tbuckley/cabot-search huggingface dataset:
SAT0209 Characterization of pure membranous lupus nephritis: A cohort of 134 patients
Authors: L. Silva, T. Otόn, A. Askanase, P. Carreira, E. Rodríguez-Almaraz, J. Lόpez-Longo, I. Rúa-Figueroa, J. Narváez, E. Ruiz, E. Calvo, F. Toyos, J.J. Alegre, E. Tomero, C. Montilla, A. Zea, E. Uriarte, C. Marras, V. Martínez-Taboada, Ά. Belmonte, J. Rosas, E. Raya, G. Bonilla, M. Freire, J. Calvo
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Few studies and small series have addressed the characteristics of pure membranous lupus nephritis (MLN). <h3>Objectives</h3> To establish the clinical characteristics, treatment and prognosis of MLN and to make international and intersocial comparisons. <h3>Methods</h3> Twenty-one Spanish centres and 1 in the US participated in the study. All SLE patients with biopsy proven MLN were included. Data on clinical and laboratory features, prescribed drugs, renal outcomes and survival were collected. Descriptive statistics were used to describe the main features of the series. Chi-squared distribution and Fisher test were use to analyse categorical variables and the U Mann-Whitney test for quantitative variable. A p value &lt;0.05 was considered significant. <h3>Results</h3> 134 patients were included (see table). Female sex (.036), a low basal serum creatinine (BSC) (0.92 Vs 1.53 mg/dl; &lt;0.001) and previous treatment with azathioprine (AZA) (.046) were predictors of a final proteinuria &lt;1 g. US patients (0.042), patients without a Health coverage (0.033), with previous venous thrombosis (0.037) and those who had not received chloroquine (0.011) or AZA (0.028) for MLN had less chances of achieving a final proteinuria &lt;0.5 g. Patients with final doubled creatinine had a greater initial 24 h-proteinuria (7.73 Vs 4.37 g; 0.04) and a lower creatinine clearance (CCr) (64 Vs 109 ml/min; .032). Moreover, male sex (&lt;0.001), basal high blood pressure (0.028), chronic cardiopathy (0.003), peripheral (0.005) or cerebral artheriopathy (.02), and not having received anticoagulant treatment were risk factors for doubling BSC. End-stage renal disease was predicted by male sex (0.009), HBP (0.019), dyslipidemia (0.002), high basal 24 h-proteinuria (8.80 Vs 4.36 g; 0.03), high BSC (2.76 Vs 0.91 mg/dl; &lt;0.001) and a low CCr (31 Vs 108 ml/min; 0.001). <h3>Conclusions</h3> MLN usually begins with nephrotic syndrome, high proteinuria and normal BSC. Its prognosis is favourable in maintaining renal function although proteinuria usually persists over time. Cardiovascular disease and some socio-sanitary factors are related with bad prognosis. <h3>Disclosure of Interest</h3> None Declared
The Diagnostic Value of Tc-99m Human Polyclonal Immunoglobulin Imaging Compared to Tc-99m HMPAO Labeled Leukocytes in Inflammatory Bowel Disease
Authors: MONTSERRAT DELGADO CASTRO, CARMEN LANCHA, ENRIQUE PRATS, MERCEDES MITJAVILLA, DOLORES ABÓS, L. MIGUEL MARTÍN-CURTO, ANGEL CRESPO, JAVIER BANZO
Journal: Clinical Nuclear Medicine (1997)

The aim of this study was to establish the usefulness of Tc-99m human polyclonal immunoglobulin (HIG) imaging in a group of patients who were suspected of having inflammatory bowel disease (IBD). The authors performed 30 scans (15 with Tc-99m HMPAO leukocytes and 15 with Tc-99m HIG) on 15 patients with IBD. Ten patients had Crohn's disease and five had ulcerative colitis. The sensitivity of Tc-99m HIG scintigraphy for detecting IBD was 33%, while the sensitivity of Tc-99m HMPAO leukocyte imaging was 100%. The Tc-99m HMPAO leukocyte imaging also detected a larger number of affected segments and provided better image quality of the extent of disease than Tc-99m HIG. On the basis of these results, the authors believe that Tc-99m HIG imaging is not a useful technique in the evaluation of patients with IBD, in the identification of location, or the extension or degree of disease activity.
