tbuckley/cabot-search huggingface dataset:
The Subsyndromal Phenomenology of Borderline Personality Disorder: A 10-Year Follow-Up Study
Authors: Mary C. Zanarini, Frances R. Frankenburg, D. Bradford Reich, Kenneth R. Silk, James I. Hudson, Lauren B. McSweeney
Journal: American Journal of Psychiatry (2007)

Objective: The purpose of this study was to characterize the course of 24 symptoms of borderline personality disorder in terms of time to remission. Method: The borderline psychopathology of 362 patients with personality disorders, all recruited during inpatient stays, was assessed using two semistructured interviews of proven reliability. Of these, 290 patients met DSM-III-R criteria as well as Revised Diagnostic Interview for Borderlines criteria for borderline personality disorder, and 72 met DSM-III-R criteria for another axis II disorder. Over 85% of the patients were reinterviewed at five distinct 2-year follow-up waves by interviewers blind to all previously collected information. Results: Among borderline patients, 12 of the 24 symptoms studied showed patterns of sharp decline over time and were reported at 10-year follow-up by less than 15% of the patients who reported them at baseline. The other 12 symptoms showed patterns of substantial but less dramatic decline over the follow-up period. Symptoms reflecting core areas of impulsivity (e.g., self-mutilation and suicide efforts) and active attempts to manage interpersonal difficulties (e.g., problems with demandingness/entitlement and serious treatment regressions) seemed to resolve the most quickly. In contrast, affective symptoms reflecting areas of chronic dysphoria (e.g., anger and loneliness/emptiness) and interpersonal symptoms reflecting abandonment and dependency issues (e.g., intolerance of aloneness and counterdependency problems) seemed to be the most stable. Conclusions: The results suggest that borderline personality disorder may consist of both symptoms that are manifestations of acute illness and symptoms that represent more enduring aspects of the disorder.
Allogeneic and autologous stem-cell transplantation in advanced Ewing tumors
Authors: S. Burdach, B. van Kaick, H.J. Laws, S. Ahrens, R. Haase, D. Körholz, H. Pape, J. Dunst, T. Kahn, R. Willers, B. Engel, U. Dirksen, C. Kramm, W. Nürnberger, A. Heyll, R. Ladenstein, H. Gadner, H. Jürgens, U. Göbel
Journal: Annals of Oncology (2000)
Exenatide and the treatment of patients with Parkinson’s disease
Authors: Iciar Aviles-Olmos, John Dickson, Zinovia Kefalopoulou, Atbin Djamshidian, Peter Ell, Therese Soderlund, Peter Whitton, Richard Wyse, Tom Isaacs, Andrew Lees, Patricia Limousin, Thomas Foltynie
Journal: Journal of Clinical Investigation (2013)

Background. There is increasing interest in methods to more rapidly and cost-efficiently investigate drugs that are approved for clinical use in the treatment of another condition. Exenatide is a type 2 diabetes treatment that has been shown to have neuroprotective/neurorestorative properties in preclinical models of neurodegeneration.
Time-Restricted Feeding without Reducing Caloric Intake Prevents Metabolic Diseases in Mice Fed a High-Fat Diet
Authors: Megumi Hatori, Christopher Vollmers, Amir Zarrinpar, Luciano DiTacchio, Eric A. Bushong, Shubhroz Gill, Mathias Leblanc, Amandine Chaix, Matthew Joens, James A.J. Fitzpatrick, Mark H. Ellisman, Satchidananda Panda
Journal: Cell Metabolism (2012)
Characterisation of TNF-alpha lectin-like domain derived peptides associated with improved alveolar fluid clearance in pulmonary oedema
Authors: Susan Tzotzos, Bernhard Fischer, Helmut Pietschmann, Hendrik Fischer, Rudolf Lucas, Waheed Shabbir, Rosa Lemmens-Gruber
Journal: European Respiratory Journal (2011)

