tbuckley/cabot-search huggingface dataset:
Traffic Deaths Go Up Again
Authors: H. Emerson Campbell
Journal: JAMA (1967)

The fact that the number of motor-vehicle deaths in this country has climbed steadily from 36,981 in 1958 to 52,500 in 1966 must mean that we have not discovered the principal cause, or applied the definitive remedy. Our experiences with malaria, pneumonia, and cancer would tell us that this is so. At the outset, the point must be made clear that the fatal and very-serious-injury "accident" is quite a different entity from the ordinary fenderbender, or even the accident in which people are cut by flying glass and get a broken bone or two. Not always, but in most cases, there is marked crushing or deformation of the cars involved. This is due, of course, to the fact that there are mostly high-speed crashes, and this is where the slogan "SPEED KILLS" came from. But we must push back farther to a more basic question, "Why were these high-speed cars
Cetuximab Attenuates Metastasis and u-PAR Expression in Non–Small Cell Lung Cancer: u-PAR and E-Cadherin are Novel Biomarkers of Cetuximab Sensitivity
Authors: Dessislava A. Nikolova, Irfan A. Asangani, Laura D. Nelson, Dennis P.M. Hughes, Doris R. Siwak, Gordon B. Mills, Andrea Harms, Erika Buchholz, Lothar R. Pilz, Christian Manegold, Heike Allgayer
Journal: Cancer Research (2009)

Abstract Cetuximab, which blocks ligand binding to epidermal growth factor receptor (EGFR), is currently being studied as a novel treatment for non–small cell lung cancer (NSCLC). However, its mechanisms of action toward metastasis, and markers of drug sensitivity, have not been fully elucidated. This study was conducted to (a) determine the effect of Cetuximab on invasion and NSCLC-metastasis; (b) investigate urokinase-type plasminogen activator receptor (u-PAR), a major molecule promoting invasion and metastasis, as a target molecule; (c) delineate molecular mediators of Cetuximab-induced metastasis inhibition; and (d) identify biomarkers of drug sensitivity in NSCLC. Cetuximab treatment resulted in reduced growth and Matrigel invasion of H1395 and A549 NSCLC cell lines, in parallel with reduced u-PAR mRNA and protein. u-PAR down-regulation was brought about by suppressing the binding of JunD and c-Jun to u-PAR promoter motif −190/−171 in vivo, and an inhibition of MAP/ERK kinase signaling. Furthermore, Cetuximab inhibited NSCLC proliferation and metastasis to distant organs in vivo as indicated by the chicken embryo metastasis assay. Low E-cadherin and high u-PAR, but not EGFR, was associated with resistance to Cetuximab in seven NSCLC cell lines. Furthermore, siRNA knockdown of u-PAR led to a resensitization to Cetuximab. Moreover, low E-cadherin and high u-PAR was found in 63% of resected tumor tissues of NSCLC patients progressing under Cetuximab therapy. This is the first study to show u-PAR as a target and marker of sensitivity to Cetuximab, and to delineate novel mechanisms leading to metastasis suppression of NSCLC by Cetuximab. [Cancer Res 2009;69(6):2461–70]
Synchronous pulmonary carcinoid tumour and non-Hodgkin's lymphoma: report of two cases.
Authors: F M Juettner, C Fellbaum, H Popper, M Lehnert, M Neubauer, W Wagner, H Becker
Journal: Thorax (1989)

Abstract Two cases of synchronous pulmonary carcinoid tumour and non-Hodgkin's lymphoma are described.
Pathophysiologic Differences Among Asians, Native Hawaiians, and Other Pacific Islanders and Treatment Implications
Authors: William C. Hsu, Edward J. Boyko, Wilfred Y. Fujimoto, Alka Kanaya, Wahida Karmally, Andrew Karter, George L. King, Mele Look, Gertraud Maskarinec, Ranjita Misra, Fahina Tavake-Pasi, Richard Arakaki
Journal: Diabetes Care (2012)

Differences in pathophysiology may affect the diagnosis, prevention, and treatment of diabetes in Asian Americans, Native Hawaiians, and Pacific Islanders (AANHPIs). Equally important are differences in cultural beliefs, dietary habits, and behavioral patterns among AANHPIs that require culturally effective translation of interventions into the community. These issues were discussed by clinicians and investigators at a conference held in Honolulu, Hawaii, in September 2011 with the theme “Diabetes in Asian Americans, Native Hawaiians, and Pacific Islanders: A Call to Action” by a coalition of health care organizations, clinicians, and scientists with strong interests in the topic and in the health of AANHPI populations (1). The discourse begins with an evaluation of pathophysiologic differences, followed by a discussion of the standard diagnostic criteria and current treatment algorithms as well as dietary recommendations. The focus then shifts to various diabetes prevention studies specific to AANHPIs and their relevance to this growing ethnic minority group in America. This review concludes with two investigations that demonstrate culturally appropriate interventions and a brief description of the role played by the National Diabetes Education Program (NDEP).

