tbuckley/cabot-search huggingface dataset:
PTPS-29UBIQUITIN CARBOXYL TERMINAL HYDROLASE-L1 (UCH-L1) IS A TUMOR SUPPRESSOR IN ATYPICAL TERATOID RHABDOID TUMORS (ATRTs)
Authors: Lin Li, James Xu, Jim Davie, Sachin Katyal, Marc Symons, Magimairajan Issai Vanan
Journal: Neuro-Oncology (2015)

BACKGROUND: Atypical teratoid rhabdoid tumor (ATRTs) constitute 20% of brain tumors in young children (<3 yrs of age) and is characterized by bi-allelic mutations of the INI-1 gene. The cell of origin in this tumor is not known and the mechanism by which INI-1 causes tumor is still not clear. Ubiquitin carboxyl-terminal hydrolase isoenzyme 1 (UCHL1), is an abundant neuronal de-ubiquitinating enzyme which acts as a tumor suppressor gene that is inactivated by promoter methylation / gene deletion in several cancers as well as an oncogene with overexpression in other cancers. The role of UCHL1 in brain tumors has not yet been studied. METHODS/RESULTS: We identified UCHL1 is silenced in ATRT cell lines (BT-12, BT-16) along with absent basal expression of p53 and NOXA by western blotting. UCHL1 silencing is mediated by promoter hyper-methylation (detected by using methylation specific PCR (MSP)); and pharmacologic de-methylation reactivated UCHL1 expression in these cell lines along with expression of p53 and NOXA. Ectopic expression of UCHL1 dramatically inhibited the growth of ATRT cell lines (using colony forming assay and MTT assay) and increased sensitivity to radiation. The growth inhibition was mediated by promoting tumor cell apoptosis resulting from activating the p53 tumor suppressor pathway. CONCLUSIONS: We have shown that UCHL1 is silenced in ATRT cell lines and acts as a tumor suppressor gene. We hypothesize that loss of p53 function due to silencing of UCHL1 drives tumor formation in the background of bi-allelic INI1 mutation in ATRT. We will further test this hypothesis using patient derived primary cell cultures and animal models (using genetically engineered mouse models INI1 +/- / UCHL1-/- mice).
OC-023 Salvage endoscopic resection of scarred polyps after failed previous endoscopic resection attempt: sense study
Authors: FJQ Chedgy, R Bhattacharyya, K Kandiah, G Longcroft-Wheaton, P Bhandari
Journal: Gut (2015)

<h3>Introduction</h3> Current standard of care for recurrent/residual polyps after previous endoscopic resection is surgery. This study analyses the outcomes of salvage endoscopic resection of polyps with severe scarring following a previously failed endoscopic resection. <h3>Method</h3> Prospective cohort study of patients referred to a Tertiary-centre for resection of scarred polyps with failed previous endoscopic resection attempts. Resection techniques: ESD knife and Snare combination (Knife Assisted Resection, KAR) or Snare and APC assisted resection (SAR). <h3>Results</h3> We identified 64 consecutive patients referred to us following a previously failed endoscopic resection attempt. All these patients had severely scarred polyps which were being considered for surgery at the referring centre. The mean polyp size 46 mm (20–150 mm). 83% were left-sided and 17% right–sided. 67% of resections were performed by KAR with mean polyp size 50 mm. 33% of resections were by SAR with mean polyp size 38 mm. <b>Referral to surgery</b>: 2/64 for technically difficult so no attempt made, 5/64 for cancer. <b>Endoscopic follow up and cure</b>: mean follow up of 3 years (range:1–8 years), 97% overall cure rate which was the same for left and right sided lesions as well as KAR and SAR. The only complication was bleeding seen in 3 patients (4.6%). <b>Cost saving: </b>Had all 64 patients been sent for surgery the total cost would have been £343,224. The total cost of the endoscopic approach, including the cost of patients requiring surgery, was £149,820 representing an average cost saving of £3021.94 per patient. <h3>Conclusion</h3> Severely scarred polyps due to failed previous endoscopic mucosal resection attempts can be successfully treated by experts. The techniques of KAR and SAR are equally effective when used for appropriate polyps. The complication rate is low. Further recurrence after first salvage resection can be treated successfully. Surgery can be avoided in most patients and an endoscopic approach is very cost effective. We would therefore, advocate an aggressive endoscopic resection strategy over surgery when dealing with severely scarred polyps. <h3>Disclosure of interest</h3> None Declared.
