tbuckley/cabot-search huggingface dataset:
Multifunctional analysis of cultivated primary adenocarcinoma cells after treatment with different chemotherapeutic drugs
Authors: Annika Sprussel, Jana Kruger, Jana Hennesen, Jorg Spangenberg, Kevin Sullivan, Hartmut Juhl, Kerstin David
Journal: Clinical Cancer Research (2008)

AACR Centennial Conference: Translational Cancer Medicine-- July 20-23, 2008; Monterey, CA

A47 

Background: The discovery of new anticancer drugs is currently performed by using common cancer cell lines. However, it has been shown that long term cultured cell lines are limited in forecasting in vivo drug sensitivities. Therefore, we developed a standardized procedure to isolate pure epithelial cells directly from gastrointestinal tumor tissues and used them to examine chemotherapeutic effects of various cancer agents.    Methods: Primary epithelial cells were freshly derived from adenocarcinoma patients, cultivated for 0, 24, 48 and 72 hours and either treated with various single tumor therapeutics such as Oxaliplatin, Gemcitabine, Iressa and 5-FU or by using drug combinations (Leucovorin/5-FU; FOLFOX; IFOX; and GOLF). Drug responses were analysed by immunofluorescence, ATP measurement and electrochemiluminescence and compared to either similarly treated HT29 cells or short and long term cultivated primary cells.    Results: Application of the GOLF regimen showed in all cell cultures the strongest effect on cell proliferation and metabolism. We observed that compared to the single drug treatments, the different drugs composing GOLF were highly synergistic in inducing growth inhibition. The GOLF combination induced apoptosis in all colorectal cancer cells as measured by caspase-3 activation, PARP cleavage, as well as increased levels of total and phosphorylated p53. Since apoptosis onset in eukaryotic cells is substantially regulated by the balance between apoptotic and survival pathways the effects of the different drug treatments on expression and activity of the components of the Erk and Akt dependent pathways were also evaluated. In all cell cultures the induction of apoptosis due to GOLF treatment was paralleled by increased levels of total as well as phosphorylated ERK, whereas the expression and activation of EGFR, MEK, P70s6K, GSK3β and especially AKT were decreased. All these effects were also seen in cells treated with the single drugs or combinations thereof although less pronounced.    Conclusions: Primary cells from gastrointestinal patients could provide a cellular platform beyond the common cancer cell lines for in vitro drug screening and might allow individualization of chemotherapies for patient treatments.
Echocardiographic parameters that predict poor outcomes in acute pulmonary embolism
Authors: Danai Khemasuwan, Teerapat Yingchoncharoen, Pichapong Tungsupon, Ajit Moghekar, Adriano Tonelli
Journal: European Respiratory Journal (2013)

Introduction:  Limited information exists on the utility of modern echocardiographic measurements in predicting need for ICU care, hospital mortality and length of stay in acute pulmonary embolism (PE).  Methods:  We confirmed diagnosis of PE by reviewing CT angiogram. The patients were admitted between March 2010 and December 2012. We included 56 patients with acute PE in the present study. Patients with poor echocardiographic window were excluded. A large number of traditional and modern echocardiographic variables were measured. Binary logistic regression was used to identify echocardiographic predictors of hospital mortality. Results are given as hazard ratio (HR) and 95% confidence interval.  Results:  Age (mean (SD)) was 61 (15). A total of 52 (93 %) patients were admitted to the medical ICU and the rest to regular nursing floor. On admission HR was 99 (18) bpm, hemodynamic instability on admission was observed in 8 (14 %) patients, FIO2 was 51 (35) %. Thrombolytic therapy was given to 13 (23 %) of individuals. Only 7 (13%) patients died during hospitalization.  Right ventricular diastolic diameter at mid-cavity (HR: 3.2 (1.2-8.7)), tricuspid annular plane systolic excursion (TAPSE) (HR: 0.8 (0.5-1)) and paradoxical interventricular septal motion (HR: 0.09 (0.02-0.54)) predicted hospital mortality. Of the patients that did not die during the hospitalization, echocardiographic parameters obtained on admission could not adequately predict the length of hospital stay.  Conclusions:  Right ventricular diameter, TAPSE and paradoxical septal motion predicted hospital mortality. In those patients that survived the hospitalization, echocardiographic parameters did not predict length of hospital stay.
The transcription factor XBP-1 in neurodegenerative diseases
Authors: Frédéric Checler, Eric Duplan, Cristine Alves da Costa
Journal: Molecular Neurodegeneration (2013)