### Pathophysiology—type 1 diabetes

Diabetes has reached an epidemic level around the world, with most of the increase attributable to type 2 diabetes in developing Asian countries such as India and China (2). Type 1 diabetes is also increasing, although at a much less dramatic rate than type 2 diabetes and is now also increasingly associated with obesity and insulin resistance (3). The highest rates for type 1 diabetes are found in Northern European and Scandinavian countries and among the Caucasian population of the U.S. In contrast, type 1 diabetes is approximately 5 to 10 times lower in prevalence in those of Asian than those of European descent (4). In the U.S., the incidence of type 1 diabetes is lower by two- to fivefold in …
beta2 adrenoceptor promoter polymorphisms: extended haplotypes and functional effects in peripheral blood mononuclear cells
Authors: B Lipworth
Journal: Thorax (2002)

Background: The β<sub>2</sub> adrenoceptor and its 5′ untranslated region contain a number of genetic variants. The aim of this study was to investigate the potential for genetic variation at this locus to influence the expression of β<sub>2</sub> adrenoceptors on circulating peripheral blood mononuclear cells (PBMCs). Methods: Genotype was determined in 96 individuals with asthma for four polymorphisms at the β<sub>2</sub> adrenoceptor locus. β<sub>2</sub> adrenoceptor binding and cyclic AMP responses to isoprenaline in PBMCs were determined and the relationship between genotype/haplotype and β<sub>2</sub> adrenoceptor expression and response to isoprenaline examined. Results: β<sub>2</sub> adrenoceptor promoter polymorphisms were found to be common in white subjects. Strong linkage disequilibrium exists across this locus, resulting in the occurrence of several common haplotypes. No single polymorphism or haplotype was correlated with the level of β<sub>2</sub> adrenoceptor expression or cyclic AMP responses to isoprenaline in vitro. Conclusion: β<sub>2</sub> adrenoceptor polymorphisms, when considered in isolation or by extended haplotypes, do not determine the basal level of expression or coupling of β<sub>2</sub> adrenoceptors in PBMCs from asthmatic subjects.
Is the sensitivity of primary ciliary dyskinesia detection by ciliary function analysis 100%?
Authors: Massimo Pifferi, Andrew Bush, Francesca Montemurro, Giovanni Pioggia, Martina Piras, Gennaro Tartarisco, Maria Di Cicco, Iolanda Chinellato, Angela M. Cangiotti, Attilio L. Boner
Journal: European Respiratory Journal (2013)

From the authors :

We wish to thank M. Boon and co-workers for their careful reading of our manuscript and to apologise to them and the readers for our mistake in the preparation of table 2 of our original article [ …
A STUDY OF GENERALIZED VACCINIA IN THE CHICK EMBRYO
Authors: G. J. Buddingh
Journal: The Journal of Experimental Medicine (1936)

1. Chick embryos infected by the chorio-allantoic route with a bacteria-free strain of vaccinia virus develop a general dissemination of the virus throughout the entire organism with the exception of the central nervous system. 2. Quantitative estimation of the distribution of the virus in the various organs of the infected chick by cutaneous inoculation on the rabbit skin offers no evidence for a heightened affinity of the virus for special tissues. 3. Histological study of the lesions in the various organs demonstrates the focal character of the lesions which apparently originate as perivascular infiltrations around the smaller blood vessels. No lesions could be demonstrated in the central nervous system proper. 4. In the earlier stages of the disease Guarnieri bodies are clearly demonstrable in the cells of the epidermis and the squamous epithelium of the buccal mucosa. Inclusion bodies closely resembling Guarnieri bodies are demonstrated in all the lesions occurring in the various other organs. 5. It was not possible to demonstrate conclusively the presence of Paschen bodies in the lesions of the internal organs by the Morosow method usually used for the demonstration of these bodies in the membranal lesion.
PWE-150 Chemotherapy associated liver injury: a systematic review and meta-analysis
Authors: S Robinson, C Wilson, A Burt, D Manas, S White
Journal: Gut (2012)