The beneficial effect of the lectin-like domain of TNF-alpha, including the TIP peptide which mimics this domain, on activation of oedema resorption, improved alveolar clearance and protection of lung function after transplantation, is well documented from several independent  in vitro and  in vivo  studies using animal models. The effect is mediated by activation of sodium uptake through the amiloride-sensitive epithelial sodium ion channel (ENaC), which plays a major role in alveolar fluid clearance in normal and diseased lungs. Several peptides mimicking the lectin-like domain of human TNF-alpha, and differing from the human TIP peptide by mutation or substitution of amino acid residues with non-natural derivatives, were synthesised and tested for their ability to enhance sodium current through ENaC in A549 cells with the patch clamp technique.  For all ENaC-activating TIP peptides a maximum effect was observed at 120 nM. Compared to TNF-alpha (EC 50  8.2 nM) and the original human TIP peptide (EC 50  54.3 nM), several of the newly-designed peptides were more effective at enhancing amiloride-sensitive current than the latter: the most active peptide had an EC 50  of 19.9 nM. Our data suggest that TIP peptides with charge distribution and interatomic distances most closely resembling the 3D structure of the native lectin-like domain of TNF-alpha, are those with greater ability to enhance activation of sodium current through ENaC. No standard therapy exists for pulmonary oedema, thus these TIP peptides represent promising therapeutic agents for activating sodium uptake from the alveolar fluid through ENaC and improving clinical outcome in this condition.
Quantitative Imaging Methods for the Development and Validation of Brain Biomechanics Models
Authors: Philip V. Bayly, Erik H. Clayton, Guy M. Genin
Journal: Annual Review of Biomedical Engineering (2012)

Rapid deformation of brain tissue in response to head impact or acceleration can lead to numerous pathological changes, both immediate and delayed. Modeling and simulation hold promise for illuminating the mechanisms of traumatic brain injury (TBI) and for developing preventive devices and strategies. However, mathematical models have predictive value only if they satisfy two conditions. First, they must capture the biomechanics of the brain as both a material and a structure, including the mechanics of brain tissue and its interactions with the skull. Second, they must be validated by direct comparison with experimental data. Emerging imaging technologies and recent imaging studies provide important data for these purposes. This review describes these techniques and data, with an emphasis on magnetic resonance imaging approaches. In combination, these imaging tools promise to extend our understanding of brain biomechanics and improve our ability to study TBI in silico.
Human malignant and mitogen-transformed cells contain retroviral P15E-related antigen.
Authors: G J Cianciolo, D Phipps, R Snyderman
Journal: The Journal of Experimental Medicine (1984)

Virus-related oncogenes have been demonstrated in human tumor cells and may play a role in neoplastic transformation. Cancerous effusions contain inhibitors of monocyte function and are absorbed by monoclonal antibodies to the immunosuppressive retroviral structural protein, P15E. We therefore examined eight human malignant cell lines for P15E-related antigens, by indirect immunofluorescence. Up to 87% of fixed malignant cells were reactive with two different monoclonal anti-P15E antibodies, while under identical conditions approximately 7% of freshly isolated human mononuclear cells were positive. Differentiation of two tumor cell lines with dibutyryl cyclic AMP resulted in decreased anti-P15E reactivity. Blast transformation of human mononuclear cells with mitogens induced reactivity with anti-P15E. Thus human malignant and blast-transformed cells contain antigens related to P15E. Expression of this viral-related gene may occur during rapid cell division and be abnormally regulated in cancer cells, thus rendering them more resistant to immune destruction.
Kruppel-like transcription factor 5 promotes breast cell survival through pERK-mediated MKP-1 protein stabilization.
Authors: R Liu, Z Zhou, C Chen
Journal: Cancer Research (2009)

Abstract Abstract #3019 Kruppel-like Factor 5 (KLF5) is a transcription factor promoting cell survival and tumorigenesis in multiple cancers. High level of KLF5 mRNA is associated with a shorter survival for breast cancer patients. However, the role of KLF5 and mechanism of KLF5 actions in breast cancer remain unclear. In this study, we found that KLF5 knockdown by siRNA in two basal type breast cell lines MCF10A and BT20 induces apoptosis, as indicated by loss of cell viability and cleaved PARP and caspase 3. Interestingly, a survival phosphotase, MKP-1, is downregulated at protein level by KLF5 ablation. Consistently, KLF5 over-expression increases the MKP-1 protein expression. However, MKP-1 is not a KLF5 direct target gene because the MKP-1 mRNA level is not regulated by KLF5. By the cycloheximide chase assays, we found that KLF5 decreases the MKP-1 protein degradation. However, KLF5 does not decrease the MKP-1 E3 ubiquitin ligase SKP2 expression. The ERK inhibitor U0126 specifically blocks the KLF5 induced MKP-1, suggesting that KLF5 up-regulates MKP-1 through activating ERK signaling. Finally, we demonstrated that MKP-1 over-expression blocks KLF5 knockdown induced apoptosis in MCF10A cells. These findings suggest that KLF5 is a survival factor which promotes breast cell survival partially through pERK-mediated MKP-1 stabilization. The KLF5-pERK-MKP-1 signaling axis may provide new therapeutic targets for invasive breast cancer. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3019.
Short-Term Effects of Actinomycin D and Nitrogen Mustard on Murine Lymphocytic Leukemia P388&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: L D Hazlett, G A Ackerman
Journal: JNCI Journal of the National Cancer Institute (1971)

