tbuckley/cabot-search huggingface dataset:
9G4 expression on autoantibodies to citrullinated peptides in patients with early inflammatory arthritis and established rheumatoid arthritis
Authors: Rita A Moura, Inmaculada de la Torre, Maria J Leandro, Jonathan C W Edwards, João E Fonseca, Geraldine Cambridge
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background</h3> The rat monoclonal antibody 9G4 recognises VH4-34-encoded proteins, enabling the identification of inherently autoreactive B cells. In rheumatoid arthritis (RA), evidence for a humoral immune response encoded by VH4-34 gene has been described in the synovial membrane and within hybridomas derived from rheumatoid synovial tissue. The authors have recently described an expansion of circulating 9G4<sup>+</sup> plasmablasts in patients with active RA. <h3>Objectives</h3> The aim of this study was to determine whether 9G4+ was expressed on autoantibodies commonly associated with RA. <h3>Materials and methods</h3> Serum from 27 patients with established RA and 46 polyarthritis patients (&lt;6 weeks duration) of whom 23/46 were subsequently diagnosed with RA (Early RA, ERA) and 23/46 with other arthritis (early non-RA, ENRA) was studied. 9G4 expression on anti-CCP, antitetanus toxoid (TT), pneumococcal capsular polysaccharide (PCP) antibodies and total serum IgG and IgM was measured by ELISA. <h3>Results</h3> 23/27 patients with established RA had anti-CCP antibodies, in which eight expressed 9G4. All were positive for both IgM and IgG anti-CCP. Levels of 9G4 expression correlated more closely with IgM than IgG-CCP. In ERA group, 15/23 patients had anti-CCP and 4/23 had 9G4+ anti-CCP. All 4 patients had both IgM and IgG anti-CCP. In ENRA, only one patient had 9G4+ IgM anti-CCP, albeit at low titre. 9G4 was not expressed on TT or PCP antibodies. <h3>Conclusions</h3> The authors describe the use of the VH4-34 heavy chain gene by autoantibodies to citrullinated peptides early after RA onset. In established RA, usage of VH4-34 by anti-CCP antibodies increased with increasing titre, particularly in IgM-CCP. Therefore, it is possible that the expansion of CCP-specific B cell clones may be due to robust expansion of un-switched B cell clones, possibly including or analogous to those in the splenic marginal zone. This is the first description of the use of the VH4-34 heavy chain gene by autoantibodies to citrullinated peptides. 9G4 expression was largely confined to CCP antibodies from patients with RA.
Os Trigonum Syndrome on Bone SPECT/CT
Authors: Jianmin Huang, Sabah Servaes, Hongming Zhuang
Journal: Clinical Nuclear Medicine (2014)

A 16-year-old female athlete presented with increased pain in the distal left lower extremity. A possible stress fracture or shin splint of the left tibia was first considered. A 3-phase bone scintigraphy showed a very small focus of increased activity in the posterior left foot. A diagnosis of os trigonum syndrome was made after SPECT/CT images pinpointed the activity at the left os trigonum.
Cyclosporine Therapy for Autoimmune Disease
Authors: C. Garrison Fathman, Bryan D. Myers
Journal: New England Journal of Medicine (1992)

THE potential for immunosuppressive agents to control the poorly understood pathophysiologic consequences of autoimmunity has intrigued clinical immunologists for decades. Unfortunately, the toxicity of these agents has often outweighed their clinical benefit. In the mid-1970s cyclosporine was shown to have pronounced immunosuppressive activity without causing myelotoxicity or other severe side effects, and it was quickly proved to be effective in a wide variety of animal models of transplantation and autoimmunity.1 During the ensuing years, great strides have been made in understanding the basic immunopharmacology of cyclosporine and in demonstrating its effectiveness in human transplantation and autoimmune disorders.2 In studies using . . .
Surgical Treatment of Mitral Stenosis by the Transventricular Approach with a Mechanical Dilator
Authors: W. Gerald Austen, Geoffery H. Wooler
Journal: New England Journal of Medicine (1960)

