tbuckley/cabot-search huggingface dataset:
Systematic Errors in the Evaluation of Side Effects
Authors: CHARLES W. AVERY, BERTRAM P. IBELLE, BETTY ALLISON, NANCY MANDELL
Journal: American Journal of Psychiatry (1967)

Twenty-three inpatients at Hartford Hospital were selected for the pilot study of NIMH Collaborative Study III, testing the feasibility of high-dosage chlorpromazine in depressed patients. After random assignment to either a nonchecklist group or a checklist group, both groups were asked the following question: "Have you noticed any change in bodily function or had any physical complaints in the past week?" The nonchecklist group was asked no further questions, and only spontaneously reported symptoms were recorded. The checklist group was also asked specific questions from a list of possible drug side effects. Statistical analysis in terms of both quantity and severity of side effects showed significantly greater numbers and greater severity of side effects reported in the checklist group. On the basis of these resuits the authors feel that unless reports of medication side effects are obtained in a uniform manner, the data collected under varying conditions of inquiry will not be comparable. Research findings based on such data could be invalid.
Identification of novel androgen receptor target genes in prostate cancer
Authors: Unnati Jariwala, Jennifer Prescott, Li Jia, Artem Barski, Steve Pregizer, Jon P Cogan, Armin Arasheben, Wayne D Tilley, Howard I Scher, William L Gerald, Grant Buchanan, Gerhard A Coetzee, Baruch Frenkel
Journal: Molecular Cancer (2007)

The androgen receptor (AR) plays critical roles in both androgen-dependent and castrate-resistant prostate cancer (PCa). However, little is known about AR target genes that mediate the receptor's roles in disease progression.Using Chromatin Immunoprecipitation (ChIP) Display, we discovered 19 novel loci occupied by the AR in castrate resistant C4-2B PCa cells. Only four of the 19 AR-occupied regions were within 10-kb 5'-flanking regulatory sequences. Three were located up to 4-kb 3' of the nearest gene, eight were intragenic and four were in gene deserts. Whereas the AR occupied the same loci in C4-2B (castrate resistant) and LNCaP (androgen-dependent) PCa cells, differences between the two cell lines were observed in the response of nearby genes to androgens. Among the genes strongly stimulated by DHT in C4-2B cells--D-dopachrome tautomerase (DDT), Protein kinase C delta (PRKCD), Glutathione S- transferase theta 2 (GSTT2), Transient receptor potential cation channel subfamily V member 3 (TRPV3), and Pyrroline-5-carboxylate reductase 1 (PYCR1)--most were less strongly or hardly stimulated in LNCaP cells. Another AR target gene, ornithine aminotransferase (OAT), was AR-stimulated in a ligand-independent manner, since it was repressed by AR siRNA knockdown, but not stimulated by DHT. We also present evidence for in vivo AR-mediated regulation of several genes identified by ChIP Display. For example, PRKCD and PYCR1, which may contribute to PCa cell growth and survival, are expressed in PCa biopsies from primary tumors before and after ablation and in metastatic lesions in a manner consistent with AR-mediated stimulation.AR genomic occupancy is similar between LNCaP and C4-2B cells and is not biased towards 5' gene flanking sequences. The AR transcriptionally regulates less than half the genes nearby AR-occupied regions, usually but not always, in a ligand-dependent manner. Most are stimulated and a few are repressed. In general, response is stronger in C4-2B compared to LNCaP cells. Some of the genes near AR-occupied regions appear to be regulated by the AR in vivo as evidenced by their expression levels in prostate cancer tumors of various stages. Several AR target genes discovered in the present study, for example PRKCD and PYCR1, may open avenues in PCa research and aid the development of new approaches for disease management.
Optimisation of the continuum of supportive and palliative care for patients with breast cancer in low-income and middle-income countries: executive summary of the Breast Health Global Initiative, 2014
Authors: Sandra R Distelhorst, James F Cleary, Patricia A Ganz, Nuran Bese, Rolando Camacho-Rodriguez, Fatima Cardoso, Henry Ddungu, Julie R Gralow, Cheng-Har Yip, Benjamin O Anderson
Journal: The Lancet Oncology (2015)
Mechanisms of human eosinophil migration induced by the combination of IL-5 and the endocannabinoid 2-arachidonoyl-glycerol
Authors: Marie-Chantal Larose, Caroline Turcotte, François Chouinard, Claudine Ferland, Cyril Martin, Véronique Provost, Michel Laviolette, Nicolas Flamand
Journal: Journal of Allergy and Clinical Immunology (2014)
Psychological, behavioural, and social adjustment in children and adolescents with juvenile chronic arthritis
Authors: A C J Huygen
Journal: Annals of the Rheumatic Diseases (2000)

