tbuckley/cabot-search huggingface dataset:
Abstract 2910: Mono- or double-site phosphorylation distinctly regulates the proapoptotic function of Bax
Authors: Qinhong Wang, Ton Wang, Fengqin Gao, Shi-Yong Sun, Fadlo R. Khuri, Walter J. Curran, Xingming Deng
Journal: Cancer Research (2010)

Abstract Bax is the major multidomain proapoptotic molecule that is required for apoptosis. It has been reported that phosphorylation of Bax at serine(S) 163 or S184 activates or inactivates its proapoptotic function, respectively. To uncover the mechanisms by which phosphorylation at these two sites regulate the proapoptotic function of Bax, a series of serine (S)→ alanine/glutamate (A/E) mutants, including S163A, S184A, S163E, S184E, S163E/S184A (EA), S163A/S184E (AE), S163A/S184A (AA) and S163E/S184E (EE), were created to mimic or abrogate, respectively, either single or double-site phosphorylation. The compound Bax mutants (i.e. EA and AE) can flesh out the functional contribution of individual phosphorylation site(s). WT and each of these Bax mutants were overexpressed in Bax−/− MEF or human lung cancer H157 cells and the proapoptotic activities were compared. Intriguingly, expression of any of Bax mutants containing the mutation S→A at S184 (i.e. S184A, EA or AA) represents more potent proapoptotic activity as compared to WT Bax in association with conformational change, mitochondrial localization/insertion and prolonged half-life. In contrast, all Bax mutants containing the mutation S→E at S184 (i.e. S184E, AE or EE) have decreased protein stability and less apoptotic activity without conformational change and mitochondrial localization/insertion. Unexpectedly, mutation either S→A or S→E at S163 site does not significantly affect the proapoptotic activity of Bax. These findings indicate that S184 but not S163 is the major phosphorylation site for functional regulation of Bax's activity. Thus, manipulation of the phosphorylation status at S184 may represent a novel strategy for treatment of cancers that express Bax. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2910.
TRANS-CATHETER CLOSURE OF PATENT DUCTUS ARTERIOSUS IN SEVERELY PREMATURE NEONATES: A NEW TECHNIQUE FOR A VEXING PROBLEM
Authors: Daniel Peck, Ruchira Garg, Marion McRae, Phillip Nevin, Kaylan Basaker, Alistair Phillips, Charles Simmons, Evan Zahn
Journal: Journal of the American College of Cardiology (2016)
Remissions in Hairy-Cell Leukemia with Pentostatin (2′-Deoxycoformycin)
Authors: Alexander S.D. Spiers, Dirk Moore, Peter A. Cassileth, David P. Harrington, Frank J. Cummings, Richard S. Neiman, John M. Bennett, Michael J. O'Connell
Journal: New England Journal of Medicine (1987)

The Eastern Cooperative Oncology Group conducted a study of pentostatin (2'-deoxycoformycin) in 37 patients with hairy-cell leukemia. Among the 27 patients who met all the study's entry criteria, the response rate was 96 percent, with 16 patients (59 percent) entering complete remission and 10 patients (37 percent) partial remission. In one patient no response was observed. These results were not significantly changed by the inclusion of nine additional patients who were found retrospectively not to have fulfilled the entry criteria. When complete remission was attained, maintenance therapy was not given. Despite this, no patient has had a relapse, and the duration of complete remission ranges from 1 to 375 days. Pentostatin appears to be equally effective in untreated patients and in those who have progressive disease after splenectomy or after both splenectomy and treatment with interferon. Whether pentostatin is superior to splenectomy or interferon as therapy for hairy-cell leukemia will have to be assessed by direct comparison in randomized studies. Lengthy follow-up will be required to determine a median duration for the responses of hairy-cell leukemia to pentostatin.