Clinical features of the borderline personality disorder
Authors: J C Perry, G L Klerman
Journal: American Journal of Psychiatry (1980)

The authors compared 18 patients diagnosed as having borderline personality disorder with 102 patients with orther diagnoses in a psychiatric emergency service. They found that 81 of 129 items obtained from the literature on borderline personality disorder were significantly more characteristic of the patients diagnosed as borderline than patients with other diagnoses. When these items were included in a Borderline Personality Scale they significantly distinguished patients diagnosed as borderline from those with other diagnoses. The patients diagnosed as borderline were not psychotic but were angry, demanding, and difficult to interview; specific histories, interpersonal relationships, defenses, and other judgments of personality functioning were also prominent characteristics of these patients. On the basis of these findings and other studies, the authors maintain that the patients diagnosed as borderline actually had a borderline personality disorder.
FRI0221 High Disease Activity in Axial Spondyloarthritis is Associated with Reduced Work Productivity
Authors: L. Van Hoeven, A. Boonen, J. Hazes, A. Weel
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Previous studies have shown that up to 24% of primary care patients are misdiagnosed as chronic low back pain (CLBP) while actually having axial spondyloarthritis (axSpA). It is well known that axSpA affects employment, sick leave and presenteeism. However little is known about the association between disease activity and work participation in newly diagnosed axSpA patients. <h3>Objectives</h3> To examine the association between work productivity and disease activity in newly diagnosed axSpA patients. <h3>Methods</h3> Our study population included patients (18-45 years) newly diagnosed with axSpA by the ASAS criteria from a Dutch cross-sectional study in primary care patients with CLBP. Disease activity was measured by BASDAI and ASDAS. Work participation assessed in the past 7 days using the Work Productivity and Activity Impairment (WPAI) questionnaire. Four sub scores (all percentages) can be derived; absenteeism (% work time lost), presenteeism (% productivity loss at work, score 0-10), work impairment (combines absenteeism and presenteeism) and activity impairment (% activity loss, score 0-10). Higher percentages indicates worse outcomes. Univariable logistic regressions were used to test for associations between covariates and 'any restriction' in each sub score of the WPAI. <h3>Results</h3> 95 newly diagnosed axSpA patients participated (38% male, mean age 37 years), after screening for axSpA in primary care CLBP patients. (Table 1) Already 25 (26%) patients (all in working age) were not employed. In the employed patients 11% (n=7) reported absenteeism, 49% (n=34) reported presenteeism, 53% (n=37) reported work impairment. In all axSpA patients, 67% (n=62) reported activity impairment. The univariate logistic regression, distinguish no from "any" absenteeism, presenteeism, work and activity impairment shows that a higher ASDAS score is associated with increased presenteeism, work and activity impairment. (Figure 1) A higher BASDAI score is associated with increased work and activity impairment. <h3>Conclusions</h3> Higher disease activity is associated with absenteeism and reduced work productivity in newly diagnosed axSpA patients. ASDAS seems to perform somewhat better than BASDAI. <h3>Acknowledgements</h3> An unrestricted research grant was provided by AbbVie. <h3>Disclosure of Interest</h3> None declared
Non-coding RNAs in muscle differentiation and musculoskeletal disease
Authors: Monica Ballarino, Mariangela Morlando, Alessandro Fatica, Irene Bozzoni
Journal: Journal of Clinical Investigation (2016)

RNA is likely to be the most rediscovered macromolecule in biology. Periodically, new non-canonical functions have been ascribed to RNA, such as the ability to act as a catalytic molecule or to work independently from its coding capacity. Recent annotations show that more than half of the transcriptome encodes for RNA molecules lacking coding activity. Here we illustrate how these transcripts affect skeletal muscle differentiation and related disorders. We discuss the most recent scientific discoveries that have led to the identification of the molecular circuitries that are controlled by RNA during the differentiation process and that, when deregulated, lead to pathogenic events. These findings will provide insights that can aid in the development of new therapeutic interventions for muscle diseases.
Neurophysiological correlates of sibling pairs discordant for bipolar affective disorder
Authors: V Knott, B Waters, Y Lapierre, R Gray
Journal: American Journal of Psychiatry (1985)

Eleven sibling pairs discordant for bipolar disorder were compared on the basis of computerized EEGs and auditory evoked potentials. The findings suggest that CNS overarousal may be characteristic of trait bipolar disorder.
