tbuckley/cabot-search huggingface dataset:
VSV-G Pseudotyped Lentiviral Vector Particles Produced in Human Cells Are Inactivated by Human Serum
Authors: Nicholas J. DePolo, Joyce D. Reed, Philip L. Sheridan, Kay Townsend, Sybille L. Sauter, Douglas J. Jolly, Thomas W. Dubensky
Journal: Molecular Therapy (2000)

Lentiviral vectors transduce dividing and postmitotic cells and thus are being developed toward therapies for many diseases affecting diverse tissues. One essential requirement for efficacy will be that vector particles are resistant to inactivation by human serum complement. Most animal studies with lentiviral vectors have utilized VSV-G pseudotyped envelopes. Here we demonstrate that VSV-G pseudotyped HIV and FIV vectors produced in human cells are inactivated by human serum complement, suggesting that alternative envelopes may be required for therapeutic efficacy for many clinical applications of lentiviral vectors.
AB0983 Moves: Magnitude of osteoarthritis disadvantage on people’s lives: Burden of self-reported osteoarthritis
Authors: L. Cunha-Miranda, A. Faustino
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The social impact of a disease can be related to its mortality but also to the prevalence and disability associated. In osteoarthritis (OA), pain, joint limitation and overall disability are the main components of its social and individual impact. <h3>Objectives</h3> To evaluate the impact of self-reported OA and to study its correlation with several clinical and socio-demographics factors. <h3>Methods</h3> Observational, population-based, cross-sectional study was conducted in mainland Portugal by Eurotrials Consultants, between September and October 2011, by random route. Citizens aged ≥45 years who agreed to participate completed a survey in home interviews including socio-demographics and presence of OA. Prevalent cases of OA were characterized regarding treatment, comorbidities, impact of OA (VAS 0-10, none to higher impact), pain of OA (VAS 0-10, no pain to worse pain), patient's perception of importance of OA given by current physician (VAS 0-10, none to higher importance), disability due to OA (VAS 0-10, none to maximum disability) and health status (SF-12 v2.0®; physical and mental health, 0 no health - 100 better health). Spearman correlation coefficient (r) was calculated <h3>Results</h3> A representative sample of 1039 participants completed the screening survey. About 54% were female, mean age of 62 years (range: 45-99), average of 7 school-years, 18% obese (body mass index ≥30 kg/m<sup>2</sup>) and 77% retired (0.8% due to OA). OA was self-reported by 9.9% of participants (95% CI 8.1-11.7%), 92% of those with OA diagnosis confirmed by x-ray (self-reported). In this population, the score for OA impact averaged 6.1. The mean score for mental and physical health was 45.9 and 38.5, respectively. About 30% of OA cases referred previous sick leave or temporarily work stop due to OA (absenteeism varied between 3 days and 3 years). 41.4% of OA participants had to change from job activity, 34.5% had to change the way their occupational tasks were done and 10.3% had to stop working definitely. OA had a higher impact in participants which had already been in sick leave or temporarily had to stop working due to OA (8.1 vs 6.0; p=0.001). Impact of OA showed to be associated with physical (r=-0.582; p&lt;0.001) and mental health (r=-0.460; p&lt;0.001) and severity of the disease (r=0.506; p&lt;0.001). <h3>Conclusions</h3> OA is related in our study to a low psychological but even lower physical outcome in the SF-12. Sick leave was present in almost a third of the cases and work adjustments or change of occupation was even more relevant. One in ten patients had to stop working due to OA. In an ageing population that has to work more years than before, we have to take in to account that disease can influence the work productivity and performance and that OA is a serious issue as an occupational and as an overall economic burden to the society. <h3>Disclosure of Interest</h3> None Declared
Adjuvant chemotherapy in breast cancer: is TC a cost-effective regimen compared to AC?.
Authors: T Younis, D Rayson, C Skedgel
Journal: Cancer Research (2009)

