tbuckley/cabot-search huggingface dataset:
Inhibition of MEK Sensitizes Human Melanoma Cells to Endoplasmic Reticulum Stress-Induced Apoptosis
Authors: Chen Chen Jiang, Li Hua Chen, Susan Gillespie, Yu Fang Wang, Kelly A. Kiejda, Xu Dong Zhang, Peter Hersey
Journal: Cancer Research (2007)

Abstract Past studies have shown that activation of mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK is a common cause for resistance of melanoma cells to death receptor–mediated or mitochondria-mediated apoptosis. We report in this study that inhibition of the MEK/ERK pathway also sensitizes melanoma cells to endoplasmic reticulum (ER) stress-induced apoptosis, and this is mediated, at least in part, by caspase-4 activation and is associated with inhibition of the ER chaperon glucose-regulated protein 78 (GRP78) expression. Treatment with the ER stress inducer tunicamycin or thapsigargin did not induce significant apoptosis in the majority of melanoma cell lines, but resistance to these agents was reversed by the MEK inhibitor U0126 or MEK1 small interfering RNA (siRNA). Induction of apoptosis by ER stress when MEK was inhibited was caspase dependent with caspase-4, caspase-9, and caspase-3 being involved. Caspase-4 seemed to be the apical caspase in that caspase-4 activation occurred before activation of caspase-9 and caspase-3 and that inhibition of caspase-4 by a specific inhibitor or siRNA blocked activation of caspase-9 and caspase-3, whereas inhibition of caspase-9 or caspase-3 did not inhibit caspase-4 activation. Moreover, overexpression of Bcl-2 inhibited activation of caspase-9 and caspase-3 but had minimal effect on caspase-4 activation. Inhibition of MEK/ERK also resulted in down-regulation of GRP78, which was physically associated with caspase-4, before and after treatment with tunicamycin or thapsigargin. In addition, siRNA knockdown of GRP78 increased ER stress-induced caspase-4 activation and apoptosis. Taken together, these results seem to have important implications for new treatment strategies in melanoma by combinations of agents that induce ER stress and inhibitors of the MEK/ERK pathway. [Cancer Res 2007;67(20):9750–61]
The Protein and Lipid Composition of Arterial Elastin and Its Relationship to Lipid Accumulation in the Atherosclerotic Plaque
Authors: Dieter M. Kramsch, Carl Franzblau, William Hollander
Journal: Journal of Clinical Investigation (1971)

Elastin preparations from intimal layers and the media of normal and atherosclerotic human aortae were analyzed for protein and lipid content. In atherosclerotic aortae, elastin from plaques was compared with elastin from adjacent normal appearing areas of the same aorta.
Dictyostelium Nucleoside Diphospate Kinase Highly Homologous to Nm23 and Awd Proteins Involved in Mammalian Tumor Metastasis and Drosphila Development
Authors: V. Wallet, R. Mutzel, H. Troll, O. Barzu, B. Wurster, M. Vernon, M.-L. Lacombe
Journal: JNCI Journal of the National Cancer Institute (1990)

Journal Article Dictyostelium Nucleoside Diphospate Kinase Highly Homologous to Nm23 and Awd Proteins Involved in Mammalian Tumor Metastasis and Drosphila Development Get access Valérie Wallet, Valérie Wallet Unité de Biochimie Cellulaire75724 Paris, France Search for other works by this author on: Oxford Academic PubMed Google Scholar Rupert Mutzel, Rupert Mutzel Fakultät für Biologie, Universität KonstanzKonstanz, 7750 Federal Republic of Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Heike Troll, Heike Troll Fakultät für Biologie, Universität KonstanzKonstanz, 7750 Federal Republic of Germany H. Troll was a recipient of a fellowship by Claussen-Slifeung. Search for other works by this author on: Oxford Academic PubMed Google Scholar Octavian Barzu, Octavian Barzu Unité de Biochimie des Régulations Cellulaires, Institut Pasteur75724 Paris, France Search for other works by this author on: Oxford Academic PubMed Google Scholar Bernd Wurster, Bernd Wurster Fakultät für Biologie, Universität KonstanzKonstanz, 7750 Federal Republic of Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Michel Vernon, Michel Vernon Unité de Biochimie Cellulaire75724 Paris, France Search for other works by this author on: Oxford Academic PubMed Google Scholar Marie-Lise Lacombe Marie-Lise Lacombe Unité de Biochimie Cellulaire75724 Paris, France Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 82, Issue 14, 18 July 1990, Pages 1199–1202, https://doi.org/10.1093/jnci/82.14.1199 Published: 18 July 1990 Article history Received: 19 April 1990 Accepted: 23 April 1990 Published: 18 July 1990
Loss of HIV-1–specific CD8<b>+</b> T Cell Proliferation after Acute HIV-1 Infection and Restoration by Vaccine-induced HIV-1–specific CD4<b>+</b> T Cells
Authors: Mathias Lichterfeld, Daniel E. Kaufmann, Xu G. Yu, Stanley K. Mui, Marylyn M. Addo, Mary N. Johnston, Daniel Cohen, Gregory K. Robbins, Eunice Pae, Galit Alter, Alysse Wurcel, David Stone, Eric S. Rosenberg, Bruce D. Walker, Marcus Altfeld
Journal: The Journal of Experimental Medicine (2004)

