tbuckley/cabot-search huggingface dataset:
Drug-Metabolizing Enzyme Polymorphisms Predict Clinical Outcome in a Node-Positive Breast Cancer Cohort
Authors: Angela DeMichele, Richard Aplenc, Jeffrey Botbyl, Theresa Colligan, Lisa Wray, Melissa Klein-Cabral, Andrea Foulkes, Phyllis Gimotty, John Glick, Barbara Weber, Edward Stadtmauer, Timothy R. Rebbeck
Journal: Journal of Clinical Oncology (2005)

Adjuvant chemotherapy cures only a subset of women with nonmetastatic breast cancer. Genotypes in drug-metabolizing enzymes, including functional polymorphisms in cytochrome P450 (CYP) and glutathione S-transferases (GST), may predict treatment-related outcomes.We examined CYP3A4*1B, CYP3A5*3, and deletions in GST mu (GSTM1) and theta (GSTT1), as well as a priori-defined combinations of polymorphisms in these genes. Using a cohort of 90 node-positive breast cancer patients who received anthracycline-based adjuvant chemotherapy followed by high-dose multiagent chemotherapy with stem-cell rescue, we estimated the effect of genotype and other known prognostic factors on disease-free survival (DFS) and overall survival (OS).Patients who carried homozygous CYP3A4*1B and CYP3A5*3 variants and did not carry homozygous deletions in both GSTM1 and GSTT1 (denoted low-drug genotype group) had a 4.9-fold poorer DFS (P = .021) and a four-fold poorer OS (P = .031) compared with individuals who did not carry any CYP3A4*1B or CYP3A5*3 variants but had deletions in both GSTT1 and GSTM1 (denoted high-drug genotype group). After adjustment for other significant prognostic factors, the low-drug genotype group retained a significantly poorer DFS (hazard ratio [HR] = 4.9; 95% CI, 1.7 to 14.6; P = .004) and OS (HR = 4.8; 95% CI, 1.8 to 12.9; P = .002) compared with the high- and intermediate-drug combined genotype group. In the multivariate model, having low-drug genotype group status had a greater impact on clinical outcome than estrogen receptor status.Combined genotypes at CYP3A4, CYP3A5, GSTM1, and GSTT1 influence the probability of treatment failure after high-dose adjuvant chemotherapy for node-positive breast cancer.
Gastroenteropancreatic neuroendocrine tumours
Authors: Irvin M Modlin, Kjell Oberg, Daniel C Chung, Robert T Jensen, Wouter W de Herder, Rajesh V Thakker, Martyn Caplin, Gianfranco Delle Fave, Greg A Kaltsas, Eric P Krenning, Steven F Moss, Ola Nilsson, Guido Rindi, Ramon Salazar, Philippe Ruszniewski, Anders Sundin
Journal: The Lancet Oncology (2008)
BRANCHED-CHAIN AMINOACIDS IN AMYOTROPHIC LATERAL SCLEROSIS
Authors: R.J. Guiloff, J.M. Emami, MatthewJ. During, Andrew Freese, Andreas Plaitakis, John Mandeli, Jeffrey Smith, MelvinD. Yahr, Andreas Plaitakis, Pullanipally Shashidharan, Susanne Malessa, Nigel Leigh, Oleh Hornykiewicz
Journal: The Lancet (1988)
Modulating effect of regional myocardial performance on local myocardial perfusion in the dog.
Authors: M Marzilli, S Goldstein, H N Sabbah, T Lee, P D Stein
Journal: Circulation Research (1979)

