tbuckley/cabot-search huggingface dataset:
Stress, Immunity, and Cervical Cancer: Biobehavioral Outcomes of a Randomized Clinical Trail
Authors: Edward L. Nelson, Lari B. Wenzel, Kathryn Osann, Aysun Dogan-Ates, Nissa Chantana, Astrid Reina-Patton, Amanda K. Laust, Kevin P. Nishimoto, Alexandra Chicz-DeMet, Nefertiti du Pont, Bradley J. Monk
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Cancer diagnosis and treatment imparts chronic stressors affecting quality of life (QOL) and basic physiology. However, the capacity to increase survival by improving QOL is controversial. Patients with cervical cancer, in particular, have severely compromised QOL, providing a population well-suited for the evaluation of novel psychosocial interventions and the exploration of mechanisms by which modulation of the psychoneuroimmune axis might result in improved clinical outcomes. Experimental Design: A randomized clinical trial was conducted in cervical cancer survivors that were enrolled at ≥13 and &amp;lt;22 months after diagnosis (n = 50), comparing a unique psychosocial telephone counseling (PTC) intervention to usual care. QOL and biological specimens (saliva and blood) were collected at baseline and 4 months post-enrollment. Results: The PTC intervention yielded significantly improved QOL (P = 0.011). Changes in QOL were significantly associated with a shift of immune system T helper type 1 and 2 (Th1/Th2) bias, as measured by IFN-γ/interleukin-5 ELISpot T lymphocyte precursor frequency; improved QOL being associated with increased Th1 bias (P = 0.012). Serum interleukin-10 and the neuroendocrine variables of cortisol and dehydroepiandrosterone revealed trends supporting this shift in immunologic stance and suggested a PTC-mediated decrease of the subject's chronic stress response. Conclusions: This study documents the utility of a unique PTC intervention and an association between changes in QOL and adaptive immunity (T helper class). These data support the integration of the chronic stress response into biobehavioral models of cancer survivorship and suggests a novel mechanistic hypotheses by which interventions leading to enhanced QOL could result in improved clinical outcome including survival.
Simple sequential treatment for primary spontaneous pneumothorax: one step closer
Authors: M. T. Henry
Journal: European Respiratory Journal (2006)

Primary spontaneous pneumothorax (PSP) remains a significant clinical problem in emergency departments and respiratory medicine units. The management of minimally symptomatic patients presenting with their first small PSP on a chest radiograph is straightforward; a period of simple observation with follow-up chest radiography will usually suffice. Attempts to prevent recurrence at this stage are generally not recommended, as 50–70% of these patients will not have a recurrence 1–3. However, despite literature replete with discussions on the assessment and management of PSP, no standard approach to symptomatic or “large” PSPs has been universally adopted. Two significant guidelines for management of pneumothoraces have addressed this problem, one of which was evidence-based and the other consensus-based 4, 5.

Objectives for managing these patients should be straightforward. Ideally, a diagnosis and treatment algorithm should be adopted that would predict those who need intervention. It should facilitate the treatment and discharge of a significant proportion of these patients in the emergency department without the need for hospital admission. It should also allow for continuing management of patients who require in-patient pleural drainage without further invasive procedures, until it becomes apparent that they have a persistent air leak necessitating surgical intervention. Finally, these young and otherwise fit patients should be managed in a setting that allows them to remain mobile during their pleural drainage.

Predicting which patients require treatment for their PSPs seems relatively straightforward. Breathless patients or those with persistent significant chest pain should not be left without intervention, regardless of the size of the pneumothorax on the chest radiograph 4, 6. What is less apparent is when to intervene in clinically stable patients with large pneumothoraces. The definition of what constitutes a large pneumothorax varies, with the American College of Chest Physicians (ACCP) defining it as ≥3 cm …
Engagement of Collagen-Binding Integrins Promotes Matrix Metalloproteinase-9–Dependent E-Cadherin Ectodomain Shedding in Ovarian Carcinoma Cells
Authors: Jaime Symowicz, Brian P. Adley, Kara J. Gleason, Jeffrey J. Johnson, Supurna Ghosh, David A. Fishman, Laurie G. Hudson, M. Sharon Stack
Journal: Cancer Research (2007)

