tbuckley/cabot-search huggingface dataset:
Is Noncentral Obesity Metabolically Benign?
Authors: T. Kue Young
Journal: JAMA (1995)

To determine if individuals who are overall obese but have low waist-to-hip ratios have unfavorable lipid profiles, blood pressures, and glucose statuses.Cross-sectional study.The Manitoba Heart Health Survey surveyed a representative sample of residents of the Canadian province of Manitoba.--A total of 2,792 adults aged 18 to 74 years were interviewed, 2,339 of whom underwent clinical examinations.Blood pressure, fasting plasma glucose, total cholesterol, triglycerides, high-density lipoprotein, and low-density lipoprotein measurements were compared across categories of body mass index (BMI) and waist-to-hip ratio (WHR).Manitobans with noncentral obesity tend to occupy positions between those of the nonobese and the centrally obese in terms of the effect on blood pressure, plasma lipids, and glucose. In multiple linear regression models involving age, BMI, and WHR as independent variables and one of the metabolic variables as dependent variables, both BMI and WHR are significant independent predictors of most metabolic variables. Where both are significant, BMI tends to be the stronger predictor, with a larger standardized regression coefficient.Noncentral obesity is not metabolically benign; BMI as an overall measure of obesity is as important as, and sometimes more important than, WHR in predicting metabolic effects. The recognition of the epidemiological significance of the WHR as a centrality measure of obesity should not divert attention from the metabolic risk status of noncentrally obese individuals who require continued health education to reduce weight.
Gankyrin plays an essential role in Ras-induced tumorigenesis through regulation of the RhoA/ROCK pathway in mammalian cells
Authors: Jiang-Hong Man, Bing Liang, Yue-Xi Gu, Tao Zhou, Ai-Ling Li, Tao Li, Bao-Feng Jin, Bing Bai, Hai-Ying Zhang, Wei-Na Zhang, Wei-Hua Li, Wei-Li Gong, Hui-Yan Li, Xue-Min Zhang
Journal: Journal of Clinical Investigation (2010)

Activating mutations in Ras proteins are present in about 30% of human cancers. Despite tremendous progress in the study of Ras oncogenes, many aspects of the molecular mechanisms underlying Ras-induced tumorigenesis remain unknown. Through proteomics analysis, we previously found that the protein Gankyrin, a known oncoprotein in hepatocellular carcinoma, was upregulated during Ras-mediated transformation, although the functional consequences of this were not clear. Here we present evidence that Gankyrin plays an essential role in Ras-initiated tumorigenesis in mouse and human cells. We found that the increased Gankyrin present following Ras activation increased the interaction between the RhoA GTPase and its GDP dissociation inhibitor RhoGDI, which resulted in inhibition of the RhoA effector kinase Rho-associated coiled coil-containing protein kinase (ROCK). Importantly, Gankyrin-mediated ROCK inhibition led to prolonged Akt activation, a critical step in activated Ras-induced transformation and tumorigenesis. In addition, we found that Gankyrin is highly expressed in human lung cancers that have Ras mutations and that increased Gankyrin expression is required for the constitutive activation of Akt and tumorigenesis in these lung cancers. Our findings suggest that Gankyrin is a key regulator of Ras-mediated activation of Akt through inhibition of the downstream RhoA/ROCK pathway and thus plays an essential role in Ras-induced tumorigenesis.
A CALCITONIN-SECRETING THYROID CARCINOMA
Authors: W.J. Cunliffe, M.M. Black, R. Hall, I.D.A. Johnston, P. Hudgson, S. Shuster, T.V. Gudmundsson, G.F. Joplin, E.D. Williams, N.J.Y. Woodhouse, L. Galante, I. Macintyre
Journal: The Lancet (1968)
On the Complexity of Chloroplast RNA Metabolism: psaA Trans-splicing Can be Bypassed in Chlamydomonas
Authors: Linnka Lefebvre-Legendre, Livia Merendino, Cristian Rivier, Michel Goldschmidt-Clermont
Journal: Molecular Biology and Evolution (2014)

