tbuckley/cabot-search huggingface dataset:
Traffic-Related Air Toxics and Term Low Birth Weight in Los Angeles County, California
Authors: Michelle Wilhelm, Jo Kay Ghosh, Jason Su, Myles Cockburn, Michael Jerrett, Beate Ritz
Journal: Environmental Health Perspectives (2011)

Numerous studies have linked criteria air pollutants with adverse birth outcomes, but there is less information on the importance of specific emission sources, such as traffic, and air toxics.We used three exposure data sources to examine odds of term low birth weight (LBW) in Los Angeles, California, women when exposed to high levels of traffic-related air pollutants during pregnancy.We identified term births during 1 June 2004 to 30 March 2006 to women residing within 5 miles of a South Coast Air Quality Management District (SCAQMD) Multiple Air Toxics Exposure Study (MATES III) monitoring station. Pregnancy period average exposures were estimated for air toxics, including polycyclic aromatic hydrocarbons (PAHs), source-specific particulate matter < 2.5 μm in aerodynamic diameter (PM2.5) based on a chemical mass balance model, criteria air pollutants from government monitoring data, and land use regression (LUR) model estimates of nitric oxide (NO), nitrogen dioxide (NO2) and nitrogen oxides (NOx). Associations between these metrics and odds of term LBW (< 2,500 g) were examined using logistic regression.Odds of term LBW increased approximately 5% per interquartile range increase in entire pregnancy exposures to several correlated traffic pollutants: LUR measures of NO, NO2, and NOx, elemental carbon, and PM2.5 from diesel and gasoline combustion and paved road dust (geological PM2.5).These analyses provide additional evidence of the potential impact of traffic-related air pollution on fetal growth. Particles from traffic sources should be a focus of future studies.
640. A Novel Herpes Simplex Virus Vector Expressing Endomorphin-2: Characterization and Antinociceptive Properties
Authors: Darren Wolfe, Shuanglin Hao, Jian Hu, Marina Mata, Joseph Glorioso, David Fink
Journal: Molecular Therapy (2005)

We have previously demonstrated that herpes simplex virus (HSV) vector-mediated transfer to dorsal root ganglion (DRG) in vivo to effect the release of enkephalin or GABA provides significant analgesic effects in rodent models. Endomorphin-2 is a recently identified peptide with high affinity for the mu-opiate receptor. The gene coding for this amidated tetrapeptide has not been identified. In this study we sought to create a herpes simplex virus (HSV)-based gene transfer vector that would express endomorphin-2 and to examine its effect in models of neuropathic anti-inflammatory pain.
P63 Ribavirin uptake by primary human hepatocytes corresponds to equilibrative nucleoside transporter 1 expression
Authors: B. K. Baloch, L. Chen, M. Ilyas, W. Irving, B. J. Thomson
Journal: Gut (2011)

<h3>Introduction</h3> Combined therapy with pegylated interferon (INF) and ribavirin (RV) is the current standard of care for HCV infection, with a 40% to 80% success rate depending on viral genotype. The achievable concentration of RV is an important determinant of therapeutic outcome. A preliminary study used cryopreserved hepatocytes (<i>J Hepatology</i> 2010;<b>52</b>:469–71) to show that equilibrative nucleoside transporter 1 (ENT1) is a major RV transporter. In this study we confirm this observation and demonstrate that the level of ENT1 expression is variable and strongly and directly correlated with RV uptake in primary human hepatocytes. We also provide evidence that ENT1 expression alone may not be sufficient for RV uptake and observe that its levels are not influenced by interferon α. <h3>Aim</h3> The aim of this study was to assess RV uptake levels and compare it with ENT1 expression in freshly isolated primary hepatocytes. We also aimed to see effects of interferon α on ENT1 expression and ribavirin uptake. <h3>Method</h3> Primary hepatocytes were isolated from liver tissue obtained from six human donors. Hepatocytes were cultured on collagen coated plates and exposed to RV diluted in culture medium. Parallel samples were taken for High Performance Liquid Chromatography to assess RV uptake and for quantitative PCR to evaluate ENT1 expression. Similar assays were performed on human hepatoma cell line (Huh7). ENT1 (SLC29A1) gene sequence was analysed by cloning of PCR amplified cDNA followed by direct sequencing. <h3>Results</h3> We have studied six human livers. As illustrated in Abstract P63 figure 1, there was a strong direct correlation between levels of expression of ENT1 and RV uptake at 24 h (r<sub>s</sub>=0.94; p value =0.01). Addition of interferon did not influence RV uptake or ENT1 expression. Strikingly, Huh7 cells expressed ENT1 at similar levels to the majority of primary hepatocytes, but did not take up RV. Sequencing data revealed that ENT1 in Huh7 is wild type. <h3>Conclusion</h3> ENT1 has been previously identified as a major transporter involved in RV uptake. In this study, we clearly demonstrate that RV uptake in different sets of primary human hepatocytes is variable and correlates with ENT1 expression. This variation in ENT1 expression may account for differences in response rate in patients receiving anti-HCV therapy. Interferon modulation of ENT1 seems to be a highly unlikely mode of RV and interferon synergistic action in HCV infection. Outcomes in the Huh 7 cell line suggest that, while ENT1 may be necessary, other factors are required to mediate RV uptake.
Toll-like Receptor 4 Polymorphisms and Aspergillosis in Stem-Cell Transplantation
Authors: Pierre-Yves Bochud, Jason W. Chien, Kieren A. Marr, Wendy M. Leisenring, Arlo Upton, Marta Janer, Stephanie D. Rodrigues, Sarah Li, John A. Hansen, Lue Ping Zhao, Alan Aderem, Michael Boeckh
Journal: New England Journal of Medicine (2008)