Clinical Use of Genetic Markers Expanding
Authors: H. McIntosh
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article Clinical Use of Genetic Markers Expanding Get access Hugh McIntosh Hugh McIntosh Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 7, April 1992, Pages 476–478, https://doi.org/10.1093/jnci/84.7.476 Published: 01 April 1992
Abstract 4379: Framing therapeutic opportunities in tumor-activated gametogenic programs.
Authors: Kathleen Corcoran, Patrick Taus, Rebecca Sinnott, Kimberly Maxfield, Joshua Wooten, Angelique Whitehurst
Journal: Cancer Research (2013)

Tumors frequently activate genes whose expression is otherwise restricted to testes, and which can invoke a humoral immune response in cancer patients. Given their germline-biased expression pattern, these Cancer-Testes antigens (CT-antigens, CTAs) may afford the potential for an extraordinary therapeutic window, if they are required for tumorigenic behaviors. While the function of CTAs in normal and neoplastic settings remains obscure, mounting evidence suggests that specific CTAs can contribute to tumor cell autonomous behaviors. To generate a more comprehensive understanding of the functional roles of CTAs, we have employed an unbiased, multi-dimensional, loss of function discovery platform to systematically assess the contribution of CT-antigens to a range of tumorigenic signaling pathways and phenotypes. By employing a diverse panel of 11 tumor-derived cell lines to screen 120 CTAs, we find that these tumor-activated genes are required to support a number of the hallmarks of cancer. For example, we reveal multiple MAGE family members that mitigate response to mitotic stress and hypoxia. Additionally, we find that the SPANX family of CTAs contributes to β-catenin signaling. Finally, we reveal a role for GAGE proteins in supporting the viability of a range of tumor types. The diversity of neoplastic settings analyzed in our primary screen allowed for the identification of CTAs that support tumor cell fitness in multiple disease backgrounds. For example, we have uncovered CTAs that contribute to mitochondrial integrity in lung, breast, melanoma and sarcoma. Alternatively, we find that CTAs can display lineage selective dependencies, such as supporting TGFβ signaling in claudin-low breast tumors. Taken together, these observations support the hypothesis that CTAs are frequently integrated into the tumor cell regulatory environment to support cell division, survival and modulate stress responses by regulating key signaling pathways. Thus, CT-antigens present previously unrecognized tumor-specific vulnerabilities that may be exploited for therapeutic intervention.Citation Format: Kathleen Corcoran, Patrick Taus, Rebecca Sinnott, Kimberly Maxfield, Joshua Wooten, Angelique Whitehurst. Framing therapeutic opportunities in tumor-activated gametogenic programs. [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 4379. doi:10.1158/1538-7445.AM2013-4379
Increase of pertussis incidence in 2010 to 2012 after 12 years of low circulation in Spain
Authors: V Sizaire, M Garrido-Estepa, J Masa-Calles, M V Martinez de Aragon
Journal: Eurosurveillance (2014)

In Spain, whole cell pertussis vaccination started in 1975, with three doses before the age of 6-7 months. Doses at 15-18 months and 4-6 years were introduced in 1996 and 2001, respectively. Spain switched to an acellular vaccine in 2005. From 1998 to 2009, pertussis incidence rates remained ≤1.5 cases/100,000 inhabitants but increased from 2010 to 7.5 cases/100,000 in 2012. Data from 1998 to 2012 were analysed to assess disease trends and susceptible populations. We defined four epidemic periods: 1998-2001 (reference), 2002-05, 2006-09 and 2010-12. In 2002-05, the incidence rate increased in individuals aged 15-49 years (IRR: 1.41 (95% CI: 1.11-1.78)) and ≥50 years (IRR: 2.78 (95% CI: 1.78-4.33)) and in 2006-09 increased also in infants aged <3 months (IRR: 1.83 (95% CI: 1.60-2.09)). In 2010-12, the incidence rate increased notably in all age groups, with IRRs ranging between 2.5 (95% CI: 2.3-2.8) in 5-9 year-olds and 36.0 (95% CI: 19.4-66.8) in 20-29 year-olds. These results, consistent with the country's vaccination history, suggest a progressive accumulation of susceptible individuals due to waning immunity after years of low incidence. Further vaccination strategies should be assessed and implemented to prevent pertussis in pre-vaccinated infants, in whom the disease is more severe.