<h3>OBJECTIVE</h3> To assess the psychological, behavioural and social adjustment of children (7–11 years) and adolescents (12–16 years) with juvenile chronic arthritis (JCA). Higher rates of maladjustment were expected to be found in these patients. <h3>METHODS</h3> Self report questionnaires were used within the context of personal interviews. Family functioning and social support were studied as well. Forty seven patients with JCA, 52 healthy peers and their respective parents participated in the study. <h3>RESULTS</h3> Self esteem, perceived competence and body image in patients with JCA were as positive as they were in healthy participants. There were no differences between ill and healthy youngsters with respect to the incidence of psychopathology. Patients with JCA, in general, perceived themselves as socially competent, but they seemed to have somewhat less opportunity or energy to participate in social activities. Children with JCA showed a high level of aspiration to cope with social expectations. This aspiration seemed to be even stronger in case the disease caused more strains, for example, in periods of inflammation and in the systemic onset type. The high level of social adjustment in children with JCA seemed to be supported by highly cohesive family structures. Generally, adolescents with JCA experienced much social support. <h3>CONCLUSIONS</h3> In contrast with our expectation, children and adolescents with JCA seemeed to cope quite well with the psychological and social consequences of their long term condition. For future studies, it is hypothesised that the high levels of adaptation might imply an enduring psychological strain, which is reflected in an altered function of the autonomic nervous system.
Increased treatment requirements of patients with cystic fibrosis who harbour a highly transmissible strain of Pseudomonas aeruginosa
Authors: A M Jones
Journal: Thorax (2002)

<b>Background:</b> A group of patients who harbour the same highly transmissible strain of <i>Pseudomonas aeruginosa</i> were identified at a cystic fibrosis (CF) centre. Isolates of this strain display a number of unusual phenotypic features including resistance to most typical antipseudomonal antibiotics. A study was undertaken to see if there was a difference in treatment requirements between CF patients with chronic infection with their own unique <i>P aeruginosa</i> strains (group 1) and those who harbour a highly transmissible strain (group 2). <b>Methods:</b> Data on treatment requirements for the year 2000 were collected from the case records of CF patients with chronic <i>P aeruginosa</i> infection who had received inpatient treatment. Patients co-infected with <i>Burkholderia cepacia</i> or other highly transmissible strains of <i>P aeruginosa</i> were excluded. <b>Results:</b> There were 2/56 and 3/22 deaths in groups 1 and 2, respectively; these patients were excluded from the analysis. No difference was found between the two groups for mean age, % predicted forced expiratory volume in 1 second (FEV<sub>1</sub>), % predicted forced vital capacity (FVC), and body mass index. Patients in group 2 had a greater median (range) number of intravenous antibiotic days (60 (17–216) <i>v</i> 33 (4–237) days; p=0.01), inpatient days (39 (7–183) <i>v</i> 16 (1–172) days; p&lt;0.01), and inpatient episodes (3 (1–9) <i>v</i> 2 (1–6); p&lt;0.01), and more respiratory exacerbations (mean (SD) 8.2 (3.4) <i>v</i> 6.1 (3.2); p=0.01). <b>Conclusions:</b> Patients who harbour the highly transmissible <i>P aeruginosa</i> strain have a greater treatment burden than patients with CF who harbour their own unique strains. These findings support the need for microbiological surveillance for highly transmissible <i>P aeruginosa</i> and the implementation of infection control measures to prevent cross infection.
Gray Matter Decrease of the Anterior Cingulate Cortex in Anorexia Nervosa
Authors: Mark Mühlau, Christian Gaser, Rüdiger Ilg, Bastian Conrad, Carl Leibl, Marian H Cebulla, Herbert Backmund, Monika Gerlinghoff, Peter Lommer, Andreas Schnebel, Afra M Wohlschläger, Claus Zimmer, Sabine Nunnemann
Journal: American Journal of Psychiatry (2007)