Abstract Abstract #6110 Background: Adjuvant TC (taxotere 75 mg/m2 and cyclophosphamide 600 mg/m2 q 21 days X 4 cycles) has recently been shown to improve disease-free and overall survival compared to AC (adriamycin 60 mg/m2 and C 600 mg/m2 q 21 days X 4 cycles) for women with breast cancer. Given the possible differences in cost between the two regimens, an economic evaluation was undertaken to examine the cost-utility (CU) of TC relative to AC in terms of cost per quality-adjusted life year (QALY) gained. Methods: A Markov model was developed to calculate the cumulative costs and QALYs gained over a 10-year horizon for hypothetical cohorts of women with breast cancer treated with AC or TC. Event rates, costs, and utilities were derived from the literature. Costs expected with the delivery of standard courses of TC and AC at the Queen Elizabeth II Health Sciences Centre in Halifax, Canada were estimated. Costs included chemotherapy drug acquisition, supportive medications, laboratory investigations, health resource utilization, and significant adverse events associated with chemotherapy. Efficacy outcomes were based on the updated results of the clinical study of TC vs AC (Jones et al, SABCS 2007). The model took a third-party direct payer perspective and reports results in 2008 Canadian dollars ($). Both costs and benefits were discounted at 3%. Sensitivity analysis for key parameters in the model was conducted. Results: TC is associated with $4,080 incremental cost and 0.25 QALY gain compared to AC at 10-year horizon, with a favorable CU of $16,611/QALY gained. Results were robust to model assumptions and input parameters. Conclusions: TC is cost-effective compared to AC with a cost-effectiveness ratio well below commonly employed thresholds. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6110.
AB0576 Gastrointestinal Involvement among Patients with Systemic Vasculitis
Authors: N. Esatoglu, G. Hatemi, I. Hancı, I. Hatemi, Y. Erzin, A.S. Pala, S.D. Karagoz-Ozen, H. Ozdogan, A.F. Celik
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Gastrointestinal involvement can be a challenging complication of systemic vasculitis. It is a relatively common finding in polyarteritis nodosa and IgA realted vasculitis, an infrequent manifestation of ANCA associated vasculitis, and it can rarely manifest as a type of single organ vasculitis. <h3>Objectives</h3> To analyze the frequency and types of gastrointestinal (GI) involvement among our patients with systemic vasculitis and report the treatment modalities and outcome in these patients. <h3>Methods</h3> Clinical features of all patients with vasculitis who were hospitalized in our department have been prospectively recorded with a standard form between 2000 and 2010. Patients with Behçet9s syndrome were not included since they are being recorded in a different database. We identified all vasculitis patients with GI involvement. Information regarding clinical, imaging and histological findings, treatment modalities and prognosis of these patients were obtained from patient charts. Patients who have not visited our department during the last 3 months were invited to the clinic for a final evaluation. Those who were not able to come were interviewed on the phone. <h3>Results</h3> A total of 236 patients were hospitalized in our clinic between 2000 and 2010 with a diagnosis of systemic vasculitis. Among these patients we identified 30 (13%) patients with GI involvement (mean age 40.2±17 years, 53% men, mean follow-up duration 56 (1–133) months). The main diagnoses were Takayasu arteritis (10/58, 17%), IgA related vasculitis (8/29, 27%), poliarteritis nodosa (6/20, 30%), GPA (Wegener9s) (2/32, 6%) and others (4/97, 4%). The diagnosis of GI vasculitis was based on their having: mesenteric vascular (14/30), GI tract (18/30) and/or solid GI organ involvement (2/30). 12/30 patients had presented with either GI bleeding or perforations. Among those who had GI tract lesions, gastro-duodenal involvement was present in 4/18 and intestinal in 16/18. 8 patients (35%) were dead 31 months (1-96) after their diagnosis. The causes of death were gastrointestinal involvement in 4/8 patients (3 bleeding, 1 perforation). The other 4 patients had died due to infections. Seven patients were lost to follow-up and 15 patients were doing well. <h3>Conclusions</h3> GI involvement was present in 13% of our patients with systemic vasculitis on long term follow-up. Mortality and morbidity rates were considerably high. Mortality was either related to GI complications such as perforation and bleeding or infections associated with high dose immunosuppressives. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5970
Cutaneous Leishmaniasis with a Paronychia-like Lesion
Authors: Hend Chaabane, Hamida Turki
Journal: New England Journal of Medicine (2014)

An otherwise healthy 63-year-old man from a rural area in Tunisia presented with ulcerated paronychia, with a verrucous lesion at the base of the right thumb. Physical examination revealed seven crusty, ulcerated skin lesions on the limbs.
Novel Protein Disulfide Isomerase Inhibitor with Anticancer Activity in Multiple Myeloma
Authors: Sergei Vatolin, James G. Phillips, Babal K. Jha, Shravya Govindgari, Jennifer Hu, Dale Grabowski, Yvonne Parker, Daniel J. Lindner, Fei Zhong, Clark W. Distelhorst, Mitchell R. Smith, Claudiu Cotta, Yan Xu, Sujatha Chilakala, Rebecca R. Kuang, Samantha Tall, Frederic J. Reu
Journal: Cancer Research (2016)

