tbuckley/cabot-search huggingface dataset:
Single-Dose Effect of Marihuana Smoke
Authors: Louis Vachon, Muiris X. FitzGerald, Norman H. Solliday, Ira A. Gould, Edward A. Gaensler
Journal: New England Journal of Medicine (1973)

Abstract Normal volunteers with previous marihuana smoking experience inhaled the total smoke from 3.23 mg per kilogram of marihuana, using a bag-in-box technic. Randomly, nine received marihuana containing a high (2.6 per cent), and eight a low (1.0 per cent) concentration of delta-9 tetrahydrocannabinol. Physiologic variables were monitored before and for 20 minutes after smoking. In the high-dose group the heart rate increased 28 per cent. Concomitantly, airway resistance, measured in a body plethysmograph, fell 38 per cent; the functional residual capacity remained unchanged (± 50 ml) throughout, and specific airway conductance increased 44 per cent. Flow-volume loops showed a 45 per cent increase in flow rate at 25 per cent of vital capacity. The low-dose group showed no increase in heart rate but significant, if lesser changes, in airways dynamics. Carbon dioxide sensitivity, measured by rebreathing remained unchanged in both groups. Marihuana smoke, unlike cigarette smoke, causes bronchodilatation ...
Orally active gnRH-antagonist AEZS-115 inhibits growth of human ovarian and breast cancers in vitro.
Authors: JB Engel, M Ivanisevic, E Guenther, J Dietl, U Kaemmerer, A Hoenig
Journal: Cancer Research (2009)

Abstract Abstract #3065 Introduction: AEZS-115 is an orally active peptidomimetic antagonist of GnRH, which has been shown to block the pituitary GnRH receptor in nanomolar range. Recently an increasing number of human cancers have been demonstrated to express receptors for GnRH, which mediate growth promoting signals. Accordingly, we tested the antitumor activity of AEZS-115 in in vitro models of human breast and ovarian cancer.&amp;#x2028; Material and Methods: Human ovarian SKOV3, Ovcar 3 as well breast cancer cell line MDA-MB 468 were analyzed for GnRH receptor expression by immunocytochemistry. To screen for a putative anti-tumor effect, these cell lines were incubated with increasing concentrations of AEZS-115, peptidic GnRH-antagonist Cetrorelix and GnRH-agonist Triptorelin (1, 10, 100 µm) for 48 hours and the number of viable cells was determined by crystal violet staining as well as by ATP-dependent luminometric assay.&amp;#x2028; Results: Cell lines SKOV3, OVCAR3 and MDA-MB 468 expressed GnRH I receptors as demonstrated by immunehistochemistry. Both GnRH-antagonists dose dependently inhibited growth of all three cell lines, while GnRH-agonist Triptorelin showed marginal growth inhibition. At 10 µM AEZS-115 inhibited cell growth by 40-60%, at 100 µM growth inhibition was 60-80%. Inhibition with Cetrorelix at 100 µM ranged from 20-40%, while only minor effects on cell growth were seen at 10 µM. These results obtained by crystal violet staining were confirmed by additional luminometric evaluation of the ATP content after treatment with the respective substances.&amp;#x2028; Conclusions: To our knowledge here we report for the first time in vitro anti-cancer activity for a peptidomimetic GnRH antagonist.&amp;#x2028; AEZS-115 showed substantial anti-tumor activity in human ovarian and breast cancer cell lines, while GnRH-agonist Triptorelin showed only minor growth inhibition. Surprisingly AEZS-115 was somewhat more potent than peptidic GnRH-antagonist Cetrorelix. Due to the good antitumor-activity and the possible oral administration AEZS-115 should be a promising candidate for in vivo studies. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3065.