In the chloroplast, the posttranscriptional steps of gene expression are remarkably complex. RNA maturation and translation rely on a large cohort of nucleus-encoded proteins that act specifically on a single target transcript or a small set of targets. For example in the chloroplast of Chlamydomonas, trans-splicing of the two split introns of psaA requires at least 14 nucleus-encoded proteins. To investigate the functional significance of this complex trans-splicing pathway, we have introduced an intron-less copy of psaA in the chloroplast genomes of three mutants deficient in trans-splicing and of the wild type. We find that the intron-less psaA gene rescues the mutant phenotypes. The growth of strains with the intron-less psaA is indistinguishable from the wild type under the set of different experimental conditions that were investigated. Thus, the trans-splicing factors do not appear to have any other essential function and trans-splicing of psaA can be bypassed. We discuss how these observations support the hypothesis that complex RNA metabolism in the chloroplast may in part be the result of a nonadaptive evolutionary ratchet. Genetic drift may lead to the accumulation of chloroplast mutations and the recruitment of compensatory nuclear suppressors from large preexisting pools of genes encoding RNA-binding proteins.
Thiopurinol and purine metabolism. Metabolic and radioisotope studies.
Authors: H A Simmonds, A Cadenhead, J S Cameron, T J Rising, R Grahame, B M Dean
Journal: Annals of the Rheumatic Diseases (1974)

TREATMENTMale castrate pigs weighing 30-35 kg, from a minimal disease breed of large white/landrace cross, were housed in metabolic cages.They were maintained on a purine-free diet of barley and skim milk and given thiopurinol (600 mg/day) twice daily with the food.After a stabilization period of 6 days on the unlabelled drug, [6-14C]thiopurinol (1 mCi) was administered to one animal in capsule copyright.
Differential evaluation of bronchoalveolar lavage cells and leukotrienes in unilateral acture lung injury and ARDS patients
Authors: M. Antonelli, L. Lenti, M. Bufi, R. A. De Blasi, G. Vivino, G. Conti, P. Pelaia, A. Zicari, G. Pontieri, A. Gasparetto
Journal: Intensive Care Medicine (1989)
Scaling up of HIV treatment for men who have sex with men in Bangkok: a modelling and costing study
Authors: Lei Zhang, Nittaya Phanuphak, Klara Henderson, Siriporn Nonenoy, Sasiwan Srikaew, Andrew J Shattock, Cliff C Kerr, Brenda Omune, Frits van Griensven, Sutayut Osornprasop, Robert Oelrichs, Jintanat Ananworanich, David P Wilson
Journal: The Lancet HIV (2015)
Diagnosis and treatment of viral diseases in recipients of allogeneic hematopoietic stem cell transplantation
Authors: Ren Lin, Qifa Liu
Journal: Journal of Hematology & Oncology (2013)

Viral infections are important causes of morbidity and mortality after allogeneic stem cell hematopoietic transplantation (allo-HSCT). Although most viral infections present with asymptomatic or subclinical manifestations, viruses may result in fatal complications in severe immunocompromised recipients. Reactivation of latent viruses, such as herpesviruses, is frequent during the immunosuppression that occurs with allo-HSCT. Viruses acquired from community, such as the respiratory and gastrointestinal viruses, are also important pathogens of post-transplant viral diseases. Currently, molecular diagnostic methods have replaced or supplemented traditional methods, such as viral culture and antigen detection, in diagnosis of viral infections. The utilization of polymerase chain reaction facilitates the early diagnosis. In view of lacking efficacious agents for treatment of viral diseases, prevention of viral infections is extremely valuable. Application of prophylactic strategies including preemptive therapy reduces viral infections and diseases. Adoptive cellular therapy for restoring virus-specific immunity is a promising method in the treatment of viral diseases.
Elevated Exhaled Nitric Oxide in Newborns of Atopic Mothers Precedes Respiratory Symptoms
Authors: Philipp Latzin, Claudia E. Kuehni, David N. Baldwin, Hanna L. Roiha, Carmen Casaulta, Urs Frey
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Rationale: Exhaled nitric oxide (NO) is a well-known marker of established airway inflammation in asthma. Its role in the disease process before the onset of respiratory symptoms remains unclear.Objectives: To examine whether elevated NO in newborns with clinically naive airways is associated with subsequent respiratory symptoms in infancy.Methods: We measured exhaled NO concentration and output after birth and prospectively assessed respiratory symptoms during infancy in a birth cohort of 164 unselected healthy neonates. We examined a possible association between NO and respiratory symptoms using Poisson regression analysis.Results: In infants of atopic mothers, elevated NO levels after birth were associated with increased risk of subsequent respiratory symptoms (risk ratio [RR], 7.5; 95% confidence interval [CI], 1.7–32.4 for each nl/s increase in NO output; p = 0.007). Similarly, a positive association between NO and symptoms was seen in infants of smoking mothers (RR, 6.6; 95% CI, 2.3–19.3; p = 0.001), with the strongest association in infants whose mothers had both risk factors (RR, 21.8; 95% CI, 5.8–81.3; p < 0.001).Conclusions: The interaction of NO with maternal atopy and smoking on subsequent respiratory symptoms is present early in life. Clinically, noninvasive NO measurements in newborns may prove useful as a new means to identify high-risk infants. Future confirmation of a role for NO metabolism in the evolution of respiratory disease may provide an avenue for preventative strategies.
Mental competence to stand trial
Authors: W. B. Smith
Journal: JAMA (1969)