Toll-like receptors (TLRs) are essential components of the immune response to fungal pathogens. We examined the role of TLR polymorphisms in conferring a risk of invasive aspergillosis among recipients of allogeneic hematopoietic-cell transplants.We analyzed 20 single-nucleotide polymorphisms (SNPs) in the toll-like receptor 2 gene (TLR2), the toll-like receptor 3 gene (TLR3), the toll-like receptor 4 gene (TLR4), and the toll-like receptor 9 gene (TLR9) in a cohort of 336 recipients of hematopoietic-cell transplants and their unrelated donors. The risk of invasive aspergillosis was assessed with the use of multivariate Cox regression analysis. The analysis was replicated in a validation study involving 103 case patients and 263 matched controls who received hematopoietic-cell transplants from related and unrelated donors.In the discovery study, two donor TLR4 haplotypes (S3 and S4) increased the risk of invasive aspergillosis (adjusted hazard ratio for S3, 2.20; 95% confidence interval [CI], 1.14 to 4.25; P=0.02; adjusted hazard ratio for S4, 6.16; 95% CI, 1.97 to 19.26; P=0.002). The haplotype S4 was present in carriers of two SNPs in strong linkage disequilibrium (1063 A/G [D299G] and 1363 C/T [T399I]) that influence TLR4 function. In the validation study, donor haplotype S4 also increased the risk of invasive aspergillosis (adjusted odds ratio, 2.49; 95% CI, 1.15 to 5.41; P=0.02); the association was present in unrelated recipients of hematopoietic-cell transplants (odds ratio, 5.00; 95% CI, 1.04 to 24.01; P=0.04) but not in related recipients (odds ratio, 2.29; 95% CI, 0.93 to 5.68; P=0.07). In the discovery study, seropositivity for cytomegalovirus (CMV) in donors or recipients, donor positivity for S4, or both, as compared with negative results for CMV and S4, were associated with an increase in the 3-year probability of invasive aspergillosis (12% vs. 1%, P=0.02) and death that was not related to relapse (35% vs. 22%, P=0.02).This study suggests an association between the donor TLR4 haplotype S4 and the risk of invasive aspergillosis among recipients of hematopoietic-cell transplants from unrelated donors.
The adenosine/neutrophil paradox resolved: human neutrophils possess both A1 and A2 receptors that promote chemotaxis and inhibit O2 generation, respectively.
Authors: B N Cronstein, L Daguma, D Nichols, A J Hutchison, M Williams
Journal: Journal of Clinical Investigation (1990)