Parkinson’s disease (PD) is a neurodegenerative disorder that is either associated with an autosomal dominant or recessive mode of inheritance. The latter forms are mostly linked to mutations in the genes of parkin, Pink-1 and DJ-1. Several lines of evidence indicate that DJ-1 could act as an antioxidant while parkin has been characterized as an ubiquitin-ligase. Parkin was reported to interact physically with DJ-1 monomers in oxidative stress conditions but did not promote its ubiquitin-linked proteasomal degradation. This led us to examine whether parkin could control DJ-1 via its function as transcription factor that we documented recently [1]. We have shown [2] that parkin controls DJ-1 by a mechanism independent of its ubiquitin-ligase activity and that this regulation is abolished by PD-related pathogenic mutations. Thus, parkin increases DJ-1 promoter trans-activation, mRNA levels and protein expression via a transcriptional cascade involving p53 repression and subsequent activation of ER-stress induced X-box-binding protein-1S (XBP-1S). Then, XBP-1S physically interacts with DJ-1 promoter, thereby raising DJ-1 mRNA and protein levels. Overall, our study unravels a functional dialogue by which parkin and DJ-1 could control ER-stress response in physiopathological conditions. We will discuss the potential involvement of XBP-1 in other neurodegenerative diseases.
PP2Acα positively regulates the termination of liver regeneration in mice through the AKT/GSK3β/Cyclin D1 pathway
Authors: Shan-Shan Lai, Dan-Dan Zhao, Peng Cao, Ke Lu, Ou-Yang Luo, Wei-Bo Chen, Jia Liu, En-Ze Jiang, Zi-Han Yu, Gina Lee, Jing Li, De-Cai Yu, Xiao-Jun Xu, Min-Sheng Zhu, Xiang Gao, Chao-Jun Li, Bin Xue
Journal: Journal of Hepatology (2015)
PAin SoluTions In the Emergency Setting (PASTIES)--patient controlled analgesia versus routine care in emergency department patients with pain from traumatic injuries: randomised trial
Authors: J. E. Smith, M. Rockett, S. C. S, R. Squire, C. Hayward, P. Ewings, A. Barton, C. Pritchard, V. Eyre, L. Cocking, J. Benger
Journal: BMJ (2015)

<b>Objective</b> To determine whether patient controlled analgesia (PCA) is better than routine care in patients presenting to emergency departments with moderate to severe pain from traumatic injuries. <b>Design</b> Pragmatic, multicentre, parallel group, randomised controlled trial. <b>Setting</b> Five English hospitals. <b>Participants</b> 200 adults (71% (n=142) male), aged 18 to 75 years, who presented to the emergency department requiring intravenous opioid analgesia for the treatment of moderate to severe pain from traumatic injuries and were expected to be admitted to hospital for at least 12 hours. <b>Interventions</b> PCA (n=99) or nurse titrated analgesia (treatment as usual; n=101). <b>Main outcome measures</b> The primary outcome was total pain experienced over the 12 hour study period, derived by standardised area under the curve (scaled from 0 to 100) of each participant's hourly pain scores, captured using a visual analogue scale. Pre-specified secondary outcomes included total morphine use, percentage of study period in moderate/severe pain, percentage of study period asleep, length of hospital stay, and satisfaction with pain management. <b>Results</b> 200 participants were included in the primary analyses. Mean total pain experienced was 47.2 (SD 21.9) for the treatment as usual group and 44.0 (24.0) for the PCA group. Adjusted analyses indicated slightly (but not statistically significantly) lower total pain experienced in the PCA group than in the routine care group (mean difference 2.7, 95% confidence interval −2.4 to 7.8). Participants allocated to PCA used more morphine in total than did participants in the treatment as usual group (mean 44.3 (23.2) <i>v</i> 27.2 (18.2) mg; mean difference 17.0, 11.3 to 22.7). PCA participants spent, on average, less time in moderate/severe pain (36.2% (31.0) <i>v</i> 44.1% (31.6)), but the difference was not statistically significant. A higher proportion of PCA participants reported being perfectly or very satisfied compared with the treatment as usual group (86% (78/91) <i>v</i> 76% (74/98)), but this was also not statistically significant. <b>Conclusions</b> PCA provided no statistically significant reduction in pain compared with routine care for emergency department patients with traumatic injuries. <b>Trial registration</b> European Clinical Trials Database EudraCT2011-000194-31; Current Controlled Trials ISRCTN25343280.
Drug points: Transverse myelitis after measles, mumps, and rubella vaccine
Authors: K A Joyce, J E Rees
Journal: BMJ (1995)