Objective: The brain regions that are critically involved in the pathophysiology of anorexia nervosa have not been clearly elucidated. Moreover, decrease in cerebral tissue during extreme malnutrition has been demonstrated repeatedly in anorexia nervosa, but data regarding the reversibility of this cerebral tissue decrease are conflicting. The authors examined region-specific gray matter changes and global cerebral volumes in recovered patients with anorexia nervosa. Method: High-resolution, T1-weighted magnetic resonance imaging (MRI) and voxel-based morphometry were performed in 22 recovered women with anorexia nervosa and in 37 healthy comparison women. Recovery was defined as a body mass index above 17.0 kg/m 2 and regular menses for at least 6 months. Results: The global volumes of gray matter (but not white matter) were decreased in patients with anorexia nervosa by approximately 1%. Analyses of region-specific gray matter changes revealed a gray matter decrease bilaterally in the anterior cingulate cortex of approximately 5%, which remained significant after correction for global effects. This gray matter decrease correlated significantly with the lowest body mass index of lifetime but not with other clinical variables. Conclusions: In anorexia nervosa, part of the global gray matter loss persists over the long run. Region-specific gray matter loss in the anterior cingulate cortex is directly related to the severity of anorexia nervosa, indicating an important role of this area in the pathophysiology of the disorder. Further research is warranted to determine the cause, specificity, and functional consequences of this structural brain change in anorexia nervosa.
The effect of increasing hematocrit on peritoneal transport kinetics.
Authors: J M Burkart, B I Freedman, M V Rocco
Journal: Journal of the American Society of Nephrology (1994)

Although it is well established that an increase in hematocrit results in a small decrease in solute transport in hemodialysis patients, the effect of hematocrit on solute transport in peritoneal dialysis patients remains controversial. In hemodialysis patients, the inverse relationship between hematocrit and the transport of small solutes may be explained by the dependence of solute clearance on the rapidity of solute movement from the red blood cell to the dialysate. This movement is determined by several in vivo factors, the most important of which is blood flow. However, in peritoneal dialysis, the effective peritoneal capillary blood flow is several times the maximal urea clearance. Therefore, clearances are usually considered to be independent of blood flow rate and variations in hematocrit should not affect solute transport across the peritoneal membrane. In this study, the effect of an increase in hematocrit on the transport of small solutes in peritoneal dialysis patients is analyzed. The peritoneal equilibration test was performed in 25 continuous ambulatory peritoneal dialysis patients before and after an increase in hematocrit of at least seven points. No significant change was found in ultrafiltration rate or in peritoneal transport characteristics as measured by the peritoneal equilibration test or by mass transfer area coefficients for creatinine, urea, or glucose. In addition, there was no change in these parameters in a control group of 13 continuous ambulatory peritoneal dialysis patients with no significant change in hematocrit. These findings are consistent with the observation that solute clearance for urea and creatinine in peritoneal dialysis is not blood flow dependent.(ABSTRACT TRUNCATED AT 250 WORDS)
Reconstruction of regulatory and metabolic pathways in metal-reducing delta-proteobacteria.
Authors: Dmitry A Rodionov, Inna Dubchak, Adam Arkin, Eric Alm, Mikhail S Gelfand
Journal: Genome biology (2004)

Abstract Background Relatively little is known about the genetic basis for the unique physiology of metal-reducing genera in the delta subgroup of the proteobacteria. The recent availability of complete finished or draft-quality genome sequences for seven representatives allowed us to investigate the genetic and regulatory factors in a number of key pathways involved in the biosynthesis of building blocks and cofactors, metal-ion homeostasis, stress response, and energy metabolism using a combination of regulatory sequence detection and analysis of genomic context. Results In the genomes of δ-proteobacteria, we identified candidate binding sites for four regulators of known specificity (BirA, CooA, HrcA, sigma-32), four types of metabolite-binding riboswitches ( RFN -, THI -, B12 -elements and S-box), and new binding sites for the FUR, ModE, NikR, PerR, and ZUR transcription factors, as well as for the previously uncharacterized factors HcpR and LysX. After reconstruction of the corresponding metabolic pathways and regulatory interactions, we identified possible functions for a large number of previously uncharacterized genes covering a wide range of cellular functions. Conclusions Phylogenetically diverse δ-proteobacteria appear to have homologous regulatory components. This study for the first time demonstrates the adaptability of the comparative genomic approach to de novo reconstruction of a regulatory network in a poorly studied taxonomic group of bacteria. Recent efforts in large-scale functional genomic characterization of Desulfovibrio species will provide a unique opportunity to test and expand our predictions.
British Association of Dermatologists Annual Meeting, 1996 Bournemouth
Authors: J.L. BURTON
Journal: British Journal of Dermatology (1996)