AB0857 Medicolegal Implications of the 2012 Canadian Fibromyalgia Guidelines
Authors: M.-A. Fitzcharles, P.A. Ste-Marie, Y. Shir
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Guidelines are intended to facilitate patient care, but may be used in other settings. When judges adjudicate issues pertaining to fibromyalgia (FM), guidance is provided by the health community and published literature. <h3>Objectives</h3> We have examined the recently published 2012 Canadian Fibromyalgia Guidelines with reference to the adjudicating process of a Canadian workman9s compensation tribunal, the Ontario Workers Safety and Insurance Appeals Tribunal (WSIAT). <h3>Methods</h3> Factors weighting the evidence in reaching decisions pertaining to FM by the WSIAT were recorded, and thereafter the 2012 Canadian Fibromyalgia Guidelines were examined for statements that could facilitate reaching legal decisions. <h3>Results</h3> Weighting of evidence or medico legal challenges vs. new guideline statements were as follows: 1) Diagnosis of FM confirmed by tender points vs. a polysymptomatic clinical construct without tender points; 2) diagnosis confirmed by specialist vs. emphasis on family MD report; 3) Poor attention to previous health status vs. emphasis on previous physical and psychological health leading to vulnerable health status; 4) trauma as causation in FM vs. triggering event reported by 1/4 to 1/3 persons; 5) presence of mitigating factors for claimant vs. importance of self-management strategies; 6) disablement in FM vs. recommendation to remain in the work force with rehabilitation if necessary. <h3>Conclusions</h3> Statements and recommendations in the 2012 Canadian Fibromyalgia Guidelines may help the courts in adjudicating issues concerning FM. <h3>References</h3> Fitzcharles, M. A., et al. (2013). 2012 Canadian Guidelines for the diagnosis and management of fibromyalgia syndrome: executive summary. Pain Res Manag 18(3): 119-126. Fitzcharles, M. A., et al. (2013). A Medicolegal Analysis of Worker Appeals for Fibromyalgia as a Compensable Condition Following Workplace Soft-tissue Injury. J Rheumatol. 40(3): 323-328. <h3>Disclosure of Interest</h3> M.-A. Fitzcharles Speakers bureau: Lilly, Pfizer, Purdue, Valeant, P. Ste-Marie: None declared, Y. Shir Consultant for: McKesson Canada Corporation, Palladin Inc. Canada <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5680
In-111 Octreotide Uptake in Substernal Colloid
Authors: RAJINDER P. SINGH, GARY T. SMITH, KARL F. HUBNER
Journal: Clinical Nuclear Medicine (1996)

In-111 octreotide, a somatostatin analog, has been used for detecting gastrinomas, insulinomas, glucagonomas, apudomas, carcinoids, medullary thyroid carcinomas, lung carcinomas, as well as other malignacies. The case presented is that of a 76-year-old woman with a history of recurrent gastrointestinal bleeding. Endoscopy showed a gastric ulcer. A secretin stimulation test showed positive results and serum gastrin levels were markedly elevated. An In-111 octreotide scan demonstrated increased mediastinal uptake. On thoracotomy, the lesion was identified as a substernal goiter.
Case 39-2008
Authors: Jeremy S. Abramson, Manjil Chatterji, Aliyah Rahemtullah
Journal: New England Journal of Medicine (2008)

A 51-year-old woman was admitted to this hospital because of anemia and splenomegaly. Fatigue, night sweats, leg swelling, dyspnea on exertion, and early satiety had begun 2 months earlier. Examination and imaging studies disclosed a massively enlarged spleen, extending below the pelvic brim, with slightly enlarged intraabdominal lymph nodes; an IgM paraprotein was present in the serum, and the partial-thromboplastin time was prolonged. A diagnostic procedure was performed.