<h3>Introduction</h3> Chemotherapy associated liver injury (CALI) has been associated with increased morbidity and mortality in patients undergoing major hepatectomy to treat colorectal liver metastases (CRLM). In addition a link has recently been made between CALI and poorer long term disease specific outcome. The aim of this review was to determine the pathological effect of specific chemotherapy regimens on the hepatic parenchyma as well as surgical morbidity, mortality and overall survival. <h3>Methods</h3> A literature search of MEDLINE, EMBASE and the Cochrane Library identified 14 619 potentially relevant reports. Of these 37 full text reports which included patients only with CRLM and provided either histological data or patient outcome data were considered suitable for inclusion in this review. For each report data relating to study design characteristics, histological scoring of the liver parenchyma and peri-operative outcomes were extracted using a standardised proforma. Study quality was assessed using the Newcastle-Ottawa score for non-randomised studies and the grade of evidence assessed according to the Oxford centre for Evidence Based Medicine scale. A meta-analysis was performed utilising the random effects model of DerSimmonian and Laird. Results are reported as RR (±95% CI). Statistical significance was set at p&lt;0.05. <h3>Results</h3> No association could be demonstrated between the use of pre-operative chemotherapy and the development of hepatic steatosis &gt;30%. The presence of steatohepatitis was associated with the use of pre-operative Irinotecan based chemotherapy (RR 3.45; 95% CI 1.12 to 10.62; p=0.03). Calculating the number needed to harm suggests that one in every 12 patients treated with Irinotecan based chemotherapy could be expected to develop steatohepatitis. Oxaliplatin based chemotherapy regimens are associated with grade 2 or greater sinusoidal injury (RR 4.36; 95% CI 1.12 to 10.62; p=0.03) with a number needed to harm of 8. The use of Bevacizumab alongside Oxaliplatin reduces the risk of grade 2 or greater sinusoidal injury. <h3>Conclusion</h3> The use of pre-operative chemotherapy is associated with an increased risk of injury to the liver parenchyma in patients with CRLM. This injury occurs in a regimen specific manner with Irinotecan being associated with steatohepatitis whereas Oxaliplatin is associated with sinusoidal injury. This injury may have implications on the functional reserve of the liver following major hepatic resection. <h3>Competing interests</h3> None declared.
Thrombin Stimulates Vascular Smooth Muscle Cell Polyamine Synthesis by Inducing Cationic Amino Acid Transporter and Ornithine Decarboxylase Gene Expression
Authors: William Durante, Lan Liao, Kelly J. Peyton, Andrew I. Schafer
Journal: Circulation Research (1998)

Abstract —Thrombin, a serine protease, is a potent mitogen for vascular smooth muscle cells (SMCs), but its mechanism of action is not known. Since l -ornithine is metabolized to growth-stimulatory polyamines, we examined whether thrombin regulates the transcellular transport and metabolism of l -ornithine by vascular SMCs. Treatment of SMCs with thrombin initially (0 to 2 hours) decreased l -ornithine uptake, whereas longer exposures (6 to 24 hours) progressively increased transport. Kinetic studies indicated that thrombin-induced inhibition was associated with a decrease in affinity for l -ornithine, whereas stimulation was mediated by an increase in transport capacity. Thrombin induced the expression of both cationic amino acid transporter (CAT)-1 and CAT-2 mRNA. Furthermore, thrombin stimulated l -ornithine metabolism by inducing ornithine decarboxylase (ODC) mRNA expression and activity. The stimulatory effect of thrombin on both l -ornithine transport and ODC activity was reversed by hirudin, a thrombin inhibitor, and was mimicked by a 14–amino acid thrombin receptor–activating peptide. Thrombin also markedly increased the capacity of SMCs to generate putrescine, a polyamine, from extracellular l -ornithine. The thrombin-mediated increase in putrescine production was reversed by N G -methyl- l -arginine, a competitive inhibitor of cationic amino acid transport, or by α-difluoromethylornithine (DFMO), an ODC inhibitor. DFMO also inhibited thrombin-induced SMC proliferation. These results demonstrate that thrombin stimulates polyamine synthesis by inducing CAT and ODC gene expression and that thrombin-stimulated SMC proliferation is dependent on polyamine formation. The ability of thrombin to upregulate l -ornithine transport and direct its metabolism to growth-stimulatory polyamines may contribute to postangioplasty restenosis and atherosclerotic lesion formation.
Localised airway narrowing in sarcoidosis.
Authors: J W Hadfield, R L Page, C D Flower, J E Stark
Journal: Thorax (1982)