Drs K A JOYCE and J E REES (Hurst-wood Park Neurological Centre, Haywards Heath, West Sussex RH16 4EX) write: A 20 year old man who planned to work with children in the United States was instructed to be vaccinated against rubella and was given measles, mumps, and rubella vaccine. Five days later he developed fever, malaise, sore throat, and a transient rash over his …
Beyond the guidelines? Case review of thrombolysis for pulmonary embolism at a district general hospital
Authors: Stephanie Hobbins, Stephen O'Hickey
Journal: European Respiratory Journal (2013)

Introduction   British Thoracic Society guidelines state that thrombolysis for pulmonary embolism (PE) should only be given for massive PE associated with circulatory collapse. Review by NICE found no evidence that haemodynamically stable patients should be thrombolysed, but debate remains about its use in patients with right heart dysfunction. We assessed the practice and outcomes for PE thrombolysis in our district general hospital.   Method   A retrospective case review of patients treated with thrombolysis for PE at Worcestershire Royal Hospital in 2012.   Results   16 of 355 patients with PE underwent thrombolysis. 43.75% were thrombolysed according to current guidelines; 6 for massive PE with circulatory collapse and 1 in cardiac arrest. 5 were thrombolysed for PE with right heart dysfunction (echo/CTPA), and 4 after clinical assessment of extensive clot burden. 8 patients underwent echo prior to thrombolysis and 75% revealed pulmonary hypertension or dilated right ventricle. 5 of these patients had a post thrombolysis echo and 60% had resolution of the right heart dysfunction. A further 5 patients only had a follow up echo. 50% of all patients with follow up echo had right heart dysfunction, but this did not differ according to patient group.   Conclusion   More than half of our patients were thrombolysed outside current guidelines. This suggests that other patient groups can successfully be thrombolysed and it may help prevent chronic thromboembolic pulmonary hypertension.
Phase II trial of hepatic arterial infusion of fluorouracil and recombinant human interferon alfa-2b for liver metastases of colorectal cancer refractory to systemic fluorouracil and leucovorin.
Authors: Y Z Patt, A Hoque, R Lozano, R Pozdur, J Chase, H Carrasco, V Chuang, E S Delpassand, L Ellis, S Curley, M Roh, D V Jones
Journal: Journal of Clinical Oncology (1997)

To determine the toxicity, response rate, and survival in patients treated with hepatic arterial infusion (HAI) of fluorouracil (5-FU) plus recombinant human interferon alfa-2b (rIFN-alpha 2b) (Intron-A; Schering-Plough, Inc, Kenilworth, NJ) for colorectal carcinoma (CRC) liver metastases refractory to systemic 5-FU plus leucovorin (LCV).Forty-eight patients were given a 6-hour HAI of rIFN-alpha 2b 5 MU/m2 followed by an 18-hour HAI of 5-FU, 1,500 mg/m2 daily for 5 days. Twenty-nine patients were treated through percutaneously placed catheters and 19 through implantable infusion pumps (Shiley Infusaid Inc, Noorwood, MA). Treatment cycles were repeated every 28 to 35 days.There were three (6.6%) complete remissions (CRs) and 12 (26.6%) partial remissions (PRs), for a CR plus PR rate of 33.3% among 45 assessable patients (95% confidence interval [CI], 20% to 49%). The median response duration was 7 months, while median survival duration was 15 months. Grade 3 to 4 treatment-related toxic effects included mucositis (40%), neutropenia (42%), and thrombocytopenia (12%). No hepatobiliary toxicity was encountered in any of the patients. Treatment was discontinued because of progressive liver disease in 23 patients and extrahepatic progression in 16, while six patients continue treatment through an infusaid pump.HAI of 5-FU plus rIFN-alpha 2b is well tolerated, devoid of hepatobiliary toxicity, and can produce a response rate of 33.3% among patients refractory to bolus intravenous (IV) 5-FU plus LCV. The lack of hepatobiliary toxicity may permit salvage HAI with floxuridine (FUDR) in patients whose liver tumors fail to respond to HAI of 5-FU plus rIFN-alpha 2b. Because diarrhea was not a common side effect of HAI of 5-FU plus rIFN-alpha 2b, it would be of interest to investigate whether alternating HAI of 5-FU and rIFN-alpha 2b with systemic irinotecan (CPT-11) will decrease the incidence of both hepatic and extrahepatic disease progression.
Growth and Differentiation of Hyperplastic Outgrowths Derived From Mouse Mammary Epithelial Cells Transformed in Organ Culture&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;
Authors: N Ganguly, R Ganguly, N M Mehta, M R Banerjee
Journal: JNCI Journal of the National Cancer Institute (1982)