OP0162 Prevalence of Comorbidities in Rheumatoid Arthritis. Does Gross Domestic Product Matter? Results from 34 Countries in the QUEST-RA Program
Authors: K. L. Grøn, L. M. Ørnbjerg, M. L. Hetland, T. Sokka-Isler
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Comorbid medical conditions are common in patients with RA. It is unknown how the comorbid burden is distributed in countries with different economic status. <h3>Objectives</h3> To investigate prevalences of 31 comorbidities in patients with rheumatoid arthritis (RA) and their association with the Gross Domestic Product (GDP) of the patient's resident country. <h3>Methods</h3> 9,874 patients from 34 countries (16 with high-GDP (&gt;24.000 US dollars (USD) pr. capita) and 18 with low-GDP countries (&lt;24.000 USD)) participated in the Quantitative Standard monitoring of Patients with RA (QUEST-RA) study. 31 comorbid conditions were assessed by interview of patients and review of patient's file: hypertension, angina, heart attack, coronary artery disease, other heart disease, hyperlipidemia, peripheral vascular disease, peptic ulcer, inflammatory bowel disease, impaired renal function, asthma, chronic bronchitis, diabetes, thyroid disease, cancer, stroke, Parkinson's disease, chronic back pain, musculoskeletal trauma, low energy fractures, osteoporosis, osteoarthritis, infection requiring hospitalization, herpes zoster/shingles, fibromyalgia, psoriasis, cataracts, psychiatric disease, AIDS, alcohol abuse and obesity. <h3>Results</h3> Overall, patients had a median of 2 comorbid condition. 0, 1, 2, 3, 4, 5, and &gt;5 comorbidities were present in 25.8%, 23.1%, 17.9%, 12.6%, 8.0%, 5.2%, 7.4% of patients, respectively. In high-GDP countries patients had a median of 2 comorbidities, while patients in low-GDP had 1 (p&lt;0.001). <h3>Conclusions</h3> In &gt;9.800 RA patients in 34 countries a median of 2 comorbid conditions was found. The most frequent comorbidities were hypertension, osteoporosis at scan, osteoarthritis, hyperlipidemia, obesity and chronic back pain. Comorbidities were more prevalent in high-GDP countries, perhaps due to under-diagnosis in low-GDP countries. <h3>Disclosure of Interest</h3> None Declared
AB1176 Juvenile systemic lupus erythematosus and anca - associated vasculitis
Authors: M. Frkovic, J. Vukovic, Z. Mustapic, K. Bojanic, B. Malenica, M. Jelusic
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Systemic lupus erythematosus (SLE) is a common multisystemic autoimmune disease characterised by antibodies against nuclear components, so-called ANAs. Group of vasculitedes which are characterised by the presence of antineutrophilic cytoplasmatic antibodies (ANCA) usually affect small vessels. These two are most commonly two distinguishable pathologies and even when SLE patients develop vasculitis, they are rarely ANCA positive. On the other hand, those who are ANCA positive, usually do not develop concommitant vasculitis symptoms.Therefore, very few SLE patients have been described having both laboratory and clinical proof of ANCA vasculitis. <h3>Results</h3> We present five patients ranging from 12 up to 17 years of age diagnosed and treated at our Department over the last 14 months (November 2010 to January 2012). All of them were diagnosed with SLE according to ACR criteria but developed ANCA positive vasculitis as well. Three of the patients were diagnosed with autoimmune hepatitis and one with lupus nephritis class V. All of them presented with fever, severe general distress and vasculitic rash. Three of the patients demonstrated hepatosplenomegaly and elevated liver function tests, and in two patients imaging confirmed retroperitoneal lymphadenopathy and laboratory tests revealed polyclonal gammopathy. They were treated with pulse methylprednisolone and pulse cyclophosphamide (6x). At present, all patients except one, are without clinical symptoms with improved immunological findings. <h3>Conclusions</h3> We conclude that, although there is limited evidence, juvenile SLE and ANCA positive vasculitis overlap syndrome is more often than recognized. Since these patients usually present with severe clinical pattern and therefore require fast and intensive treatment, this pathology represents a topic to consider in the future. <h3>Disclosure of Interest</h3> None Declared
Abstract 1959: Identification of inhibitors specific for torc2 as strategy to overcome feedback erk activation in multiple myeloma cells when treated with second generation mtor inhibitors
Authors: Bao Hoang, Angelica Benavides, Andrew Bernath, Cheri Cloninger, Nicholas Artinian, Tariq Bashir, Joe Gera, Alan Lichtenstein
Journal: Cancer Research (2011)