Complete recovery of hemopoiesis following bone marrow transplant in a patient with unresponsive congenital hypoplastic anemia (Blackfan- Diamond syndrome)
Authors: A Iriondo, J Garijo, J Baro, E Conde, JM Pastor, A Sabanes, V Hermosa, MC Sainz, L Perez de la Lastra, A Zubizarreta
Journal: Blood (1984)
S82 An Economic Evaluation Of Self-management Programs Delivered At Discharge After Acute Exacerbation, In Copd Patients In The Uk
Authors: D. Blissett, S. Jowett, R. Jordan, K. Jolly, A. Turner, P. Barton
Journal: Thorax (2014)

<h3></h3> This abstract summarises independent research funded by the National Institute for Health Research (NIHR) under its HTA Programme (Ref 11/27/01). The views expressed are those of the author (s) and not necessarily those of the NHS, the NIHR or the Department of Health. <h3>Background</h3> Self-management interventions delivered to COPD patients at discharge following admission for exacerbation aim to enable patients to better manage and control their symptoms but it is not clear if they are beneficial. Our systematic review concluded that there was no evidence of a reduction in the risk of admissions or mortality but noted a dearth of good quality studies and a direction of effect for readmissions in favour of self-management. <h3>Methods</h3> A hypothetical Markov model was built to estimate the cost-effectiveness of self-management interventions in COPD patients recently discharged from hospitals, compared to usual care. It estimated the effect in terms of Quality Adjusted Life Years (QALYs) in a cohort of UK COPD patients, applying a reduced risk of admissions obtained from the hazard ratio of 0.82 (0.50, 1.36) reported in a meta-analysis in a systematic review. Due to uncertainty around this effect, extensive sensitivity analysis was conducted to estimate the likelihood being cost-effective at alternative thresholds. <h3>Results</h3> This model found that self-management delivered at discharge was more costly, but resulted in better outcomes, with a £683 cost difference and a gain of 0.0831 QALYs. To be cost-effective it would need to cost £2200 or less if the hazard ratio remained at 0.82. Sensitivity analysis found that self-management had a 68% probability of being cost-effective at a threshold of £20,000 per QALY, with most of this uncertainty being around the effect, duration of effect and cost. <h3>Conclusion</h3> If self-management interventions are effective in reducing readmissions for up to two years, they are likely to be cost-effective. This speculative economic model describes the uncertainty around this conclusion.