Occupancy of specific receptors on neutrophils by adenosine or its analogues diminishes the stimulated release of toxic oxygen metabolites from neutrophils, while paradoxically promoting chemotaxis. We now report evidence that two distinct adenosine receptors are found on neutrophils (presumably the A1 and A2 receptors of other cell types). These adenosine receptors modulate chemotaxis and O2- generation, respectively. N6-Cyclopentyladenosine (CPA), a selective A1 agonist, promoted neutrophil chemotaxis to the chemoattractant FMLP as well as or better than 5'N-ethylcarboxamidoadenosine (NECA). In contrast, CPA did not inhibit O2- generation stimulated by FMLP. Pertussis toxin completely abolished promotion of chemotaxis by CPA but enhanced inhibition by NECA of O2- generation. Disruption of microtubules by colchicine or vinblastine also abrogated the enhancement by NECA of chemotaxis whereas these agents did not markedly interfere with inhibition by NECA of O2- generation. FMLP receptors, once they have bound ligand, shift to a high affinity state and become associated with the cytoskeleton. NECA significantly increased association of [3H]FMLP with cytoskeletal preparations as it inhibited O2-. Disruption of microtubules did not prevent NECA from increasing association of [3H]FMLP with cytoskeletal preparations. Additionally, CPA (A1 agonist) did not increase binding of [3H]FMLP to the cytoskeleton as well as NECA (A2 agonist). These studies indicate that occupancy of one class of adenosine receptors (A1) promotes chemotaxis by a mechanism requiring intact microtubules and G proteins whereas engagement of a second class of receptors (A2) inhibits O2- generation. Signalling via A2 receptors is independent of microtubules, insensitive to pertussis toxin and is associated with binding of [3H]FMLP to cytoskeletal preparations.
Treatment of Gonorrheal Conjunctivitis.
Authors: Wm. T. Belfield
Journal: JAMA (1895)

Minneapolis, Minn., Feb. 23, 1895. <h3>To the Editor:</h3> —Two recent cases of conjunctivitis have interested me and are perhaps worth publishing. Jan. 7,1895, Dr. B. asked me to visit and take charge of a case of purulent conjunctivitis, to which he had been called during the night. A young bride of two weeks, a healthy blonde, had suffered for four days from a profuse muco-purulent discharge of left eye, for which she had used some domestic eye wash and warm fomentations. Dr. B. had been called on account of severe pain which was relieved by morphia and hot water. I found intense congestion of entire conjunctiva, pupil strongly contracted, and a muco-purulent discharge which under the microscope showed only a few pus cells and streptococci, some of the latter in pairs. The eye was thoroughly washed out with boracic solution, mopped with 2 per cent, silver and again flushed with
The influence of exercise and circadian rhythm of haemoglobin concentration associated changes in plasma volume on the biological passport
Authors: S C Voss, M Alsayrafi, N Alsowaidi, M Elzain Elgingo, P Bourdon, N Robinson, P E Sottas, F Klodt, D Nonis, Y O Schumacher
Journal: British Journal of Sports Medicine (2011)

In the fight against doping in sports, indirect detection methods using Hb and Hct are starting to play a more and more important role. The goal of this investigation was to quantify the changes in PV during a 2 week study of endurance exercise simulating a cycling stage race and to test for PV changes relative to the circadian rhythm of the athlete. 15 endurance trained triathletes and cyclists performed a standardised 3 day taper (no exercise), followed by a 9 day cycling stage race simulation. Hb showed a mean increase of 4% during the 3 day taper period which was caused by a reduction in PV. During the exercise phase Hb dropped by 1.5 g/dl or 11%, which relates to an average expansion of PV by 0.6 l or 16%. The fluctuations in morning PV showed a wide inter-subject variability. The smallest change was 493 ml (10%), which was accompanied with a drop in Hb from 14.8 g/dl to 13.7 g/dl. The largest increase was 1277 ml (or 25%). The corresponding Hb values for this subject dropped from 15.8 g/dl to 13.1 g/dl (figure 2). The Hb concentration of the morning and evening samples showed a mean difference of approximately 0.6 g/dl or 3.7%, which was observed both during the taper (without exercise) and stage race phases. This study showed that exercise induced changes of PV in healthy trained endurance athletes can be up to 1277 ml or 25% when tested at the same time of the day. This fact needs to be considered in the interpretation of blood profiles as this value might even be higher if the test was to be performed at different times of the day. In our study we were able to demonstrate that the circadian rhythm of Hb concentration remains stable even under maximal PV expansion and reaction to exercise. This finding could be implemented in the athlete biological passport model to help reduce the variation of biological markers.
Conference Report: Meeting of minds in Moscow
Authors: J. Smith
Journal: BMJ (1987)

Smith reports on the annual congress of the International Physicians for the Prevention of Nuclear War (IPPNW), held June 1987 in Moscow. The IPPNW declared its support for the total abolition of nuclear weapons, a theme addressed by many of the speakers to the assembly of delegates. While much attention was directed toward relations between the superpowers, the impact of the arms race on expenditures for health in developing countries was also emphasized. The congress closed with discussions of ways to encourage peaceful international cooperation and the use of satellite communication technology to promote world health.
The role of DJ-1 in anti-apoptosis
Authors: Haigang Ren, Kai Fu, Jun Fan, Guanghui Wang
Journal: Molecular Neurodegeneration (2012)