Multiple myeloma cells secrete more disulfide bond-rich proteins than any other mammalian cell. Thus, inhibition of protein disulfide isomerases (PDI) required for protein folding in the endoplasmic reticulum (ER) should increase ER stress beyond repair in this incurable cancer. Here, we report the mechanistically unbiased discovery of a novel PDI-inhibiting compound with antimyeloma activity. We screened a 30,355 small-molecule library using a multilayered multiple myeloma cell-based cytotoxicity assay that modeled disease niche, normal liver, kidney, and bone marrow. CCF642, a bone marrow-sparing compound, exhibited a submicromolar IC50 in 10 of 10 multiple myeloma cell lines. An active biotinylated analog of CCF642 defined binding to the PDI isoenzymes A1, A3, and A4 in MM cells. In vitro, CCF642 inhibited PDI reductase activity about 100-fold more potently than the structurally distinct established inhibitors PACMA 31 and LOC14. Computational modeling suggested a novel covalent binding mode in active-site CGHCK motifs. Remarkably, without any further chemistry optimization, CCF642 displayed potent efficacy in an aggressive syngeneic mouse model of multiple myeloma and prolonged the lifespan of C57BL/KaLwRij mice engrafted with 5TGM1-luc myeloma, an effect comparable to the first-line multiple myeloma therapeutic bortezomib. Consistent with PDI inhibition, CCF642 caused acute ER stress in multiple myeloma cells accompanied by apoptosis-inducing calcium release. Overall, our results provide an illustration of the utility of simple in vivo simulations as part of a drug discovery effort, along with a sound preclinical rationale to develop a new small-molecule therapeutic to treat multiple myeloma. Cancer Res; 76(11); 3340-50. ©2016 AACR.
AGE AND HUMAN REGENERATIVE CAPACITY: IMPACT OF CARDIOVASCULAR RISK FACTORS
Authors: Ibhar Al Mheid, Faysal Akbik, Salim Hayek, Nima Ghasemzadeh, Qunna Li, Long Qi, Greg Martin, A. Maziar Zafari, Viola Vaccarino, Edmund Waller, Arshed Quyyumi
Journal: Journal of the American College of Cardiology (2015)
Charcot-Marie-Tooth Disease Type 1A -- Association with a Spontaneous Point Mutation in the PMP22 Gene
Authors: Benjamin B. Roa, Carlos A. Garcia, Ueli Suter, Deanna A. Kulpa, Carol A. Wise, Jane Mueller, Andrew A. Welcher, G. Jackson Snipes, Eric M. Shooter, Pragna I. Patel, James R. Lupski
Journal: New England Journal of Medicine (1993)

Charcot-Marie-Tooth disease (CMT) is the most common inherited peripheral neuropathy. CMT type 1A is associated with a 1.5-megabase (Mb) DNA duplication in region p11.2-p12 of chromosome 17 in most patients. An increased dosage of a gene within the duplicated segment appears to cause the disease. The PMP22 gene, which encodes a myelin protein, has been mapped within the duplication and proposed as a candidate gene for CMT type 1A.
Abstract 2297: MicroRNAs inhibit breast canncer metastasis via targeting CXC chemokine receptor 4
Authors: Zhongxing Liang, Ke Huang, Samuel Hong, Jeffrey Ahn, Hyunsuk Shim
Journal: Cancer Research (2012)