Virus-specific CD8+ T cells are associated with declining viremia in acute human immunodeficiency virus (HIV)1 infection, but do not correlate with control of viremia in chronic infection, suggesting a progressive functional defect not measured by interferon γ assays presently used. Here, we demonstrate that HIV-1–specific CD8+ T cells proliferate rapidly upon encounter with cognate antigen in acute infection, but lose this capacity with ongoing viral replication. This functional defect can be induced in vitro by depletion of CD4+ T cells or addition of interleukin 2–neutralizing antibodies, and can be corrected in chronic infection in vitro by addition of autologous CD4+ T cells isolated during acute infection and in vivo by vaccine-mediated induction of HIV-1–specific CD4+ T helper cell responses. These data demonstrate a loss of HIV-1–specific CD8+ T cell function that not only correlates with progressive infection, but also can be restored in chronic infection by augmentation of HIV-1–specific T helper cell function. This identification of a reversible defect in cell-mediated immunity in chronic HIV-1 infection has important implications for immunotherapeutic interventions.
Weight Loss–Associated Induction of Peroxisome Proliferator–Activated Receptor-α and Peroxisome Proliferator–Activated Receptor-γ Correlate With Reduced Atherosclerosis and Improved Cardiovascular Function in Obese Insulin-Resistant Mice
Authors: Wim Verreth, Dieuwke De Keyzer, Michel Pelat, Peter Verhamme, Javier Ganame, John K. Bielicki, Ann Mertens, Rozenn Quarck, Nora Benhabilès, Gérard Marguerie, Bharti Mackness, Mike Mackness, Ewa Ninio, Marie-Christine Herregods, Jean-Luc Balligand, Paul Holvoet
Journal: Circulation (2004)

Background— Weight loss in obese insulin-resistant but not in insulin-sensitive persons reduces coronary heart disease risk. To what extent changes in gene expression are related to atherosclerosis and cardiovascular function is unknown. Methods and Results— We studied the effect of diet restriction–induced weight loss on gene expression in the adipose tissue, the heart, and the aortic arch and on atherosclerosis and cardiovascular function in mice with combined leptin and LDL-receptor deficiency. Obesity, hypertriglyceridemia, and insulin resistance are associated with hypertension, impaired left ventricular function, and accelerated atherosclerosis in those mice. Compared with lean mice, peroxisome proliferator–activated receptors (PPAR)-α and PPAR-γ expression was downregulated in obese double-knockout mice. Diet restriction caused a 45% weight loss, an upregulation of PPAR-α and PPAR-γ, and a change in the expression of genes regulating glucose transport and insulin sensitivity, lipid metabolism, oxidative stress, and inflammation, most of which are under the transcriptional control of these PPARs. Changes in gene expression were associated with increased insulin sensitivity, decreased hypertriglyceridemia, reduced mean 24-hour blood pressure and heart rate, restored circadian variations of blood pressure and heart rate, increased ejection fraction, and reduced atherosclerosis. PPAR-α and PPAR-γ expression was inversely related to plaque volume and to oxidized LDL content in the plaques. Conclusions— Induction of PPAR-α and PPAR-γ in adipose tissue, heart, and aortic arch is a key mechanism for reducing atherosclerosis and improving cardiovascular function resulting from weight loss. Improved lipid metabolism and insulin signaling is associated with decreased tissue deposition of oxidized LDL that increases cardiovascular risk in persons with the metabolic syndrome.
Evolution of the TCP Gene Family in Asteridae: Cladistic and Network Approaches to Understanding Regulatory Gene Family Diversification and Its Impact on Morphological Evolution
Authors: P. A. Reeves
Journal: Molecular Biology and Evolution (2003)