Reversible modulation of cell-cell adhesion, cell-matrix adhesion, and proteolytic activity plays a critical role in remodeling of the neoplastic ovarian epithelium during metastasis, implicating cadherins, integrins, and proteinases in i.p. metastatic dissemination of epithelial ovarian carcinoma (EOC). Aberrant epithelial differentiation is an early event in ovarian carcinogenesis; thus, in contrast to most carcinomas that lose E-cadherin expression with progression, E-cadherin is abundant in primary EOC. Metastasizing EOCs engage in integrin-mediated adhesion to submesothelial interstitial collagens and express matrix metalloproteinases (MMP) that facilitate collagen invasion, thereby anchoring secondary lesions in the submesothelial matrix. As metalloproteinases have also been implicated in E-cadherin ectodomain shedding, the current study was undertaken to model the effects of matrix-induced integrin clustering on proteinase-catalyzed E-cadherin ectodomain shedding. Aggregation of collagen-binding integrins induced shedding of an 80-kDa E-cadherin ectodomain [soluble E-cadherin (sE-cad)] in a MMP- and Src kinase-dependent manner, and sE-cad was prevalent in ascites from ovarian cancer patients. Expression of MMP-9 was elevated by integrin aggregation, integrin-mediated ectodomain shedding was inhibited by a MMP-9 function blocking antibody, and incubation of cells with exogenous MMP-9 catalyzed E-cadherin ectodomain shedding. In contrast to other tumors wherein sE-cad is released into the circulation, EOC tumors maintain direct contact with sE-cad-rich ascites at high concentration, and incubation of EOC cells with physiologically relevant concentrations of recombinant sE-cad disrupted adherens junctions. These data support a novel mechanism for posttranslational modification of E-cadherin function via MMP-9 induction initiated by cell-matrix contact and suggest a mechanism for promotion of EOC metastatic dissemination.
Comparative Effectiveness of Infliximab and Adalimumab for Crohn's Disease
Authors: Mark T. Osterman, Kevin Haynes, Elizabeth Delzell, Jie Zhang, Meenakshi Bewtra, Colleen Brensinger, Lang Chen, Fenlong Xie, Jeffrey R. Curtis, James D. Lewis
Journal: Clinical Gastroenterology and Hepatology (2013)
Reduced Interferon- γ Production in Infants with Bronchiolitis and Asthma
Authors: PAOLO M. RENZI, JEAN P. TURGEON, JACQUES E. MARCOTTE, SUSAN P. DRBLIK, DENIS BÉRUBÉ, MARIE F. GAGNON, SHELDON SPIER
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Infants are at increased risk of developing asthma after acute bronchiolitis. We assessed the hypothesis that cytokine production is related to the development of asthma after bronchiolitis. The smoking history and the presence of atopy or asthma in parents or siblings were recorded and blood mononuclear cell interferon (IFN)- γ and interleukin (IL)-4 production in response to IL-2 were assessed in 32 infants hospitalized for bronchiolitis and in a subgroup (n = 19) in which pulmonary function tests were performed approximately 4.9 mo later. The presence of asthma was determined by the Delphi consensus method 2 yr after hospitalization. Infants were classified as follows: asthma absent (A, n = 14), possible (Po, n = 9), or probable (Pr, n = 9). Infants with possible and probable asthma had lower IFN- γ production at the time of bronchiolitis and a trend to lower IFN- γ production 4.9 mo later when compared with those who had no asthma. At the time of bronchiolitis, IFN- γ production was: 123 ± 31 versus 34 ± 20 versus 21 ± 14 pg/ml, A versus Po versus Pr (p = 0.02, ANOVA) and 4.9 mo after bronchiolitis, IFN- γ production was: 147.3 ± 45 versus 47.4 ± 30 versus 22.3 ± 32 pg/ml, No versus Po versus Pr (p = 0.08 ANOVA). IL-4 production did not differ between groups. Infants who went on to develop asthma had more parent smokers (21.4% versus 55.6% versus 55.6%, A versus Po versus Pr, p < 0.04), lower V˙maxFRC (122 ± 18 versus 77 ± 7 versus 67 ± 8% predicted, A versus Po versus Pr, p < 0.02), lower PC40 histamine (6.4 ± 3.3 versus 1.2 ± 0.6 mg/ml, A versus Po + Pr, p < 0.03) but no increase in atopy or asthma in their family. Significant positive correlations were found between IFN- γ production at the time of bronchiolitis and V˙maxFRC (r = 0.606) or PC40 histamine (r = 0.648) 4.9 mo after bronchiolitis. Lower IFN- γ production at the time of bronchiolitis is an indicator of lower pulmonary function and increased responsiveness to histamine 4.9 mo after bronchiolitis and is related to the development of asthma after bronchiolitis in infants.
1206 PHARMACODYNAMICS OF ORAL TLR-7 AGONIST GS-9620 IN TREATMENT-NAIVE PATIENTS WITH CHRONIC HEPATITIS C
Authors: E. Lawitz, D. Gruener, T. Marbury, J. Hill, L. Webster, D. Hassman, S. Pflanz, B. Massetto, M. Subramanian, J. McHutchison, I.M. Jacobson, B. Freilich, M. Rodriguez-Torres
Journal: Journal of Hepatology (2013)
Gene Therapy Using TRAIL-Secreting Human Umbilical Cord Blood–Derived Mesenchymal Stem Cells against Intracranial Glioma
Authors: Seong Muk Kim, Jung Yeon Lim, Sang In Park, Chang Hyun Jeong, Ji Hyeon Oh, Moonsup Jeong, Wonil Oh, Sang-Hoon Park, Young-Chul Sung, Sin-Soo Jeun
Journal: Cancer Research (2008)

