tbuckley/cabot-search huggingface dataset:
Coping with loss: The doctor's losses: ideals versus realities
Authors: G. Bennet
Journal: BMJ (1998)

A radioimmunoassay for the measurement of gonadotrophin releasing hormone (GnRH) in plasma and urine using readily available reagents was developed. The GnRH assay showed good precision, recovery, and parallelism over a wide range of GnRH concentrations with a sensitivity of 15 pg/ml. The assay was compared with a commercially available kit (Buhlmann Laboratories). Although the Buhlmann kit showed acceptable precision, recovery, sensitivity, and correlation with the developed GnRH assay for plasma samples, lack of parallelism of serially diluted plasma and urine samples was consistently observed, together with a poor correlation with the developed GnRH assay for urine, suggesting a matrix effect with the Buhlmann kit. The developed assay is suitable for measuring GnRH in samples obtained from patients receiving pulsatile infusions of GnRH. In contrast, the commercially available Buhlmann kit was unsuitable for measuring plasma GnRH as the kit had a top standard of only 160 pg/ml, well below the peak plasma concentration. It would not be possible to dilute samples for analysis because of the lack of parallelism of diluted samples compared with standards obtained with the Buhlmann assay.
Abstract A112: Eradication of cancer stem-like cells in PDAC
Authors: Thiruvengadam Arumugam, Vijaya Ramachandran, Craig Logsdon
Journal: Cancer Research (2015)

Abstract Background: Pancreatic Ductal Adenocarcinoma (PDAC) is resistant to conventional chemotherapy. Cancer Stem-Like Cells (CSLCs) are drug resistant and can act as tumor initiating cells. Evidence suggests that CSLCs can be selected by chemotherapy that targets the more sensitive somatic cancer cells. In the current study we found that Gem treatment can not only select CSLCs, but can also induce transformation of somatic cancer cells into CSLCs. We also observed that p21 is required to maintain CSLCs in a quiescent state. Methods: Cell growth, cell cycle and apoptosis were analyzed by using MTS and FACS analysis. ALDH and p21 were localized by immunohistochemistry and immunofluorescence. CLSCs were analyzed by ALDH assay, clonogenic in vitro assays and in vivo tumor initiation. Both in vitro and in vivo silencing of p21 was accomplished using nanoparticle coupled siRNA. Results: Gem treatment induced the p21 and led to a transient cytostasis and chemoresistance in PDAC cell lines. Analysis of resected tumor samples revealed that Gem treatment also induced p21 expression and ALDH positivity in tumors of Gem treated but not untreated patients. In vitro studies indicated that Gem induced the acquisition of a CSLC phenotype and the expression of pluripotent transcription factors (PFTs). Silencing of p21 blocked the both basal and Gem induced CSLC numbers, the maintenance of quiescence, and resistance to Gem in vitro. In vivo, silencing of p21 greatly increased the effectiveness of Gem treatments to inhibit tumor growth and did not increase toxicity. Conclusion: These data indicate that p21 maintains chemotherapy induced CSLCs quiescence and drug resistance such that targeting p21 in combination with cytotoxic therapies is beneficial in eradicating both basal and Gem transformed CSLCs. Note: This abstract was not presented at the conference. Citation Format: Thiruvengadam Arumugam, Vijaya Ramachandran, Craig Logsdon. Eradication of cancer stem-like cells in PDAC. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr A112.
Acquired resistance to cisplatin is accompanied by the increased export of secretory and lysosomal components via exosomes
Authors: Roohangiz Safaei, Barrett J. Larson, Shinji Otani, Timothy C. Cheng, Michael A. Gibson, Wiltrud Naerdemann, Stephen B. Howell
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