In the plant subclass Asteridae, bilaterally symmetrical flowers have evolved from a radially symmetrical ancestral phenotype on at least three independent occasions: in the Boraginaceae, Solanaceae, and Lamiales. Development of bilateral flower symmetry has been shown to be determined by the early-acting cycloidea (cyc) and dichotoma (dich) genes in Antirrhinum, a member of the Lamiales. cyc and dich belong to the TCP gene family of putative transcription factors. TCP gene sequences were isolated from 11 Asteridae taxa using an array of degenerate PCR primers. Closely related species exhibiting either ancestral actinomorphic or derived zygomorphic flowers were sampled for each independent origin of bilateral flower symmetry. Cladistic and network-based analyses were performed to establish viable hypotheses regarding the evolution of bilateral symmetry in Asteridae. For the TCP gene family, the use of cladistic phylogenetic analysis to identify orthologous genes is complicated by a paucity of alignable data, frequent gene duplication and extinction, and the possibility of reticulate evolution via intergenic recombination. These complicating factors can be generalized to many regulatory gene families. As an alternative to cladistic analysis, we propose the use of network analysis for the reconstruction of regulatory gene family phylogenetic and functional relationships. Results of analyses support the hypothesis that the origin of bilaterally symmetrical flowers in the Boraginaceae and Solanaceae did not require orthologs or functional analogs of cyc or dich. This suggests that the genetic mechanism that determines bilateral flower symmetry in these taxa is not homologous to that of the Lamiales. Results of analyses are consistent with the hypothesis that the evolution of bilateral floral symmetry in the Lamiales required the origin of a novel gene function subsequent to gene duplication.
Changes in Sexual Functioning and Sex Hormone Levels in Women Following Bariatric Surgery
Authors: David B. Sarwer, Jacqueline C. Spitzer, Thomas A. Wadden, James E. Mitchell, Kathryn Lancaster, Anita Courcoulas, William Gourash, Raymond C. Rosen, Nicholas J. Christian
Journal: JAMA Surgery (2013)

<h3>Importance</h3> Obesity has been associated with impairments in sexual function and untoward changes in reproductive hormones in women. Relatively few studies have investigated changes in these domains following bariatric surgery. <h3>Objective</h3> To investigate changes in sexual functioning, sex hormone levels, and relevant psychosocial constructs in women who underwent bariatric surgery. <h3>Design, Setting, and Participants</h3> A prospective cohort study of 106 women from phase 2 of the Longitudinal Assessment of Bariatric Surgery who underwent bariatric surgery (median [interquartile range] body mass index, 44.5 [41.4-49.7]). Assessments were completed between 2006 and 2012. <h3>Interventions</h3> Bariatric surgery was performed by a surgeon certified by the Longitudinal Assessment of Bariatric Surgery (85 women underwent a Roux-en-Y gastric bypass, and 21 women underwent laparoscopic adjustable gastric banding). <h3>Main Outcomes and Measures</h3> Sexual functioning was assessed by use of the Female Sexual Function Index. Hormones were assessed by use of a blood assay. Quality of life, body image, depressive symptoms, and marital adjustment were assessed by use of validated questionnaires. <h3>Results</h3> Women lost a mean 32.7% (95% CI, 30.7%-34.7%) of initial body weight at postoperative year 1 and a mean 33.5% (95% CI, 31.5%-35.6%) at postoperative year 2. Two years following surgery, women reported significant improvements in overall sexual functioning and specific domains of sexual functioning: arousal, lubrication, desires, and satisfaction. They also experienced significant changes at 2 years in all hormones of interest. Women reported significant improvements in most domains of quality of life, as well as body image and depressive symptoms, within the first year after surgery, with these improvements being maintained through the second postoperative year. <h3>Conclusions and Relevance</h3> Women who underwent bariatric surgery had significant improvements in overall sexual functioning, in most reproductive hormones of interest, and in psychosocial status. Improvements in sexual health can be added to the list of health benefits associated with bariatric surgery. <h3>Trial Registration</h3> clinicaltrials.gov Identifier:NCT00670098
Optimizing Insulin Glargine Plus One Injection of Insulin Glulisine in Type 2 Diabetes in the ELEONOR Study
Authors: Antonio Nicolucci, Stefano Del Prato, Giacomo Vespasiani
Journal: Diabetes Care (2011)