Journal Article British Association of Dermatologists Annual Meeting, 1996 Bournemouth: Programme of Meeting Get access J.L. BURTON J.L. BURTON Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 135, Issue s47, 1 July 1996, Pages 1–12, https://doi.org/10.1111/j.1365-2133.1996.tb15166.x Published: 01 July 1996
Measles Still Has a Devastating Impact in Unvaccinated Populations
Authors: William J Moss
Journal: PLoS Medicine (2006)

Measles has caused millions of deaths since its emergence thousands of years ago, probably as a zoonosis [1]. Deaths from measles are due largely to an increased susceptibility to secondary bacterial and viral infections. This period of increased susceptibility lasts for several weeks to months after the onset of rash [2] and is attributed to a prolonged state of immune suppression. Most deaths associated with measles are due to pneumonia [3]. Although the global mortality from measles is falling [4], a new study in PLoS Medicine found that children in Nigeria, Niger, and Chad still recently faced unacceptably high mortality from measles [5], a largely preventable disease.
Intracellular ATP Levels Are a Pivotal Determinant of Chemoresistance in Colon Cancer Cells
Authors: Yunfei Zhou, Federico Tozzi, Jinyu Chen, Fan Fan, Ling Xia, Jinrong Wang, Guang Gao, Aijun Zhang, Xuefeng Xia, Heather Brasher, William Widger, Lee M. Ellis, Zhang Weihua
Journal: Cancer Research (2011)

Abstract Altered metabolism in cancer cells is suspected to contribute to chemoresistance, but the precise mechanisms are unclear. Here, we show that intracellular ATP levels are a core determinant in the development of acquired cross-drug resistance of human colon cancer cells that harbor different genetic backgrounds. Drug-resistant cells were characterized by defective mitochondrial ATP production, elevated aerobic glycolysis, higher absolute levels of intracellular ATP, and enhanced HIF-1α–mediated signaling. Interestingly, direct delivery of ATP into cross-chemoresistant cells destabilized HIF-1α and inhibited glycolysis. Thus, drug-resistant cells exhibit a greater “ATP debt” defined as the extra amount of ATP needed to maintain homeostasis of survival pathways under genotoxic stress. Direct delivery of ATP was sufficient to render drug-sensitive cells drug resistant. Conversely, depleting ATP by cell treatment with an inhibitor of glycolysis, 3-bromopyruvate, was sufficient to sensitize cells cross-resistant to multiple chemotherapeutic drugs. In revealing that intracellular ATP levels are a core determinant of chemoresistance in colon cancer cells, our findings may offer a foundation for new improvements to colon cancer treatment. Cancer Res; 72(1); 304–14. ©2011 AACR.
WOX Gene Phylogeny in Poaceae: A Comparative Approach Addressing Leaf and Embryo Development
Authors: Judith Nardmann, Roman Zimmermann, Diego Durantini, Erhard Kranz, Wolfgang Werr
Journal: Molecular Biology and Evolution (2007)

The phylogeny based on the homeodomain (HD) amino acid sequence of the WOX (WUSCHEL-related homeobox gene family) was established in the 3 major radiations of the Poaceae family: Pooideae (Brachypodium distachyon), Bambusoideae (Oryza sativa), and Panicoideae (Zea mays). The genomes of all 3 grasses contain an ancient duplication in the WOX3 branch, and the cellular expression patterns in maize and rice indicate subfunctionalization of paralogues during leaf development, which may relate to the architecture of the grass leaf and the encircling of the stem. The use of maize WOX gene family members as molecular markers in maize embryo development for the first time allowed us to visualize cellular decisions in the maize proembryo, including specification of the shoot/root axis at an oblique angle to the apical-basal polarity of the zygote. All molecular marker data are compatible with the conclusion that the embryonic shoot/root axis comprises a discrete domain from early proembryo stages onward. Novel cell fates of the shoot and the root are acquired within this distinct morphogenic axis domain, which elongates and thus separates the shoot apical meristem and root apical meristem (RAM) anlagen in the maize embryo.
Impaired Nitric Oxide Synthase Pathway in Diabetes Mellitus
Authors: Ken Y. Lin, Akira Ito, Tomoko Asagami, Philip S. Tsao, Shanthi Adimoolam, Masumi Kimoto, Hideaki Tsuji, Gerald M. Reaven, John P. Cooke
Journal: Circulation (2002)