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Aldosterone Potentiates Angiotensin II–Induced Signaling in Vascular Smooth Muscle Cells
Authors: Istvan Mazak, Anette Fiebeler, Dominik N. Muller, Joon-Keun Park, Erdenechimeg Shagdarsuren, Carsten Lindschau, Ralf Dechend, Christiane Viedt, Bernhard Pilz, Hermann Haller, Friedrich C. Luft
Journal: Circulation (2004)

Background— In a double-transgenic human renin and human angiotensinogen rat model, we found that mineralocorticoid receptor (MR) blockade ameliorated angiotensin II (Ang II)–induced renal and cardiac damage. How Ang II and aldosterone (Ald) might interact is ill defined. Methods and Results— We investigated the effects of Ang II (10 −7 mol/L) and Ald (10 −7 mol/L) on extracellular signal–regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) signaling in vascular smooth muscle cells (VSMCs) with Western blotting and confocal microscopy. Ang II induced ERK 1/2 and JNK phosphorylation by 2 minutes. Ald achieved the same at 10 minutes. Ang II+Ald had a potentiating effect by 2 minutes. Two oxygen radical scavengers and the epidermal growth factor receptor (EGFR) antagonist AG1478 reduced Ang II–, Ald-, and combination-induced ERK1/2 phosphorylation. Preincubating the cells with the MR blocker spironolactone (10 −6 mol/L) abolished Ang II–induced ROS generation, EGFR transactivation, and ERK1/2 phosphorylation. Conclusions— Ald potentiates Ang II–induced ERK-1/2 and JNK phosphorylation. Oxygen radicals, the MR, and the EGFR play a role in early signaling induced by Ang II and Ald in VSMCs. These in vitro data may help explain the effects of MR blockade on Ang II–induced end-organ damage in vivo.
Functional Evidence for a Role of Vascular Chymase in the Production of Angiotensin II in Isolated Human Arteries
Authors: Vincent Richard, Sonia Hurel-Merle, Elizabeth Scalbert, Gilles Ferry, Françoise Lallemand, Jean-Paul Bessou, Christian Thuillez
Journal: Circulation (2001)

Background In human arteries, angiotensin-converting enzyme (ACE) inhibitors incompletely block the production of angiotensin (Ang) II from Ang I. This ACE-independent production of Ang II appears to be caused by serine proteases, one of which presumably is chymase. However, several serine proteases may produce Ang II, and the exact role of chymase in the vascular production of Ang II has never been directly evaluated using selective chymase inhibitors. Methods and Results Rings of human mammary arteries were subjected to either Ang I or the chymase-selective substrate [pro, 11 D-Ala 12 ] Ang I in the absence or the presence of the ACE inhibitor captopril, the serine protease inhibitor chymostatin, or the selective chymase inhibitor C41. Captopril only partially inhibited (by 33%) the response to Ang I. In the absence of captopril, C41 markedly reduced (by 44%) the response to Ang I, and this effect was identical to that of chymostatin. C41 also significantly reduced the response to Ang I in the presence of captopril, although this inhibitory effect was slightly less than that of captopril in combination with chymostatin. [Pro, 11 D-Ala 12 ] Ang I induced potent contractions that were not affected by captopril but were abolished by chymostatin and markedly reduced by C41. In addition, we found that prior treatment of the patients with an ACE inhibitor did not affect the in vitro response to Ang I (in the absence or the presence of captopril) or to [Pro, 11 D-Ala 12 ] Ang I. Conclusions Our results reinforce the hypothesis that chymase is a major serine protease implicated in the ACE-independent production of Ang II in human arteries.
Complications of gastrointestinal endoscopy
Authors: K. R Palmer
Journal: Gut (2007)