To determine the functional health status and treatment satisfaction in patients with type 2 diabetes from the Evaluation of Lantus Effect ON Optimization of use of single dose Rapid insulin (ELEONOR) study that investigated whether a telecare program helps optimization of basal insulin glargine with one bolus injection of insulin glulisine.Functional health status and treatment satisfaction were investigated using the 36-Item Short-Form (SF-36) Health Survey, the World Health Organization Well-Being Questionnaire (WBQ), and the Diabetes Treatment Satisfaction Questionnaire.Of 291 randomized patients, 238 completed the study (telecare: 114; self-monitoring blood glucose: 124). Significant improvements were detected in most SF-36 domains, in WBQ depression and anxiety scores, and in treatment satisfaction, without differences between study groups.An insulin regimen that substantially improves metabolic control, while minimizing the risk of hypoglycemia, can positively affect physical and psychologic well-being and treatment satisfaction irrespective of the educational support system used.
Occurrence of an incomplete C8 molecule in homozygous C8 deficiency in man.
Authors: J Tschopp, A F Esser, T J Spira, H J Müller-Eberhard
Journal: The Journal of Experimental Medicine (1981)

Sera from unrelated individuals with recurrent Neisserial infections lacked C8 hemolytic activity, but contained a protein that is antigenically related to C8. Immunochemical analysis revealed complete identity of the C8-related protein of all three sera and a marked antigenic deficiency compared with normal C8. The C8-related protein was isolated from serum by adsorption to immobilized anti-C8 IgG, elution with 3 M guanidine, and subsequent gel filtration. Upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis, the abnormal protein resembled the alpha-gamma subunit of normal C8 with respect to mobility and its ability to be cleaved upon reduction into the alpha and gamma chains. The beta chain present in normal C8 was absent. Sedimentation equilibrium analysis indicated a molecular weight of 86,000 for the abnormal C8 protein, which is identical to that of the alpha-gamma subunit of normal C8. Amino acid analysis revealed no significant difference between the abnormal C8 and normal alpha-gamma. Unlike normal C8, the abnormal protein did not bind to EAC1-7 or to SC5b-7; however, upon addition to the deficient serum of beta chain isolated from normal C8, hemolytic activity was restored and formation of SC5b-9 occurred. We concluded that the dysfunctional C8 protein in the three individuals' serum is identical to the alpha-gamma subunit of normal C8 and that this form of C8 deficiency is distinct from the C8 deficiencies previously reported in which the entire three-chain protein is lacking.
Association of Fetal Hormone Levels with Stem Cell Potential: Evidence for Early Life Roots of Human Cancer
Authors: Inkyung Baik, William J. DeVito, Karen Ballen, Pamela S. Becker, William Okulicz, Qin Liu, Ellen Delpapa, Pagona Lagiou, Susan Sturgeon, Dimitrios Trichopoulos, Peter J. Quesenberry, Chung-Cheng Hsieh
Journal: Cancer Research (2005)

Abstract Intrauterine and perinatal factors have been linked to risk of childhood leukemia, testicular cancer, and breast cancer in the offspring. The pool of stem cells in target tissue has been suggested as a critical factor linking early life exposures to cancer. We examined the relation between intrauterine hormone levels and measurements of stem cell potential in umbilical cord blood. Cord blood donors were 40 women, ages ≥18 years, who delivered, from August 2002 to June 2003, a singleton birth after a gestation of at least 37 weeks. We assayed plasma concentrations of estradiol, unconjugated estriol, testosterone, progesterone, prolactin, sex hormone binding globulin, insulin-like growth factor-I (IGF-I), and IGF binding protein-3. For stem cell potential, we measured concentrations of CD34+ and CD34+CD38− cells and granulocyte-macrophage colony-forming unit (CFU-GM). We applied linear regression analysis and controlled for maternal and neonatal characteristics. We found strong positive associations between IGF-I and stem cell measures, 1 SD increase in IGF-I being associated with a 41% increase in CD34+ (P = 0.008), a 109% increase in CD34+CD38− (P = 0.005), and a 94% increase in CFU-GM (P = 0.01). Similar associations were observed for IGF binding protein-3. Among steroid hormones, estriol and testosterone were significantly positively associated with CD34+ and CFU-GM. These findings indicate that levels of growth factors and hormones are strongly associated with stem cell potential in human umbilical cord blood and point to a potential mechanism that may mediate the relationship between in utero exposure to hormones and cancer risk in the offspring.
223 SEDATION FOR ENDOSCOPY IN PATIENTS WITH END- STAGE LIVER DISEASE: RESULTS OF A PROSPECTIVE CONTROLLED STUDY
Authors: M. De Cento, C. Giordanino, E. Fagà, C. Barletti, M. Bruno, P. Carucci, C. De Angelis, W. Debernardi Venon, A. Musso, M. Rizzetto, G. Saracco
Journal: Journal of Hepatology (2009)
North Central Cancer Treatment Group (NCCTG) N0432: phase II trial of docetaxel with capecitabine and bevacizumab as first-line chemotherapy for patients with metastatic breast cancer
Authors: E.A. Perez, D.W. Hillman, T. Dentchev, N.A. Le-Lindqwister, L.H. Geeraerts, T.R. Fitch, H. Liu, D.L. Graham, S.P. Kahanic, H.M. Gross, T.A. Patel, F.M. Palmieri, A.C. Dueck
Journal: Annals of Oncology (2009)
Rotational atherectomy for in-stent restenosis: acute and long-term results of the first 100 cases
Authors: Samin K. Sharma, Srinivas Duvvuri, George Dangas, Annapoorna Kini, Raghuraman Vidhun, Kakarala Venu, John A. Ambrose, Jonathan D. Marmur
Journal: Journal of the American College of Cardiology (1998)
The Open Medical School
Authors: E. Grey Dimond
Journal: JAMA (1965)