Abstract Recent data indicate that the second generation mTOR inhibitor, pp242, which inhibits TORC2 as well as TORC1, is much more effective against multiple myeloma (MM) cells than rapamycin, a first generation inhibitor which only curtails TORC1 activity. A major reason for this improved efficacy may be that pp242 prevents the feedback activation of AKT that results from rapamycin's inhibition of TORC1. It does this by inhibiting TORC2-induced AKT phosphorylation on S473. However, an additional feedback cascade that results from TORC1 inhibition is activation of MEK/ERK. Indeed, our data show that ERK activation is significant in MM cells exposed to either rapamycin or pp242. Pp242 was comparably potent for activating ERK in rictor-knocked down MM cells, supporting the contention that feedback activation was due to TORC1 inhibition. To examine whether this pp242-induced activation of ERK antagonizes pp242's cytotoxic effects, we co-exposed MM cells with pp242 + the ERK inhibitor U0126, using concentrations of the latter that abrogated ERK phosphorylation in pp242-treated MM cells. There was a marked synergistic effect, indicating ERK feedback activation is a mechanism of resistance to pp242. To address this problem, we performed a drug screen in a yeast-two hybrid system to identify compounds that prevented an interaction between rictor and mTOR. Our reasoning was that such an agent could be a specific TORC2 inhibitor without effects on TORC1 and, thus, without induction of feedback ERK activation. We identified several potential compounds and have begun to characterize their molecular activity. One of the most active agents in the drug screen is capable of inducing cytoreduction of MM cells in MTT assays with ED50s of approx 0.7-0.9 uM and significant MM cell apoptosis when used at 1 uM. This cytotoxic effect was accompanied by a down-regulation of TOR activity which was specific for TORC2 (ie., decreased S473 AKT phosphorylation). Most importantly, there was no activation of ERK in cells treated with this TORC2-specific agent. These data indicate feedback ERK activation may be a resistance mechanism when second generation mTOR inhibitors are used and suggest a strategy for preventing activation. 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 1959. doi:10.1158/1538-7445.AM2011-1959
Rotation of the Liver in Pneumoperitoneum
Authors: Salomone Di Saverio, Fausto Catena
Journal: New England Journal of Medicine (2014)

A previously well 76-year-old woman underwent elective colonoscopy for the investigation of persistent rectal bleeding and abdominal pain. The procedure was prolonged owing to the presence of a redundant sigmoid colon, and considerable manipulation was required in order to advance to the cecum. After the procedure, sudden abdominal distention developed, with signs of peritoneal irritation. A chest radiograph obtained while the patient was in the upright position showed a tension pneumoperitoneum with medial displacement of the liver (Panel A, arrow), raising concern about torsion of vessels in the porta hepatis. A radiograph of the abdomen showed Rigler's sign — air . . .
SAT0540 Gout Patients Treated with Conventional Urate-Lowering Therapy: Association between Disease Control and Work Productivity
Authors: R. Wood, J. Johnson, R. Morlock, S. Baumgartner, S. Ramachandran
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Inadequate control of hyperuricaemia in gout patients can lead to loss of work productivity, activity limitations [1] and higher gout-related treatment costs [2]. Some patients treated with conventional urate-lowering therapy (ULT) are inadequately controlled [3]. <h3>Objectives</h3> To evaluate the impact of inadequate control on work productivity and activity limitations in gout patients. <h3>Methods</h3> A retrospective database analysis of gout patients currently receiving conventional ULT for at least 3 months. Data were drawn from the Adelphi Disease Specific Programme (DSP)™, a cross-sectional survey of patients with gout in France, Germany, UK and US. Participating physicians submitted extensive clinical data for each patient including most recent serum uric acid (sUA) level and number of flares in last 12 mos. Patients were invited to complete a patient self-completion questionnaire, containing the Work Productivity and Activity Impairment (WPAI) questionnaire. Inadequate control was defined as sUA level &gt;6 mg/dL or ≥2 flares. Adequate control was defined as sUA level ≤6 mg/dL and 0 flares. Mann-Whitney tests investigated differences between inadequately and adequately controlled patients in productivity measured by WPAI. <h3>Results</h3> Of 1204 gout patients in this analysis, 836 (69%) were inadequately controlled; 82% of patients were male, mean age was 61 yrs, and mean duration on current ULT was 32 