Multiple Intraabdominal Purulent Collections Demonstrated on FDG PET/CT in Staging of Non-Hodgkin Lymphoma
Authors: Jonathan Tow, Han Loh, Chuong Bui, Stephen Fuller, Robert Mansberg
Journal: Clinical Nuclear Medicine (2012)

A 56-year-old man, recently diagnosed with non-Hodgkin lymphoma, was referred for a FDG PET/CT scan to stage disease. Unexpected large fluid collections with FDG-avid peripheries and central photopenia were demonstrated in the abdomen and pelvis on the FDG PET/CT study. The collections were urgently drained with subsequent resolution. After antibiotic treatment, repeat FDG PET/CT study confirmed rapidly progressive lymphoma necessitating urgent chemotherapy.
AB0345 Osmic acid synovectomy; is there still a need for this treatment?
Authors: C. Mercieca, G. Bezzina, A. A. Borg
Journal: Annals of the Rheumatic Diseases (2013)

Background Osmic acid synovectomy has been shown to be an effective and safe treatment for patients with chronic knee inflammatory arthritis unresponsive to intra-articular glucocortcoids and DMARDs. With the introduction of biologics and improvement in DMARD therapeutic strategies the utility of osmic synovectomy may be questioned. Objectives To ascertain the efficacy, safety and quality of life in patients with inflammatory arthritis and inflammatory osteoarthritis in current practice Methods This was a prospective study of patients who underwent osmic synovectomy of the knee in 2011-2012. All patients had knee effusions and had failed intra-articular glucocorticoid injections. Patients were assessed by a clinician and filled a number of questionnaires (Lequesne, WOMAC, pain scores visual analogue scale (VAS) at rest, weight bearing and on movement) at baseline, 1 month, 3 months and 6 months post-injection. Results Twenty four patients (14 females, 10 males) were recruited. The mean age was 36 years (SD 13.4, range 34-82). Nine patients had rheumatoid arthritis (RA) (5 were on a biologic and DMARDs, 4 on DMARDs only), four had psoriatic arthritis (PsA) (all were on DMARDs and a biologic) and 11 had inflammatory osteoarthritis (OA). The median time of knee pain and swelling was 12 months (range 3-120). One patient had bilateral osmic acid synovectomy. Six patients had previously undergone the procedure, 3 of the same knee. No complications were reported Mean VAS pain scores at baseline, 1 month and 6 months were as follows; at rest 46.9, 29.3, 21.5 (p=0.001), on weight bearing 62.1, 44.8, 40.4 (p=006) and on movement 54.4, 45.8, 32.2 (p=0.005). The WOMAC at baseline, 1 month and 6 months were; 52.2, 39.4 and 36.9 (p= 0.005) and Lequesne scores were 15.5, 12.4 and 9.4 (p=0.001). Patients with inflammatory arthritis showed a more significant improvement compared to those with OA. Knee swelling was present in 8 patients at 1 month and 10 patients at 6 months. Conclusions Osmic acid synovectomy of the knee is a safe and efficacious therapy as evidenced by the marked response in pain, swelling and quality of life. The main advantages include the sustained fast acting response and a minimally invasive procedure which allows immediate initiation of rehabilitation. Despite the availability of more effective biologic therapy osmic acid synovectomy is still a useful adjuvant therapeutic option particularly in cases of monoarthritis or knee inflammatory arthritis resistant to intra-articular glucocorticoids, DMARDs and biologics. Its efficacy in inflammatory OA is also very useful and should be considered more often as a treatment option. References Bessant R, Steuer A, Rigbi S, Gumpel M. Osmic acid revisited: factors that predict a favourable response. Rheumatology 2003;42:1036–1043 Disclosure of Interest None Declared
