tbuckley/cabot-search huggingface dataset:
Abstract 600: Liposomal C6 ceramide appears to potentiate enhanced chemotoxicity of pancreatic cancer.
Authors: Harold J. Wanebo, Cao Cong, Li Shu, David Shrayer, Yeushung Wan, Wayne Bowen
Journal: Cancer Research (2013)

Abstract Introduction: Pancreatic adenocarcinoma a highly lethal malignancy (5 yr survival ∼ 5%) is poorly responsive to all chemotherapy, in part related to presence of chemo resistant pathways: prosurvival (AKT/PI3K/mTOR and mutant KRAS. We previously demonstrated reversal of these resistant pathways by C6 Ceramide and now pursue optimum intracellular delivery using selected liposomal preparations of C6 Ceramide. Methods: C6 Ceramide(C6Cer) in 4 different liposomal vesicle formulations were tested by MTT assay against pancreatic cell lines L3.6, PANC1 and MIA, combined with chemotherapy: Gemcitabine, Paclitaxel and Cetuximab.Liposomal preparations included : (#1)18:1 PC (1,2-dioleoyl-sn-glycero-3-phosphocholine; (#3),18:0 PC (1,2-distearoyl-sn-glycero-3-phosphocholine;(#5) DPGG (1,2-dipalmitoyl-sn-glycero-3-galloyl); and (#7) 18:0 PEG2 PE (1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N[methoxy(polyethylene glycol)-2000. (#1)18:1 PC- has low transition temp.(T*) and is fluid at body T*(# 3). 18:0 PC-is rigid with high transition (T*) . #5 DPGG- avoids RE System (is fluid at body T*, induces long circulations)#7. 18:0 PEG 2 PE - industry standard (also avoids RE system).Biologic effects of the 4 lipid formulations with/without C6 Ceramide were initially assessed invitro. Results: Dose response MTT assay demonstrated no distinctive response of C6 combined liposomes vesicles # 1 &amp; 3, but confirmed high activity in preparations #5 &amp; 7. MTT ResponseFractionControlTaxolGemcitabineCetuximab100%87%70%90%#5(C6)90%42%40%33%# 6 PPS control108%76%36%77%# 7 C6101%31%45%59%# 8 PBS control110%60%58%62%*Control-cell survival 72 hours ∼ 90%-100%(Drug Dose - C6 1 ug/ml, Pac. 1ug/ml,Gem 5ug/ml, Cetux 25ug/ml) Conclude: Liposomal C6 preparations show high activity in potentiating chemo toxicity by Gemcitabine, Paclitaxel and Cetuximab against Pancreatic Cancer. Confirmatory in vivo studies are in process. Citation Format: Harold J. Wanebo, Cao Cong, Li Shu, David Shrayer, Yeushung Wan, Wayne Bowen. Liposomal C6 ceramide appears to potentiate enhanced chemotoxicity of pancreatic cancer. [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 600. doi:10.1158/1538-7445.AM2013-600
The Genetics of Hirschsprung's Disease
Authors: Eberhard Passarge
Journal: New England Journal of Medicine (1967)

ALTHOUGH Hirschsprung's disease (congenital intestinal ganglion-cell aplasia or aganglionosis) has been known clinically for nearly eighty years, only recently has progress been made in an understanding of its pathogenesis and the development of effective therapy. However, there is still much to be learned about the etiology of the disease. Although most cases are sporadic and remain unexplained, genetic determination is suggested in others. Familial cases of Hirschsprung's disease have frequently been reported, but only a few systematic genetic studies have been published.1 2 3 4 5 Another etiology for Hirschsprung's disease is suggested by its association with Down's syndrome (mongolism).6 , 7 Therefore, a systematic genetic . . .
Bacterial-Viral Interrelations in Respiratory Infections of Children
Authors: Kathryn P. Nichol, James D. Cherry
Journal: New England Journal of Medicine (1967)

