem Cell Signaling Network
Authors: Masuko Katoh, Masaru Katoh
Journal: Clinical Cancer Research (2007)

Abstract WNT signals are transduced to the canonical pathway for cell fate determination, and to the noncanonical pathway for control of cell movement and tissue polarity. Canonical WNT signals are transduced through Frizzled family receptors and LRP5/LRP6 coreceptor to the β-catenin signaling cascade. Microtubule affinity–regulating kinase (PAR-1) family kinases, casein kinase Iε (CKIε), and FRAT are positive regulators of the canonical WNT pathway, whereas APC, AXIN1, AXIN2, CKIα, NKD1, NKD2, βTRCP1, βTRCP2, ANKRD6, Nemo-like kinase (NLK), and peroxisome proliferator–activated receptor γ (PPARγ) are negative regulators. Nuclear complex, consisting of T-cell factor/lymphoid enhancer factor, β-catenin, BCL9/BCL9L, and PYGO, activates transcription of canonical WNT target genes such as FGF20, DKK1, WISP1, MYC, CCND1, and Glucagon (GCG). Noncanonical WNT signals are transduced through Frizzled family receptors and ROR2/RYK coreceptors to the Dishevelled-dependent (Rho family GTPases and c-jun NH2-terminal kinase) or the Ca2+-dependent (NLK and nuclear factor of activated T cells) signaling cascades. WNT signals are context-dependently transduced to both pathways based on the expression profile of WNT, SFRP, WIF, DKK, Frizzled receptors, coreceptors, and the activity of intracellular WNT signaling regulators. Epigenetic silencing and loss-of-function mutation of negative regulators of the canonical WNT pathway occur in a variety of human cancer. WNT, fibroblast growth factor (FGF), Notch, Hedgehog, and transforming growth factor β/bone morphogenetic protein signaling network are implicated in the maintenance of tissue homeostasis by regulating self-renewal of normal stem cells as well as proliferation or differentiation of progenitor (transit-amplifying) cells. Breakage of the stem cell signaling network leads to carcinogenesis. Nonsteroidal anti-inflammatory drugs and PPARγ agonists with the potential to inhibit the canonical WNT signaling pathway are candidate agents for chemoprevention. ZTM000990 and PKF118-310 are lead compounds targeted to the canonical WNT signaling cascade. Anti-WNT1 and anti-WNT2 monoclonal antibodies show in vitro effects in cancer treatment. After the optimization, derivatives of small-molecule compound and human monoclonal antibody targeted to the WNT signaling pathway could be used in cancer medicine.
Combined Androgen and Estrogen Receptor Status in Breast Cancer: Treatment Prediction and Prognosis in a Population-Based Prospective Cohort
Authors: Karin Elebro, Signe Borgquist, Maria Simonsson, Andrea Markkula, Karin Jirström, Christian Ingvar, Carsten Rose, Helena Jernström
Journal: Clinical Cancer Research (2015)

To evaluate whether tumor androgen receptor (AR) expression was prognostic and/or predictive for endocrine treatment alone or in combination with estrogen receptor (ER). The AR has been hypothesized to have differential prognostic roles in breast cancer depending on tumor ER status, and to influence endocrine treatment response.A population-based prospective cohort of 1,026 patients diagnosed with primary invasive breast cancer in Lund, Sweden, between 2002 and 2012 was followed until June 2014. Associations between immunohistochemical AR expression in tumor tissue microarrays, patient and tumor characteristics, and AR genotypes were analyzed. Disease-free survival (DFS) by AR status, and combined ER/AR status was assessed in various treatment groups.AR expression was assessable in 913 tumors. AR(+) tumors (85.0%) were associated with higher age (P = 0.036) and favorable tumor characteristics. The AR(+) status was a prognostic marker for DFS (LogRank P = 0.025). There was an interaction between AR and ER expression with respect to prognosis (adjusted P(interaction) ≤ 0.024). Tumors with discordant hormone receptor expressions (ER(+)AR(-) or ER(-)AR(+)) demonstrated worse prognosis compared with concordant tumor expressions (ER(+)AR(+) or ER(-)AR(-)) in multivariable models [adjusted HRs (95% confidence intervals); ≥ 1.99 (1.28-3.10), P ≤ 0.002]. ER(+)AR(-) indicated early treatment failure with aromatase inhibitors (AI) among chemonaïve patients aged 50 or older.Prediction of breast cancer prognosis and treatment response was improved by combining AR and ER status. AR negativity predicted early treatment failure with AI but not tamoxifen, a finding that warrants confirmation in a randomized setting. Patients may benefit from anti-androgens or selective AR modulators.
Abstract 1764: Inhibition of R-spondin (RSPO) signaling reduces the growth of multiple human tumors
Authors: Austin Gurney, Fumiko Axelrod, Chris Bond, Jennifer Cain, Cecile Chartier, Marcus Fischer, May Ji, Chris Murriel, Janak Raval, Jalpa Shah, Min Wang, Wan-Ching Yen, Ann Kapoun, John Lewicki, Timothy Hoey
Journal: Cancer Research (2014)