AB0747 Golimumab in Refractory Uveitis Related to Spondyloarthritis. Multicenter Study of 9 Patients
Authors: M. Santos Gόmez, V. Calvo-Río, R. Blanco, E. Rubio-Romero, M. Cordero-Coma, A. Gallego, A. Atanes, F. Francisco, L. Riancho-Zarrabeitia, J. Loricera, M. Ά. González-Gay
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Objectives</h3> To assess the efficacy of golimumab (GLM) in refractory uveitis associated to spondyloarthritis (SpA) <h3>Methods</h3> Multicenter study of uveitis related to SpA that had been refractory to at least one immunosuppressive drug. The main outcome measures were degree of anterior and posterior chamber inflammation, visual acuity, and macular thickness in cases of macular edema. <h3>Results</h3> Nine patients (9 men) (11 affected eyes) with a mean age ± SD of 42.1±5.25 years (range 32-48) were evaluated. The pattern of ocular involvement was anterior uveitis (n=5) and anterior+intermediate (n=4). According to the course, uveitis was acute (n=1), chronic (n=4) or recurrent (n=4). Besides oral steroids and before GLM onset they had received: intraocular corticosteroids (n=2), immunosupressive conventional drugs: MTX (n=7), AZA (3), SZP (4) and LFN (n=1) and biologic therapy: IFX ev 5mg/kg/6-8 week (n=3), ETN sc 50 mg/week (n=3), and ADA 40mg/2 week (n=2). GLM was started because of lack of efficacy of the previous treatments, at the standard dose of 50 mg/sc/month as a monotherapy (n=5) or combined (n=4) with MTX (n=2), AZA (n=1) and LFN (n=1). Significant improvement of anterior chamber cells was observed (baseline: median 1 [IQR 0-3]), and (0 [0-1]) (p=0.01) and (0 [0-0]) (p=0.01) at 2 weeks and 6 months, respectively. The mean visual acuity also improved from a mean of 0.75±0.24 at baseline to 0.77±0.26 (p=0.1) and 0.85±0.27 (p=0.1) at 3 and 6 months, respectively, and the macular thickness (OCT) from a mean of 280±30 to 263±16 microns at 6 months. Corticosteroids were also tapered from a mean dose of prednisone at baseline of 31±20 mg/day to 27±18 and 14±11 mg/day at 2 weeks and 6 months respectively. After a mean follow-up of 13±7 months, 7 of 9 patients were on remission and the side-effects observed were not severe (injection site erythema in 1 case). <h3>Conclusions</h3> Golimumab seems to be effective and safe in refractory uveitis related to SpA. <h3>Disclosure of Interest</h3> None declared
Carcinoma of the Bile Ducts: A Case Report
Authors: A K Mighton
Journal: JAMA (1963)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
THU0408 How we are Treating Our Systemic Patients with Primary Sjögren Syndrome? Analysis of 1120 Patients (GEAS-SS Spanish Registry)
Authors: H. Gheitasi, B. Kostov, R. Solans, G. Fraile, C. Suárez-Cuervo, A. Casanovas, F.-J. Rascόn, R. Qanneta, R. Pérez-Alvarez, M. Ripoll, M. Akasbi, B. Pinilla, X. Bosch, J. Nava-Mateos, B. Díaz-Lόpez, L. Morera-Morales, S. Retamozo, M. Ramos-Casals, P. Brito Zeron
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Objectives</h3> To describe how systemic disease is treated in a large cohort of Spanish patients with primary Sjögren syndrome in daily practice, focusing on the adequacy of drug therapies for the level of systemic activity measured by the ESSDAI score. <h3>Methods</h3> By December 2014, our database included 1120 consecutive patients who fulfilled the 2002 classification criteria for primary SS. Therapeutic schedules were classified into 4 categories: no systemic therapies, hydroxychloroquine and/or low dose of glucocorticoids (≤20 mg/d), high dose of glucocorticoids (&gt;20 mg/d) and use of second-line therapies (immunosuppressive agents, intravenous immunoglobulins and/or rituximab). <h3>Results</h3> The cohort consisted of 1120 patients, including 1048 (94%) females and 72 (6%) males, with a mean age at diagnosis of 54 years. The main drug-based therapeutic approaches for systemic Sjögren ever used during the follow-up were hydroxychloroquine (HCQ) in 282 (25%) patients, glucocorticoids in 475 (42%, used at doses &gt;20 mg/d in 255 -23%&gt;), immunosuppressive agents in 148 (13%), intravenous immunoglobulins (IVIG) in 25 (2%) and rituximab in 35 (3%) patients. The use of systemic therapies was more frequent in males (p=0.036) and was associated with the presence at diagnosis of anemia (p&lt;0.001), thrombocytopenia (p=0.001), neutropenia (p=0.002), rheumatoid factor (p&lt;0.001), anti-Ro/SS-A (p=0.033), monoclonal band (p=0.002), cryoglobulins (p=0.003), low C3 (p=0.003) and low C4 (p=0.014). The ESSDAI score at diagnosis was higher in patients who received systemic therapy than in those who did not (8.12 vs. 4.20, p&lt;0.001). Multivariate