SINCE 1948 when Bailey,1 in Philadelphia, Harken,2 in Boston, and Brock,3 in London, successfully relieved mitral stenosis by surgical exploration through the left atrium and rupture of the commissures, the transatrial digital approach has been the accepted form of treatment. Certainly, in a great many patients the atrial approach has been very successful indeed. As surgeons have gained experience with this clinical problem, however, it has become increasingly obvious that digital pressure alone frequently gives only limited improvement. Consequently, many ingenious instruments and technics have been devised to overcome the resistance of the mitral valve and to improve upon the . . .
110P Treatment patterns &amp; safety of docetaxel in Chinese real-world clinical practice: a multicenter non-interventional observational study of docetaxel administration as adjuvant therapy in operable early breast cancer patients
Authors: S. Wang, H. Xie, J. Liu, S. Yu, Y. Chen, M. Zheng, Y. Deng, S. Wang, J. Jiang, Y. Li
Journal: Annals of Oncology (2015)
Increase in scarlet fever notifications in the United Kingdom, 2013/2014
Authors: R Guy, C Williams, N Irvine, A Reynolds, J Coelho, V Saliba, D Thomas, L Doherty, V Chalker, B von Wissmann, M Chand, A Efstratiou, M Ramsay, T Lamagni
Journal: Eurosurveillance (2014)

Increases in scarlet fever above usual seasonal levels are currently being seen across the United Kingdom. Medical practitioners have been alerted to the exceptional increase in incidence. Given the potential for this to signal a population increase in invasive group A streptococcal disease, close monitoring of invasive disease is essential.
Recanalization of the Umbilical Vein Seen on Multiplanar SPECT Technetium-99m Tagged Erythrocytes
Authors: S. NIMU GANGULI, MARLON HERSHKOP
Journal: Clinical Nuclear Medicine (1999)

A 71-year-old man with no history of liver disease underwent a Tc-99m tagged erythrocyte scan to confirm the presence of several hemangiomas suspected on an ultrasound from an outside institution. The planar and SPECT images showed collateral blood flow in a patent umbilical vein. No activity consistent with hemangiomas was seen. However, after conveying the findings to the referring clinician, further history taking revealed that the patient was an alcoholic. A repeated ultrasound at our institution revealed the patent umbilical vein and a lesion in the medial segment of the left lobe, which was examined by biopsy and found to be a hepatocellular carcinoma.
Improvement in Cyclosporine-Associated Gingival Hyperplasia with Azithromycin Therapy
Authors: Erik Wahlstrom, Jose U. Zamora, Siegmund Teichman
Journal: New England Journal of Medicine (1995)

To the Editor: Gingival hyperplasia is a known complication of cyclosporine therapy. It appears to be worsened by the concomitant administration of nifedipine or phenytoin. Two transplant recipients had dramatic improvements in symptomatic gingival hyperplasia after a short course of azithromycin. The first patient was a 49-year-old man with chronic glomerulonephritis who received a cadaveric renal transplant on September 16, 1987. He received immunosuppressive therapy with corticosteroids, azathioprine, and cyclosporine. An early episode of rejection was treated with intravenous methylprednisolone. Gingival hyperplasia was noted on June 6, 1989. In September 1992, a further increase in the gingival tissue was noted. . . .
S37 Comparison of dynamic contrast enhanced MRI (DCE-MRI) parameters with integrated PET-CT and serum mesothelin in the baseline assessment of malignant pleural mesothelioma
Authors: C. Hooper, D. Hall, P. Virgo, P. White, M. Darby, T. Hall, J. Braybrooke, J. Searle, I. Lyburn, N. Maskell
Journal: Thorax (2010)

Integrated PET-CT scans and serum mesothelin measurement have shown early promise in predicting prognosis and evaluating treatment response in malignant pleural mesothelioma (MPM) but may be less reliable with sarcomatoid histology or prior talc pleurodesis. Dynamic Contrast Enhanced-MRI (DCE-MRI) with pharmacokinetic analysis is a novel metabolic imaging modality providing a measure of tumour blood flow and angiogenesis. We prospectively examined the relationship between pharmacokinetic parameters on DCE-MRI with PET-CT, serum mesothelin and histological sub-type in MPM patients at diagnosis. <h3>Method</h3> 30 pre-treatment patients with a histologically proven MPM underwent DCE-MRI and integrated PET-CT and serum mesothelin assay (MESOMARK) at a single visit. SUVmax and total glycolytic volume (TGV) were reported from PET-CT scans with TGV calculated using MIM software version 4.2.2 (MIMvista corp.). Gadolinium washout rate (GWR) on DCE-MRI was defined at a region of interest from a straight line fit to the kinetic curve data (CAD software—ViewForum R6.3 V1L3, Philips Medical Systems) between peak enhancement in the first 2 min and the last data point. <h3>Results</h3> 70% (21/30) epithelioid and 30% (9/30) sarcomatoid histology. 43% (13/30) had undergone prior talc pleurodesis. Histology did not statistically significantly affect SUVmax, TGV or GWR. Serum mesothelin was significantly greater in the epithelioid group (3.2 nM/l (2.0, 6.3) vs 0.6 nM/l (0.5, 0.8) p&lt;0.001). There was no significant difference in mesothelin, SUVmax, TGV or GWR between talc pleurodesed and non-pleurodesed patients in the whole group, but in the epithelioid sub-group there was a trend to significantly higher TGV with talc pleurodesis (talc: 2799 (1931,11257) no talc: 955.5(146.8,2354) p=0.053) that was not observed with GWR (p=0.4179). While SUVmax strongly correlated to TGV (r=0.725, p&lt;0.001), there was no correlation between GWR and TGV (r=0.203, p=0.282) or between mesothelin levels and any of the imaging values. <h3>Conclusion</h3> Metabolic imaging has been proposed as an important component of the assessment and management of patients with malignant pleural mesothelioma. Gadolinium washout rate on DCE-MRI may be less sensitive to talc pleurodesis than PET-CT parameters and MRI is a cheaper, more readily available modality that involves shorter patient appointment times, warranting further study in MPM prognostic evaluation and treatment response monitoring.
Abstract LB-279: SIRT6 expression is regulated by cAMP signaling system in non small cell lung cancer cells
Authors: Eui-Jun Kim, Yong-Sung Juhnn
Journal: Cancer Research (2012)