Respiratory, histochemical, and ultrastructural alterations were seen in leukemia P388 after exposure to either actinomycin D or nitrogen mustard during the 5- to 60-minute period studied. Respiratory activity was immediately and significantly depressed as determined by oxygen probe analyses after in vitro exposure to either of these agents, whereas oxygen consumption of the leukemic cells decreased progressively during the 1-hour in vivo analyses. Specific histochemical changes induced by treatment with actinomycin D included depression of malic and lactic dehydrogenase recctivities, with a concomitant increase in glucose-6phosphate dehydrogenase activity. Nitrogen mustard depressed malic dehydrogenase reactivity and transiently decreased reactive sulfhydryls. Morphological alterations were apparent after 15-minutes' exposure to either of these drugs. Actinomycin D principally induced nucleolar redistribution and increased nuclear condensation; minimal mitochondrial damage was seen after exposure to th is drug and was evidenced by swelling and vesiculation of these organelles. Preparations treated with nitrogen mustard revealed increased numbers of degenerating cells, and many cells exhibited mitochondrial swelling, cristal damage and autolysis, cytoplasmic vacuolization, and slight chromatin clumping. The detection of early metabolic alterations in this cell system indicates that the oxygraph could be used to facilitate analysis of various potential antineoplastic agents. Changes in the respiratory capacity of the leukemic cells were evident before ultrastructural and/or histochemical alterations.
Relationship Between<i>ERCC1</i>Polymorphisms, Disease Progression, and Survival in the Gynecologic Oncology Group Phase III Trial of Intraperitoneal Versus Intravenous Cisplatin and Paclitaxel for Stage III Epithelial Ovarian Cancer
Authors: Thomas C. Krivak, Kathleen M. Darcy, Chunqiao Tian, Deborah Armstrong, Bora E. Baysal, Holly Gallion, Christine B. Ambrosone, Julie A. DeLoia
Journal: Journal of Clinical Oncology (2008)

We hypothesized that common polymorphisms in excision repair cross-complementation group 1 (ERCC1), involved in nucleotide excision repair of platinum-induced damage, would be associated with progression-free survival (PFS) and overall survival (OS) in women with optimally resected, stage III epithelial ovarian cancer (EOC) treated with cisplatin and paclitaxel (C+P).Single nucleotide polymorphism analysis was carried out by direct pyrosequencing at two sites (codon 118 and C8092A) in ERCC1 in leukocyte DNA from women who participated in the Gynecologic Oncology Group (GOG) phase III protocol-172 and were randomly assigned to intraperitoneal or intravenous C+P.ERCC1 genotyping was performed in 233 of the 429 women who participated in GOG-172. The genotype distribution at codon 118 was 17% with C/C, 43% with C/T, and 40% with T/T, and the genotype distribution at C8092A was 56% with C/C, 37% with C/A, and 7% with A/A. Adjusted Cox regression analysis revealed that the codon 118 polymorphism in ERCC1 was not significantly associated with disease progression or death. Women with the C8092A C/A or A/A genotypes compared with the C/C genotype had an increased risk of disease progression (hazard ratio [HR] = 1.44; 95% CI, 1.06 to 1.94; P = .018) and death (HR = 1.50; 95% CI, 1.07 to 2.09; P = .018). Median PFS and OS were 6 and 17 months shorter for women with the C8092A C/A or A/A genotypes versus the C/C genotype, respectively.Although the ERCC1 codon 118 polymorphism does not seem to be associated with clinical outcome, the C8092A polymorphism was an independent predictor of PFS and OS in women with optimally resected EOC.
Follow-up of adult celiac patients: which noninvasive test reflects mucosal status most reliably?
Authors: A. Vécsei, U. Graf, H. Vogelsang
Journal: Endoscopy (2009)

See also: Commentaire de travail de A. K. W. Vécsei et al., pp. 123Endoscopy 2009; 41(02): 251-251DOI: 10.1055/s-0032-1306730
Health-Related Quality of Life in Younger Patients With Chronic Lymphocytic Leukemia Treated With Fludarabine Plus Cyclophosphamide or Fludarabine Alone for First-Line Therapy: A Study by the German CLL Study Group
Authors: Barbara F. Eichhorst, Raymonde Busch, Tanja Obwandner, Ingrid Kuhn-Hallek, Peter Herschbach, Michael Hallek
Journal: Journal of Clinical Oncology (2007)

