tbuckley/cabot-search huggingface dataset:
A1.13 Ultrasound-guided assessement of axillary lymph nodes in rheumatoid arthritis: cross-sectional and prospective clinico-pathologic significance
Authors: A Manzo, F Benaglio, S Bugatti, B Vitolo, S Alessi, R Caporali, F Calliada, C Montecucco
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background and Objectives</h3> Joint-draining lymph nodes (LN) and afferent lymphatics are relevant components of the induction-resolution phases of immune responses, acting through the control of cell efflux from the joint and regulation of peripheral inflammation. LN reactivity to exogenous stimuli associates with morphological and vascular flow dynamic changes. While the dynamics of draining LN have been extensively investigated in infectious and neoplastic diseases, much remains to be understood regarding their involvement in human autoimmune conditions. In this study, we have developed of a non-invasive power Doppler ultrasound (PDUS) system for the assessment of human axillary LN blood flow characteristics and investigated its significance in relationship with disease activity and outcome in rheumatoid arthritis (RA). <h3>Materials and Methods</h3> 101 subjects were recruited in the study: 20 healthy volunteers, 33 RA patients with active disease candidate to biologic therapy and 48 RA patients in stable clinical remission candidate to drug-free follow-up. All patients underwent complete clinical-laboratory evaluations and joint-axillary LN PDUS assessments. LN were evaluated for volume (by ellipsoid formula), cortex hypertrophy and vascular flow distribution. All evaluations were performed at baseline and at 6 months after biologic treatment initiation, and every 3 months following DMARD suspension. <h3>Results</h3> Vascular flow characteristics were assessed semi-quantitatively according to the degree of PD distribution in LN cortex (0-1 PD signals/2-3/4-5 /≥6). Validation assessments showed good inter-rater agreement (k = 0.86) and strong correlation between the score and overall PD+vascular signal defined by digital image analysis (rho = 0.9, p&lt;0.01). A grading system referring to the maximum observed score was adopted to define a patient-related index. In subjects with detectable LN, the LN PD grade significantly discriminated active RA from controls. RA patients in remission revealed a trend towards reduction in the prevalence of high PD grades compared to active RA, but not a systematic return to normalcy. In active RA a significant correlation was observed between LN PD grade and joint PD score (p&lt;0.05), but not with DAS28, SJC28, TJC28, ESR, CRP. Pilot prospective evaluations following biologic treatment pointed at the axillary LN PD grade as the only predictor of DAS28 remission at 6 months (OR 2.53, 95% CI 1,21-5,31, p = 0.01). <h3>Conclusions</h3> Non-invasive vascular flow assessment by PDUS of axillary LN seems a feasible, reliable and valid tool to capture clinically-relevant changes of draining LN status. This may be important to better focus invasive procedures for biological studies and as a novel approach for biomarker discovery in RA.
P778Physiological and pharmacological characterization of human engineered heart tissue
Authors: I Vollert, S Schaaf, C Neuber, D Letuffe-Breniere, K Breckwoldt, A Shibamiya, D Stimpel, A Eder, T Eschenhagen, A Hansen
Journal: Cardiovascular Research (2014)