1481 

We have previously documented that the intracellular sequestration and trafficking of cisplatin (DDP) is altered in DDP-resistant ovarian carcinoma cells. In this study we examined the lysosomal and secretory compartments of DDP-resistant cells using deconvoluting microscopy of cells stained with antibodies and compartment-specific dyes, microarray analyses of mRNA expression, Western blot analysis and drug accumulation measurements. Major findings are: 1) the lysosomal compartment is reduced in DDP-resistant cells 2008/C13*5.25, IGROV-1/CP and A2780/CP, compared to parental sensitive lines, 2008, IGROV-1, and A2780 as demonstrated by staining with antibodies for LAMP1, LAMP2 (lysosome associated proteins 1 and 2) and lysotracker red. Quantitative analysis showed that the lysosomal compartment in the 2008/C13*5.25 was only 40% of that in the sensitive 2008 cells (p<0.002). 2) Reduction in the lysosomal compartment was confirmed by Western blot analysis of whole cell lysates from the same 3 pairs of cell lines using antibodies against LAMP1 and LAMP2. The levels of LAMP1 in the 2008/C13*5.25, IGROV-1/CP, and A2780/CP cells were, respectively, 65%, 23%, and 32% of those in their sensitive counterparts; the levels of LAMP2 expression in these 3 resistant cells were, respectively, 31%, 34%, and 67% of the levels in the parental cells. 3) Analysis of microarray data from these and 3 additional pairs of DDP-sensitive and resistant ovarian lines demonstrated altered expression of genes involved in the formation and vesiculation of multivesicular bodies in the DDP-resistant cell lines. 4) SELDI mass spectrometry of the exosomal fractions from the 2008 and 2008/C13*5.25 demonstrated that the exosomes contained ≈ 200 protein species, several of which show substantial differences in abundance between the exosomes from sensitive and resistant cells. 5) Exosomes from resistant cells contained more total protein and were enriched in lysosomal proteins LAMP1 and LAMP2 and the secretory pathway proteins ATP7A, ATP7B, and MRP2. LAMP1 was only present in exosomes from DDP resistant cells. The levels of LAMP2, ATP7A, ATP7B, and MRP2 in exosomes of DDP-resistant cells were 3.4-, 1.5-, 2.6-, and 2.6-fold higher than those in sensitive cells respectively. 6) Exosomes released from DDP-resistant cells, loaded with DDP for 1 hr, contained 2.6 ± 0.8 fold more Pt than exosomes released from similarly treated DDP-sensitive cells (p = 3.8 x 10-5). The results of this study confirm that DDP-resistant cells exhibit major alterations in their lysosomes and secretory traffic patterns as well as enhanced exosomal export of Pt following exposure to DDP. Supported by NIH grant CA95298.
Phase III study of induction chemotherapy (docetaxel and carboplatin) with or without radiotherapy followed by surgery in patients with stage IIIA (pN2) non-small cell lung cancer (NSCLC): WJTOG9903
Authors: H. Tada, M. Tanaka, N. Katakami, T. Kurata, T. Mitsudomi, S. Negoro, S. Kudoh, H. Nishiyama, Y. Nishimura, K. Nakagawa
Journal: Journal of Clinical Oncology (2009)

7556 Background: Standard treatment of resectable N2 disease is not yet established. To gain insights on significance of preoperative chemoradiotherapy, we tried to evaluate feasibility and efficacy of induction chemotherapy with or without radiotherapy followed by surgery in patients with stage IIIA NSCLC with mediastinal lymph node metastases. Methods: Patients with histologically proven N2 disease were randomized either to receive induction chemotherapy (taxotere 60 mg/m2 and carboplatin AUC 5x2 cycles) with concurrent radiation therapy of 40Gy/20fr (CRS group) or without it (CS group). Patients subsequently underwent pulmonary resection if the tumor was judged resectable. Original sample size was 180 to detect a 20% of survival difference (2 sided P=0.05) with a power of 0.8. The primary endpoint was overall survival. Results: Between Jan. 2001 and Dec 2005, 60 patients were randomized Because of poor accrual of the patients, the study was prematurely terminated. Two patients assigned to CRS group were ineligible due to staging misconducts. Median age was 57 years (range 34–70 years), and 66% were male. Two groups were well balanced with regard to age, gender, histology, and operative procedures. Induction therapy was well tolerated, and there was no treatment related death. Grade 3 and 4 neutropenia occurred in 74 and 89%, respectively. Objective response rate was 25% for the both groups. Surgical resection was performed in 86% and 89%of the patients in CS and CRS groups, respectively. There have been 37 deaths to date. Event free survival at 3 year was 18% and 32% for patients in CS and CRS group, respectively (HR=0.64; 95% CI: 0.36–1.17, P=0.15). Overall survival at 3 year was 44.4 %. and 52.7% (HR=0.84; 95% CI: 0.44–1.62, P=0.62), respectively. Conclusions: Because of small sample size, there was no statistically significant difference. However, our study suggested that addition of radiotherapy to induction chemotherapy could potentially prolong survival of NSCLC patients with N2 disease. [Table: see text]
Abstract 12763: Ischemic Memory Imaging with a Selectin-targeted Microbubble Contrast Agent: Efficacy and Safety Testing in a Non-human Primate Model of Myocardial Ischemia
Authors: Brian Davidson, Scott M Chadderdon, Todd Belcik, Saurabh Gupta, Thierry Bettinger, Michel Schneider, Jonathan R Lindner
Journal: Circulation (2010)