Abstract Overexpressed CXC chemokine receptor (CXCR4) strongly contributes to breast cancer metastasis. However, the underlying mechanisms of CXCR4 overexpression need still to be explored. MicroRNAs (miRNA) have been implicated as a class of critical regulators controlling diverse biological processes. In the present study, we investigated whether miR-302 and miR-588 are involved in the regulation of CXCR4 and play a functional role in breast cancer metastasis. We have shown that miR-302 and miR-588 were downregulated in highly metastatic breast cancer cell lines and tissue specimens compared to low metastatic cell lines and breast cancer tissues. The decreased expression levels were inversely consistent with overexpression of CXCR4 in highly breast cancer cell lines and tissues. In addition, we found that restoration of miR-302 and miR-588 resulted in a dramatic reduction of CXCR4 expression at protein levels by directly targeting its 3′ untranslated region. Furthermore, the elevated expression of miR-302 and miR-588 significantly inhibited the invasion of breast cancer cells. More promisingly, our data have demonstrated that overexpression of miR-302 reduced metastasis and growth of breast cancer in vivo. Our findings describe a new mechanism for the regulation of CXCR4 and metastasis of breast cancer. The newly characterized miR-302/588/CXCR4 link provides potential molecular markers for predicting breast cancer metastasis. MiR-302 and miR-588 may have a therapeutic potential to suppress breast cancer metastasis. 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 2297. doi:1538-7445.AM2012-2297
P5-14-24: The Long Term Prognostic Impact of Real-Time Quantitative RT-PCR Detection of Cytokeratin 19 mRNA in Preoperative Bone Marrow Aspirates of Early Breast Cancer Patients.
Authors: K Punie, W Wynendaele, P Clement, R Paridaens, M-R Christiaens, B Jacobs, H Wildiers
Journal: Cancer Research (2011)

Abstract Purpose: Several studies have evaluated the prognostic effect of bone marrow micrometastases at the time of surgery in early breast cancer, but few studies have long term outcome data. We report here a cohort with more than ten years follow-up. Materials and methods: 131 patients with primary operable invasive breast cancer were enrolled in the protocol from February 1998 to September 1999. Bone marrow aspirates, obtained from the iliac crest or the sternum, were analyzed with real-time quantitative reverse-transcription polymerase chain reaction (RT-PCR) for the presence of cytokeratin 19 (CK19) mRNA. All patients received standard therapy and follow-up. After a median follow-up of 133 months, data about disease recurrence (invasive disease free survival, IDFS) and survival (breast cancer specific survival (BCSS) and overall survival (OS)) were collected. A control group consisted of archived cDNA samples from 38 patients with hematological malignant antecedents in complete remission and without known gene arrangements. The upper limit of the 95% confidence interval of the level of CK19 positive cells is this group was used as cut-off (260 cytokeratin 19+ cells / 5 × 106 leucocytes) to determine bone marrow status in breast cancer patients. Results: 69 bone marrow samples from breast cancer patients (52,7 %) were considered CK19 positive. IDFS was 60.9 % and 79 % for CK19+ and CK19- patients, respectively (log-rank p-value = 0,036). When CK19 was evaluated as a continuous variable, IDFS also correlated significantly with the level of CK19 mRNA in bone marrow aspirates (p-value = 0,019). Except for lymph node status (ANOVA linear regression p-value = 0.022), there was no significant correlation between the level of CK19+ cells in the bone marrow and classical prognostic factors (pathological tumor stage, tumor size, differentiation grade, hormonal receptor status). In multivariate Cox-regression analysis correcting for tumor size, differentiation grade, lymph node status, hormone receptor status, tumor stage and treatment modalities (surgical procedure, chemotherapy, radiotherapy and antihormonal therapy), the CK19 bone marrow status still was a significant predictor of IDFS. (p-value = 0.042) Differences in BCSS (78 % of CK19 + patients and 84 % of CK19 — patients) and OS (75 % in CK 19 + patients and 74 % in CK 19 — patients) were not statistically significant. (log rank p-values 0.087 and 0.883, respectively). Conclusion: This study demonstrates the long term (&amp;gt;ten years) prognostic effect of CK19 mRNA detection with RT-PCR in the bone marrow of operable breast cancer patients. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-14-24.
Asymmetric inheritance of mTORC1 kinase activity during division dictates CD8+ T cell differentiation
Authors: Kristen N Pollizzi, Im-Hong Sun, Chirag H Patel, Ying-Chun Lo, Min-Hee Oh, Adam T Waickman, Ada J Tam, Richard L Blosser, Jiayu Wen, Greg M Delgoffe, Jonathan D Powell
Journal: Nature Immunology (2016)
THROMBOLYSIS WITH TENECTEPLASE IN A PATIENT PREVIOUSLY TREATED WITH TICAGRELOR LOADING DOSE
Authors: Hugo Rodriguez Zanella, Jesus Enrique Barrios Baqueiro, Reynie Reynoso Gonell, Luis Rodrgo Gonzlez Azuara, Sofia Leonor Legorreta Armenta, Erick Alexanderson Rosas
Journal: Journal of the American College of Cardiology (2014)
Bronchodilator Effects of Terbutaline and Aminophylline Alone and in Combination in Asthmatic Patients
Authors: James D. Wolfe, Donald P. Tashkin, Barry Calvarese, Michael Simmons
Journal: New England Journal of Medicine (1978)