Potentially neoplastic outgrowths of BALB/c mouse mammary hyperplasia(s) (MH) derived from 7,12-dimethylbenz[a]anthracene-transformed epithelial cells in organ culture were characterized for responses to the hormones normally required for morphogenesis and functional differentiation of the mammary tissue. In a new culture model of the gland-free mammary fat pad, DNA synthesis in the MH outgrowths increased to a single peak during 6 days of incubation in a serum-free medium containing insulin, prolactin, aldosterone, and cortisol. The rise in DNA synthesis was accompanied by increased cell number and lobuloalveolar morphogenesis filling 50-70% of the fat pad; the rate of growth was variable among the MH outgrowth lines. Certain MH tissue showed some growth response in medium with aldosterone, cortisol, or estrogen, and progesterone in the presence of insulin. The hormone mixture insulin-prolactin was conducive to maximal growth, which suggested an altered sensitivity of the MH outgrowths to the mammogenic steroid hormones. Functional differentiation in the MH outgrowths was assessed in vivo by determination of the casein messenger RNA (mRNAcsn) levels measured by a specific complementary DNA probe. In MH-1 and MH-5 outgrowth lines, mRNAcsn was measurable in lactating hosts. In MH-9 outgrowth essentially the same concentration of mRNAcsn was present both in virgin and lactating hosts. Although mRNAcsn was present in MH outgrowths in lactating hosts, the concentration of the mRNA was only 0.056-0.88% of that present in the lactating host's own mammary gland. Virtually no mRNAcsn was measurable in the mammary tumors, regardless of the endocrine environment of the host animal. The results indicate a transformation-associated altered pattern of mammary cell-specific gene expression.
Time-to-positivity in patients with Escherichia coli bacteraemia
Authors: G. Peralta, M.P. Roiz, M.B. Sánchez, J.C. Garrido, B. Ceballos, M.J. Rodríguez-Lera, F. Mateos, I. De Benito
Journal: Clinical Microbiology and Infection (2007)
Acneiform eruptions caused by various second-generation tyrosine kinase inhibitors in patients with chronic myeloid leukaemia
Authors: Y.S. Jung, M. Kim, J. H. Lee, D.W. Kim, H.J. Park
Journal: British Journal of Dermatology (2015)

Journal Article Acneiform eruptions caused by various second‐generation tyrosine kinase inhibitors in patients with chronic myeloid leukaemia Get access Y.S. Jung, Y.S. Jung Department of Dermatology College of Medicine The Catholic University of Korea 62 Youido‐dong, Youngdeunpo‐gu Seoul Korea Search for other works by this author on: Oxford Academic Google Scholar M. Kim, M. Kim Department of Dermatology College of Medicine The Catholic University of Korea 62 Youido‐dong, Youngdeunpo‐gu Seoul Korea Search for other works by this author on: Oxford Academic Google Scholar J. H. Lee, J. H. Lee Department of Dermatology College of Medicine The Catholic University of Korea 62 Youido‐dong, Youngdeunpo‐gu Seoul Korea Search for other works by this author on: Oxford Academic Google Scholar D.W. Kim, D.W. Kim Department of Hematology College of Medicine The Catholic University of Korea 62 Youido‐dong, Youngdeunpo‐gu Seoul Korea Search for other works by this author on: Oxford Academic Google Scholar H.J. Park H.J. Park Department of Dermatology College of Medicine The Catholic University of Korea 62 Youido‐dong, Youngdeunpo‐gu Seoul Korea Correspondence: Hyun Jeong Park. E‐mail: hjpark@catholic.ac.kr Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 174, Issue 2, 1 February 2016, Pages 456–458, https://doi.org/10.1111/bjd.14185 Published: 01 February 2016
Matrix metalloproteinases gene polymorphisms in the pathogenesis of primary spontaneous pneumothorax
Authors: Svetlana Govorova, Maria Vershinina, Galina Netchaeva, Lev Grinberg
Journal: European Respiratory Journal (2013)