analysis identified neutropenia, rheumatoid factor and the ESSDAI score as independent variables. Hydroxychloroquine was associated with a lower risk of death (adjusted HR of 0.57, 95% 0.34-0.95). We classified 16 (7%) of the 255 patients treated with &gt;20 mg of corticoids and 21/148 (14%) of those treated with immunosuppressive agents patients as inadequately treated, mainly associated with articular involvement of low/moderate activity. <h3>Conclusions</h3> The management of systemic Sjögren should be organ-specific, using low doses of corticoids in patients with moderate systemic activity, limiting the use of high doses of corticoids and second-line therapies to refractory or potentially-severe scenarios. The use of systemic therapies for dryness, chronic pain or fatigue is not warranted. <h3>Disclosure of Interest</h3> None declared
Serum Vitamin A (Retinol) and Cancer Incidence in Evans County, Georgia
Authors: J D Kark, A H Smith, B R Switzer, C G Hames
Journal: JNCI Journal of the National Cancer Institute (1981)

A total community sample of 3,102 individuals from Evans County, Georgia, was followed for 12-14 years. During this period, 129 documented new cases of cancer were ascertained from medical records and death certificates. Cases were considered for inclusion only if documented at least 12 months after subjects were inducted into the cohort study. Cases were classified as definite, probable, and possible by strict criteria. Blood samples were drawn at the beginning of the study in 1960-62 and sera were frozen. Serum vitamin A (retinol) levels were measured in 1976 on the stored sera of 85 cancer patients and for 174 age-, race-, and sex-matched controls. Retinol estimations were performed by a fluorometric method after alumina column separation. Experiments conducted to simulate the exposure to light, thawing, and refreezing that sera may have undergone during the 14-16 years of storage showed retinol to be quite stable in response to these possible insults. As compared to controls, persons that eventually developed cancer had significantly lower mean serum retinol levels at least 12 months before the cancer diagnosis. The association was in the same direction for all 4 race-sex groups, although stronger overall for males than females, and was consistent for the various cancer sites and cell types. Both matched and regression residual analyses were used to control for the confounding variables considered: age, race, sex, obesity, social class, and smoking.
RAC1 activation drives pathologic interactions between the epidermis and immune cells
Authors: Mårten C.G. Winge, Bungo Ohyama, Clara N. Dey, Lisa M. Boxer, Wei Li, Nazanin Ehsani-Chimeh, Allison K. Truong, Diane Wu, April W. Armstrong, Teruhiko Makino, Matthew Davidson, Daniela Starcevic, Andreas Kislat, Ngon T. Nguyen, Takashi Hashimoto, Bernard Homey, Paul A. Khavari, Maria Bradley, Elizabeth A. Waterman, M. Peter Marinkovich
Journal: Journal of Clinical Investigation (2016)

Interactions between the epidermis and the immune system govern epidermal tissue homeostasis. These epidermis-immune interactions are altered in the inflammatory disease psoriasis; however, the pathways that underlie this aberrant immune response are not well understood. Here, we determined that Ras-related C3 botulinum toxin substrate 1 (RAC1) is a key mediator of epidermal dysfunction. RAC1 activation was consistently elevated in psoriatic epidermis and primary psoriatic human keratinocytes (PHKCs) exposed to psoriasis-related stimuli, but not in skin from patients with basal or squamous cell carcinoma. Expression of a constitutively active form of RAC1 (RACV12) in mice resulted in the development of lesions similar to those of human psoriasis that required the presence of an intact immune system. RAC1V12-expressing mice and human psoriatic skin showed similar RAC1-dependent signaling as well as transcriptional overlap of differentially expressed epidermal and immune pathways. Coculture of PHKCs with immunocytes resulted in the upregulation of RAC1-dependent proinflammatory cytokines, an effect that was reproduced by overexpressing RAC1 in normal human keratinocytes. In keratinocytes, modulating RAC1 activity altered differentiation, proliferation, and inflammatory pathways, including STAT3, NFκB, and zinc finger protein 750 (ZNF750). Finally, RAC1 inhibition in xenografts composed of human PHKCs and immunocytes abolished psoriasiform hyperplasia and inflammation in vivo. These studies implicate RAC1 as a potential therapeutic target for psoriasis and as a key orchestrator of pathologic epidermis-immune interactions.