We studied the effect of regional contractile performance on regional coronary blood flow and flow distribution in 10 dogs. The left anterior descending (LAD) coronary artery was cannulated and perfused. Maximal vasodilation was obtained with adenosine. Consequently, variations of LAD flow reflected changes of extravascular resistance. Lidocaine injected in the LAD caused a localized reduction of contractile performance as shown by the absence of systolic wall thickening. Global left ventricular performance and pressure were unchanged. Coronary extravascular resistance diminished and LAD flow increased from 4.8 +/- 0.5 to 6.2 +/- 0.6 ml/min per g (P less than 0.02). The endocardial: epicardial ratio increased from 1.02 +/- 0.07 to 1.28 +/- 0.07 (P less than 0.001). Isoproterenol in the LAD augmented systolic wall thickening. Regional coronary flow diminished from 5.1 +/- 0.5 to 3.3 +/- 0.4 ml/min per g (P less than 0.001), and the endocardial:epicardial ratio diminished from 1.08 +/- 0.07 to 0.75 +/- 0.07 (P less than 0.01). These data indicate that myocardial contractility is a major component of extravascular coronary resistance and is a mechanical determinant of coronary blood flow and its transmural distribution.
Antisense to Cyclin D1 Inhibits Vascular Endothelial Growth Factor–Stimulated Growth of Vascular Endothelial Cells: Implication of Tumor Vascularization
Authors: Masayoshi Yasui, Hirofumi Yamamoto, Chew Yee Ngan, Bazarragchaa Damdinsuren, Yurika Sugita, Hiroki Fukunaga, Jinyu Gu, Makiko Maeda, Ichiro Takemasa, Masataka Ikeda, Yasushi Fujio, Mitsugu Sekimoto, Nariaki Matsuura, I. Bernard Weinstein, Morito Monden
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Our aim was to determine the effects of cyclin D1 inhibition on tumor-associated neovascularization and endothelial cell growth. Experimental Design: We have generated adenovirus system for antisense to cyclin D1 (AS CyD1) and evaluated in vitro and in vivo effects. Small interfering RNA against cyclin D1 was also used to analyze cyclin D1 inhibition-associated vascular endothelial growth factor (VEGF) regulation. Results: The xenografts treated with adenoviral AS CyD1 showed less vessel density and displayed smaller tumor size in colon cancer cell lines HCT116 and DLD1. In vitro studies indicated that AS CyD1 decreased VEGF protein expression in DLD1 but not in HCT116. Cyclin D1 small interfering RNA caused a decrease in VEGF expression at protein and RNA levels in DLD1. A modest decrease was noted in the VEGF promoter activity, with inactivation of the STAT3 transcription factor through dephosphorylation. On the hand, the cyclin D1 inhibition plus STAT3 inhibitor markedly decreased VEGF expression in HCT116, although VEGF did not change by the STAT3 inhibitor alone. In cultures of human umbilical vein endothelial cells (HUVEC), VEGF augmented cyclin D1 expression and cell growth. AS CyD1 significantly inhibited HUVEC growth even in the presence of VEGF. AS CyD1 also significantly suppressed in vitro tube formation in VEGF-treated HUVEC and in vivo macroaneurysm formation in VEGF-treated Matrigel plug. Conclusions: Our results suggest that cyclin D1 may play a role in the maintenance of VEGF expression and that AS CyD1 could be potentially useful for targeting both cancer cells and their microenvironment of tumor vessels.
Age-dependent production of IgA and IgM autoantibodies against IgG2a in a colony of 129/Sv mice
Authors: JL Van Snick, PL Masson
Journal: The Journal of Experimental Medicine (1979)

Although much of the basic immunological work has been done with mice, little is known about anti-IgG autoantibodies in this species. Dresser (1, 2) has reported the occurrence, in CBA mice, of anti-IgG antibody (Ab)(1) detected by a hemolytic-plaque assay after stimulation with endotoxin or immunization against sheep erythrocytes. IgM rheumatoid factor has also been described in various strains of mice with a systemic lupus erythematosus-like disease (3). Recently, we have tried to induce anti-IgG in mice of the 129/Sv strain by inoculating autologous IgG. To our surprise, we found that the sera of all the animals had, before any inoculation, anti-IgG detectable by agglutination of particles coated with autologous IgG. The possibilities to investigate the mechanism of production and the biological role of this kind of Ab prompted us to undertake a study of the nature and specificity of the mouse anti-IgG.
MMP-9 Short Interfering RNA Induced Senescence Resulting in Inhibition of Medulloblastoma Growth via p16INK4a and Mitogen-Activated Protein Kinase Pathway
Authors: Jasti S. Rao, Praveen Bhoopathi, Chandramu Chetty, Meena Gujrati, Sajani S. Lakka
Journal: Cancer Research (2007)