To date, only a few studies have evaluated the health-related quality of life (HRQOL) of patients with chronic lymphocytic leukemia (CLL) receiving chemotherapy. Therefore, the German CLL Study Group assessed HRQOL in younger patients with advanced CLL receiving first-line chemotherapy with fludarabine or fludarabine plus cyclophosphamide (FC).Three hundred seventy-five patients younger than 66 years with advanced CLL were randomly assigned to receive either fludarabine alone (fludarabine 25 mg/m2/d for 5 days intravenously [IV], repeated every 28 days) or FC (fludarabine 30 mg/m2/d for 3 days IV plus cyclophosphamide 250 mg/m2/d for 3 days, repeated every 28 days). Six courses of treatment were planned to be administered. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 was sent to all patients at baseline and after 6, 12, and 24 months.Eighty-nine percent of 362 included patients completed at least one questionnaire (163 fludarabine- and 158 FC-treated patients). Comparing the baseline levels of 249 CLL patients with the general German population, significant differences in nearly all HRQOL scales were assessed between the two groups. A multivariate analysis showed no significant differences in all HRQOL scales between both arms. In both treatment arms, symptoms such as fatigue, insomnia, and appetite loss improved to lower levels after the end chemotherapy. Except for lower physical status, no significant difference in HRQOL between male and female patients was evaluated.Fludarabine-based treatment seems to improve HRQOL little to moderately in younger patients with advanced CLL. No significant difference between fludarabine- and FC-treated patients was observed.
Upregulation of the inwardly rectifying potassium channel Kir2.1 (KCNJ2) modulates multidrug resistance of small-cell lung cancer under the regulation of miR-7 and the Ras/MAPK pathway
Authors: Huanxin Liu, Jie Huang, Juan Peng, Xiaoxia Wu, Yan Zhang, Weiliang Zhu, Linlang Guo
Journal: Molecular Cancer (2015)

KCNJ2/Kir2.1, a member of the classical inwardly rectifying potassium channel family, is commonly expressed in a wide range of tissues and cell types. Previous studies indicated that Kir2.1 may be associated with SCLC multidrug resistance (MDR). However, whether Kir2.1 can regulate MDR and its underlying mechanisms remain poorly understood in SCLC.KCNJ2/Kir2.1 expression was examined in tissues from fifty-two SCLC cases by immunohistochemistry. Overexpression or knockdown of KCNJ2/Kir21 was performed in multidrug-resistant SCLC cell lines (H69AR and H446AR) and their parental cell lines (H69 and H446) to assess its influence on cell growth, apoptosis, the cell cycle and chemoresistance.KCNJ2/Kir2.1 was expressed in 44.23% (23/52) of SCLC tissues. Overexpression of KCNJ2/Kir2.1 was correlated with the clinical stage and chemotherapy response in SCLC patients. Knockdown of KCNJ2/Kir2.1 expression using KCNJ2/Kir2.1 shRNA in H69AR and H446AR cells inhibited cell growth and sensitized the cancer cells to chemotherapeutic drugs by increasing cell apoptosis and cell cycle arrest. Forced KCNJ2/Kir2.1 expression in H69 and H446 cells promoted cell growth and enhanced multidrug resistance via reduced drug-induced apoptosis accompanied by cell cycle arrest. KCNJ2/Kir2.1 expression was also influenced by PKC and MEK inhibitors. In addition, multidrug resistance protein 1 (MRP1/ABCC1) was confirmed to interact with KCNJ2/Kir2.1 by Co-IP assays.KCNJ2/Kir2.1 modulates cell growth and drug resistance by regulating MRP1/ABCC1 expression and is simultaneously regulated by the Ras/MAPK pathway and miR-7. KCNJ2/Kir2.1 may be a prognostic predictor and a potentially novel target for interfering with chemoresistance in SCLC.
Cell-Surface Estrogen Receptors Mediate Calcium-Dependent Nitric Oxide Release in Human Endothelia
Authors: George B. Stefano, Vincent Prevot, Jean-Claude Beauvillain, Patrick Cadet, Caterina Fimiani, Ingeborg Welters, Gregory L. Fricchione, Christophe Breton, Philippe Lassalle, Michel Salzet, Thomas V. Bilfinger
Journal: Circulation (2000)