Abstract Adenovirus-mediated gene therapies against brain tumors have been limited by the difficulty in tracking glioma cells infiltrating the brain parenchyma. Human umbilical cord blood–derived mesenchymal stem cells (UCB-MSC) are particularly attractive cells for clinical use in cell-based therapies. In the present study, we evaluated the tumor targeting properties and antitumor effects of UCB-MSCs as gene delivery vehicles for glioma therapy. We efficiently engineered UCB-MSCs to deliver a secretable trimeric form of tumor necrosis factor-related apoptosis-inducing ligand (stTRAIL) via adenoviral transduction mediated by cell-permeable peptides. We then confirmed the migratory capacity of engineered UCB-MSCs toward tumor cells by an in vitro migration assay and by in vivo injection of UCB-MSCs into the tumor mass or the opposite hemisphere of established human glioma in nude mice. Moreover, in vitro coculture, experiments on Transwell plates, and in vivo survival experiments showed that MSC-based stTRAIL gene delivery has more therapeutic efficacy compared with direct injection of adenovirus encoding the stTRAIL gene into a tumor mass. In vivo efficacy experiments showed that intratumoral injection of engineered UCB-MSCs (MSCs-stTRAIL) significantly inhibited tumor growth and prolonged the survival of glioma-bearing mice compared with controls. These results suggest that human UCB-MSCs have potential use as effective delivery vehicles for therapeutic genes in the treatment of intracranial glioma. [Cancer Res 2008;68(23):9614–23]
Phylogenetic Analysis Indicates Multiple Origins of Chloroplast Glyceraldehyde-3-Phosphate Dehydrogenase Genes in Dinoflagellates
Authors: Thomas F. Fagan, J. Woodland Hastings
Journal: Molecular Biology and Evolution (2002)