Abstract The involvement of matrix metalloproteinases (MMP) has been suggested in cellular mechanisms leading to medulloblastoma, the most common malignant brain tumor in children. A significant association of the expression levels of MMP-9 with survival and M stage suggests that patients with medulloblastoma metastatic disease at diagnosis may benefit from the anti-MMP therapy. Here, we have evaluated the tumorigenicity of medulloblastoma cells after infection with an adenovirus containing a 21-bp short interfering RNA sequence of the human MMP-9 gene (Ad-MMP-9). Infection of Daoy medulloblastoma cells with Ad-MMP-9 reduced MMP-9 activity and protein levels compared with parental and Ad-SV controls. Ad-MMP-9 decreased the number of viable Daoy cells in a concentration-dependent manner. Fluorescence-activated cell sorting analysis indicated that Ad-MMP-9 infection caused a dose-dependent cell cycle arrest in the G0-G1 phase. Ad-MMP-9–induced cell cycle arrest seems to be mediated by the extracellular signal-regulated kinase/mitogen-activated protein kinase pathway and the cell cycle inhibitor p16INK4a and is phenotypically indistinguishable from senescence. Ad-MMP-9 treatment inhibited medulloblastoma tumor growth in an intracranial model and was mediated by up-regulation of p16 expression. These studies validate the usefulness of targeting MMP-9 and provide a novel perspective in the treatment of medulloblastoma. [Cancer Res 2007;67(10):4956–64]
An epithelial circadian clock controls pulmonary inflammation and glucocorticoid action
Authors: Julie Gibbs, Louise Ince, Laura Matthews, Junjie Mei, Thomas Bell, Nan Yang, Ben Saer, Nicola Begley, Toryn Poolman, Marie Pariollaud, Stuart Farrow, Francesco DeMayo, Tracy Hussell, G Scott Worthen, David Ray, Andrew Loudon
Journal: Nature Medicine (2014)
Shortened Duration of Untreated First Episode of Psychosis: Changes in Patient Characteristics at Treatment
Authors: Tor K. Larsen, Thomas H. McGlashan, Jan Olav Johannessen, Svein Friis, Cato Guldberg, Ulrik Haahr, Marthe Horneland, Ingrid Melle, Lars C. Moe, Stein Opjordsmoen, Erik Simonsen, Per Vaglum
Journal: American Journal of Psychiatry (2001)

This study examined whether duration of untreated psychosis can be shortened in patients with first episodes of DSM-IV schizophrenia spectrum disorders and whether shorted duration alters patient appearance at treatment.Two study groups were ascertained in the same Norwegian health care sector: one from 1993-1994 with usual detection methods and one from 1997-1998 with early detection strategies that included education about psychosis.Patients with early detection had a shorter median duration of untreated psychosis by 21.5 weeks than patients with usual detection. The number with psychosis was greater in the early detection group; the number with schizophrenia was less. Early detection patients had more substance abuse and were younger, better adjusted premorbidly, and less ill.Early detection can shorten duration of untreated psychosis and help more patients when they are less severely ill. Given the devastation of psychosis, this is a significant treatment advance.
Orchitis of Mumps
Authors: R. Boyd
Journal: BMJ (1948)