Background: Molecular imaging of P-selectin with targeted myocardial contrast echocardiography (MCE) has been demonstrated in rodent models to accurately detect recent ischemia. The aim of this stu...
Incidental Detection of a Hodgkin Lymphoma on 18F-Choline PET/CT and Comparison With 18F-FDG in a Patient With Prostate Cancer
Authors: Aurore Goineau, Mathilde Colombié, Caroline Rousseau, Sophie Sadot-Lebouvier, Stéphane Supiot
Journal: Clinical Nuclear Medicine (2015)

Combined PET/CT scanning with 18F-FDG is in current use in Hodgkin lymphoma. New tracers have been developed, such as 18F-choline in prostate cancer. Its use is under investigation in other solid tumors (eg, brain, liver, lung). We report a case of Hodgkin lymphoma incidentally detected on 18F-choline PET/CT in a prostate cancer patient and show a comparison with 18F-FDG PET/CT. 18F-choline PET/CT detected more lymph node lesions than the 18F-FDG PET/CT for this patient. Comparative studies of the 2 tracers might help fine-tune treatments and, in particular, delineate target zones in radiation therapy.
Cellular constraints to diffusion
Authors: James A. Schafer, Thomas E. Andreoli
Journal: Journal of Clinical Investigation (1972)

These experiments were intended to evaluate the effects of antidiuretic hormone (ADH) on dissipative water transport in cortical collecting tubules isolated from rabbit kidney. In the absence of ADH, the osmotic (P(f), cm sec(-1)) and diffusional (P(DW) cm sec(-1)) water permeability coefficients were, respectively, 6+/-6 and 4.7+/-1.3 (SD). When ADH was added to the bathing solutions, P(f) and P(DW) rose to, respectively, 186+/-38 and 14.2+/-1.6 (SD). In the absence of ADH, the tubular cells were flat and the lateral intercellular spaces were closed when the perfusing and bathing solutions were, respectively, hypotonic and isotonic; in the presence of ADH, the cells swelled and the intercellular spaces dilated. These data suggest that ADH increased the water permeability of the luminal membranes of the tubules. It was possible that the ADH-dependent P(f)/P(DW) ratio was referable to the resistance of the epithelial cell layer (exclusive of luminal membranes) to water diffusion (R(DW), sec cm(-1)). Such a possibility required that R(DW) be approximately 650, i.e., approximately 25-fold greater than in an equivalent thickness of water. To test this view, it was assumed that R(Di) values for lipophilic solutes in lipid bilayer membranes and in luminal membranes were comparable. In lipid bilayer membranes, R(Di) was substantially less than 90 sec cm(-1) for pyridine, n-butanol, and 5-hydroxyindole. In renal tubules, R(Di) for these solutes ranged from 795 to 2480 with and without ADH. It was assumed that, in the tubules, R(Di) was referable to cellular constraints to diffusion; for these solutes, the latter were 12-25 times greater than in water. Accordingly, it is possible that the ADH-dependent P(f)/P(DW) ratio was also due to cellular constraints to diffusion.
Abstract 3783: Antihypertensive Medications in the Department of Veterans Affairs (VA) 1999–2006
Authors: Julio R Lopez, Sonya Wong, Joy L Meier, Fran Cunningham, David Siegel
Journal: Circulation (2007)

Objective: To evaluate national antihypertensive medication use we collected data from 2003–2006 and compared it to previously collected data from 1999 –2002. We examine the cost implications of shifts in antihypertensive medications prescribed. Methods: National VA pharmacy data were used to determine the use of beta blockers (BB), calcium channel blockers (CCB), thiazide diuretics (TD) alone or with K sparing diuretics, angiotensin converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), and combinations of the aforementioned classes for 2003–2006. Total number of treatment days, determined from days supply of the prescription, was used to determine patterns of use over time. Results: Antihypertensive medication use in the VA represented more than 1.5 billion days in 2006 and increased 2.5 fold from the 577 million estimated for 1999. ACEI were most commonly used, representing 31.8% and 31.7% of treatment days in 1999 and 2006, respectively. In the ACEI class lisinopril is the most commonly used drug. Increases in use from 1999 to 2006 were 21.2% to 25.2% for BB, 14.4% to 17.8% for TD, and 1.2% to 5.2% for ARB. Decreases in use from 1999 to 2006 were 26.7% to 17.6% for CCB. The decline in CCB was inversely correlated to the increase in BB or TD (p&lt;0.001). Shifts in medication use are estimated to save the VA $33 million annually. Conclusions: ACEI remain the most prescribed antihypertensive drug class in the VA, followed by BB, TD, CCB, and ARBs. TD use shows a slow steady increase while CCB use continues to decline. These findings suggest that VA has increasing adherence to JNC7 and VA HTN guidelines.
Abstract 4173: The Impact of Coronary Artery Endarterectomy on Outcomes During Coronary Artery Bypass Grafting
Authors: Farshad Anvari, Damien J Lapar, John A Kern, Brian R Swenson, Benjamin B Peeler, Irving L Kron, Gorav Ailawadi
Journal: Circulation (2009)