Four patients developed multiple narrowings or occlusions of bronchi during the early stages of sarcoidosis when the chest radiograph showed no evidence of pulmonary fibrosis. Three of the patients had symptoms of breathlessness and wheezing and all had an obstructive defect of ventilation. Bronchography showed stenoses that were not apparent at bronchoscopy. It is concluded that the possibility of bronchial narrowing should be considered in patients who develop breathlessness or wheezing at any stage of sarcoidosis, and that bronchoscopy should be supplemented by bronchography.
Insulin Is Protein-Anabolic in Chronic Renal Failure Patients
Authors: Victoria S. Lim, Kevin E. Yarasheski, Jan R. Crowley, Jerry Fangman, Michael Flanigan
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. To examine the protein anabolic actions of insulin in chronic renal failure, the authors measured four sets of whole body leucine fluxes during insulin alone and insulin with amino acid infusion in nine uremic patients before hemodialysis (B-HD). Seven were restudied 8 wk after initiation of maintenance hemodialysis (HD). Six normal subjects served as control (N). All values (μmol/kg/h, mean ± SEM) are presented in the sequence of B-HD, HD, and N, and only P < 0.05 are listed. During Flux 1 (baseline), D (leucine release from body protein degradation) were 114 ± 7, 126 ± 4, and 116 ± 6, respectively. C (leucine oxidation rates) were 18 ± 2, 17 ± 2, and 21 ± 3, respectively. S (leucine disappearance into body protein [index of protein synthesis]) were 96 ± 6, 107 ± 4, and 94 ± 4, respectively, and balances (net leucine flux into protein [values were negative during fasting]) were −18 ± 2, −17 ± 2, and −21 ± 3, respectively. During Flux 2 (low-dose insulin infusion), D were 89 ± 3, 98 ± 6, and 94 ± 5, respectively; C were 12 ± 1, 11 ± 2, and 18 ± 1, respectively (P = 0.02); S were 77 ± 4, 87 ± 5, and 76 ± 5, respectively, and balances were −12 ± 1, −11 ± 2, and −18 ± 1, respectively (P = 0.02). During Flux 3 (high-dose insulin infusion): D were 77 ± 3, 82 ± 7, and 84 ± 5, respectively; C were 9 ± 1, 8 ± 1, and 14 ± 1, respectively (P = 0.005); S were 68 ± 4, 74 ± 6, and 70 ± 5, respectively, and balances were −9 ± 1, −8 ± 1, and −14 ± 1, respectively (P = 0.005). In Flux 4 (insulin infused with amino acids): D were 73 ± 3, 107 ± 18, and 85 ± 7, respectively; C were 35 ± 4, 29 ± 5, and 39 ± 3, respectively; S were 105 ± 5, 145 ± 15, and 113 ± 6, respectively (P = 0.02), and balances were 32 ± 4, 38 ± 5, and 27 ± 3, respectively. These data show that B-HD and HD patients were as sensitive as normal subjects to the protein anabolic actions of insulin. Insulin alone reduced proteolysis and leucine oxidation, and insulin given with amino acids increased net protein synthesis. E-mail: [email protected]
Effect of 5-HT <sub>1A</sub> Receptor Gene Polymorphism on Negative and Depressive Symptom Response to Antipsychotic Treatment of Drug-Naive Psychotic Patients
Authors: Gavin P. Reynolds, Belen Arranz, Lucy A. Templeman, Sofia Fertuzinhos, Luis San
Journal: American Journal of Psychiatry (2006)

The serotonin 5-HT(1A) receptor may modulate some of the negative, cognitive, and affective symptoms of schizophrenia and is a potential target of action of some antipsychotic drugs. A functional polymorphism in the promoter region of the 5-HT(1A) receptor gene is associated with depression and suicidal behavior. The authors sought to determine whether this polymorphism influences symptom response to antipsychotic drug treatment.Sixty-three drug-naive patients with first-episode psychosis who were genotyped for the -1019C/G polymorphism were recruited for this study and received standard care. The Positive and Negative Syndrome Scale and the Calgary Depression Scale were used to monitor symptom changes over 3 months.The polymorphism was associated with, and accounted for much of the variance in, changes in negative and depressive symptoms but not positive symptoms.These findings identify an important genetic factor predicting much of the response in negative and depressive symptoms to antipsychotic drug treatment.
Esophagectomies With Thoracic Incisions Carry Increased Pulmonary Morbidity
Authors: Neil H. Bhayani, Aditya Gupta, Christy M. Dunst, Ashwin A. Kurian, Kevin M. Reavis, Lee L. Swanström
Journal: JAMA Surgery (2013)