Scoping our practice

The benefits of endoscopy have increased enormously as it has matured from a purely diagnostic tool to become a therapeutic subspecialty, but so too has the potential for causing harm. Endoscopic haemostasis for varices and ulcers, relief of biliary obstruction from stones or tumours, and alleviation of luminal obstruction using balloons, bougies and stents improve quality of life and may obviate the need for operative surgery, but all risk serious complications. The risks of endoscopy are worth taking only when the procedure is worth doing and when the benefits outweigh the risks. Complications are unacceptable if endoscopy is not indicated; pancreatitis after diagnostic endoscopic retrograde cholangiopancreatography (ERCP) and colonoscopic perforation done during follow-up of a single rectosigmoid polyp are examples. The risk:benefit ratio is dictated by the disease process and by the underlying health of the patient—thus (to rehearse an old chestnut), the complications of endoscopic bile duct clearance are probably fewer and better tolerated than those of surgical exploration in the elderly and frail and are therefore acceptable; the same may not be true for younger and fitter patients for whom surgery has a lower complication rate than ERCP. Relatively high-risk endoscopic procedures can be justified to palliate symptoms in patients with terminal diseases, whereas the risks become unacceptable when the same procedure is done to a patient with surgically respectable disease.

These issues received considerable airing in the National Confidential Enquiry into Patient Outcome …
Apoptin: Therapeutic Potential of an Early Sensor of Carcinogenic Transformation
Authors: Claude Backendorf, Astrid E. Visser, A.G. de Boer, Rhyenne Zimmerman, Mijke Visser, Patrick Voskamp, Ying-Hui Zhang, Mathieu Noteborn
Journal: The Annual Review of Pharmacology and Toxicology (2007)

The avian virus-derived protein apoptin induces p53-independent apoptosis in a tumor-specific way. Apoptin acts as a multimeric complex and forms superstructures upon binding to DNA. In tumor cells, apoptin is phosphorylated and mainly nuclear, whereas in normal cells it is unphosphorylated, cytoplasmic, and becomes readily neutralized. Interestingly, apoptin phosphorylation, nuclear translocation, and apoptosis can transiently be induced in normal cells by cotransfecting SV40 large T oncogene, indicating that apoptin recognizes early stages of oncogenic transformation. In cancer cells, apoptin appears to recognize survival signals, which it is able to redirect into cell death impulses. Apoptin targets include DEDAF, Nur77, Nmi, Hippi, and the potential drug target APC1. Apoptin-transgenic mice and animal tumor models have revealed apoptin as a safe and efficient antitumor agent, resulting in significant tumor regression. Future antitumor therapies could use apoptin either as a therapeutic bullet or as an early sensor of druggable tumor-specific processes.
CD69-mediated pathway of lymphocyte activation: anti-CD69 monoclonal antibodies trigger the cytolytic activity of different lymphoid effector cells with the exception of cytolytic T lymphocytes expressing T cell receptor alpha/beta.
Authors: A Moretta, A Poggi, D Pende, G Tripodi, A M Orengo, N Pella, R Augugliaro, C Bottino, E Ciccone, L Moretta
Journal: The Journal of Experimental Medicine (1991)

The effect of anti-CD69 monoclonal antibodies (mAbs) on the induction of the cytolytic activity in different types of lymphoid effector cells has been investigated. Three anti-CD69 mAbs, including the reference mAb MLR3 and two new mAbs (c227 and 31C4), have been used. All cloned CD3-CD16+ natural killer (NK) cells belonging to different subsets (as defined by the surface expression of GL183 and/or EB6 antigens) were efficiently triggered by anti-CD69 mAbs and lysed P815 mastocytoma cells in a redirected killing assay. Triggering of the cytolytic activity could also be induced in CD3-CD16- NK clones, which fail to respond to other stimuli (including anti-CD16, anti-CD2 mAbs, or phytohemagglutinin). A similar triggering effect was detected in T cell receptor (TCR) gamma/delta+ clones belonging to different subsets. On the other hand, anti-CD69 mAbs could not induce triggering of the cytolytic activity in TCR alpha/beta+ cytolytic clones. Since all thymocytes are known to express CD69 antigen after cell activation, we analyzed a series of phenotypically different cytolytic thymocyte populations and clones for their responsiveness to anti-CD69 mAb in a redirected killing assay. Again, anti-CD69 mAb triggered TCR gamma/delta+ but not TCR alpha/beta+ thymocytes. Anti-CD69 mAb efficiently triggered the cytolytic activity of "early" thymocytes lines or clones (CD3-4-8-7+), which lack all other known pathways of cell activation. Thus, it appears that CD69 molecules may initiate a pathway of activation of cytolytic functions common to a number of activated effector lymphocytes with the remarkable exception of TCR alpha/beta+ cytolytic cells.
Interference With Netrin-1 and Tumor Cell Death in Non–Small Cell Lung Cancer
Authors: Céline Delloye-Bourgeois, Elisabeth Brambilla, Marie-May Coissieux, Céline Guenebeaud, Rémy Pedeux, Virginie Firlej, Florence Cabon, Christian Brambilla, Patrick Mehlen, Agnès Bernet
Journal: JNCI Journal of the National Cancer Institute (2009)