Effect of lecithin on memory in normal adults
Authors: C M Harris, M W Dysken, P Fovall, J M Davis
Journal: American Journal of Psychiatry (1983)

In a double-blind, placebo-controlled, crossover study of the effect of lecithin on memory test performance, nine normal paid volunteers (age range = 22-55 years) took single oral doses of placebo and lecithin (20 g) 5 hours before cognitive testing. Lecithin raised plasma choline levels during the test session to nearly double the placebo levels, but a categorized serial learning task, a word recognition task, a paired associates learning task, and a test of retrieval by category demonstrated no significant change in memory performance. Lecithin did not selectively enhance memory for low-imagery words. Lecithin also had no effect on psychomotor speed.
THU0424 Osteoporosis: What is the Burden of Disease in Psoriatic Arthritis?: Table 1
Authors: G. Haugeberg, B.H. Grandaunet, H.K. Høiberg, A.P. Diamantopoulos, A. Kavanaugh
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Bone damage, including localized as well as generalized osteoporosis is a well known consequence of the inflammatory arthritides such as rheumatoid arthritis (RA). Psoriatic arthritis (PsA) can be characterized by bone destruction but also new bone formation. In PsA, the literature on osteoporosis is inconclusive and scarcer than in RA. <h3>Objectives</h3> To explore if PsA patients are at increased risk of having reduced bone mineral density (BMD) at hip and/or lumbar spine. <h3>Methods</h3> Consecutive patients from an outpatient clinic fulfilling CASPAR criteria for PsA were enrolled. We excluded PsA patients with only axial manifestation without peripheral arthritis. All patients underwent a thorough examination according to an extensive protocol. Data collection included demographics, clinical and laboratory disease measures, treatments, and previous fracture history. BMD was measured at spine (L1-4) and hip (femoral neck and total hip) by dual energy X-ray absorptiometry (DXA, Lunar Prodogy). Calibration of the DXA machine was stable during the whole measurement period. BMD was expressed as g/cm<sup>2</sup>, Z-score and T-score. The percentage of patients with T-score ≤ -2.5 SD (WHO osteoporosis definition) and with Z-score ≤ -1.0 SD was calculated. Appropriate descriptive statistics was applied for continuous and categorical variables. <h3>Results</h3> Patient characteristics among the 141 examined PsA patients (men 50.4%): mean (SD) age 52.5 (9.9) years, body mass index (BMI) 28.3 (4.4) kg/m<sup>2</sup>, disease duration 8.9 years (6.8) and current smoker 17.0%. Median (range) 68 tender joint count was 6.0 [0-55], 66 swollen joint count 0 [0-6] and CRP 2.0 [0-63] mg/dl. Mean (SD) DAS28 was 3.2 (1.2), ESR 15.9 (11.9) mm/hr, MHAQ 0.44 (0.40) and pain and fatigue on visual analogue scale 35.1 (23.5) and 45.7 (32.4) mm respectively. Biologic DMARDs were used by 33.3%, synthetic DMARDs by 56.7% and glucocorticosteroids by 9.9%. Only 11.3% of patients were using calcium and vitamin D supplementation and 2.1% antiresorptive osteoporosis treatment. Low energy fracture was reported in 8.9% of the patients. In the table below mean (SD or 95%CI) bone density values expressed as BMD, Z-score and T-score and percentage of patients with T-score ≤ -2.5 SD and Z-score ≤ -1.0 SD (by definition 16% in the reference population) is displayed. As shown the proportion of patients with Z-score ≤ -1.0 SD was comparable with the 16% seen in the reference population database. <h3>Conclusions</h3> The proportion of PsA patients with osteoporosis in our study was low. Overall BMD was comparable to that from normative bone density reference values. <h3>Disclosure of Interest</h3> G. Haugeberg Grant/research support from: Unrestricted Grant from Pfizer, B. Grandaunet: None declared, H. Høiberg: None declared, A. Diamantopoulos: None declared, A. Kavanaugh: None declared
Evaluation of the Argyrophilic Nucleolar Organizer Region, Nuclear DNA Content and Mean Nuclear Area in Transitional Cell Carcinoma of Bladder Using a Quantitative Image Analyzer
Authors: Hiroaki Shiina, Shinji Urakami, Hiroki Shirakawa, Kazushi Shigeno, Yasutoshi Himeno, Masami Mizutani, Mikio Igawa, Tomoyuki Ishibe
Journal: European Urology (1996)