CLASSICALLY, one episode of respiratory infection is considered to be produced by one etiologic agent1 2 3 4 5; occasionally, however, multiple infectious agents have been recovered from patients with respiratory illness, suggesting a more complicated pathogenesis.6 7 8 9 10 The frequent occurrence of staphylococcal pneumonia during epidemic influenza has been reported on several occasions,11 , 12 and in some cases, apparent synergism between viruses and bacteria has been noted.13 14 15 16 17 18 19 20 21 MacLeod18 has called attention to the importance of a previous viral infection in the pathogenesis of pneumococcal illness. Recent studies observed significant growth of pathogenic bacteria in throat cultures from patients with rhinovirus infections.6 The present report compares . . .
AB0245 Functional reserves decline index and severity status of rheumatoid arthritis patients
Authors: N. Dostanko, V. Yagur, V. Dostanko
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Severity status of rheumatoid arthritis (RA) patient is more extensive characteristic than disease severity as it includes concomitant diseases burden (total comorbidity) as well as decrease of organ functional reserves which steady decline with age. <h3>Objectives</h3> To develop Functional Reserves Decline Index (FRDI) including assessment of 5 key organ systems against age: cardiovascular system (cardiac output), respiratory system (maximum breathing capacity), nervous system (nerve conduction velosity), urinary tract (glomerular filtration rate) and tissue metabolism (cellular water) using of currently available nomograms [1] and to apply it to the severity status of RA patient. <h3>Methods</h3> For the calculation of FRDI we have used nomograms by J.F. Fries [1] which present the dependence of organ functional reserves decline with age for 5 organ systems in the age range 20-90. The nomograms were approximated by means of 5 linear functions: Y<sub>1</sub>=-0.64×X+77.98 (R<sup>2</sup>=1), where Y<sub>1-5</sub>– reserve capacity of the mentioned systems, X – age, years, R<sup>2</sup> – coefficient of determination; Y<sub>2</sub>=-0.97×X+100.87 (R<sup>2</sup>=1); Y<sub>3</sub>=-X+105.71 (R<sup>2</sup>=1); Y<sub>4</sub>=-0.70×X+89.91 (R<sup>2</sup>=1); Y<sub>5</sub>=-0.68×X+100.66 (R<sup>2</sup>=1). <h3>Results</h3> The functional reserve capacities of each organ system for the age of 20, 30, 40 etc. to 90 years were calculated by the presented formulas and summarized for each range of age and the sum was divided by 5. Then a new summarized linear function of the mentioned parameters was plotted against age (see picture below) and approximated by formula: Ysum = 120 – X, where X – age, years. Functional reserve capacity at 20 years was assumed to be 100%. We have suggested to determine FRDI (%) by formula: 100-(120-X) and to indicate the level of FRDI in points as follows: ≤25% – 0 points, 26% to 50% – 1 points, 51% to 75% – 2 points, ≥76% – 3 points. Example: for the age of 75 FRDI is 100-(120-75)=55%, i.e. 2 points. <h3>Image/graph</h3> <h3>Conclusions</h3> The suggested approach allows taking into account the patient's age as FRDI (0-3 points) along with disease severity (0-3 points) and total comorbidity assessed by DUSOI (0-3 points) in the severity status of RA patients. The severity status of RA patient can be determined as the sum of these three indices and graded as follows: minimal (1-3 points), moderate (4-6 points), severe (7-8 points) and critical (9 points). The ranges of severity status are refining in the group of 590 RA patients (2625 follow-ups at present). <h3>References</h3> Fries, J.F.//The Milbank Memorial Fund Quarterly.1983;1:397-419. <h3>Disclosure of Interest</h3> None Declared
Financial restraints are "no excuse" for unacceptable care, says Francis
Authors: G. Iacobucci
Journal: BMJ (2014)