Abstract Sirtuin 6 (SIRT6) is a member of the NAD+ dependent histone deacetylase (HDAC) family. HDACs play an important role in epigenetic regulation of gene expression, which is counteracted by histone acetyl-transferase (HAT). HDACs remove acetyl-group at lysine residue of histone tail, and change the conformation of chromatin complex, which eventually regulates transcription activity in of various cancer cells. SIRT6 is reported to be a site specific deacetylase acting at histone H3K9 and H3K56, but very few studies on the regulation of SIRT6 expression have been reported. Cyclic AMP (cAMP) signaling system regulates a variety of cellular responses including metabolism, gene expression, proliferation and death. Therefore, we studied the effect of cAMP signaling system on the expression of SIRT6 and its underlying mechanism in lung cancer cells. Stimulatory heterotrimeric GTP-binding proteins (Gαs) are activated by various ligand-bound receptors and stimulate adenylate cyclase to activate cAMP signaling system. Expression of constitutive active Gαs (GαsQL) decreased SIRT6 protein level without change in its mRNA level in H1299 lung cancer cells. GαsQL expression accelerated proteasomal degradation of SIRT6, resulting in a decreased half-life of the protein from 2.2 h to 1.2 h. SIRT6 expression was also decreased by forskolin (adenylate cyclase activator), but increased by H89 (PKA inhibitor). These results indicate that cAMP signaling system decreases SIRT6 expression by accelerating proteasomal degradation of SIRT6 expression via PKA-dependent pathway in lung cancer cells. This finding suggests that cAMP signaling system can contribute epigenetic regulation of cancer-related gene expression by modifying SIRT6 expression. 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 LB-279. doi:1538-7445.AM2012-LB-279
PWE-176 Trends in Gastrostomy Insertion Over a 10 Year Period. Are the Indications Changing?
Authors: C S MacLeod, R McKay, D Barber, A W McKinlay
Journal: Gut (2013)

<h3>Introduction</h3> Gastrostomy insertion is a well accepted technique for enteral feeding however the most robust evidence is for patients with dysphagic stroke or head and neck cancer. Other indications for gastrostomy insertion have developed but the proportion of patients referred for each indication is not well documented. Our aim was to examine referral patterns for feeding tube insertion in our unit over the last ten years with reference to indication for tube insertion and type of tube inserted. <h3>Methods</h3> A retrospective review of all gastrostomy insertion was performed over the period May 2001 to December 2011 using the gastrostomy database. Data collected included patient demographics, indication for tube insertion and type of tube inserted (PEG, PEJ, PEG-j or gastropexy). Indication was divided into 5 main categories; stroke with dysphagia, head and neck cancer, neurological, dementia and other. Assessment of total number of each type of tube inserted per year and, for PEG alone, the total number of insertions per indication per year. <h3>Results</h3> During the study period 1387 tube insertions were carried out (1289 PEG, 41 PEJ, 32 PEG-j and 25 gastropexy). Over the ten year period there was a significant increase in the number of all types of tubes inserted (p &lt; 0.001) with 65 PEG’s alone inserted in 2001 rising to 129 PEG’s, 7 PEJ, 4 PEG-j and 11 gastropexy’s in 2011. In 2001 the proportion of patients having a PEG inserted by indication was stroke with dysphagia 26.2%, head and neck cancer 6.2%, neurological 35.4%, dementia 1.5% and other 10.8% (indication was not recorded in 20%). In 2011 the proportion of patients having a PEG inserted by indication was significantly different with stroke with dysphagia (22.5%), head and neck cancer (12.4%), neurological (37.2%), dementia (0.0%) and other 25.6% (indication was not recorded in 2.3%). The main differences were an increase in insertions in those with head and neck cancer and other indications. <h3>Conclusion</h3> In our centre, there has been a significant increase in the number and type of feeding tubes inserted over a decade. The proportion of patients having a PEG for the traditional indications such as stroke account for around one third of all insertions. PEG insertions for the miscellaneous indications have significantly increased suggesting that longer term nutritional support is being offered for a much broader range of conditions. <h3>Disclosure of Interest</h3> None Declared.
Abstract 2464: Flavone derivatives as small-molecule probes of cytochrome P450 enzymes: Inhibitory activity and selectivity.
Authors: Jiawang Liu, Shannon Taylor, Patrick Dupart, Corey Arnold, Maryam Foroozesh
Journal: Cancer Research (2013)