Objective: Human induced pluripotent stem cell (iPS cell)-derived cardiomyocytes represent a valuable tool in cardiovascular research of tremendous potential. However, these cells are still immature and characterized by poor sarcomeric organization and cellular orientation in 2D cell culture. Therefore, the measurement of contractile force, the most important and best understood function of cardiomyocytes in vivo, is not established for these cells. This study describes the generation of three-dimensional, strip-format, force generating engineered heart tissues (EHTs) from human iPS cell-derived cardiomyocytes and presents a characterization of physiological and pharmacological parameters based on force development. Methods and results: Cardiomyocyte differentiation of human induced pluripotent cells was achieved by a growth factor-based three stage protocol. Strip-format EHTs were generated from dissociated cardiomyocytes in fibrin matrix between flexible silicone posts. Within two weeks after casting coherently beating human EHTs were formed and EHTs displayed a regular beating pattern for several weeks. Histological analysis revealed a high degree of sarcomeric organization and alignment of cardiomyocytes in EHTs. Functional analysis was performed by measuring force response to calcium concentration, pre-load, pacing frequency, beta-adrenergic and muscarinic agonists, modulators of sodium, calcium and potassium channels and revealed concentration-dependent effects. Comparison with native human heart tissue suggests an overall high level of similarity and minor differences. Conclusions: This study demonstrates feasibility to characterize human iPS cell-derived cardiomyocytes in EHTs by measuring contractile force. The analysis suggests high levels of similarity between EHTs and native human heart tissue. Human EHTs are a promising platform for automated toxicology screens in future drug development and for in vitro experiments on human cardiomyocytes in general.
Abstract 3097: Genomic instability of the breast tumor microenvironment: Stromal alterations or technological artifact
Authors: Seth K. Rummel, Allyson L. Valente, Jennifer L. Kane, Darrell L. Ellsworth, Craig D. Shriver, Rachel E. Ellsworth
Journal: Cancer Research (2012)

Abstract Introduction: The breast tumor microenvironment plays an active role in tumorigenesis. Molecular alterations, including epigenetic modifications to DNA, and changes in RNA and protein expression have been identified in tumor-associated stroma; however, there is considerable debate as to whether the stroma is characterized by genomic instability or whether detection of chromosomal alterations in the breast stroma is a reflection of technological artifact rather than the true genomic content of the tumor microenvironment. Methods: Surgically-removed breast stroma specimens from 112 women undergoing reductive mammoplasty (n=7), prophylactic mastectomy (N=6) or mastectomy for a diagnosis of breast disease (n=99) were frozen in optimal cutting temperature medium. Allelic imbalance analysis was performed in 484 stromal specimens from 98 women using a panel of 52 microsatellite markers; SNP data was generated from a subset of 86 stromal specimens using 250K SNP arrays (Affymetrix). Copy number alterations were identified using Partek Genomics Suite. Results: AI was not detected in 93% (444/484) of stroma specimens. When compared to AI generated from 77 FFPE stroma specimens, 32 (42%) of which harbored at least one detectable AI event, the frequency of AI in the FFPE specimens (4.62%) was significantly higher (P&amp;lt;0.0001) than that found in frozen specimens (0.45%). Of the stroma specimens assayed using SNP arrays 95% (82/86) had no detectable alterations and the 11 copy number changes were small and not shared between specimens. Conclusions: The data presented here support a model in which the tumor microenvironment is genetically stable. The direct comparison of copy number alterations between FFPE and frozen research-grade specimens using identical methodologies suggests that past reports of significant AI/LOH in breast stroma, both adjacent to and distant from the tumor, reflects artifact in the archival specimens caused by formalin-fixation, paraffin-embedding and tissue storage. 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 3097. doi:1538-7445.AM2012-3097
Abstract 842: Proteomics-based comparative analysis of mitochondria isolated from human cisplatin-sensitive and resistant ovarian carcinoma cell lines
Authors: Nicole P. Chappell, Pang-ning Teng, Brian L. Hood, Chad A. Hamilton, G. Larry Maxwell, Thomas P. Conrads
Journal: Cancer Research (2012)