TRATAMIENTO ENDOSCOPICO DE RESCATE (TER) EN COLECCIONES ORGANIZADAS PANCREATICAS Y RECTALES NO DRENABLES POR TECNICA HABITUAL GUIADA POR ULTRASONOGRAFIA ENDOSCOPICA (USE): EXPERIENCIA PRELIMINAR
Authors: E Vázquez Sequeiros, JA González Martín, F González-Panizo, JR Foruny Olcina, V Defarges Pons, D Boixeda De Miquel, D Juzgado, A Albillos
Journal: Endoscopy (2013)

Introducción: El drenaje USE de lesiones/colecciones semisólidas (CSS) es complejo y suele asociarse con fallos técnicos por la naturaleza semisólida de la CSS que impide el acceso al interior de la colección. La utilidad de irrigar/repleccionar la CSS con contenido líquido para facilitar el acceso y drenaje es un TER no descrito en la literatura. Objetivo: Evaluar el éxito técnico/clínico y perfil de seguridad del TER guiado por USE de CSS. Material y Método: Análisis retrospectivo de base de datos prospectiva. Periodo de inclusión: 01/07 – 07/13. Criterios de Inclusión: 1.) Paciente con CSS pancreática/perirrectal infectada (Definición: „contenido líquido < 10% de la lesión“); Criterios de Exclusión: 1.) Colección drenable por técnica convencional. Examen TER: Se realizaba PAAF bajo control USE de la zona menos densa de la CSS (aguja-19G), se instilaba a través de la aguja 50 – 100 cc de suero salino y se comprobaba como se repleccionaba la colección. Posteriormente, se seguían los pasos habituales de drenaje (1 ° guía 0.035“ a través de aguja; 2 ° esfinterotomo de aguja sobre guía; 3 ° balón de dilatación 12 – 15 mm; 4 ° prótesis metálica recubierta de10 mm o pigtail plástico 10 Fr; 5 ° catéter nasoquístico para irrigación continua de suero salino 400cc/24h). Retirada prótesis: 6 – 9meses; Catéter/irrigador: (7 – 14 días) (según respuesta). Análisis: Descriptivo. Comparación técnica convencional y TER: Test McNemar. Definición éxito clínico: „ Paciente asintomático y reducción del tamaño de CSS > 50%“. Resultados: Se ha realizado TER en 12 pacientes (H 66%; edad: 65 ± 8 años; colecciones pancreáticas: 75%, perirrectales: 25%). En 7/12 pacientes (58%) se había realizado sin éxito técnico drenaje USE convencional. Exito técnico TER (12/12 = 100%) vs. tratamiento convencional (0/7 = 0%) (p = 0.01). Exito clínico TER: 10/12 = 83% (colecciones pancreáticas: 7/9 = 78%; perirrectales: 3/3 = 100%). Complicaciones: Inmediatas: 0/12 = 0%; Tardías: 2/12 = 17% (fiebre/disfunción stent). Conclusiones: La TER mediante rellenado con suero de CSS es una alternativa eficaz y segura, incluso en casos de drenaje USE previo fallido.
Abstract 4268: Resistance to growth inhibition by transforming growth factor-beta is associated with activation of the PI3K-Akt pathway in HPV16-immortalized human keratinocytes at late stages of in vitro progression.
Authors: Rupa Velidandla, Gehana Vaswani, Sangeeta Kowli, Lucia Pirisi-Creek, Kim E. Creek
Journal: Cancer Research (2013)

Abstract Transforming growth factor-beta (TGF-ß) plays a vital role in embryonic development, cell proliferation, inflammation and wound repair. The Smad proteins are the central mediators of TGF-ß signal transduction. However, recently several non-Smad pathways (ex., Erk, Jnk, p38 MAPK, PI3K-Akt) have been determined to play key roles in TGF-ß signaling. TGF-ß signaling is often disrupted in cancer, including cervical cancer. Human papillomavirus (HPV) is the main etiological agent in cervical cancer. HPV type 16 (HPV16)-immortalized human keratinocytes (HKc/HPV16) are initially very sensitive to growth inhibition by TGF-ß. However, HKc/HPV16 become increasingly resistant to TGF-ß during in vitro progression, and are completely resistant to TGF-ß-induced growth inhibition at late-stages of transformation, when they exhibit a differentiation resistant phenotype (HKc/DR). Although HKc/DR are completely resistant to the growth inhibitory effects of TGF-ß, some Smad signaling remains. A