OP0179 Angiogenesis and blood vessel stability in giant cell arteritis
Authors: D. Molloy, J. McCormick, M. Connolly, M. Haroon, D.J. Veale, U. Fearon, E. Molloy
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Giant Cell Arteritis (GCA) is the most common form of primary vasculitis. The pathogenesis is incompletely understood, but involves neoangiogenesis and inflammatory infiltration of the arterial wall. The aim of the present study was to assess blood vessel stability and oxidative damage in patients with the condition and correlate with disease activity. <h3>Methods</h3> 20 patients with a clinical diagnosis of GCA were included, 16 of whom had a positive temporal artery biopsy. Temporal artery (TA) sections were assessed for blood vessel maturity (%BVM) by dual-immunofluorescent staining for Factor VIII/αSMA. Oxidative DNA damage (8-oxo-7,8-dihydro-2'-deoxyguanosine; 8-oxo-dG), lipid peroxidation (4-hydroxy-2-nonenal; 4-HNE), angiogenic growth factor Angiopoietin 2 (Ang2) and it receptor Tie-2 were assessed by immunohistochemistry. <i>Ex vivo</i> TA explant cultures were established directly from fresh biopsy specimens (n=4) and spontaneous release of pro-angiogenic factors were examined by ELISA and gelatin zymography. Patient were categorised into low disease activity (CRP&lt;50 mg/dL vs high disease activity (CRP&gt;50 mg/dL) <h3>Results</h3> Strong expression of 8-oxo-dG, 4HNE, Ang2 and Tie2 were demonstrated in the adventitial and intimal regions. 8-oxo-dG and 4HNE correlated with disease activity marker ESR (r=.568, p&lt;0.017: r=.451, p&lt;0.05 respectively). Expression of 8-oxodG significantly correlated with Tie2 (r=0.538, p&lt;0.017) while expression of 4HNE significantly correlated with Ang2 (r=0.0529, p&lt;0.02). A mixture of immature and mature blood vessels was demonstrated in all GCA patients, with a lower number of vessels expressing α-SMA in patients with high disease activity (41% ± 13.4) compared to low disease activity (66% ± 8.2) suggesting a more unstable vascular microenvironment is associated with high disease activity. This was further supported when we demonstrated spontaneous release of pro-inflammatory mediators Ang2, MMP-2, MMP-9, IL-6 and IL-8 from <i>ex vivo</i> TA explants in culture. Furthermore conditioned media from TA explants significantly induced angiogenic tube formation (p&lt;0.05). <h3>Conclusions</h3> This is the first study directly demonstrating that vessels in the inflamed temporal arteries from patient with GCA are unstable and are associated with incomplete EC/pericyte interactions, expression of Ang2 and oxidative damage markers. <h3>Disclosure of Interest</h3> D. Molloy: None Declared, J. McCormick: None Declared, M. Connolly: None Declared, M. Haroon: None Declared, D. Veale Grant/Research support from: Wyeth, GSK, Abbott, Opsona, Consultant for: Wyeth, GSK, Abbott, Pfizer, Schering Plough, Centocor, Speakers Bureau: Wyeth, GSK, Abbott, Pfizer, Schering Plough, Centocor, Mundipharma, U. Fearon: None Declared, E. Molloy: None Declared
AB0101 Articular Adipose Tissue from Osteoarthritis Patients is A Source of Cytokines and Adipokines
Authors: M. Plebanczyk, U. Musialowicz, T. Burakowski, I. Janicka, W. Maslinski, P. Maldyk, E. Kontny