Although the endosymbiotic theory of evolution (Margulis 1970) is widely accepted, the series of events that led to the permanent inclusion of mitochondria and chloroplasts in eukaryotic cells are poorly understood.In particular, the diverse biochemical and morphological properties of chloroplasts have led to suggestions that these organelles have been acquired through multiple primary endosymbiotic events (for a review see Delwiche 1999).Furthermore, the presence of three and sometimes four (Gibbs 1962) membranes around certain chloroplasts, some in association with a second nucleus, suggests that secondary endosymbiosis-the incorporation within a eukaryote of a heritable organelle from another eukaryote-has also occurred (Gibbs 1981).Secondary endosymbioses may also have occurred more than once (Delwiche and Palmer 1997; Delwiche 1999); in fact, the possibility that some autotrophic eukaryotes lost their photosynthetic organelles only to regain them in a later endosymbiotic event cannot be excluded.The occurrence of such multiple, sequential endosymbiotic events can only be proven if some remnant of the first endosymbiont was retained by the host cell.Nuclearencoded genes for chloroplast proteins, for example GAPDH, could provide such evidence.Although phylogenetic analyses have resolved cytosolic (GapC) and chloroplast (GapA) sequences into two distinct clades (Martin et al. 1993;Liaud et al. 1997), recent studies of gapdh isoforms from marine algae have complicated the simple cytosol-chloroplast tree structure.In the dinoflagellate Lingulodinium polyedrum (Stein) Dodge, formerly Gonyaulax polyedra, and in two cryptomonads (Guillardia theta and Pyrenomonas salina) the role of GAPDH in the Calvin cycle is filled by a modified cytosolic isoform (GapC-I), which has a signal sequence at the N-terminal end for intracellular translocation to the chloroplast and, consistent with its anabolic role, amino acid substitutions that allow binding of NADPH (Liaud et al. 1997;Fagan, Hastings, and Morse 1998).Phylogenetic analysis places GapC-I firmly in the cytosolic clade (Fagan, Hastings, and Morse 1998).Homologous isoforms have been identified subsequently in heterokonts and apicomplexans (Liaud et al. 2000;Fast et al. 2001).How the GapC-I isoform was acquired and how pervasive it is among dinoflagellates is unknown.We proposed that it was obtained through lateral transfer
<i>N</i>-(4-Hydroxyphenyl)Retinamide Inhibits Invasion, Suppresses Osteoclastogenesis, and Potentiates Apoptosis through Down-regulation of IκBα Kinase and Nuclear Factor-κB–Regulated Gene Products
Authors: Shishir Shishodia, Angelica M. Gutierrez, Reuben Lotan, Bharat B. Aggarwal
Journal: Cancer Research (2005)

Abstract N-(4-hydroxyphenyl) retinamide [4-HPR], a synthetic retinoid, has been shown to inhibit tumor cell growth, invasion, and metastasis by a mechanism that is not fully understood. Because the nuclear factor-κB (NF-κB) has also been shown to regulate proliferation, invasion, and metastasis of tumor cells, we postulated that 4-HPR modulates the activity of NF-κB. To test this postulate, we examined the effect of this retinoid on NF-κB and NF-κB–regulated gene products. We found that 4-HPR potentiated the apoptosis induced by tumor necrosis factor (TNF) and chemotherapeutic agents, suppressed TNF-induced invasion, and inhibited RANKL-induced osteoclastogenesis, all of which are known to require NF-κB activation. We found that 4-HPR suppressed both inducible and constitutive NF-κB activation without interfering with the direct DNA binding of NF-κB. 4-HPR was found to be synergistic with Velcade, a proteasome inhibitor. Further studies showed that 4-HPR blocked the phosphorylation and degradation of IκBα through the inhibition of activation of IκBα kinase (IKK), and this led to suppression of the phosphorylation and nuclear translocation of p65. 4-HPR also inhibited TNF-induced Akt activation linked with IKK activation. NF-κB–dependent reporter gene expression was also suppressed by 4-HPR, as was NF-κB reporter activity induced by TNFR1, TRADD, TRAF2, NIK, and IKK but not that induced by p65 transfection. The expression of NF-κB–regulated gene products involved in antiapoptosis (IAP1, Bfl-1/A1, Bcl-2, cFLIP, and TRAF1), proliferation (cyclin D1 and c-Myc), and angiogenesis (vascular endothelial growth factor, cyclooxygenase-2, and matrix metalloproteinase-9) were also down-regulated by 4-HPR. This correlated with potentiation of apoptosis induced by TNF and chemotherapeutic agents.
Enhanced fibroblast growth factor 5 expression in stromal and exocrine elements of the pancreas in chronic pancreatitis
Authors: T Ishiwata, M Kornmann, H G Beger, M Korc
Journal: Gut (1998)