Background DJ-1 is a protein in association with Parkinson’s disease (PD) and cancers. DJ-1 has been reported to exhibit both cytoplasmic and nuclear distribution (Bonifati et al., Science, 2003; Nagakubo et al., BBRC, 1997). It functions in multiple pathways to affect cell survival. It suppresses the JNK signaling pathway in cytoplasma (Mo et al., Cell Death Differ, 2008) and interacts with Daxx and sequesters it within the nucleus, preventing the initiation of apoptotic signaling (Junn et al., PNAS, 2005). In contrast to its functions in cell survival, deletions or loss of function point mutations in DJ-1 are reported to be responsible for recessive early-onset Parkinson’s disease (PD) (Bonifati et al., Science, 2003). The most commonly studied PD-associated mutant, L166P, is reported to be unstable and to mislocalize to the mitochondria, leading to a loss of the cytoplasmic function of DJ-1 (Bonifati et al., Science, 2003). Although lines of evidence suggest that a high expression of DJ-1 enhances cell survival and loss of DJ-1 function is associated with PD, the detailed mechanisms are still not fully understood.
NORTHAMPTON GENERAL INFIRMARY: CASE OF HAeMORRHOIDAL TUMOUR REMOVED BY THE ECRASEUR
Authors: H. Terry
Journal: BMJ (1856)

ShWe operate near the anus; but I would advise, in a similar ca", the lithotomy position to be adopted, and thus a better view to be obtained of the part, and more command afforded over the h.morrhage..Thus we can apply with greater faci- lit ligatures to the bleeding vessels if needed, as they assur- Zdly will in the larger growths, if excision alone be practised, or the ligature, which ought always to be used, should slip.Should the Ecraaeur realize the expectations held out, and
Genome-wide tissue-specific farnesoid X receptor binding in mouse liver and intestine
Authors: Ann M. Thomas, Steven N. Hart, Bo Kong, Jianwen Fang, Xiao‐bo Zhong, Grace L. Guo
Journal: Hepatology (2009)

Farnesoid X receptor (FXR) is a bile acid-activated transcription factor belonging to the nuclear receptor superfamily. FXR is highly expressed in liver and intestine and crosstalk mediated by FXR in these two organs is critical in maintaining bile acid homeostasis. FXR deficiency has been implicated in many liver and intestine diseases. However, regulation of transcription by FXR at the genomic level is not known. This study analyzed genome-wide FXR binding in liver and intestine of mice treated with a synthetic FXR ligand (GW4064) by chromatin immunoprecipitation coupled to massively parallel sequencing (ChIP-seq). The results showed a large degree of tissue-specific FXR binding, with only 11% of total sites shared between liver and intestine. The sites were widely distributed between intergenic, upstream, intragenic, and downstream of genes, with novel sites identified within even known FXR target genes. Motif analysis revealed a half nuclear receptor binding site, normally bound by a few orphan nuclear receptors, adjacent to the FXR response elements, indicating possible involvement of some orphan nuclear receptors in modulating FXR function. Furthermore, pathway analysis indicated that FXR may be extensively involved in multiple cellular metabolic pathways. This study reports genome-wide FXR binding in vivo and the results clearly demonstrate tissue-specific FXR/gene interaction. In addition, FXR may be involved in regulating broader biological pathways in maintaining hepatic and intestinal homeostasis.
Crisis deepens at the US Food and Drug Administration
Authors: Jeanne Lenzer
Journal: BMJ (2004)

The US Food and Drug Administration, rocked by controversy in recent months, has now admitted that a senior management official secretly contacted a whistleblower group. That official attempted to discredit Dr David Graham, the FDA's scientist who criticised the agency during US Senate hearings, saying that the FDA failed to protect the public when it approved rofecoxib (Vioxx, Merck)—despite evidence suggesting that the drug caused heart attacks and strokes ( BMJ 2004;329: 1255, 27 Nov).

The FDA issued a statement on 26 November saying, “FDA had no prior knowledge of any employee's contact with the Government Accountability Project.” In addition to acknowledging that the employee is “not anonymous” to the project, the FDA said the “employee has chosen to not divulge their identity, and FDA respects the right of any of its employees to protect their privacy in cases such as this.”