<h3>Background</h3> Although reinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is rare among individuals with few coronavirus disease 2019 (COVID-19) risk factors, the ability of naturally acquired immunity to prevent reinfection among patients with ESKD is not known. <h3>Methods</h3> This prospective study was conducted among adults with ESKD treated with in-center hemodialysis (ICHD) in the United States. Exposure was ascribed on the basis of the presence or absence of IgG against SARS-CoV-2 at baseline, and separately, a history of documented COVID-19 before study entry. Outcomes were assessed after an infection-free period, and were any SARS-CoV-2 infection (<i>i.e.,</i> detected by protocolized PCR tests or during routine clinical surveillance), and clinically manifest COVID-19 (consisting of only the latter). <h3>Results</h3> Of 2337 consented participants who met study inclusion criteria, 9.5% were anti–SARS-CoV-2 IgG positive at baseline; 3.6% had a history of COVID-19. Over 6679 patient-months of follow-up, 263 participants had evidence of any SARS-CoV-2 infection, including 141 who had clinically manifest COVID-19. Presence of anti–SARS-CoV-2 IgG (versus its absence) at baseline was associated with lower risk of any SARS-CoV-2 infection (incidence rate ratio, 0.55; 95% confidence interval, 0.32 to 0.95) and clinically manifest COVID-19 0.21 (95% confidence interval, 0.07 to 0.67). <h3>Conclusion</h3> Among patients with ESKD, naturally acquired anti–SARS-CoV-2 IgG positivity is associated with a 45% lower risk of subsequent SARS-CoV-2 infection, and a 79% lower risk of clinically manifest COVID-19. Because natural immunity is incomplete, patients with ESKD should be prioritized for SARS-CoV-2 vaccination, independent of their COVID-19 disease history.
Recombinant Human Erythropoietin for Patients with AIDS Treated with Zidovudine
Authors: Margaret Fischl, Jeffrey E. Galpin, James D. Levine, Jerome E. Groopman, David H. Henry, Peter Kennedy, Steven Miles, William Robbins, Barbara Starrett, Ralph Zalusky, Robert I. Abels, Huei C. Tsai, Seth A. Rudnick
Journal: New England Journal of Medicine (1990)

Bone marrow suppression and anemia are frequent side effects of treatment of the acquired immunodeficiency syndrome (AIDS) with zidovudine (formerly azidothymidine [AZT]). We conducted a randomized, double-blind, placebo-controlled clinical trial of recombinant human erythropoietin (100 U per kilogram of body weight thrice weekly by intravenous bolus) in 63 patients with AIDS treated with zidovudine (29 in the erythropoietin group and 34 in the placebo group). Reductions in the number of units of red cells transfused and the number of patients given transfusions per month became apparent in the second and third months of the trial. The reductions were observed in patients with endogenous erythropoietin levels ≤500 IU per liter at base line, but not in patients whose levels were >500 IU per liter at the beginning of the study.
THU0409 Mixed connective tissue disease and undifferentiated connective tissue disease: Do doctors classify correctly?
Authors: Y.B. Joo, J.H. Kim, C.-B. Choi, T.-H. Kim, J.-B. Jun, S.-C. Bae, D.-H. Yoo, Y.-K. Sung
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Mixed connective tissue disease (MCTD) and undifferentiated connective tissue disease (UCTD) are heterogeneous diseases which clinical manifestations are considerable overlapped with other connective tissue disease. Clinical diagnosis is usually depended on rheumatologists' perception and experiences, though the classification criteria for each disease have been exist. <h3>Objectives</h3> To evaluate agreement of expert opinion-based and classification criteria-based diagnosis in discriminating between MCTD and UCTD and impact of opinion-based diagnosis on the initial therapeutic pattern. <h3>Methods</h3> Three hundred fifty six patients, who ever had ICD-10 code of M35.1 (other overlap syndrome) or M35.0 (systemic involvement of connective tissue, unspecified) during 2000-2011 were selected and retrospective chart review was performed. Among them, patients who had been confirmed as definite rheumatologic diseases within 3rd visit (<i>n</i>=185) or who had been diagnosed in other hospital (<i>n</i>=87) were excluded. New patients with MCTD (n=64) and with UCTD (n=20) were enrolled in this study. Agreement between opinion-based and criteria-based diagnosis were examined using Cohen's Kappa. Initial clinical manifestation, autoantibody, and treatment pattern of opinion-based MCTD and UCTD were compared using the chi-squared test or Fisher's exact test, as appropriated. <h3>Results</h3> Agreement between opinion-based and criteria-based diagnosis was moderate (kappa, 0.59). When we discriminate between MCTD and UCTD according to expert opinion, high titer ANA (&gt;1:2560) and the positivity of nRNP were distinct features of MCTD (P&lt;0.05), though other clinical features were comparable. In the treatment, patients with MCTD were more often treated with prednisolone (P&lt;0.05). The prevalence of treatment using combined regimen including immunosuppressant was high in MCTD patients even though it was not statistically significant. <h3>Conclusions</h3> MCTD is often confused and is classified as UCTD in general practice and vice versa. The doctor's initial perception for diagnosis in MCTD and UCTD influences on treatment pattern. <h3>Disclosure of Interest</h3> None Declared
Abstract 1219: Tubulin binding to mitochondrial VDAC: A new regulator of oxidative metabolism and apoptosis? A new role for tubulin
Authors: Dan L. Sackett, Adrian Begaye
Journal: Cancer Research (2010)