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Recently rheumatoid adipose tissue has been suggested to play an important role in chronic inflammatory joint diseases. Its ability to synthesize cytokines and adipokines has been characterized also in our Department (Kontny E, Plebanczyk M, Lisowska B, Olszewska M, Maldyk P, Maslinski W. Comparison of rheumatoid articular adipose and synovial tissue reactivity to proinflammatory stimuli: contribution to adipocytokine network. Ann Rheum Dis, 2012, 71 (2): 262-267). These factors play fundamental role in synovial inflammation and articular destruction. <h3>Objectives</h3> The aim of present work was to investigate whether adipose tissue obtained from Osteoarthritis (OA) patients also secretes factors relevant to disease pathogenesis and/or progression. <h3>Methods</h3> Articular adipose tissue (AAT) and synovial membrane (SM) explants, obtained from OA patients who were undergoing knee joint replacement surgery, were cultured (100 mg/ml) for 24 hrs in medium (DMEM) alone or in the presence of LPS or cytokines: TNF, IFN-γ, IL-1α, IL-15, IL-17 or IL-23. Concentrations of TNF, IL-1α, IL-6, IL-8, IL-1Ra, adiponectin and leptin were measured in culture supernatants by ELISA. <h3>Results</h3> Untreated AAT spontaneously produced low levels of IL-6 and IL-8, while secretion of these cytokines by SM was significant. All stimuli increased IL-6 and IL-8 synthesis in AAT, but did not change it in SM. The levels of these cytokines were usually higher in SM than in AAT. Spontaneous secretion of TNF was negligible, LPS, IL-1α and IFN-γ triggered marked TNF synthesis (in both tissues). Spontaneous production of IL-1a was also very low and rised only after LPS (AAT and SM) and TNF (SM) stimulation. SM stronger than AAT responded to stimulation. The level of anti-inflammatory IL-1Ra was high in both tissues (higher in SM than in AAT). Stimuli increased IL-1Ra production in AAT, but not in SM. The level of adiponectin was similar in tested tissues and stayed unaffected by stimulation. AAT and SM explants secreted spontaneously moderate amount of leptin. In AAT leptin secretion raised upon LPS and IL-1α stimulation, while stayed unchanged in SM. <h3>Conclusions</h3> AAT, like SM, seems to be very active tissue. While spontaneous production of pro-inflammatory cytokines by AAT was low, it raised markedly upon stimulation. Moreover, AAT from OA patients produced spontaneously large amount of anti-inflammatory IL-1Ra. The secretion of classical adipokines did not differ between tissues. Therefore our results give direct evidence that in osteoarthritis, like in rheumatoid arthritis, adipose tissue is an active participant of cytokine and adipokines network. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6014
Abstract 956: The liver-X-receptor-α is involved in the induction by Tamoxifen of breast cancer cell differentiation and death
Authors: Gregory Segala, Philippe de Medina, Michael Paillasse, V. Craig Jordan, Sandrine Silvente-Poirot, Marc Poirot
Journal: Cancer Research (2012)

Abstract Hormonotherapy with Tamoxifen (Tam) is one of the main strategies used world-wide for the treatment of estrogen receptor positive breast cancer. However, partial responses, tumor recurrence and acquired resistance to Tam may involve mechanisms unrelated to Estrogen Receptors (ER). Studies on non-ER related mechanisms of action of Tam led us to find that it induced breast cancer cell differentiation and death through the modulation of sterol metabolism and the stimulation of sterol oxidation (de Medina et al, Cell Death Differ, 2009), and that Tam inhibited cholesterol epoxide hydrolase (ChEH). ChEH catalyzes the trans hydration of cholesterol-5,6-epoxides (CE) and this activity is a property of the microsomal antiestrogen binding site (AEBS) (de Medina et al, PNAS, 2010). In the present study we report that Tam and AEBS ligands stimulated the oxidation of cholesterol into CE and induced the accumulation of CE in MCF-7 cells through the inhibition of ChEH at therapeutic concentrations. Since CE has been reported to be a modulator of Liver-X-Receptors (LXR), we investigated the impact of Tam and other AEBS ligands on LXR-dependent gene expression: Tam and AEBS ligands modulated the expression