reporter construct containing tandem repeats of Smad binding elements was induced by TGF-ß in HKc/DR at about 50% of the level observed in HKc/HPV16. Furthermore, TGF-ß was capable of inducing epithelial-mesenchymal transition (EMT) in HKc/DR. To further explore TGF-ß signaling in HKc/HPV16 and HKc/DR, we used phospho specific antibody microarrays from Full Moon BioSystems. These arrays feature phospho and non-phospho pairs of specific antibodies pertinent to the TGF-ß pathway. Protein extracts from HKc/HPV16 and HKc/DR untreated or treated for 90 min with 40 pM TGF-ß were compared on the antibody microarrays. Activation of the Akt pathway by TGF-ß was observed in HKc/DR but not in HKc/HPV16. Similarly, PI3K and mTOR showed activation by TGF-ß in HKc/DR but not HKc/HPV16. We conclude that TGF-ß signals primarily through Smad-dependent pathways to inhibit cell proliferation in HKc/HPV16, but that non-canonical (non-smad) signaling through the PI3K-Akt-mTOR axis predominates in HKc/DR. Citation Format: Rupa Velidandla, Gehana Vaswani, Sangeeta Kowli, Lucia Pirisi-Creek, Kim E. Creek. Resistance to growth inhibition by transforming growth factor-beta is associated with activation of the PI3K-Akt pathway in HPV16-immortalized human keratinocytes at late stages of in vitro progression. [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 4268. doi:10.1158/1538-7445.AM2013-4268
Carcinoma of the Ovary: Clinical and Pathological Evaluation
Authors: Frank C. Wheelock, Robert H. Fennell, Joe V. Meigs
Journal: New England Journal of Medicine (1951)

A REPORT of the cases of ovarian cancer seen at the Massachusetts General Hospital from 1901 through 1934 showed the five-year survival rate to be only 15.5 per cent.1 In order to evaluate the results of more recent therapy and to search for a means of improving the results of treatment, the cases observed from 1935 to 1943 have been reviewed. An attempt was also made to correlate the pathological findings with the clinical course. Sixty-seven cases of primary ovarian malignant disease were found. Recognized endocrine tumors were excluded.Seventy-nine per cent of the patients were between the ages of . . .
Azathioprine and 6-thioguanine but not 6-mercaptopurine inhibit intra-macrophage replication of crohn's disease escherichia coli
Authors: P. Knight, B. J. Campbell, J. M. Rhodes
Journal: Gut (2011)

<h3>Introduction</h3> Crohn9s disease is associated with increased mucosal colonisation by <i>E. coli</i> that have an adherent, invasive phenotype that includes intracellular survival and replication within macrophages. Drugs that prevent this replication might have a therapeutic effect. We previously reported that azathioprine enhances bacterial killing by macrophages1 and therefore we evaluated the effect of its metabolites, namely 6-mercaptopurine and 6-thioguanine, at clinically relevant concentrations, on replication of <i>E. coli</i> within macrophages. <h3>Methods</h3> Azathioprine metabolites, 6-mercaptopurine (4.2 × 10<sup>−2</sup> to 4.2 μM) and 6-thioguanine (8.2 × 10<sup>−5</sup> to 820 fmol/8×10<sup>8</sup> cells) were assessed for their effect on survival and replication of Crohn9s <i>E. coli</i> isolate HM605 in J774-A1 macrophages in comparison to azathioprine (4.2 × 10<sup>−12</sup> to 4.2 μM). Macrophages were pre-treated with drugs for 24 h before bacterial infection. Cells were then infected with HM605 for 2 h to allow for internalisation. Extracellular bacteria were removed and killed with gentamicin (20 μg/mL) for 1 h. Macrophages were then either lysed (at 3 h) or parallel cultures incubated for a further 3 h in the presence of gentamicin (6 h). Internalised bacteria were enumerated by overnight growth on LB agar. <h3>Results</h3> As previously seen, Crohn9s <i>E. coli</i> HM605 significantly replicated within macrophages at 6 h compared to 3 h post-infection levels and azathioprine, at doses of 4.2 ×10<sup>−9</sup> to 4.2 μM, resulted in suppression of <i>E. coli</i> intramacrophage replication (all p&lt;0.01, N=3–8) with a peak effect at 4.2 μM (0.33 fold replication relative to controls; p&lt;0.001, N=5 Kruskal Wallis ANOVA). 