<h3>Objectives</h3> Anti-centromere antibodies (ACAs) are detected in patients with various autoimmune diseases such as Sjögren’s syndrome (SS), systemic sclerosis (SSc) and primary biliary cholangitis (PBC). However, the targeted antigens of ACAs are not fully elucidated despite the accumulating understanding of the molecular structure of the centromere. The aim of this study was to comprehensively reveal the autoantigenicity of centromere proteins. <h3>Methods</h3> A centromere antigen library including 16 principal subcomplexes composed of 41 centromere proteins was constructed. Centromere protein/complex binding beads were used to detect serum ACAs in patients with SS, SSc and PBC. ACA-secreting cells in salivary glands obtained from patients with SS were detected with green fluorescent protein-fusion centromere antigens and semiquantified with confocal microscopy. <h3>Results</h3> A total of 241 individuals with SS, SSc or PBC and healthy controls were recruited for serum ACA profiling. A broad spectrum of serum autoantibodies was observed, and some of them had comparative frequency as anti-CENP-B antibody, which is the known major ACA. The prevalence of each antibody was shared across the three diseases. Immunostaining of SS salivary glands showed the accumulation of antibody-secreting cells (ASCs) specific for kinetochore, which is a part of the centromere, whereas little reactivity against CENP-B was seen. <h3>Conclusions</h3> We demonstrated that serum autoantibodies target the centromere–kinetochore macrocomplex in patients with SS, SSc and PBC. The specificity of ASCs in SS salivary glands suggests kinetochore complex-driven autoantibody selection, providing insight into the underlying mechanism of ACA acquisition.
Genome Scans of Variation and Adaptive Change: Extended Analysis of a Candidate Locus Close to the phantom Gene Region in Drosophila melanogaster
Authors: D. J. Orengo, M. Aguade
Journal: Molecular Biology and Evolution (2007)

Nucleotide variation in populations originating from the recent range expansion of a species should reflect their adaptation to new habitats as well as their demographic history. A survey of nucleotide variation at 109 noncoding X-chromosome fragments in a European population of Drosophila melanogaster allowed identifying some candidates to have been recently affected by positive selection. Adaptive changes leave a spatial differential footprint that can be used to discriminate among candidates by extending their study to neighboring regions. Here, we surveyed variation at an approximately 190-kb region spanning a locus exhibiting a significantly skewed frequency spectrum. A stretch of approximately 12 kb with reduced variation was detected within a continuously sequenced region that included the focal fragment. Moreover, the regions flanking this stretch exhibited an excess of high-frequency derived variants. Application of maximum likelihood ratio and goodness-of-fit tests suggested that the pattern of variation detected at the studied region (at cytological bands 17C-17D) might have been shaped by a recent selective change, most probably at or around the phantom gene that encodes CYP306A1, a cytochrome P450 enzyme in the ecdysteroidogenic pathway.
Antitumor Activity of the Selective MDM2 Antagonist Nutlin-3 Against Chemoresistant Neuroblastoma With Wild-Type p53
Authors: Tom Van Maerken, Liesbeth Ferdinande, Jasmien Taildeman, Irina Lambertz, Nurten Yigit, Liesbeth Vercruysse, Ali Rihani, Martin Michaelis, Jindrich Cinatl, Claude A. Cuvelier, Jean-Christophe Marine, Anne De Paepe, Marc Bracke, Frank Speleman, Jo Vandesompele
Journal: JNCI Journal of the National Cancer Institute (2009)

BackgroundRestoring p53 function by antagonizing its interaction with the negative regulator MDM2 is an appealing nongenotoxic approach to treating tumors with wild-type p53. Mutational inactivation of p53 is rare in neuroblastoma tumors at diagnosis and occurs in only a subset of multidrug-resistant neuroblastomas.
Doxycycline Treatment of Chronic Trachoma
Authors: Isao Hoshiwara
Journal: JAMA (1973)

American Indian children with mild chronic trachoma were treated with doxycycline, 2.5 to 4 mg/kg of body weight, given as a single daily dose on five days each week, for a total of 28 doses given in 40 days. The study was carried out double-blind, with randomized placebo controls. Detailed ophthalmologic evaluation continued for five months after the treatment course. The trachoma in the doxycycline-treated children improved markedly, as compared to those receiving placebo (P &lt;.001 at 20 weeks after treatment). Few untoward drug effects were observed. Serum levels of the drug were maintained through much of the treatment period, but drug levels in tears were low and irregular. This one-dose-a-day therapy deserves consideration for mass treatment of trachoma.
DISTAL PROTECTION DEVICE DID NOT IMPROVE INFARCT SIZE NOR MYOCARDIAL SALVAGE WHEREAS AGGRAVETED MICROVASCULAR OBSTRUCTION EVALUATED BY CARDIAC MR USING DELAYED ENHANCEMENT AND T2 WEIGHTED IMAGE AFTER PRIMARY PERCUTANEOUS CORONARY INTERVENTION FOR ST-ELEVATION MYOCARDIAL INFARCTION
Authors: Chang-Hwan Yoon, Woo-Young Chung, Jung-Won Suh, Young-Seok Cho, Tae-Jin Youn, Eun-Ju Jeon, Sang-il Choi, In-Ho Chae, Dong-Ju Choi
Journal: Journal of the American College of Cardiology (2011)
Physiology and Pharmacology of Striatal Neurons
Authors: Anatol C. Kreitzer
Journal: Annual Review of Neuroscience (2009)