Abstract Deregulation of the canonical Wnt/beta-catenin signaling pathway has long been associated with cancer. Intracellular components of this pathway, including Axin, APC, and beta-catenin are frequently mutated in a range of human tumors. The identity of specific extracellular ligands that contribute to human cancer development through this signaling axis has remained unclear. Molecular characterization of the secreted beta-catenin signaling activities produced by minimally passaged human tumor xenograft models identified RSPO family members produced by multiple tumor types including ovarian, pancreatic, colon, breast and non-small cell lung cancer. In human tumor xenograft models that had RSPO overexpression, in some instances due to genomic translocation, anti-RSPO treatment markedly inhibited tumor growth. In addition, striking combination activity with standard of care chemotherapy agents resulted in regression of established tumors. These results highlight the potential for therapeutic intervention with this newly appreciated signaling axis. Citation Format: Austin Gurney, Fumiko Axelrod, Chris Bond, Jennifer Cain, Cecile Chartier, Marcus Fischer, May Ji, Chris Murriel, Janak Raval, Jalpa Shah, Min Wang, Wan-Ching Yen, Ann Kapoun, John Lewicki, Timothy Hoey. Inhibition of R-spondin (RSPO) signaling reduces the growth of multiple human tumors. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1764. doi:10.1158/1538-7445.AM2014-1764
Activating and inhibitory IgG Fc receptors on human DCs mediate opposing functions
Authors: A. M. Boruchov
Journal: Journal of Clinical Investigation (2005)

Human monocyte-derived DCs (moDCs) and circulating conventional DCs coexpress activating (CD32a) and inhibitory (CD32b) isoforms of IgG Fcgamma receptor (FcgammaR) II (CD32). The balance between these divergent receptors establishes a threshold of DC activation and enables immune complexes to mediate opposing effects on DC maturation and function. IFN-gamma most potently favors CD32a expression on immature DCs, whereas soluble antiinflammatory concentrations of monomeric IgG have the opposite effect. Ligation of CD32a leads to DC maturation, increased stimulation of allogeneic T cells, and enhanced secretion of inflammatory cytokines, with the exception of IL-12p70. Coligation of CD32b limits activation through CD32a and hence reduces the immunogenicity of moDCs even for a strong stimulus like alloantigen. Targeting CD32b alone does not mature or activate DCs but rather maintains an immature state. Coexpression of activating and inhibitory FcgammaRs by DCs reveals a homeostatic checkpoint for inducing tolerance or immunity by immune complexes. These findings have important implications for understanding the pathophysiology of immune complex diseases and for optimizing the efficacy of therapeutic mAbs. The data also suggest novel strategies for targeting antigens to the activating or inhibitory FcgammaRs on human DCs to generate either antigen-specific immunity or tolerance.
Clopidogrel Responsiveness Regardless of the Discontinuation Date Predicts Increased Blood Loss and Transfusion Requirement After Off-Pump Coronary Artery Bypass Graft Surgery
Authors: Young-Lan Kwak, Jong-Chan Kim, Yong-Seon Choi, Kyung-Jong Yoo, Young Song, Jae-Kwang Shim
Journal: Journal of the American College of Cardiology (2010)
Management of hip fracture in adults: summary of NICE guidance
Authors: S. Ftouh, A. Morga, C. Swift
Journal: BMJ (2011)

Hip fracture resulting from a fall from standing height or lower in people with osteoporosis or osteopenia (fragility fracture) is a major, growing health problem associated with population ageing. It has an annual UK incidence of 70-75 000, with a medical and social care cost of about £2bn (€2.3bn; $3.3bn),1 and one month and one year mortality of about 10% and 30% respectively2 (usually resulting from comorbidity rather than from the fracture itself). A comprehensive multidisciplinary approach, avoidance of delay, and continuity of management are needed from presentation to follow-up, including after transition from hospital back into the community. This article summarises the most recent recommendations from the National Institute for Health and Clinical Excellence (NICE) on the management of hip fracture.3 The recommendations are for all adults but are based on surgical, anaesthetic, and orthogeriatric evidence and expertise acquired among older patients (the group in whom hip fracture is most common). Prevention of hip fracture is covered by other NICE guidance (on falls4 and osteoporosis5 6). NICE recommendations are based on systematic reviews of best available evidence and explicit consideration of cost effectiveness. When minimal evidence is available, recommendations are based on the Guideline Development Group's experience and opinion of what constitutes good practice. Evidence levels for the recommendations are given in italic in square brackets. ### Timing of surgery
The Metabolic Syndrome: Time for a Critical Appraisal: Joint Statement From the American Diabetes Association and the European Association for the Study of Diabetes
Authors: Dario Giugliano, Katherine Esposito
Journal: Diabetes Care (2006)