An endogenous inhibitor of nitric oxide synthase, asymmetric dimethylarginine (ADMA), is elevated in patients with type 2 diabetes mellitus (DM). This study explored the mechanisms by which ADMA becomes elevated in DM.Male Sprague-Dawley rats were fed normal chow or high-fat diet (n=5 in each) with moderate streptozotocin injection to induce type 2 DM. Plasma ADMA was elevated in diabetic rats (1.33+/-0.31 versus 0.48+/-0.08 micromol/L; P<0.05). The activity, but not the expression, of dimethylarginine dimethylaminohydrolase (DDAH) was reduced in diabetic rats and negatively correlated with their plasma ADMA levels (P<0.05). DDAH activity was significantly reduced in vascular smooth muscle cells and human endothelial cells (HMEC-1) exposed to high glucose (25.5 mmol/L). The impairment of DDAH activity in vascular cells was associated with an accumulation of ADMA and a reduction in generation of cGMP. In human endothelial cells, coincubation with the antioxidant polyethylene glycol-conjugated superoxide dismutase (22 U/mL) reversed the effects of the high-glucose condition on DDAH activity, ADMA accumulation, and cGMP synthesis.A glucose-induced impairment of DDAH causes ADMA accumulation and may contribute to endothelial vasodilator dysfunction in DM.
Use of ganciclovir for cytomegalovirus infection.
Authors: T E Nevins, D L Dunn
Journal: Journal of the American Society of Nephrology (1992)

Ganciclovir (9-(1,3-dihydroxy-2-propoxymethyl) guanine, DHPG) is an acyclovir analog with excellent antiviral activity against human cytomegalovirus (CMV). Clinically, CMV infection occurs in from 60 to 90% of all renal transplant recipients and it is responsible for significant patient morbidity and graft loss. The likelihood of infection is closely related to the CMV status of both donor and recipient, with the greatest risk arising in the combination of a seronegative patient receiving a seropositive organ. Intracellularly, DHPG is converted to DHPG-triphosphate, which competitively inhibits DNA polymerase. This conversion is accelerated up to 10-fold in virally infected cells, providing some selectivity of action. Uncontrolled studies demonstrated DHPG efficacy in CMV disease, but experience in children remains limited. Although bone marrow suppression is a major immediate toxicity, long-term concerns about carcinogenesis and infertility mandate careful patient selection. Recently at the University of Minnesota, 93 solid organ recipients (45 renal transplants) including some children have been treated for tissue-invasive CMV with DHPG. All had a characteristic clinical picture and either a positive CMV culture or a biopsy with CMV inclusions. The patients received i.v. DHPG (10 mg/kg/day) with appropriate adjustments for renal function. In renal allograft recipients, 89% recovered within 30 days, although 21% had to be retreated with DHPG. Although no patient died, allograft survival was significantly reduced (P = 0.02). An additional subgroup of patients (N = 18) who had both biopsy-proven rejection and invasive CMV disease were simultaneously treated for both processes. All of these patients recovered from their CMV infection, but two grafts were lost to rejection.(ABSTRACT TRUNCATED AT 250 WORDS)
Drastic Down-regulation of Krüppel-Like Factor 4 Expression Is Critical in Human Gastric Cancer Development and Progression
Authors: Daoyan Wei, Weida Gong, Masashi Kanai, Christian Schlunk, Liwei Wang, James C. Yao, Tsung-Teh Wu, Suyun Huang, Keping Xie
Journal: Cancer Research (2005)

Abstract Krüppel-like factor 4 (KLF4) is highly expressed in epithelial tissues such as the gut and skin. However, the role of KLF4 in human gastric cancer development and progression is unknown. Here we show that KLF4 protein expression was decreased or lost in primary tumors and, in particular, lymph node metastases when compared with that in normal gastric mucosa. Moreover, loss of KLF4 expression in the primary tumors was significantly associated with poor survival, and also an independent prognostic marker in a multivariate analysis. Consistently, most human gastric cancer cell lines exhibited loss of or a substantial decrease in KLF4 expression at both RNA and protein levels. Enforced restoration of KLF4 expression resulted in marked cell growth inhibition in vitro and significantly attenuated tumor growth and total abrogation of metastasis in an orthotopic animal model of gastric cancer. Mechanism studies indicated that promoter hypermethylation and hemizygous deletion contributed to the down-regulation of KLF4 expression and the induction of apoptosis contributed to the antitumor activity of KLF4. Collectively, our data provide first clinical and casual evidence and potential mechanism that the alteration of KLF4 expression plays a critical role in gastric cancer development and progression.