Background —Fibroblast growth factor 5 (FGF-5) belongs to a group of mitogenic and angiogenic heparin binding growth factors but its potential role in chronic inflammatory conditions is not known. Aims —To compare FGF-5 expression in the normal pancreas and in the pancreas of patients with chronic pancreatitis (CP) and to characterise FGF-5 expression and secretion in TAKA-1 cells, an immortalised Syrian hamster pancreatic duct cell line. Methods and results —Northern blotting revealed the presence of a 4.0 kb FGF-5 mRNA transcript in both normal and CP tissue samples. Densitometric analysis indicated that the transcript levels were increased by a factor of 1.44 in CP tissue samples compared with normal tissue samples (p=0.039). By immunohistochemisty and in situ hybridisation, FGF-5 was faintly expressed in ductal and islet cells in the normal pancreas. In contrast, in CP tissue samples, there was abundant expression of FGF-5 in ductal, acinar, and islet cells, as well as in periductal fibroblasts. FGF-5 was also expressed in TAKA-1 cells as determined by Northern blotting. By immunoblotting of heparin-sepharose precipitates, TAKA-1 cells were shown to secrete FGF-5 into the medium. Conclusion —Exocrine and stromal derived FGF-5 has the potential to participate in autocrine and paracrine pathways that may contribute to the pathobiology of chronic pancreatitis.
In vivo desensitization of glycogenolysis to Ca2+-mobilizing hormones in rat liver cells.
Authors: G Tsujimoto, A Tsujimoto, K Kato, K Hashimoto
Journal: Journal of Clinical Investigation (1988)

Rat hepatocytes contain several types of Ca2+-linked receptors, all of which stimulate glycogen breakdown by increasing cytosolic free Ca2+ concentration [( Ca2+]c). In vivo desensitization of this Ca2+ messenger system was studied in hepatocytes isolated from either pheochromocytoma (PHEO)-harboring and chronically norepinephrine (NE)-infused rats. Homologous desensitization for alpha 1-adrenergic receptor-mediated phosphorylase activation developed in the early stage of PHEO rats (3-4 wk after implantation), whereas, in the later stage of tumor development or in the NE-infused rats, phosphorylase responses to all Ca2+-mobilizing stimulations were subsensitive (heterologous desensitization). In the homologous desensitization, the [Ca2+]c response to alpha 1-adrenergic stimulation was selectively reduced. We found, using the phenoxybenzamine inactivation method, that there was a linear relationship between alpha 1 receptor density and the [Ca2+]c response; consequently, the blunted [Ca2+]c response to alpha 1-adrenergic stimulation could not be explained by the 34% downregulation of alpha 1 receptors seen in these rats. These results indicated that uncoupling at a step proximal to alpha 1 receptor-stimulated [Ca2+]c increase is also of primary importance in homologous desensitization of phosphorylase activation. On the other hand, heterologous desensitization also involved alteration(s) at steps distal to the rise in [Ca2+]c. Our data demonstrate that prolonged exposure to catecholamines results in desensitization of the [Ca2+]c mobilization pathway and may involve multiple mechanisms.
Gene patents and personalized medicine - what lies ahead?
Authors: Subhashini Chandrasekharan, Robert Cook-Deegan
Journal: Genome Medicine (2009)