Background: The safety of coronary artery endarterectomy (CE) during coronary artery bypass grafting has been debated. We examined the outcome of CE compared to isolated coronary artery bypass graf...
Abstract 428: Creating Biocompatible 3-D Scaffolds for Engineering Cardiovascular Tissues: Heart, Lung, and Kidney
Authors: Thomas Matthiesen, Harald C Ott, Sak-Kia Goh, Stefan M Kren, Doris A Taylor
Journal: Circulation (2007)

Background . Biocompatibility is an essential property of any extracellular matrix (ECM) used in tissue engineering. Perfusion decellularized whole cadaveric organs could provide novel scaffolds for organogenesis but their long term biocompatibility remains unknown. . Hypothesis: Perfusion decellularization of mammalian organs yields a biocompatible matrix that influences cell growth differentially in non-perfused 2-D tissue culture conditions. Methods . Adult F344 rats were euthanized after systemic heparinization. Heart, lung, liver, and kidney were removed, canulated, and perfused with SDS to remove cellular debris. Subsequent washing with 1% Triton-X-100 and PBS was performed to remove detergent. Biocompatibility was assessed by co-culture of ECM from each organ with either rat skeletal myoblasts (SKMBs) or mouse embryonic stem cells (mESCs). Decellularized tissue was cut into 0.5x1cm pieces and seeded with 40K cells each. Cells were fed daily and photographed on day 3, 9, 13, 17 (SKMB) or day 3, 5, 10, 12, 14, 20, 24 (mESC). Double-blinded high powered field (HPF) analysis was used to quantify cell growth over time. At day 17 or 24 tissues were harvested for histological analysis and TUNEL assays to assess cell number and viability. Results . Cell viability was &gt;90% in all cases but showed no organ preference. heart + SKMB 90.2 ± 2.4 and mESC 98.3 ± 1.1; lung + SKMB 96.3 ± 1.9 and mESC 96.4 ± 1.0; liver + SKMB 90.3 ± 3.2 and mESC 97.7 ± 1.6; kidney + SKMB 89.5 ± 4.5 and mESC 98.1 ± 1.4 Cell number on the other hand increased in all ECM coculture conditions (Table 1 ;) but with two distinct patterns depending on the organ. Maximal cell density was observed in Kidney followed by Liver, Lung and Heart (Table 1 ). Conclusion. SDS-based perfusion decellularization of cadaveric heart, lung, liver, and kidney provides biocompatible scaffolds that are conducive to cell growth and viability. Kidney and liver scaffolds allowed for greatest cell proliferation over time.
Translocations and Clonality Detection in Lymphoproliferative Disorders By Capture-Based Next-Generation Sequencing. a Pilot Study By the Euroclonality-NGS Consortium
Authors: Dörte Wren, Brian A Walker, Monika Brüggemann, Mark Catherwood, Christiane Pott, Kostas Stamatopoulos, Anton W Langerak, David Gonzalez
Journal: Blood (2014)
Abstract 15872: A Founder Mutation in Desmocollin-2 Causes a Predominant Left Ventricular Arrhythmogenic Cardiomyopathy in Homozygous Carriers in a Hutterite Population
Authors: Brenda Gerull, Florian Kirchner, Oliver Strohm, Matthias Friedrich, Henry J Duff
Journal: Circulation (2011)

Background: Heterozygous mutations in desmosomal proteins have been shown to cause arrhythmogenic right ventricular cardiomyopathy (ARVC). The disease predominantly affects the right ventricle and ...
754. Intravitreal Administration of an AAV8 Retinoschisin Vector to the Rs1-KO Mouse Results in Cell Type-Specific Gene Expression and Rescue of the Disease Phenotype
Authors: T. Park, Z. Wu, S. Kjellstrom, Y. Zeng, R. A. Bush, P. A. Sieving, P. Colosi
Journal: Molecular Therapy (2009)
Desire for death in the terminally ill
Authors: H M Chochinov, K G Wilson, M Enns, N Mowchun, S Lander, M Levitt, J J Clinch
Journal: American Journal of Psychiatry (1995)