Abstract Epithelial ovarian cancer (EOC) is the leading cause of death among women with gynecologic malignancies and the fifth leading cause of cancer death in women in the United States. Cisplatin is one of the most effective and active agents in the treatment of advanced EOC, however, development of chemoresistance is a major obstacle. A recurrent theme is emerging that mitochondria and mitochondrial dysfunction are centerpiece in contributing to an aggressive carcinogenic phenotype. Similarly, we hypothesized that changes in the mitochondrial proteome are required to support development of cisplatin resistance in human EOC. We applied an organellar proteomics approach to elucidate quantitative alterations in protein abundance in mitochondria enriched from an isogenic pair of cisplatin sensitive (A2780) and resistant (A2780-CP20) human EOC cells. Protein isolates from mitochondria were analyzed by high resolution liquid chromatography-tandem mass spectrometry (LC-MS/MS) and quantitative determination of changes in the relative abundance level of identified proteins was accomplished by spectral counting. This analysis confirmed that there are substantial alterations in the mitochondrial proteomic composition in cisplatin resistant EOC cells. Differential proteins selected for western blot validation include hypoxia up-regulated protein 1 (HYOU1), activated leukocyte cell adhesion molecule (ALCAM), isoform 1 of dynamin-like 120kDa protein (OPA1), A kinase anchoring protein 12 (AKAP12), and ferredoxin reductase (FDXR). Our proteomic analysis demonstrated overexpression of HYOU1, ALCAM, AKAP12, and OPA1 in the resistant EOC cells. This panel of protein candidates have been implicated in other tumor types and are involved in relevant cell mechanisms to include evasion of apoptosis, increased tumor invasiveness, tumor hypoxia, cellular respiration, and mitochondrial fragmentation. 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 842. doi:1538-7445.AM2012-842
Abstract 4083: Reduced carbohydrates in resistant aggressive tumors, The RECHARGE Trial: A safety and feasibility nutritional study in ten patients
Authors: Eugene J. Fine, C.J. Segal-Isaacson, Richard D. Feinman, Nora Tomuta, Maria Romano, Maria Bontempo, Joseph A. Sparano
Journal: Cancer Research (2011)

Abstract Background: Many aggressive cancers share a glycolytic phenotype associated with increased 18F-2-fluoro, 2-deoxyglucose (FDG) positron emission tomography (PET) uptake. Carbohydrate restricted (CR) diets, by inhibiting insulin secretion, enlist plausible but unproven mechanisms to limit cancer growth. Objectives: We evaluated safety/feasibility of a CR diet in patients with advanced FDG-avid cancers using a change in exit vs. baseline FDG uptake as a surrogate measure of tumor response using prospective EORTC criteria. Methods: Patients with advanced, incurable cancers and FDG-positive scans were recruited. Eligibility required ECOG performance status of 0-2, normal hepatic, renal, and gastrointestinal function, no diabetes or recent weight loss (&amp;gt; 5% within 3 months), and a body mass index of &amp;gt;20 kg/M2. A supervised CR diet (5% of total kCal) was monitored weekly for macronutrient intake, body weight, serum electrolytes, betahydroxybutyrate concentrations [BHB]. An exit four-week PET scan was obtained. Results: Ten subjects with advanced cancer completed &amp;gt; 26 days of the diet without associated adverse effects. Mean daily caloric intake decreased (35 + 6) % vs. Harris-Benedict formula's predicted energy requirements, and median/mean weight loss were 4.1% (range 0.0-6.1%.) and (4.1 + 0.7) %, respectively. One patient had advanced but indolent disease (14 years without chemotherapy). Among nine patients with pre-trial progressive disease (Table 1), 4 continued to progress on PET, and 5 did not. Non-progression (n=5) vs. continued progession (n=4) correlated (p=0.02) with three fold higher dietary ketosis but not with reduced energy intake (p=0.65). Conclusions: Preliminary data suggest safety/feasibility of carbohydrate restriction in patients with advanced cancer, and that ketosis correlated with disease stabilization, supporting further evaluation of CR as a complementary approach in conjunction with standard therapies. 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 4083. doi:10.1158/1538-7445.AM2011-4083
Anesthesia for Radical Mastectomy with Intravenous Pentothal Sodium and Intercostal Nerve Block
Authors: James C. McCann
Journal: New England Journal of Medicine (1946)

THE increasing use of Pentothal Sodium as an important anesthetic agent during major surgical procedures is well attested in the current literature on methods of anesthesia. That its optimal usefulness with the greatest measure of safety is achieved when it is employed in conjunction with supplemental anesthetic agents is borne out by reports relating to such conjoint use or by those that discuss in passing the supplemental use of other agents. My1 previous report discussed the combined use of intravenous Pentothal Sodium and local nerve block (splanchnic) in upper abdominal surgery. In this earlier study, in which a new splanchnic . . .
Endoscopic mucosal resection of inflammatory fibroid polyp in the transverse colon
Authors: H. Ishibashi, K. Aoyagi, H. Kobayashi, K. Kurahara, K. Kominato, K. Kawasaki, Y. Oshiro, T. Fuchigami
Journal: Endoscopy (2012)