The basal ganglia occupy the core of the forebrain and consist of evolutionarily conserved motor nuclei that form recurrent circuits critical for motivation and motor planning. The striatum is the main input nucleus of the basal ganglia and a key neural substrate for procedural learning and memory. The vast majority of striatal neurons are spiny GABAergic projection neurons, which exhibit slow but temporally precise spiking in vivo. Contributing to this precision are several different types of interneurons that constitute only a small fraction of total neuron number but play a critical role in regulating striatal output. This review examines the cellular physiology and modulation of striatal neurons that give rise to their unique properties and function.
Two distinct pathways of specific killing revealed by perforin mutant cytotoxic T lymphocytes
Authors: Hidefumi Kojima, Nobukata Shinohara, Satoko Hanaoka, Yoshiko Someya-Shirota, Yohtaroh Takagaki, Hiroshi Ohno, Takashi Saito, Takashi Katayama, Hideo Yagita, Ko Okumura, Yoichi Shinkai, Frederick W. Alt, Akio Matsuzawa, Shin Yonehara, Hajime Takayama
Journal: Immunity (1994)
BEHAVIOR OF HYPOCHLORITE AND OF CHLORAMINE-T SOLUTIONS IN CONTACT WITH NECROTIC AND NORMAL TISSUES IN VIVO
Authors: J. Harold Austin, Herbert D. Taylor
Journal: The Journal of Experimental Medicine (1918)

1. The fall in chlorine concentration of Dakin's hypochlorite solution is more rapid in contact with necrotic than in contact with normal tissue. 2. The fall in chlorine concentration of chloramine-T solution is very slight when applied to necrotic tissue and is negligible when applied to normal tissue. 3. The action of the hypochlorite solution on tissue results in the separation of particles of necrotic tissue, hair, epithelial scales, coagulated serum, etc., and a gradual digestion of these substances, taking place over a period of at least 17 hours. 4. The fall in the chlorine concentration of the hypochlorite solution is not complete until the particles are completely dissolved. 5. Chloramine-T solution, 2 per cent, has no erosive effect comparable with that exhibited by the hypochlorite solution. 6. Repeated exposures to the three solutions show the hypochlorite solution to be superior in its cleansing ability on necrotic tissue. 7. The hypochlorite solution is much more irritating to normal rabbit skin than chloramine-T solution or the alkaline control solution. 8. Therefore, the irritating effects must be due to the readily available chlorine.
S100A9 and EGFR gene signatures predict disease progression in muscle invasive bladder cancer patients after chemotherapy
Authors: W.T. Kim, J. Kim, C. Yan, P. Jeong, S.Y. Choi, O.J. Lee, Y.B. Chae, S.J. Yun, S.C. Lee, W.J. Kim
Journal: Annals of Oncology (2014)
Prone position improves expiratory airway mechanics in severe chronic bronchitis
Authors: S. D. Mentzelopoulos, C. Roussos, S. G. Zakynthinos
Journal: European Respiratory Journal (2005)