Background —Although estrogen replacement therapy has been associated with reduction of cardiovascular events in postmenopausal women, the mechanism for this benefit remains unclear. Because nitric oxide (NO) is considered an important endothelium-derived relaxing factor and may function to protect blood vessels against atherosclerotic development, we investigated the acute effects of physiological levels of estrogen on NO release from human internal thoracic artery endothelia and human arterial endothelia in culture. Methods and Results —We tested the hypothesis that estrogen acutely stimulates constitutive NO synthase activity in human endothelial cells by acting on a cell-surface receptor. NO release was measured in real time with an amperometric probe. 17β-Estradiol exposure to internal thoracic artery endothelia and human arterial endothelia in culture stimulated NO release within seconds in a concentration-dependent manner. 17β-Estradiol conjugated to bovine serum albumin also stimulated NO release, suggesting action through a cell-surface receptor. Tamoxifen, an estrogen receptor inhibitor, antagonized this action. We further showed with the use of dual emission microfluorometry that 17β-estradiol–stimulated release of endothelial NO was dependent on the initial stimulation of intracellular calcium transients. Conclusions —Physiological doses of estrogen immediately stimulate NO release from human endothelial cells through activation of a cell-surface estrogen receptor that is coupled to increases in intracellular calcium.
Omeprazole v ranitidine for prevention of relapse in reflux oesophagitis. A controlled double blind trial of their efficacy and safety.
Authors: J Dent, N D Yeomans, M Mackinnon, W Reed, F M Narielvala, D J Hetzel, E Solcia, D J Shearman
Journal: Gut (1994)

The aim of this study was to compare recurrence rates of reflux oesophagitis (after endoscopic healing with omeprazole) over a 12 month period of randomised, double blind, maintenance treatment with either daily omeprazole (20 mg every morning; n = 53), weekend omeprazole (20 mg on three consecutive days a week, n = 55) or daily ranitidine (150 mg twice daily, n = 51). Patients were assessed for relapse by endoscopy (with gastric biopsy) at six and 12 months, or in the event of symptomatic recurrence, and serum gastrin was monitored. At 12 months, the estimated proportions of patients in remission (actuarial life table method) were 89% when receiving daily omeprazole compared with 32% when receiving weekend omeprazole (difference 57%, p < 0.001, 95% confidence intervals: 42% to 71%) and 25% when receiving daily ranitidine (difference 64%, p < 0.001, 95% confidence intervals: 50% to 78%). Median gastrin concentrations increased slightly during the healing phase, but remained within the normal range and did not change during maintenance treatment. No significant pathological findings were noted, and no adverse events were attributable to the study treatments. In conclusion, for patients who respond favourably to acute treatment with omeprazole 20 mg every morning, the drug is a safe and highly effective maintenance treatment for preventing relapse of reflux oesophagitis and its associated symptoms over 12 months. By contrast, weekend omeprazole and daily ranitidine were ineffective.
Understanding the Effects of Age, Period, and Cohort on Incidence and Mortality Rates
Authors: T R Holford
Journal: Annual Review of Public Health (1991)

Time trends for population-based disease rates often are summarized by using direct adjustment by period of diagnosis or death. Similarly, the effect of age often is presented graphically as age-specific rates for a given period of diagnosis. These approaches may be necessary if there is an absence of long-term data, as they provide a natural way for annually updating information when monitoring trends, or they may be a convenient way of summarizing a large amount of data (7, 10, 11, 39, 45). However, these summaries only can adjust for the effect of age in a given period; they implicitly ignore the cohort effect. The effect of cohort is an important factor in understanding time trends for many diseases. Thus, it is not advisable to use data analytic strategies that routinely ignore it. Another alternative to modeling is to give a graphical presentation of the age-specific rates themselves. As I noted in the introduction, some of the first analyses to identify the effect of cohort on diseases, such as tuberculosis and lung cancer, relied entirely on a graphical analysis. Although graphs certainly are an important part of the interpretation of time trends, it would be a mistake to limit your analysis to impressions of points on a graph. For example, such a perusal would not give an objective indication of the statistical significance of a particular pattern. Regression analysis forces us to recognize a fundamental problem with interpreting time trends in disease rates--a problem that you should remember, even when trying to understand a graphical display of time trends in age-specific rates.The article is concerned with the effects of age, period, and cohort on disease incidence and with mortality from that disease. The emphasis is on the interpretation of results from fitting regression models to data that include age, birth cohort, and period or year of diagnosis. Some examples are presented using U.S. data for lung cancer.