Dr Graham's attorney, Tom Devine, …
Preservation of complement-induced lung injury in mice with deficiency of NADPH oxidase.
Authors: H Kubo, D Morgenstern, W M Quinian, P A Ward, M C Dinauer, C M Doerschuk
Journal: Journal of Clinical Investigation (1996)

Mice with chronic granulomatous disease (X-CGD mice) generated by mutating the X-linked gene for a subunit of NADPH oxidase have been analyzed for their ability to respond to intravenous injection of purified cobra venom factor (CVF). This agent in wild-type mice produces a neutrophil-dependent and catalase-sensitive form of lung injury. Lung injury was evaluated by measuring the accumulation of extravascular albumin. Quite unexpectedly, the lungs of X-CGD mice showed no difference in the increased accumulation of extravascular albumin after injection of CVF when compared to wild-type mice. In both X-CGD and wild-type mice, full development of injury required neutrophils. While catalase was highly protective in wild-type mice, its protective effects were completely lost in the X-CGD mice. Furthermore, a competitive antagonist of L-arginine, N(G)-methyl-L-arginine, was protective in X-CGD mice but not in wild-type mice. Allopurinol was protective in both types of mice. Both the basal and the CVF-inducible lung mRNA for inducible nitric oxide synthase and IL-1beta was similar in X-CGD and wild-type mice. These data indicate that oxygen radical production and lung injury in response to injection of CVF occurs through alternative pathways in mice with genetic deletion of NADPH oxidase.
Regression of microalbuminuria in type 1 diabetes is associated with lower levels of urinary tubular injury biomarkers, kidney injury molecule-1, and N-acetyl-β-D-glucosaminidase
Authors: Vishal S. Vaidya, Monika A. Niewczas, Linda H. Ficociello, Amanda C. Johnson, Fitz B. Collings, James H. Warram, Andrzej S. Krolewski, Joseph V. Bonventre
Journal: Kidney International (2010)
Editor Ripped: Rippers Triumphant
Authors: STEVE HAAS
Journal: Annals of Internal Medicine (1971)

Letters and Comments1 June 1971Editor Ripped: Rippers TriumphantSTEVE HAAS, M.D.STEVE HAAS, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-74-6-1015 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: It is with great disappointment that I have viewed the January and February issues of the ANNALS. What happened to the policy of separating articles by filler material so that back-to-back articles could be torn and filed?As an avowed "ripper" and one who has saved almost all the ANNALS articles, I am now frustrated monthly. Other journals at least have been considerate enough to throw in enough worthless articles to ease the pain of decision, although they do tend to put the good ones back to back with unfortunate frequency.Please reconsider the recent change in...Reference1. Rip or bind? A ripping response (letter). Ann Intern Med 71:864-867, 1969 LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: 60-53 ½ Way N.E. Fridley, Minn. 55432 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 June 1971Volume 74, Issue 6Page: 1015-1016KeywordsLower back pain Issue Published: 1 June 1971 PDF DownloadLoading ...
Rethinking childhood depression
Authors: D B Double
Journal: BMJ (2005)

Editor—For the debate about rethinking childhood depression to degenerate into a semantic argument about its existence would be unfortunate.1 Reification of biomedical diagnosis acts as a justification for so called evidence based treatments, which currently in the case of childhood depression are antidepressant drugs, cognitive behaviour therapy, and interpersonal therapy. The question is whether this process of reification is necessary for clinical practice, and I agree with Timimi that it is not.1

The onus is on Spender and Wilkinson to define exactly what they mean when they use the term childhood depression, which they do not do in their commentaries.1

In the same issue Wade and Halligan ask whether biomedical models of illness make for good healthcare systems.2 The potential danger of the biomedical model is reductionism. By contrast, psychosocial diagnosis does not necessarily require a single word label, and that single word label may not add much to the understanding and meaning of emotional problems. Such an approach is consistent with patient centred medicine and means that the patient is not merely seen as a passive recipient of treatment for which he or she has no responsibility.3 A psychosocial perspective in clinical practice therefore has advantages.

I suspect that the issue in this debate boils down to the readiness to use antidepressant drugs in children. Both Spender and Wilkinson quote the treatment for adolescents with depression study (TADS) in favour of the use of fluoxetine,4 but they do not mention criticisms of it.5 Fluoxetine was not in fact statistically better than placebo in this study and only became so when added to cognitive behaviour therapy in an unblinded arm. Strictly speaking, Spender and Wilkinson have therefore not provided support for their position. I prefer Timimi's critical approach, which takes a sceptical stance on the evidence, more in keeping with the spirit of scientific inquiry.