Abstract Tubulin binding to the outer mitochondrial membrane (OMM) was first reported many years ago but the function was unknown; we showed recently that dimeric tubulin binds to VDAC, the major metabolite channel in the OMM, and that this results in closing the channel to ATP-ADP exchange, with a consequent drop in oxidative phosphorylation. This could act as a regulator of normal oxidative metabolism, but excess tubulin binding could also lead to changes in the inner membrane potential, and possibly lead to mitochondrial swelling and triggering of apoptosis. To evaluate the plausibility of this mechanism for either regulation of normal metabolism or induction of apoptosis, the concentrations of tubulin and VDAC in the cell need to be known, as a huge discrepancy in either direction could make the mechanism unlikely. We have used semiquantitative Western blots to measure the concentrations of tubulin and VDAC in total cell extracts from a number of cancer cell lines. As expected, we found tubulin to be an abundant protein (∼0.5 % of total protein), but we also found VDAC to be more abundant than perhaps commonly thought (∼0.2 % of total protein). Thus we conclude that tubulin regulation of VDAC permeability is a plausible mechanism. Further experiments are underway to test this mechanism and its role in induction of apoptosis by chemotherapy agents, especially microtubule-directed ones. 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 1219.
Dual-Phase 99mTc-MIBI Imaging Findings in Sporadic Primary Hyperplasia of Parathyroid Glands
Authors: Qi-Sheng Yang, Chang-Yin Wang, Bi-Cheng Wang
Journal: Clinical Nuclear Medicine (2015)

Primary hyperplasia of parathyroid is uncommon and rarely documented in literatures. We report an 18-year-old female patient with hyperparathyroidism due to unifocal primary hyperplasia of parathyroid glands. Dual-phase Tc-MIBI imaging was performed for this patient. We found remarkably increased MIBI uptake in the hyperplastic lesion in early imaging and no extinction of the uptake in delayed imaging. These results suggest that the dual-phase Tc-MIBI imaging is useful in localizing the hyperfunctioning lesions of primary hyperplasia of parathyroid glands.
Nodular Glomerulosclerosis (Kimmelstiel-Wilson) After Total Pancreatectomy
Authors: Takashi Kadowaki, Ryoko Hagura, Kazuhide Yamaoki, Hiroshi Kajinuma, Nobusada Kuzuya, Akira Hirayama, Masanobu Kitagawa, Tomoyuki Kitagawa, Keijiro Kuno
Journal: Diabetes Care (1987)
Abstract 3376: Cord blood stem cells revert EMT to MET in glioma stem cells by downregulating synergistic transcriptional activation of Sox2 and Twist1
Authors: Kiran Kumar Velpula, Venkata Ramesh Dasari, Andrew J. Tsung, Dzung H. Dinh, Jasti S. Rao
Journal: Cancer Research (2012)

Abstract The dynamic nature of cancer stem cells that underlie metastasis or their ability to switch between different cellular identities, as in epithelial to mesenchymal transition and mesenchymal to epithelial transition has profound implications for cancer therapy. The functional relationship between molecules involved in cancer cell stemness and metastasis is not clear. In this regard, our studies on human glioblastoma tissue grade IV specimens showed significant expression of Twist1 and Sox2, known mesenchymal and stemness related markers, respectively, indicating their association with glial tumorigenesis and metastasis. The glioma stem cells obtained from CD133+ cells demonstrated increased expression of Twist1 and Sox2 accompanied by significant increase in the mesenchymal markers such as N-cadherin, vimentin and β-catenin. Our studies on glioma stem cells treatment with human umbilical cord blood derived mesenchymal stem cells, showed down regulation of Twist1 and Sox2 proteins, apart from other mesenchymal stem cell markers. Based on the in vitro experiments and in vivo intracranial xenograft mouse model studies we elucidated the potential therapeutic role of hUCBSC in suppressing glioma cancer stemness by the induction of mesenchymal to epithelial transition. 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 3376. doi:1538-7445.AM2012-3376
Abstract LB-274: Mutant p53 cooperates with ETS2 to promote etoposide resistance
Authors: Luis A. Martinez, Phi M. Do, Lakshman Varanasi
Journal: Cancer Research (2012)