Thoracic incisions are not required for all esophagectomies and may increase pulmonary morbidity.To compare the pulmonary and overall morbidity of esophagectomies with and without thoracic incisions.Observational study.Hospitals participating in the National Surgical Quality Improvement Project.Patients without metastatic cancer undergoing nonemergency total esophagectomies with reconstruction from 2005 through 2010. Patients who underwent transhiatal esophagectomy (THE) were compared with a THORACIC group (Ivor Lewis and McKeown techniques).Pulmonary and overall morbidity, infection, and thromboembolic complications.Of 1568 patients, 717 (45.7%) underwent THE, and 851 (54.3%) were in the THORACIC group (Ivor Lewis technique in 487 [31.1%] and McKeown technique in 364 [23.2%]). The population was 80.5% male, with a mean age of 62.9 years. Patients undergoing THE were older (P = .02). Diabetes mellitus was less common in the THORACIC group (11.2% vs 15.9% for THE; P = .02), and cancer was more common (91.0% vs 87.0%; P = .01). Morbidity was 49.2% and mortality was 3.3%, without differences between groups. The mean length of stay was 1.6 days shorter (P = .009) in the THE group. Multivariable analysis showed that thoracic incisions increased rates of pneumonia (odds ratio [OR], 1.47; P = .007), ventilator dependence (OR, 1.35; P = .04), and septic shock (OR, 1.86; P = .001) but not mortality. Compared with the Ivor Lewis technique, the McKeown technique worsened the odds of superficial wound infections (OR, 1.71; P = .02) but not septic shock (OR, 0.84; P = .47).Esophagectomies have an acceptable mortality rate but a significant morbidity rate. We demonstrated that rates of pneumonia, ventilator dependence, and septic shock are increased with the use of thoracic incision. Avoiding thoracic incisions may therefore decrease the risk of pulmonary morbidity and septic shock.
Genome analysis of a major urban malaria vector mosquito, Anopheles stephensi
Authors: Xiaofang Jiang, Ashley Peery, A. Brantley Hall, Atashi Sharma, Xiao Guang Chen, Robert M. Waterhouse, Aleksey Komissarov, Michelle M. Riehle, Yogesh Shouche, Maria V. Sharakhova, Dan Lawson, Nazzy Pakpour, Peter Arensburger, Victoria L M Davidson, Karin Eiglmeier, Scott Emrich, Phillip George, Ryan C. Kennedy, Shrinivasrao P. Mane, Gareth Maslen, Chioma Oringanje, Yumin Qi, Robert Settlage, Marta Tojo, Jose M C Tubio, Maria F. Unger, Bo Wang, Kenneth D. Vernick, Jose M C Ribeiro, Anthony A. James, Kristin Michel, Michael A. Riehle, Shirley Luckhart, Igor V. Sharakhov, Zhijian Tu
Journal: Genome biology (2014)

Abstract Background Anopheles stephensi is the key vector of malaria throughout the Indian subcontinent and Middle East and an emerging model for molecular and genetic studies of mosquito-parasite interactions. The type form of the species is responsible for the majority of urban malaria transmission across its range. Results Here, we report the genome sequence and annotation of the Indian strain of the type form of An. stephensi . The 221 Mb genome assembly represents more than 92% of the entire genome and was produced using a combination of 454, Illumina, and PacBio sequencing. Physical mapping assigned 62% of the genome onto chromosomes, enabling chromosome-based analysis. Comparisons between An. stephensi and An. gambiae reveal that the rate of gene order reshuffling on the X chromosome was three times higher than that on the autosomes. An. stephensi has more heterochromatin in pericentric regions but less repetitive DNA in chromosome arms than An. gambiae . We also identify a number of Y-chromosome contigs and BACs. Interspersed repeats constitute 7.1% of the assembled genome while LTR retrotransposons alone comprise more than 49% of the Y contigs. RNA-seq analyses provide new insights into mosquito innate immunity, development, and sexual dimorphism. Conclusions The genome analysis described in this manuscript provides a resource and platform for fundamental and translational research into a major urban malaria vector. Chromosome-based investigations provide unique perspectives on Anopheles chromosome evolution. RNA-seq analysis and studies of immunity genes offer new insights into mosquito biology and mosquito-parasite interactions.