Netrin-1 may promote colorectal and breast tumorigenesis, by inhibiting apoptosis induced by its dependence receptors, deleted in colorectal cancer (DCC) and uncoordinated-5-homolog (UNC5H). The status of netrin-1 and its receptors in non-small cell lung cancer (NSCLC) was unknown.The levels of netrin-1 and its receptors were analyzed in a panel of 92 NSCLC and 25 human lung cancer cell lines by quantitative reverse transcription-polymerase chain reaction and immunohistochemistry. In lung cancer cell lines that express netrin-1, the expression of netrin-1 was inhibited by using small interfering RNA (siRNA), or interference with netrin-1 was performed by treatment with a decoy recombinant DCC ectodomain protein (DCC-5Fbn). Cell death was monitored with a trypan blue exclusion assay or by measuring caspase-3 activity. The effect of netrin-1 interference on tumor growth was analyzed by DCC-5Fbn intratumoral or netrin-1 siRNA intraperitoneal injection in mice engrafted with lung cancer cell lines. All statistical tests were two-sided.High levels of netrin-1 were found in 43 of the 92 NSCLC tumor samples (47%). Interference with netrin-1 in human lung cancer cell lines was associated with UNC5H-mediated cell death in vitro (percentage of cell death in untreated and in DCC-5Fbn-treated cells = 8% and 26%, respectively, difference = 18%, 95% confidence interval [CI] = 10% to 26%; P = .049) and with lung tumor growth inhibition and/or regression in xenografted nude mice (12 mice in DCC-5Fbn-treated group and 13 mice in control group). Mean volume of control and DCC-5Fbn-treated tumors on day 46 was 489 and 84 mm(3), respectively (difference = 404 mm(3), 95% CI = 145 to 664 mm(3); P < .001).Almost half of the NSCLC tissue samples examined expressed high levels of netrin-1. Extracellular targeting of the interaction between netrin-1 and UNC5H may be a promising therapeutic approach for NSCLCs that express netrin-1.
Risk of Prostate Cancer Recurrence in Men Treated With Radiation Alone or in Conjunction With Combined or Less Than Combined Androgen Suppression Therapy
Authors: Anthony V. D'Amico, Ming-Hui Chen, Andrew A. Renshaw, Brittany Loffredo, Philip W. Kantoff
Journal: Journal of Clinical Oncology (2008)

We determined the risk of recurrence in men enrolled on a randomized trial for prostate cancer who were treated with radiation therapy (RT) alone or in conjunction with combined or less than combined androgen suppression therapy (AST).Between 1995 and 2001, 206 men with localized but unfavorable-risk adenocarcinoma of the prostate were randomly assigned to receive RT or RT and AST, which was defined as 6 months of both a luteinizing hormone-releasing hormone agonist and an antiandrogen. A post-random assignment hypothesis that was generated by multivariable Cox regression analyses was used to evaluate whether the risk of prostate-specific antigen (PSA) recurrence was significantly associated with months of antiandrogen use; regression analysis adjusted for known prognostic factors, comorbidity score, and medications that can elevate liver function tests sufficiently to necessitate discontinuation of the antiandrogen.After a median follow-up of 8.2 years (interquartile range,7.0 to 9.5 years), 81 men sustained PSA recurrence. An increasing PSA level (P < .001); Gleason score of 8, 9, or 10 (P < .001); and clinical category T2 disease (P = .005) were significantly associated with an increased risk of recurrence. However, recurrence risk was significantly decreased (adjusted hazard ratio, 0.81; 95% CI, 0.72 to 0.92; P = .001) with each additional month of antiandrogen use after analysis was adjusted for these known prognostic factors.Men with localized but unfavorable-risk prostate cancer who were treated with RT and 6 months of planned combined AST appear to have an increased risk of recurrence when treated with less than as compared with 6 months of the antiandrogen.