Abstract Cytochrome P450 enzymes are the most important enzymes involved in the conversion of environmental procarcinogens such as polycyclic aromatic hydrocarbons (PAHs) from fuels, cigarette smoke, and charcoal-grilled foods into carcinogenic species. These carcinogenic species have the potential to bond to cellular macromolecules such as DNA and can lead to cancer formation. Therefore, selectively inhibiting certain P450 enzymes involved in carcinogenesis is a potential approach to cancer prevention. To investigate the 3D-structural features of the active site cavities of our target P450s, our approach in this project is to use the natural P450 substrate, flavone, as a lead compound. Here we report the synthesis of six novel flavonoids (5,6-pyranflavone, 6,5-pyranflavone, 7,8-pyranflavone, 2’,3’-pyranflavone, 3’,2’-pyranflaovne, and 4’,3’-pyranflavone) and the evaluation of their inhibitory activities, mechanisms of action, and selectivity towards P450 enzymes 1A1, 1A2, 2A6, and 2B1. All of these target compounds were found to be competitive inhibitors of these P450 enzymes. A high inhibitory activity represents a high affinity between the compound and the enzyme. Our data show that the α-naphthoflavone-like flavone derivative, 7,8-pyranflavone, has a high affinity for P450 1A2 (IC50: 0.05 μM), and a relatively low affinity for P450 1A1 (IC50: 0.25 μM). On the contrary, β-naphthoflavone-like flavone derivatives, 5,6-pyranflavone and 6,5-pyranflavone, show higher affinities for P450 1A1 compared to P450 1A2. However, none of these three compounds shows any inhibitory activity towards P450s 2A6 and 2B1. Interestingly, the C-ring modified derivatives (2’,3’-pyranflavone, 3’,2’-pyranflaovne, and 4’,3’-pyranflavone) have relatively low inhibitory activities toward the P450s 1A1 and 1A2, while showing a weak inhibition of P450 2B1 (IC50s: ca. 7.0 μM). These structural data suggest that the length of the P450 1A1 active site cavity is probably longer than that of P450 1A2, while the width of the P450 1A2 active site cavity may be larger than that of P450 1A1. Further studies of 7,8-pyranflavone, 5,6-pyranflavone, and 6,5-pyranflavone will provide us with more detailed structural information about the target P450 enzymes. Citation Format: Jiawang Liu, Shannon Taylor, Patrick Dupart, Corey Arnold, Maryam Foroozesh. Flavone derivatives as small-molecule probes of cytochrome P450 enzymes: Inhibitory activity and selectivity. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2464. doi:10.1158/1538-7445.AM2013-2464
P131 Understanding Health Beliefs And Behaviour In Workers With Occupational Asthma
Authors: G. Walters, A. Robertson, P. Burge, J. Ayres, A. Soundy
Journal: Thorax (2014)