mos. 368 (31%) patients were adequately controlled with a mean age of 63 yrs and mean duration on current ULT of 57 mos. There were no significant differences between patients deemed adequately controlled vs inadequately controlled on number of renal, autoimmune, GI or CV comorbidities. Inadequately controlled patients were significantly more impaired by gout compared to adequately controlled patients (Work time missed: 4.50% vs 1.34%, p=0.0003; Impairment while working: 19.08% vs 5.17%, p&lt;0.0001; Overall work impairment: 20.40% vs 5.57%, p&lt;0.0001; Activity impairment: 20.34% vs 5.28%, p&lt;0.0001). <h3>Conclusions</h3> Only 31% of gout patients currently treated with a ULT were adequately controlled. Inadequately controlled patients reported greater impairment in productivity. Gout treatment strategies to improve control of hyperuricaemia may lead to improvement in productivity. <h3>References</h3> Perry M. Rheumatology (Oxford) 2010;49:2233-4. Saseen JJ. Rheumatology (Oxford) 2012;51:2004-12. Perez-Ruiz F. Adv Ther 2012;29:935-46. <h3>Acknowledgements</h3> Research sponsored by Ardea Biosciences/AstraZeneca. <h3>Disclosure of Interest</h3> R. Wood Employee of: Adelphi Real World, J. Johnson Employee of: Adelphi Real World, R. Morlock Employee of: Ardea Biosciences, Inc, S. Baumgartner Employee of: Ardea Biosciences, Inc, S. Ramachandran Employee of: AstraZeneca <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4482
Doxycycline-induced pill esophagitis
Authors: Doron Boltin, Yaron Niv
Journal: Endoscopy (2014)

A 23-year-old white woman with a past history of chronic urticaria presented to our department following 2 weeks of progressive dysphagia for solids and liquids. She also complained of chest pain, odynophagia, and a 3-kg weight loss. She denied having prior episodes of food impaction, heartburn, or acid regurgitation.
Abstract 2843: Caspase-8 gene SNPs in prostate cancer susceptibility: a replication study
Authors: Marina Parry, Graeme Elliott, Ryan Abo, Nicola J. Camp, David E. Neal, Jenny L. Donovan, Freddie C. Hamdy, Angela Cox
Journal: Cancer Research (2010)

Abstract Introduction A single nucleotide polymorphism (SNP) in the caspase-8 gene, (CASP8 D302H), has been reported to be involved in susceptibility to breast and pancreatic cancer, melanoma and glioma, but not colorectal or ovarian cancer. We previously have used a tagging-SNP approach to test the hypothesis that this SNP, or other variants in CASP8, were associated with prostate cancer, in 1009 cases, 987 men with normal serum prostate specific antigen (PSA) levels and 961 men with low serum PSA (&amp;lt;0.5ng/ml). These subjects were drawn from those participating in the UK ProtecT (Prostate Testing for Cancer and Treatment) trial. Of the 15 tagging SNPs in caspase-8 that were genotyped, 7 showed some evidence of association with prostate cancer (P&amp;lt;0.05). The aim of the present study was to attempt to replicate these results in an independent set of case and control subjects. Methods A further independent sample of men from the ProtecT trial formed the replication cohort for this study. Blood DNA samples were available for 1262 men with prostate cancer, 1258 men with normal serum PSA, and 609 men with low serum PSA. SNP genotyping was carried out by 5-prime nuclease PCR (TaqmanTM, Applied Biosystems). The association with prostate cancer was tested using logistic regression, controlling for sample set. Results Two SNPs with duplicate concordance rates of less than 98% were not included in the analysis. Genotype call rates for the remaining 5 SNPs were all greater than 95%, and genotype frequencies in control subjects were consistent with those expected under Hardy-Weinberg equilibrium. None of the 5 SNPs yielded significant evidence of association in the replication cohort, although some odds ratios were consistent between the two data sets. We combined the data from the test and replication cohorts to evaluate the overall evidence for association. The rare alleles of rs3769826 and rs6723097 conferred a reduced risk of prostate cancer with per-allele odds ratios (95% confidence interval) [OR(95%CI)] of 0.90 (0.82-0.98) and 0.88 (0.80-0.96), and P=0.013 and P=0.004 respectively. In addition, the deletion allele of the promoter indel rs3834129 conferred an increased risk of prostate cancer, with OR (95%CI) of 1.15 (1.05-1.27), P=0.003. While these results await further replication, it is interesting to note that the rare alleles of rs3769826 and rs6723097 are carried on European haplotypes that are associated with increased risk of breast cancer, suggesting the possibility of a different mode of action of caspase-8 in the two tumour types. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2843.