In 17 patients with moderate to severe asthma, we compared acute bronchodilator effects of the following drugs or drug combinations using a double-blind crossover design: terbutaline, 5; aminophylline, 400; terbutaline, 5, plus aminophylline, 400; terbutaline, 2.5; aminophylline, 200; terbutaline, 2.5, plus aminophylline, 200 mg; and placebo. The higher doses of terbutaline and aminophylline alone produced comparable bronchodilatation and similarly frequent adverse side effects; low doses of each drug also had comparable effects. The high-dose combination produced significantly (P<0.05) greater bronchodilatation than either drug alone. The low-dose combination had bronchodilator effects comparable to those produced by the higher dose of either drug alone. These findings suggest therapeutic advantages in combining high doses of theophylline and an oral β-adrenergic agonist (terbutaline) in asthma not well controlled on high doses of either drug alone and in combining these drugs in lower doses in patients experiencing intolerable side effects from a high dose of either drug. (N Engl J Med 298:363–367, 1978)
Rectal tonsil associated with Epstein-Barr virus
Authors: P. Grube-Pagola, A. Canales-Kay, A. Meixueiro-Daza, J. Remes-Troche
Journal: Endoscopy (2012)

Reactive polypoid proliferation of lymphoid tissue has been described along the gastrointestinal tract [1]. Endoscopically, when a non-lymphomatous lymphoid reaction resembling tonsillar tissue is present in the rectum, the polyp is named as "rectal tonsil". Few cases have been reported in the literature [1] [2], and the etiology of this rare condition is unknown [3] [4] [5].
Childhood Plumbism Identified after Lead Poisoning in Household Pets
Authors: Robert Dowsett, Michael Shannon
Journal: New England Journal of Medicine (1994)

To the Editor: Lead poisoning in children is endemic in many areas of the United States. Because of inadequate primary preventive measures, health providers must rely on secondary preventive measures, such as screening of children who have close contact with other children known to have lead poisoning.1 Occasionally, the development of lead poisoning in household pets leads to the identification of children with asymptomatic lead intoxication. In our lead-treatment program we have identified three such children in two families. In the first family, a pet dog had persistent vomiting and weight loss one month after the exterior renovation of the . . .
Abstract 2003: Detecting clonal relationships of multifocal tumors
Authors: Aleah K. Fox, Shane T. Jensen, Antoine M. Snijders, Brian L. Schmidt, Donna G. Albertson, Carlo C. Maley
Journal: Cancer Research (2010)

Abstract Understanding the development and progression of tumors is fundamental for the improvement of patient treatment and care. Proliferative verrucous leukoplakia (PVL) is a recurrent, multifocal, precancerous lesion that often transforms into oral squamous cell carcinoma (SCC). Multifocal lesions may be separated in either space (synchronous) or time (metachronous). It is essential to determine the relationship between multifocal lesions in order to properly understand the progression of the disease and treat it accordingly. It has yet to be determined whether PVL lesions arise independently or are derived from a common ancestral clone of cells. We have developed a permutation algorithm to test the null hypothesis that the tumors from the same patient share no more genetic alterations than tumors originating from different patients. The alternative hypothesis is that tumors from the same patient, though separated by time and/or space, share a greater number of chromosomal abnormalities than would be expected by chance and so likely share a common premalignant ancestor cell. This will allow us to determine if the tumors arise as independent events or share some clonal relationship. Biopsy data from nine patients, each with multiple tumors, was used to run individual BAC arrays for each lesion. The breakpoints of genetic alterations were determined using Circular Binary Segmentation (CBS) and served as input for our permutation algorithm which counts the number of shared breakpoint positions between tumors. Though many regions in the genome may be prone to gain or loss in a tumor, the exact start and stop of a breakpoint likely defines a unique event such that two or more lesions sharing this alteration can be considered a signature of clonality. We found that five of the nine patients share a significant number of genetic aberrations between their SCC lesions, leading to the conclusion that in approximately half of patients, multifocal PVL tumors are clonally related. Our algorithm for identifying clonality between multiple samples from a patient could be used on a variety of platforms including high density SNP arrays, measuring loss of heterozygosity and copy number alterations, as well as high throughput sequencing. All that is required is multiple, spatially or temporally distinct samples from each patient and multiple patients. 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 2003.