<h3>Introduction</h3> Long delays from symptom onset to the diagnosis of occupational asthma have been reported in the UK, Europe and Canada and workers are often reluctant to seek medical help or workplace solutions for their symptoms.<sup>1,2</sup> Reducing this delay could improve workers’ quality of life, and reduce the societal cost of occupational asthma. This study aimed to explore reasons behind such delays. <h3>Methods</h3> A purposive sample of 20 individuals diagnosed with, or under investigation for, occupational asthma (median age=52; 70% male; 80% white British) undertook a single semi-structured interview. Interviews were transcribed verbatim and thematic analysis was undertaken in order to explore health beliefs and identify barriers to diagnosis. <h3>Results</h3> Four themes were identified: (1) workers’ understanding of symptoms, (2) working relationships, (3) workers’ course of action and (4) workers’ negotiation with healthcare professionals. Understanding of symptoms varied between individuals, from a lack of insight into the onset, pattern and nature of symptoms, through to misunderstanding of what they represented, or ignorance of the existence of asthma as a disease entity. Workers described reluctance to discuss health issues with managers and peers, through fear of job loss and a perceived lack of ability to find a solution. <h3>Conclusion</h3> The evolution of workers’ understanding depended upon how actively they looked to define symptoms or seek a solution. Proactive workers were motivated to seek authoritative help and negotiate inadequate healthcare encounters with GPs. In summary there appear to be a number of key influences motivating a worker to seek an explanation for their symptoms or a definitive solution, which are represented in the model in Figure 1. Understanding workers’ health beliefs will enable policy makers and clinicians to develop better workplace interventions for identifying occupational asthma. <h3>References</h3> Fishwick D <i>et al</i>.<i> Prim Care Respir J</i> 2007;16: 304–10 Poonai N <i>et al</i>.<i> Can J Public Health</i> 2005;96:230–3
Transesophageal drainage of an infected bronchogenous cyst via endoscopic ultrasound-guided implantation of a 7-Fr nasocystic drainage catheter
Authors: Martin Floer, Henning Dörner, Tobias Meister
Journal: Endoscopy (2014)

A 47-year-old woman was admitted to our emergency department with dysphagia and retrosternal pain. The patient's history revealed the existence of an asymptomatic bronchogenic cyst. Computed tomography (CT) demonstrated a cyst ([Fig. 1]) which had compressed the esophagus and which was in close contact with the left atrium. Echocardiography showed an intact pericardium. Esophagoscopy showed the external compression of the esophagus by the lesion ([Fig. 2]). Endoscopic ultrasound (EUS) was performed, demonstrating a non-anechoic bronchogenic cyst ([Fig. 3]). For diagnostic reasons, fine-needle aspiration was performed which revealed pus. We decided to switch to a conventional cystotome. Under EUS guidance, a 0.038-inch guidewire was introduced into the cyst and a 7-Fr nasocystic drainage catheter was applied ([Fig. 4]) and flushed with saline 0.9 % solution every 4 hours. After 5 days, a further CT scan was performed ([Fig. 5]), showing a slowly narrowing cyst. By then, the results of the resistogram had become available and showed Staphylococcus aureus resistant to ceftriaxone and meropenem, but sensitive to co-trimoxazole. After changing the antibiotic regimen, the cyst had almost disappeared after 11 days ([Fig. 6]) and the drainage was removed.
Abstract LB-417: Identification of calreticulin as an invasion-associated protein in ovarian cancer by proteomic approach.
Authors: Fan-Ying Chiang, Ho-Jun Shih, Lu-Ping Chow, Pao-Ling Torng, Chin-Tarng Lin
Journal: Cancer Research (2012)

Abstract Ovarian cancer is the most lethal gynecological cancer among women worldwide. The majority of malignant ovarian tumors are epithelial ovarian cancer and metastasis has occurred in most patients at the time of diagnosis with worse outcome. In our previous study, we have established an ovarian endometrioid carcinoma cell line OVTW59. The original lines were designated as P0, and the highly invasive subline P4 was isolated from 4 rounds of invasion selection. By cDNA microarray analysis and further functional analysis, we have reported insulin-like growth factor binding protein-3 (IGFBP-3) as an invasion suppressor gene that correlated with poor patient survival outcome. In this study, we compared the protein profiles between OVTW59 P0 and P4 using 2D-electrophoresis to select metastasis-associated proteins. The potential candidates were subsequently analyzed by LC-MS/MS. We identified 49 positive invasion-associated proteins and 20 negative invasion-associated proteins. Gene-Ontology analysis showed that more than 50% of these proteins were invasion-related proteins. We then built up a potential network involving these differentially expressed proteins by Ingenuity Pathway Analysis. From these data, we selected Calreticulin for further analysis. Calreticulin has been reported in associated with cell adhesion, apoptosis, wound healing, removal of cancer cells, and autoimmune. By q-RT-PCR, Western blot and scratch test, we found Calreticulin positively associated with cancer invasion in our in-vitro system. In addition, higher Calreticulin expression was found in SCID mice with higher metastasitc capability. Clinically, immunohistochemical staining in 58 cases of ovarian endometiroid cancer will be performed. The result will be further correlated with patient outcome. In this study, we found Calreticulin a novel invasion-associated protein in ovarian endometrioid cancer. 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 LB-417. doi:1538-7445.AM2012-LB-417