Gene patents have generally not impeded biomedical research, but some problems that arise in genetic diagnostics can be attributed to exclusively licensed gene patents. Gene patents for therapeutics have often been litigated but have received surprisingly little public outcry. In stark contrast, genetic diagnostics have been highly controversial but rarely litigated: no case has gone to trial and there is little case law to guide policy. Most recently the Secretary's Advisory Committee for Genetics Health and Society (SACGHS) released a draft report examining how patenting and licensing affect access to clinical genetic testing in the US. The SACGHS reported that patents neither greatly hindered nor facilitated patient access to genetic testing; both the harms and the benefits of patents on genetic diagnostics have been exaggerated. Problems do occur when patents are exclusively licensed to a single provider and no alternative is available. Courts have been changing the thresholds for what can be patented, and how strongly patents can be enforced. Technologies for sequencing, genotyping and gene expression profiling promise to guide clinical decisions in managing common chronic diseases and infectious diseases, and will likely be an integral part of personalized medicine. Developing such genomic tests may require mapping a complex intellectual property landscape and cutting through thickets of patented DNA sequences and related methods. Our preliminary studies have found patent claims that, if strictly enforced, might block the use of multi-gene tests or full-genome sequence data. Yet new technologies promise to reduce the costs of complete genomic sequencing to prices that are comparable to current genetic tests for a single condition. Courts, companies, and policy makers seem unlikely to allow intellectual property to obstruct such technological advance, but prudent policy will depend on careful analysis and foresight. The SACGHS report signals that the US government is paying attention, and increases the odds that policy will foster socially beneficial uses of genetic testing while preserving intellectual property incentives and mitigating the problems that arise from legal monopolies.
Differential Effect of Intracoronary Infusion of Mobilized Peripheral Blood Stem Cells by Granulocyte Colony–Stimulating Factor on Left Ventricular Function and Remodeling in Patients With Acute Myocardial Infarction Versus Old Myocardial Infarction
Authors: Hyun-Jae Kang, Hae-Young Lee, Sang-Hoon Na, Sung-A Chang, Kyung-Woo Park, Hyung-Kwan Kim, Song-Yi Kim, Ho-Joon Chang, Whal Lee, Won Jun Kang, Bon-Kwon Koo, Yong-Jin Kim, Dong Soo Lee, Dae-Won Sohn, Kyou-Sup Han, Byung-Hee Oh, Young-Bae Park, Hyo-Soo Kim
Journal: Circulation (2006)

The efficacy of intracoronary infusion of granulocyte colony-stimulating factor (G-CSF) mobilized peripheral blood stem cells (PBSCs) has not been compared between patients with acute (AMI) versus old myocardial infarction (OMI). In addition, the potential risk of restenosis associated with G-CSF-based stem cell therapy has not been evaluated in the setting of drug eluting stent (DES) implantation.We randomly allocated 96 patients with myocardial infarction who underwent coronary revascularization with DES for the culprit lesion into 4 groups. Eighty-two patients completed 6-month follow-up; AMI cell infusion (n=25), AMI control (n=25), OMI cell infusion (n=16), and OMI control group (n=16). In cell infusion groups, PBSCs were mobilized by G-CSF for 3 days and delivered to infarcted myocardium via intracoronary infusion. The AMI cell infusion group showed a significant additive improvement in left ventricular ejection fraction (LVEF) and remodeling compared with controls (change of LVEF: +5.1+/-9.1% versus -0.2+/-8.6%, P<0.05; change of end-systolic volume: -5.4+/-17.0 mL versus 6.5+/-21.9 mL, P<0.05). In OMI patients, however, there was no significant change of LVEF and ventricular remodeling in spite of significant improvement of coronary flow reserve after cell infusion. G-CSF-based cell therapy did not aggravate neointimal growth with DES implantation.Intracoronary infusion of mobilized PBSCs with G-CSF improves LVEF and remodeling in patients with AMI but is less definite in patients with OMI. G-CSF-based stem cell therapy with DES implantation is both feasible and safe, eliminating any potential for restenosis.