Primary spontaneous pneumothorax (SP) is one of the common thoracic surgical conditions requiring hospital admission. Screening and prevention SP have not been developed so far, because the lung bullae pathogenesis is not known. One of the possible directions is the study of matrix metalloproteinases (MMP) that provide the catabolism of the extracellular matrix components of connective tissue.  DNA samples from 148 patients with primary SP and 152 volunteers were studied. The frequencies of genes polymorphisms MMP1 (1607insG), MMP9 (C-1562T), MMP12 (A-82G), TIMP1 (S536T) were identified. With sample isolated DNA was performed two parallel amplification reaction with two pairs of allele-specific primers. For the analysis of mixtures of restriction applied by horizontal electrophoresis in 3% agarose gel.  For gene MMP1 (-1607insG) reported a significant decrease in the frequency of normal homozygous genotype G/G, which was associated with a lower risk of the primary SP (OR=0,27). GG allele carrier status was significantly more frequent in patients with primary SP and was associated with a twofold increase in risk (OR=2,27).  In patients with primary SP significantly rarer normal genotype C/C gene MMP9. Heterozygous genotype C/T is dominant and met with primary SP twice as often. Predisposition to primary SP associated with carriage of the heterozygous genotype C/T (OR=2,43), the homozygous genotype T/T (OR=4,38) and T allele (OR=2,78). For polymorphic loci and genes MMP12 and TIMP1 were no statistically significant difference between groups.  Our data confirm that mutant alleles of polymorphic loci MMP genes may be responsible for increased risk of SP.
The effect of hyperinflation on respiratory muscle work in acute induced asthma
Authors: J R Wheatley, S West, S J Cala, L A Engel
Journal: European Respiratory Journal (1990)

To examine the relationship between end-expiratory lung volume and respiratory muscle work during acute bronchoconstriction, we measured the work of breathing in nine asthmatic subjects, in whom bronchoconstriction was induced with histamine aerosol. When the forced expiratory volume in one second (FEV1) fell below 60% of the control value, work was measured at the spontaneously hyperinflated lung volume (VLS), at a volume equivalent to the control functional residual capacity (FRC) and at a volume 30% of vital capacity (VC) above the control FRC. Hyperinflation to VLS caused a 39% decrease in the total positive work per breath from 2.8 +/- 0.4 to 1.7 +/- 0.1 J, entirely due to a decrease in expiratory work per breath from 1.6 +/- 0.4 to 0.10 +/- 0.05 J. Inspiratory work did not change at any lung volume, because the increase in inspiratory elastic work due to hyperinflation was offset by the decrease in flow resistive work. Breathing above VLS did not alter the total positive muscle work, but did increase the negative work of the inspiratory muscles from 0.4 +/- 0.1 to 0.8 +/- 0.1 J.breath. We conclude that during induced asthma spontaneous hyperinflation minimizes the total respiratory muscle work and may constitute a mechanism for minimizing energy expenditure.
The effect of insulin upon glucose metabolism by adipose cells of different size
Authors: Lester B. Salans, James W. Dougherty
Journal: Journal of Clinical Investigation (1971)

Glucose metabolism and insulin sensitivity of isolated rat epididymal fat cells and of their delipidated derivatives ("ghosts") was studied as a function of cellular lipid content (fat cell size), cellular protein content, animal age, and state of nutrition in an effort to examine the relationship of adipose cell size to adipose tissue insulin sensitivity.In ad libitum-fed rats, basal rates of glucose-1-(14)C incorporation into CO(2) and triglyceride are similar over a wide range of adipose cell size. In contrast, the insulin sensitivity of intact fat cells from rats fed ad libitum is inversely related to their lipid content: the larger the cell, the less the response to insulin. This "resistance" of the enlarged adipose cell to the action of insulin was demonstrated by a reduction in the per cent rise above the basal rate as well as in the absolute rate of glucose oxidation and lipogenesis caused by insulin. The protein content of fat cells was found to be relatively constant over a wide range of fat cell size. Thus, enlarged insulin "resistant" fat cells contained the same amount of protein as smaller insulin "sensitive" cells. These relationships between insulin sensitivity and cellular lipid or protein content were true regardless of whether cells of different sizes were obtained from animals of different body weights and ages, or from different portions of the epididymal fat pads of animals of the same weight and age.Acute delipidation of intact fat cells did not appear to alter these relationships between basal glucose metabolism, insulin sensitivity, and cell size. "Ghosts" prepared from fat cells of widely different sizes metabolized glucose to CO(2) and triglyceride at similar rates. The insulin sensitivity of the fat cell "ghost" appeared to be inversely related to the size of the intact cell from which it was derived: the larger the intact cell the less insulin sensitive its "ghost."Although the insulin "resistance" of adipose tissue was reversed by weight loss and reduction of fat cell size, these studies also demonstrate that the insulin sensitivity of adipose cells of similar sizes can vary widely depending upon the state of nutrition and growth of the animal. Thus, factors other than cell size can also influence the insulin sensitivity of the adipose tissue.