LXR-dependent genes in MCF-7 cells. This effect had a 24 to 48 hour lag time while the effect of direct LXR modulators was observable after 6 hours, suggesting an indirect action of AEBS ligands. The involvement of CE in the control of transcription by Tam and AEBS ligands was supported by the observation that vitamin E, which inhibited the formation and the accumulation of CE, totally blocked this transcriptional modulation. We found that knocking down LXR-α using interfering RNAs in MCF-7 cells blocked the transcriptional modulation of LXR-controlled genes induced by CE, Tam and AEBS ligands. Finally, we found that the knock down of LXR-α reproduced the vitamin E inhibition of the induction of differentiation and death of MCF-7 cells. Altogether, these data showed that LXR-α is implicated in the anticancer action of Tam and identified a new signaling pathway that could explain sensitivity and resistance to Tam. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 956. doi:1538-7445.AM2012-956
P16 A Systematic Characterisation Of Inflammation In Chronic Thromboembolic Pulmonary Hypertension
Authors: C. Hadinnapola, M. Southwood, D. Jenkins, K. Sheares, M. Toshner, J. Pepke-Zaba
Journal: Thorax (2014)

<h3>Introduction</h3> The pathogenesis of chronic thromboembolic pulmonary hypertension (CTEPH) is poorly understood. Idiopathic pulmonary arterial hypertension (IPAH) is associated with systemic and localised inflammation. Distal vasculopathy is seen in IPAH and CTEPH (2 compartment model). Inflammation has also been implicated in CTEPH pathogenesis. We undertook a systematic assessment of inflammatory markers and immune cells to determine the role of inflammation in CTEPH. <h3>Methods</h3> We examined the distal tails of 26 pulmonary endarterectomy (PEA) specimens and explanted lungs (5 CTEPH, 11 IPAH). Formalin fixed samples were immunostained with anti-human CD45 (inflammatory cell), CD79a (B cell), CD68 (macrophage) or CD3 (T cell) antibodies. Cell counts were normalised to the area surrounding vessels bounded by airspace structures for perivascular cell counts; to vessel area for media cell counts and per high powered field for lung parenchymal cell counts. Serum was collected from 61 patients pre and 6 months post PEA. Cytokines were measured using a multiplex array (pg/ml; mean±SD). <h3>Results</h3> Table 1. CD3<sup>+</sup> cells were less abundant in the media of small vessels (mean 0.03 ± 0.01 mm<sup>2</sup>) in CTEPH vs. IPAH (p = 0.02). Perivascular and parenchymal cell counts showed non-significant reductions of CD3<sup>+</sup> cells in CTPEH (p = 0.19 and 0.08 respectively). More CD68<sup>+</sup> cells were seen in the parenchyma in CTEPH (p = 0.03). Few CD20<sup>+</sup> cells were seen in parenchyma with no difference. Neovascularisation correlated to CD45<sup>+</sup> cells in PEA specimens when normalised to specimen area (r = 0.4, p = 0.01). <h3>Conclusions</h3> In CTEPH, most serum cytokines were not elevated sufficiently to suggest systemic inflammation is important in pathogenesis. The change in IL10 and TNFα are possibly due to improvement in cardiac function post PEA as described previously. The relative lack of CD3<sup>+</sup> T cells in the media of small arteries in CTEPH suggests that localised inflammation is also less important. The significance of CD68<sup>+</sup> cells in CTEPH lung parenchyma needs further assessment. The correlation of CD45<sup>+</sup> cells and neovascularisation in PEA specimens may suggest an association between inflammation and neovascularisation. Inflammatory signals maybe related to thrombus remodelling and cardiac dysfunction rather than to CTEPH pathogenesis. Isolating these processes is required to expand on this descriptive study.