We read with interest the American Diabetes Association statement about the metabolic syndrome (1). The idea that the aggregation of borderline risk factors could result in cardiovascular damage equal or superior to that occurring in individuals carrying a full-weight risk factor disease was intriguing. However, this intuition was soon polluted by inclusion of patients with frank diseases. If the philosophy of the metabolic syndrome is to draw firm attention upon “at very high …
Histopathological prevalence of subchondral insufficiency fracture of the femoral head
Authors: T Yamamoto, Y Iwamoto, R Schneider, P G Bullough
Journal: Annals of the Rheumatic Diseases (2007)

<h3>Objective:</h3> Subchondral insufficiency fracture of the femoral head (SIF) is a recently recognised cause of acute onset arthritis mostly in older women, which previously had been commonly considered either as osteonecrosis or osteoarthritis. The purpose of this study is to report the histopathological incidence of SIF using surgically removed femoral heads. <h3>Methods:</h3> We reviewed 7718 consecutive femoral heads from 7286 patients removed over a 4-year period (2001–2004). There were 4211 women and 3507 men. The age range was from 13 to 96, average age was 60. There were 7349 hips with a preoperative clinical diagnosis of osteoarthritis and 369 with a preoperative clinical diagnosis of osteonecrosis. <h3>Results:</h3> SIF was diagnosed histologically as the primary process in 501 of 7718 resected femoral heads (6.5%). The age range in these patients was from 20 to 93, with an average age of 68, in which 79% (394 hips) were over 60. They were 305 hips in women and 196 in men. The affected side was the right one in 253 hips and left in 248. The prevalence of SIF in cases with a preoperative diagnosis of osteoarthritis was 6.3% (460 of 7349), and with osteonecrosis was 11.1% (41 of 369). In all cases, callus and granulation tissue were observed histologically along the fracture line. <h3>Conclusions:</h3> In this large series of total hip replacements SIF as the cause of disease was diagnosed histologically in 6.5% of the surgically removed femoral heads.
Phase II Randomized Trial Comparing High-Dose IFN-α2b with Temozolomide Plus Cisplatin as Systemic Adjuvant Therapy for Resected Mucosal Melanoma
Authors: Bin Lian, Lu Si, Chuanliang Cui, Zhihong Chi, Xinan Sheng, Lili Mao, Siming Li, Yan Kong, Bixia Tang, Jun Guo
Journal: Clinical Cancer Research (2013)

Mucosal melanoma is rare and associated with extremely poor prognosis. However, standard adjuvant therapy for mucosal melanoma has not been established. We conducted a randomized phase II clinical trial in patients with resected mucosal melanoma to compare the efficacy and safety of high-dose IFN-α2b (HDI) and temozolomide-based chemotherapy as adjuvant therapy.Patients with mucosal melanoma in stage II/III after surgery were randomized into three groups: observation group (group A, surgery alone), HDI group (group B, treated with 15 × 10(6) U/m(2)/d IFN-α2b, followed by 9 × 10(6) U IFN-α2b), and temozolomide (200 mg/m(2)/d) plus cisplatin (75 mg/m(2)) group (group C). The endpoints were relapse-free survival (RFS), overall survival (OS), and toxicities.One hundred and eighty-nine patients were enrolled and finally analyzed. With a median follow-up of 26.8 months, the median RFS was 5.4, 9.4, and 20.8 months for group A, B, and C, respectively. Estimated median OS for group A, B, and C was 21.2, 40.4, and 48.7 months, respectively. Patients treated with temozolomide plus cisplatin showed significant improvements in RFS (P < 0.001) and OS (P < 0.01) than those treated with either HDI or surgery alone. Toxicities were generally mild to moderate.Both temozolomide-based chemotherapy and HDI are effective and safe as adjuvant therapies for resected mucosal melanoma as compared with observation alone. However, HDI tends to be less effective than temozolomide-based chemotherapy for patients with resected mucosal melanoma in respect to RFS. The temozolomide plus cisplatin regimen might be a better choice for patients with resected mucosal melanoma.