Based on lung parenchyma-airways' interdependence, the present authors hypothesised that prone positioning may reduce airway resistance in severe chronic bronchitis. A total of 10 anaesthetised/mechanically ventilated patients were enrolled. Partitioned respiratory system (RS) mechanics during iso-flow experiments (flow = 0.91 L·s −1 , tidal volume ( V T ) varied within 0.2–1.2 L), haemodynamics, gas-exchange, expiratory airway resistance ( R aw,exp ), functional residual capacity (FRC), change in FRC (ΔFRC), end-expiratory lung volume (EELV), expiratory airway resistance at EELV ( R aw,exp,EELV ), intrinsic positive end-expiratory pressure (PEEPi), and mean end-expiratory flow were determined in baseline semirecumbent (SR BAS ), prone, and post-prone semirecumbent (SR PP ) postures. Pronation versus SR BAS resulted in significantly reduced R aw,exp (at V T ≥0.8 L), R aw,exp,EELV (18.3±1.4 versus 31.6±2.6 cm H 2 O·L −1 ·s −1 ), inspiratory airway resistance (at V T ≥1.0 L), static lung elastance (at V T ≤0.6 L), “additional” RS/lung resistance (at a range of V T s), ΔFRC (0.35±0.03 versus 0.47±0.03 L), EELV (4.92±0.49 versus 5.65±0.65 L), RS/lung PEEPi (6.7±1.1/5.4±0.6 versus 8.9±1.7/7.8±1.1 cm H 2 O), mean end-expiratory flow (63.9±4.2 versus 47.9±4.0 mL·s −1 ), and shunt fraction (0.16±0.03 versus 0.21±0.03); benefits were reversed in SR PP . In severe chronic bronchitis, prone positioning reduces airway resistance and dynamic hyperinflation.
Pharmacokinetics of radiolabelled PAR j 1 administered intranasally to allergic and healthy subjects
Authors: G. Passalacqua, V. Altrinetti, G. Mariani, P. Falagiani, G. Mistrello, R. Brizzolara, G.W. Canonica, M. Bagnasco
Journal: Journal of Allergy and Clinical Immunology (2005)
Platelet-Derived Growth Factor Ligand and Receptor Expression in Response to Altered Blood Flow In Vivo
Authors: J. Sheppard Mondy, Volkhard Lindner, Jody K. Miyashiro, Bradford C. Berk, Richard H. Dean, Randolph L. Geary
Journal: Circulation Research (1997)

Abstract Blood flow and the tractive force shear stress are important determinants of artery caliber, and reduced shear predisposes arteries to intimal thickening and atherosclerosis. The molecular basis for shear-induced changes in artery wall structure is poorly defined. A number of factors associated with normal and pathological artery wall remodeling are induced by shear stress in endothelial cell cultures. These include platelet-derived growth factor (PDGF), a potent mitogen, chemoattractant, and vasoconstrictor. To determine whether similar changes occur in vivo, we examined the effects of reduced blood flow on endothelial cell PDGF expression and proliferation in the rat carotid artery. Branches of the right internal and external carotid arteries were ligated, reducing common carotid artery blood flow from 8.0±0.6 to 0.5±0.1 mL/min while increasing flow in the left carotid from 7.1±0.6 to 10.8±0.7 mL/min. Shear stress following the procedure was 1.4±0.2 and 33.4±1.1 dyne/cm 2 in carotids with reduced blood flow (RF) and increased blood flow (IF), respectively. Arteries were harvested 6, 24, 48, or 72 hours after ligation, perfusion-fixed, and opened longitudinally. Endothelial cell proliferation (bromodeoxyuridine [BrdU] labeling) was assessed en face at 24, 48, and 72 hours; expression of mRNA for PDGF-A and -B chains and PDGF α- and β-receptors (in situ hybridization) was determined at 6, 48, and 72 hours after unilateral flow reduction. RF induced endothelial cell proliferation, which peaked at 48 hours (RF BrdU labeling: 24 hours, 0.4±0.2%; 48 hours, 7.2±2.0%; and 72 hours, 4.1±0.6%; n=5). PDGF-B expression increased in RF compared with IF endothelium within 48 hours and persisted at 72 hours (percent labeling [RF/IF×100]: 6 hours, 76±20%; 48 hours, 395±179%; and 72 hours, 208±44%; n=3). PDGF-A expression was similarly increased in RF endothelium. In contrast, expression of PDGF α- and β-receptors was undetectable in RF and IF endothelium at all times. We conclude that endothelial cell PDGF ligand expression is induced by reduced shear stress in vivo and may play an important role in flow-mediated remodeling and atherogenesis.