AB0921 Microrna in synovial fluid of ankylosing spondylitis compared with rheumatoid arthritis
Authors: Y.B. Joo, J.-J. Kim, E. Kwon, B.N.R. Lee, J.D. Ji, S.I. Sung, Y.B. Kim, T.-H. Kim
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> MicroRNAs have shown different expression patterns in immune disease such as rheumatoid arthritis and systemic lupus erythematosus. However, expression alterations and roles of these microRNAs in ankylosing spondylitis have not be addressed. We hypothesized that ankylosing spondylitis may have distingushed miRNA profiles compared with rheumatoid arthritis, which may play a critical role in pathogenesis and clinical manifestation. <h3>Objectives</h3> To compare microRNA in synovial fluid of ankylosing spondylitis with of rheumatoid arthritis. To identify microRNA associated with bone homeostasis in ankylosing spondylitis. <h3>Methods</h3> We determined the levels of 780 miRNAs of synovial fluid macrophages in 9 ankylosing spondylitis and 8 rheumatoid arthritis using TaqMan miRNA microarrays. Multiple test was done with Benjamini-Hochberg correction and miRNAs more than 1.5 fold change were selected. <h3>Results</h3> One hundreds fourty three probes were selected after multiple test: 61 miRNAs were down-regulated and 82 miRNAs were up-regulated in AS. Among them, eight miRNAs associated with osteoclast or osteoblast were revealed: miR-129-5p and miR-1233 were down-regulated and miR-330-5p, miR-1226, miR-610, miR-1179, miR-335, and miR-625 were up- regulated in synovial fluid of ankylosing spondylitis. <h3>Conclusions</h3> MicroRNA levels are distinctly increased or decreased in synovial fluid of ankylosing spondylitis compare with rheumatoid arthritis. Further validation studies with larger scale are warranted to fully explore the role of circulating microRNAs in ankylosing spondylitis. <h3>Disclosure of Interest</h3> None Declared
Abstract 1962: <i>Helicobacter pylori</i> cytotoxin associated protein CagA represses TGF-β signaling through interaction with Smad proteins
Authors: Ho-Jae Lee, Thuy Trang Nguyen, Han-Yang Cho, Kyoung-Mi Kim, Cho-Rong Kim, Ki-Baek Hahm
Journal: Cancer Research (2011)

Abstract Helicobacter pylori infection causes chronic gastric inflammation and peptic ulceration, and is the strongest risk factor for the development of gastric cancer. The cagA (cytotoxin-associated gene A) gene which is one of the most important virulence factors of H. pylori, is believed to contribute to the gastric tissue injury and cancer development. Transforming growth factor-β (TGF-β) signaling plays a pivotal role in modulating gastric mucosal inflammatory responses. Recently, H. pylori infection has been associated with attenuated TGF-β signaling in gastric mucosa. However, the precise underlying mechanism of H. pylori infection on TGF-β signaling and inflammatory response remains unclear. In this study, we examined the mechanism of inhibition of TGF-β signaling by H. pylori CagA protein. CagA suppressed TGF-β/Smad transcriptional responses. CagA interacted constitutively with Smad proteins, and most strongly with Smad3. Expression of CagA on AGS cells inhibited TGF-β-induced down-regulation of proinflammatory chemokines, such as CXCL1, CXCL3 and IL-8, as well as TGF-β-induced transcription of target genes. These results suggest that the attenuated TGF-β signaling associated with cagA-positive H. pylori infection could be an important determinant for the degree of inflammation provoked by H. pylori. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1962. doi:10.1158/1538-7445.AM2011-1962
The Diagnostic and Therapeutic Value of Liver Biopsies
Authors: Wade Volwiler, Chester M. Jones
Journal: New England Journal of Medicine (1947)

ACCURATE information regarding the particular phase of any morbid process under observation is essential to the institution of adequate therapeutic measures. Such an obvious and desirable goal, until recent years, has been only vaguely obtainable in intrahepatic disease. Numerous liver-function tests of simple or complex nature have been devised but have proved useful primarily as a means of estimating the degree of functional damage and of following the progress of intrahepatic disease rather than as a measure of exact diagnosis. The multiplicity of the liver's functions and its notable reserve capacity are such that at best, even when the entire . . .
The People Who Make Cancer Clinical Trials Happen
Authors: L. F. Anderson
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article The People Who Make Cancer Clinical Trials Happen Get access Linda F. Anderson Linda F. Anderson Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 2, 18 January 1995, Pages 81–83, https://doi.org/10.1093/jnci/87.2.81 Published: 18 January 1995