Abstract Mutant p53 (mtp53) promotes chemotherapy resistance through multiple mechanisms including disabling pro-apoptotic proteins and by regulating gene expression. Analysis of promoter regions identified through CHIP-on-CHIP and CHIP-seq platforms reveal that the ETS motif (EBS) is prevalent within predicted mtp53 binding sites. We demonstrate that mtp53 regulates gene expression through EBS in promoters, and that ETS2 mediates the interaction with this motif. Importantly, we identified TDP2, a 5′-tyrosyl DNA phosphodiesterase involved in the repair of DNA damage caused by etoposide, as a transcriptional target of mtp53. We demonstrate that suppression of TDP2 sensitizes mtp53 expressing cells to etoposide, and that mtp53 and TDP2 are frequently overexpressed in human lung cancer; thus, our analysis identifies a potentially “druggable” component of mtp53's gain-of-function activity. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-274. doi:1538-7445.AM2012-LB-274
Thrombosis of a Mechanical Mitral Valve
Authors: Kevin Christopher Harris, Andrew I M Campbell
Journal: New England Journal of Medicine (2011)

An 8-year-old girl with a history of congenital mitral stenosis and mitral-valve replacement presented with dyspnea on exertion, fatigue, and orthopnea. On examination, she had tachypnea, a heart rate of 130 bpm, and oxygen saturation of 85 to 87% while breathing ambient air.
A2.14 Potential in Vitro Immunomodulatory Effects of the Recombinant Human Alpha-Enolase on Peripheral Blood Mononuclear Cells (PBMCs) from Healthy Donors
Authors: C Guillou, G Avenel, C Derambure, M Verdet, ML Golinski, M Hiron, S Adriouch, O Boyer, T Lequerré, O Vittecoq
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Identification of autoantibodies associated with rheumatoid arthritis has been of major interest. In this context, we have previously identified for the first time α-enolase (ENO) as a new auto-antigen in early RA. ENO is an evolutionary conserved protein involved both in glycolysis pathway and as a plasminogen receptor which confer it a role in anti-infectious inflammatory response. In vivo, preliminary studies showed that ENO had immunomodulatory effect in the collagen induced arthritis mouse model. [1] To better understand the immunological mechanisms of ENO, the aim of this in vitro study was to determine the effects of ENO on PBMCs from healthy donors. <h3>Methods</h3> In one hand, PBMCs or different cell types (monocytes, B and T cells, and immature dendritic cells [iDC]) (n = 3) were cultured with ENO (20 µg/mL) or Bovine Serum Albumin (20 µg/mL). TNFα and IL-10 production was measured in the supernatants by ELISA at different times. On the other hand, TNFα and IL-10 production were evaluated in PBMCs, monocytes or B and T cells after LPS stimulation and pre-incubation with ENO for 24 h (n = 3). Cytometric analyses have evaluated the ability of ENO to inhibit the differentiation of monocytes into iDC. Before differentiation into iDC (GM-CSF and IL-4), monocytes (1.10<sup>6</sup> cells/mL) were incubated with ENO (20 or 50 µg/mL) for 24 h. <h3>Results</h3> In cultures of PBMCs, monocytes or iDC, ENO induces, dose dependently, an early production of TNFα followed by extended secretion of IL-10. PBMCs or individual cells (monocytes, B and T cells) stimulated by LPS secreted successively TNFα and IL-10, while PBMCs or individual cells, stimulated by LPS but previously incubated with ENO for 24 h did not secrete these cytokines. In contrast to LPS, ENO did not induce differentiation of immature dendritic cells into mature cells. But ENO has not the capacity to inhibit differentiation from monocytes to iDC. <h3>Conclusions</h3> This study suggests that ENO has no pro-inflammatory effect unlike LPS. Indeed, ENO might have immunomodulatory properties via IL-10 production. Others studies focused on an extended cytokine panel and different signalling pathways are underway to better understand the immunological mechanisms induced by ENO. <h3>Reference</h3> C Guillou <i>et al</i>, <i>Arthritis and Rheumatism</i> 2011; 63:S815.