A 70-year-old woman visited our hospital complaining of anemia. Laboratory testing revealed a peripheral blood hemoglobin concentration of 9.4 g/dL. Upper and lower gastrointestinal endoscopic examinations were performed to investigate the cause of the anemia. The findings of the upper endoscopic examination were normal. However, the lower endoscopic examination revealed a semipedunculated polyp with a flat elevated lesion in the transverse colon ([Fig. 1]). The surface of the broad-based polyp was erythematous and eroded. The pathological analysis of the biopsy specimen from the polyp suggested inflammatory fibroid polyp (IFP). It was considered that the polyp was the cause of the anemia and that excision was therefore indicated.
Abstract 1593: Cellular effects of the mitochondrially-directed antioxidant Tempol.
Authors: Aparna H. Kesarwala, William DeGraff, Janet Gamson, Rajani Choudhuri, John A. Cook, Murali C. Krishna, James B. Mitchell
Journal: Cancer Research (2013)

Abstract The mitochondrial respiratory chain is a major source of reactive oxygen species, making it a high-yield target for antioxidants and potential radioprotection. The lipophilic cation triphenylphosphonium (TPP) has been used to target antioxidants to the mitochondrial membrane. Its lipophilicity permits it free passage through biological membranes while its positive charge traps it in the mitochondrial membrane, which is characterized by a large membrane potential. Among the agents localized to mitochondria via TPP have been stable nitroxide radicals, superoxide dismutase mimetics which also demonstrate the ability to scavenge free radicals. 4-Hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl, or Tempol (TP), is a nitroxide which is radioprotective both in vitro and in vivo when present during ionizing radiation. As with most chemical radioprotectors, relatively high concentrations of Tempol are required for protection. We questioned whether mito-Tempol (MTP), Tempol directed to mitochondria via TPP, would provide protection against radiation or hydrogen peroxide (HP) cytotoxicity as measured by the clonogenic assay in Chinese hamster V79 cells. MTP (10-500 μM) present 10 min prior to, during, and 4 hr after 12 Gy provided no radioprotection. MTP exhibited no cytotoxicity alone. In contrast, both TP and MTP (500 μM), when present immediately before and during a 1 hr exposure to HP, provided significant protection against HP cytotoxicity. We next evaluated the effects of continuous exposure to TP or MTP (100 μM) on the growth rate of several human tumor cell lines (MCF7, HT29, 786-0). TP had little effect on growth of these cell lines while MTP completely inhibited cell growth. The effects of the TPP-carbon linker alone will be presented; in short-term studies it did not exhibit cytotoxicity to V79 cells. These preliminary data with mitochondrial targeting of Tempol demonstrate that MTP exhibited antioxidant properties similar to TP with regard to protection against HP; at concentrations up to 500 μM, however, MTP did not protect against radiation. The latter finding is consistent with the requirement that chemical radioprotectors be present in sufficient concentration in the nucleus to afford radioprotection. Additional studies will be presented addressing the mechanism of MTP-mediated growth inhibition in human tumor cell lines. Citation Format: Aparna H. Kesarwala, William DeGraff, Janet Gamson, Rajani Choudhuri, John A. Cook, Murali C. Krishna, James B. Mitchell. Cellular effects of the mitochondrially-directed antioxidant Tempol. [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 1593. doi:10.1158/1538-7445.AM2013-1593
Prevention of the First Occurrence of Neural-Tube Defects by Periconceptional Vitamin Supplementation
Authors: Andrew E. Czeizel, István Dudás
Journal: New England Journal of Medicine (1992)