Euthanasia and physician-assisted suicide have become prominent medical and social issues. This study investigated the prevalence of the desire for death in terminally ill patients, the stability of this desire over time, and its association with psychiatric disorders.Two hundred terminally ill inpatients were given semistructured interviews that assessed their desire for death and evaluated them for major and minor depressive episodes according to the Research Diagnostic Criteria. Each patient also completed a short form of the Beck Depression Inventory and provided ratings of pain and social support. When possible, patients who expressed a desire for death received a follow-up interview after a 2-week interval.Although occasional wishes that death would come soon were common (reported by 44.5% of the patients), only 17 (8.5%) of these individuals acknowledged a serious and pervasive desire to die. The desire for death was correlated with ratings of pain and low family support but most significantly with measures of depression. The prevalence of diagnosed depressive syndromes was 58.8% among patients with a desire to die and 7.7% among patients without such a desire. Follow-up interviews were conducted with six patients; in four cases, the desire to die had decreased during the 2-week interval.The desire for death in terminally ill patients is closely associated with clinical depression--a potentially treatable condition--and can also decrease over time. Informed debate about euthanasia should recognize the importance of psychiatric considerations, as well as the inherent transience of many patients' expressed desire to die.
Arsenic trioxide modulates p53 and bcl-2 expression in breast and lung carcinoma cells
Authors: Alice Walker, Jacqueline Stevens, Paul Tchounwou
Journal: Cancer Research (2008)

4372  Arsenic is a potent toxicant that may exist in several valence states and in a number of inorganic and organic forms. Most cases of arsenic-induced toxicity in humans are due to exposure to inorganic arsenic, and there is an extensive database on the human health effects of the common arsenic oxides such as arsenic trioxide. The primary source of human exposure is through drinking water and food. The p53 gene plays a key role in mediating cell response to various stresses, mainly by inducing or repressing a number of genes involved in cell cycle arrest, senescence, apoptosis, DNA repair, and angiogenesis. The p53 gene exerts its anti-proliferative action by inducing reversible or irreversible (senescence) cell cycle arrest or apoptosis. It may also enhance DNA repair and inhibit angiogenesis. The bcl-2 gene can act as a pro or anti-apoptotic regulator that is involved in wide variety of cellular activities. The bcl-2 gene has been implicated in several cancers such as melanoma, breast, prostate and lung. Arsenic has also shown to be cytotoxic and able to induce stress-related genes and proteins in a number of cell lines, mainly of the skin and liver. Although arsenic has been reported to cause DNA damage to liver and hematopoetic cells, its effects on breast and lung cells are not well elucidated. The primary objective of this research is to evaluate the effects of arsenic trioxide on p53 and bcl-2 expression in breast and lung carcinoma cells. To achieve this goal, breast cancer (MCF-7) and lung cancer (A549) cells were cultured following standard protocols, and exposed to various doses (0, 2, 4, 6, 8, and 10 µg/ml) of arsenic trioxide for 48 h. Protein and western blot analyses were performed using standard protocols. The Western blot analysis revealed an up-regulation of p53 with the exposure of arsenic trioxide, showing a peak expression at 4µg/ml. Experiments on bcl-2 expression are underway, and it is anticipated that arsenic exposure would induce its down-regulation in arsenic-treated cells.
Dead sober or dead drunk?
Authors: Derrick Pounder
Journal: BMJ (1998)

Assessing the validity of an alcohol concentration in a postmortem blood sample can be complex. Appreciating the difficulties, some experts challenged the result of 38 mmol/l (175 mg/100 ml) found in Mr Henri Paul, the driver of Princess Diana's car in her fatal car crash. In the current review of the Hillsborough football stadium disaster, by Lord Justice Stuart Smith, the meaning of alcohol concentrations in those deaths is also likely to be disputed. Although the technical aspects of measuring ethanol in body fluids are much the same in the living and the dead,1 the interpretation of results obtained from necropsy samples is confounded by several problems.

The two most important are microbial alcohol production and alcohol diffusion from gastric residue or airways contaminated by vomitus. Distinguishing between alcohol ingestion in life and microbial production after death is a common problem.2 Within a few hours …