6-thioguanine also suppressed <i>E. coli</i> replication in a dose dependent fashion with peak suppression at 82 fmol/8×10<sup>8</sup> cells (0.47 fold replication relative to control; p&lt;0.001, N=4). However, 6-mercaptopurine did not suppress <i>E. coli</i> replication at any concentration tested. <h3>Conclusion</h3> The enhancement of macrophage killing of intracellular <i>E. coli</i> by azathioprine and 6-thioguanine but not 6-mercaptopurine is intriguing. It might reflect the known ability of azathioprine but not 6-mercaptopurine to inhibit inducible nitric oxide synthase2. The effect of 6-thioguanine on nitric oxide synthase has yet to be assessed. These effects of azathioprine and 6-thioguanine on bacterial killing by macrophages may be relevant to some of their therapeutic effects, perhaps particularly in fistulating Crohn9s disease.
Abstract LB-463: Proteomic patterns of colonic submucosa delineates the inflammatory colitides. This could aid understand IBD-related colorectal malignancy
Authors: Michael W. Schäffer, Joan C. Smith, Tanusri Ghosh Roy, Paul E. Wise, Erin H. Seeley, Mary K. Washington, David A. Schwartz, Samuel E. Adunyah, Roberta L. Muldoon, Alan J. Herline, Harold L. Moses, Richard M. Caprioli, Amosy E. M'Koma
Journal: Cancer Research (2011)

Abstract Purpose: Differentiating Crohn's colitis (CC) and ulcerative colitis (UC) can be challenging even in combination of clinical, endoscopic, radiologic and histopathology examination. Biomarker studies have thus far been unsuccessful for disease delineation. We aim to use unique tissue proteomic methods to evaluate colonic tissue layers for potential biomarkers to identify CC vs. UC. Methods: Fresh-frozen colon specimens from resections for IBD and/or colorectal cancer were retrospectively retrieved. Colitis diagnoses were histologically re-confirmed by a blinded gastrointestinal pathologist. Three sample groups (n=5 each group) were examined: normal colon from CRC specimens (control), UC &amp; CC. MALDI-MS was used to profile mucosal and submucosal compartments individually. Frozen tissues were sectioned at ∼10–15 μm for mounting onto either metal or conductive glass target plates (the glass plates allowing for histologic and MALDI-MS analysis on the same section). Sinapinic acid (20 mg/mL in 50:50 acetonitrile: 0.1% TFA in water) was used to give the best combination of uniform crystal coverage and signal quality for direct tissue protein analysis. Results: MALDI-MS achieved high mass accuracy (±0.01 Daltons) in the lower mass range (&amp;lt;15 kDa). There was distinguishable isotopic resolution of mass-to-charge ratio (m/z) values between normal vs the IBD and more strikingly between CC vs. UC (p&amp;lt; 0.0009) of SAM and FDR tests. There were 5 statistically significant discriminative m/z peaks observed in CC vs UC submucosa. The mucosa did not yield such distinctive peaks. Both the mucosa and submucosa provided signatures that differentiated IBD (CC or UC)) from control tissues (p&amp;lt; 0.001). Conclusions: MALDI-MS tissue profiling as described distinguished the colitides. The methodology revealed 5 m/z peaks of interest. Analyses are underway to identify these IBD discriminative proteins. We hypothesize that these biomarker candidates that distinguish UC from CC will allow delineation of indeterminate colitis into UC or CC. Whether these protein fingerprints play a role in colonic carcinogenesis remains to be elucidated. 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 LB-463. doi:10.1158/1538-7445.AM2011-LB-463