The risk of recurrent neural-tube defects is decreased in women who take folic acid or multivitamins containing folic acid during the periconceptional period. The extent to which such supplementation can reduce the first occurrence of defects is not known.
Exposure to Free and Conjugated Forms of Bisphenol A and Triclosan among Pregnant Women in the MIREC Cohort
Authors: Tye E. Arbuckle, Leonora Marro, Karelyn Davis, Mandy Fisher, Pierre Ayotte, Patrick Bélanger, Pierre Dumas, Alain LeBlanc, René Bérubé, Éric Gaudreau, Gilles Provencher, Elaine M. Faustman, Eric Vigoren, Adrienne S. Ettinger, Michael Dellarco, Susan MacPherson, William D. Fraser
Journal: Environmental Health Perspectives (2014)

Bisphenol A (BPA) and triclosan (TCS) are two nonpersistent chemicals that have been frequently measured in spot urine samples from the general population but less so in pregnant women; however, data are limited on the free (bioactive) and conjugated forms of these phenols.The Maternal-Infant Research on Environmental Chemicals (MIREC) Study addressed these data gaps by utilizing stored maternal urine samples from a large multicenter cohort study of Canadian pregnant women.Concentrations of free and conjugated forms of BPA and TCS were measured in about 1,890 first-trimester urine samples by ultra performance liquid chromatography-tandem mass spectrometry using isotope dilution.The glucuronides of BPA and TCS were the predominant forms of these chemicals measured (detected in 95% and 99% of samples, respectively), whereas the free forms were detected in 43% and 80% of samples, respectively. The geometric mean urinary concentrations for glucuronides of BPA and TCS were 0.80 μg/L (95% CI: 0.75, 0.85) and 12.30 μg/L (95% CI: 11.08, 13.65), respectively. Significant predictors of BPA included maternal age < 25 vs. ≥ 35 years, current smoking, low vs. high household income, and low vs. high education. For TCS, urinary concentrations were significantly higher in women ≥ 25 years of age, never vs. current smokers, and women with high household income and high education.The results from this study represent the largest national-level data on urinary concentrations of free and conjugated forms of BPA and TCS in pregnant women and suggest that maternal characteristics predicting elevated urinary concentrations of these phenols largely act in opposite directions.
Defective Glucose Counterregulation after Strict Glycemic Control of Insulin-Dependent Diabetes Mellitus
Authors: Stephanie A. Amiel, William V. Tamborlane, Donald C. Simonson, Robert S. Sherwin
Journal: New England Journal of Medicine (1987)

We infused small doses of insulin (0.3 mU per kilogram of body weight per minute; range, 0.9 to 1.7 U per hour) for three hours into 8 subjects who did not have diabetes, 11 patients with well-controlled diabetes (hemoglobin A1, 7.6 +/- 0.7 percent), and 10 patients with poorly controlled diabetes (hemoglobin A1, 11.5 +/- 1.7 percent) to simulate the mild peripheral hyperinsulinemia observed during insulin treatment. Normoglycemia was established in the patients during the night before study. During the insulin infusion, the plasma glucose level stabilized at 60 to 70 mg per deciliter (3.3 to 3.9 mmol per liter) in the subjects without diabetes and the patients with poorly controlled diabetes, because of a rebound increase in hepatic glucose production. In contrast, hypoglycemia developed in the patients with well-controlled diabetes (42 +/- 2 mg of glucose per deciliter, or 2.3 +/- 0.1 mmol per liter, P less than 0.01) as glucose production remained suppressed. The hypoglycemia in the patients with well-controlled diabetes was associated with a lowering of the plasma threshold of glucose that triggered a release of epinephrine (less than 45 mg of glucose per deciliter, or 2.5 mmol per liter, vs. greater than 55 mg per deciliter, or 3.1 mmol per liter, in the other groups, P less than 0.01) as well as an enhanced sensitivity to the suppressive effects of insulin on hepatic glucose production. Nearly identical disturbances in glucose counterregulation and decreased perception of hypoglycemia developed when four of the subjects with poorly controlled diabetes were restudied after intensive treatment. We conclude that strict control of diabetes induces physiologic alterations (delayed release of epinephrine and persistent suppression of glucose production) that impair glucose counterregulation to doses of insulin in the therapeutic range. These defects may contribute to the increased incidence of severe hypoglycemia reported during intensive insulin therapy.