A school of language, of music, of science can have (but may not have, of course) a neutral existence within the community, yet still be a satisfactory member of both community and college. A medical school may also aim for the neutral role by confining its activities to medical student education and to its own internal hospital functions and research programs. However, the nature of a medical school makes possible for it to have a different relationship to its community than any other school within the university. If careful effort and thought are devoted to the premedical years, to the intern and resident programs of the regional hospitals, and, beyond this, to the continuing education of the physicians in private practice, the school could serve as a catalyst—bringing life to a regional medical concept, with values beyond the numerical addition of a medical school to the community. The walls of
Treatment of Sensorineural Hearing Loss by Cochlear Implantation
Authors: Joseph B. Nadol, Donald K. Eddington
Journal: Annual Review of Medicine (1988)

Cochlear implantation, a form of neural prosthesis, is now being employed for some profoundly deaf individuals. The pathophysiology of profound deafness, the strategies inherent in cochlear implantation, the differences between various cochlear implant strategies and designs, medical and otologic evaluation of implant candidates, and the surgical procedure are each discussed. The results in speech recognition and speech reading that have been obtained with four commonly used cochlear implant systems are also presented.
Legal Remedies for Medical Ghostwriting: Imposing Fraud Liability on Guest Authors of Ghostwritten Articles
Authors: Simon Stern, Trudo Lemmens
Journal: PLoS Medicine (2011)

There are persistent concerns about the influence of the pharmaceutical and device industries on the medical literature, and particularly on the reporting of clinical trials, which can include the distortion of the true evidence base of medical interventions and overestimation of the clinical benefit of a drug used to treat patients [1]. An especially problematic issue involves the industry practice of publishing studies prepared by hired medical writers but signed by academic “guest authors” who are invited to add their names without fulfilling authorship criteria. In this case, “guest authorship” is accompanied by “ghostwriting,” which occurs when a published article fails to acknowledge the original writer or writers' contributions [2]–[4]. Ghostwriting can also occur when an academic research group uses a professional writer to draft an article based on data generated by the group. When the research group retains control of the data and the final analysis, however, there is less of a concern about possible bias in the reporting of the results, and the appropriate remedy in that case is to report explicitly the role and contribution of the medical writer in the article. Here, we concentrate on ghostwriting and guest authorship in industry-controlled research, where several examples have revealed the use of ghostwriters to insert concealed marketing messages favourable to a company's product, and the recruitment of academics as “guest” authors despite not fulfilling authorship criteria [5]–[9].

Commentators have condemned the practice as unethical and unacceptable and have discussed the harms resulting from this form of medical ghostwriting, recommending that journal submissions be policed more aggressively and that the “guest authors” be suitably sanctioned by journals, academic institutions, and regulatory agencies [1]–[14]. However, these recommendations have not yet been widely embraced by the academic institutions, medical journals, and medical licensing organizations that would seem to have the most at stake in curbing this practice. Here, we discuss some of the reasons for this lack of response and suggest that the law may offer a solution, given these other institutions' failure to impose sanctions.