tbuckley/cabot-search huggingface dataset:
Further evidence that the wealthier are healthier: negative life events and asthma-specific quality of life
Authors: R J Wright
Journal: Thorax (2007)

Association between psychological stress and asthma expression and morbidity

In this issue of Thorax , Archea et al 1 (see p 139) add to the growing number of studies linking psychological stress to asthma expression and morbidity. To date, studies have reported an association between various measures of life stress and both the onset of asthma or precedent phenotypes2,3 and exacerbations of established disease.4–6 Hypothesised mechanisms underlying the association between stress and asthma expression implicate reciprocal relationships between neural, hormonal and immunological pathways that have been extensively reviewed previously.7,8 Evidence demonstrating that psychological stress influences the expression of inflammatory cytokine patterns in patients with asthma or those at risk of developing the disease supports these theories.9,10 Others have shown that physiological changes, including neuroimmune and genetic processes, may lead to differential responses to therapeutic interventions for asthma and atopic disorders.11,12

The current work by Archea et al 1 underscores that psychological factors may also be more indirect, albeit equally important, determinants of asthma morbidity by influencing how individuals perceive and manage their disease. They aimed to examine the relationship between negative life events (NLEs) and asthma-specific quality of life (AQoL), and also to understand the interrelationships among AQoL, asthma severity and socioeconomic status (SES). These cross-sectional results show a relationship between the frequency of experiencing NLEs, a measure of psychological stress, and AQoL among 189 adults with asthma. Those experiencing a greater number of NLEs reported a worse AQoL, a relationship seen across all …
Rate of Kidney Function Decline Associates with Increased Risk of Death
Authors: Csaba P. Kovesdy
Journal: Journal of the American Society of Nephrology (2010)

The current classification scheme for chronic kidney disease (CKD) does not differentiate between patients who show a progressive course of CKD and those whose kidney function remains stable over a long period. There is an association of faster progression of CKD with worse mortality, suggesting that an individual's slope of estimated GFR (eGFR) over time could help us refine the prognosis for patients with any given stage of CKD. Many questions still need to be answered before the mainstream application of the slopes of eGFR is possible.

The estimation formula-based CKD classification by the Kidney Disease Outcomes Quality Initiative (K/DOQI)1 has proved to be an eye opener to the medical community and has raised awareness about the common frequency of decreased eGFR and the high mortality associated with lower eGFR.2–5 The immediate impact of this awareness has been a significant increase of clinical referrals to nephrologists from various practitioners6 who suddenly discovered that many of their patients had CKD,7 a condition that became easy to diagnose but whose management still befuddles many nonspecialists. Those of us on the receiving end of these consultations have quickly come to realize that some patients who are labeled as having CKD received a misdiagnosis because of deficiencies in our estimation formulas or of standardization of serum creatinine measurements,8 and many patients, of course, who indeed have …
Phase II study of receptor-enhanced chemosensitivity using recombinant humanized anti-p185HER2/neu monoclonal antibody plus cisplatin in patients with HER2/neu-overexpressing metastatic breast cancer refractory to chemotherapy treatment.
Authors: M D Pegram, A Lipton, D F Hayes, B L Weber, J M Baselga, D Tripathy, D Baly, S A Baughman, T Twaddell, J A Glaspy, D J Slamon
Journal: Journal of Clinical Oncology (1998)

PURPOSE To determine the toxicity, pharmacokinetics, response rate, and response duration of intravenous (i.v.) administration of recombinant, humanized anti-p185HER2 monoclonal antibody (rhuMAb HER2) plus cisplatin (CDDP) in a phase II, open-label, multicenter clinical trial for patients with HER2/neu-overexpressing metastatic breast cancer. PATIENTS AND METHODS The study population consisted of extensively pretreated advanced breast cancer patients with HER2/neu overexpression and disease progression during standard chemotherapy. Patients received a loading dose of rhuMAb HER2 (250 mg i.v.) on day 0, followed by weekly doses of 100 mg i.v. for 9 weeks. Patients received CDDP (75 mg/m2) on days 1, 29, and 57. RESULTS Of 37 patients assessable for response, nine (24.3%) achieved a PR, nine (24.3%) had a minor response or stable disease, and disease progression occurred in 19 (51.3%). The median response duration was 5.3 months (range, 1.6-18). Grade III or IV toxicity was observed in 22 of 39 patients (56%). The toxicity profile reflected that expected from CDDP alone with the most common toxicities being cytopenias (n = 10), nausea/vomiting (n = 9), and asthenia (n = 5). Mean pharmacokinetic parameters of rhuMAb HER2 were unaltered by coadministration of CDDP. CONCLUSION The use of rhuMAb HER2 in combination with CDDP in patients with HER2/neu-overexpressing metastatic breast cancer results in objective clinical response rates higher than those reported previously for CDDP alone, or rhuMAb HER2 alone. In addition, the combination results in no apparent increase in toxicity. Finally, the pharmacology of rhuMAb HER2 was unaffected by coadministration with CDDP.
Mitochondrial DNA of Clathrina clathrus (Calcarea, Calcinea): Six Linear Chromosomes, Fragmented rRNAs, tRNA Editing, and a Novel Genetic Code
Authors: Dennis V. Lavrov, Walker Pett, Oliver Voigt, Gert Wörheide, Lise Forget, B. Franz Lang, Ehsan Kayal
Journal: Molecular Biology and Evolution (2012)

Sponges (phylum Porifera) are a large and ancient group of morphologically simple but ecologically important aquatic animals. Although their body plan and lifestyle are relatively uniform, sponges show extensive molecular and genetic diversity. In particular, mitochondrial genomes from three of the four previously studied classes of Porifera (Demospongiae, Hexactinellida, and Homoscleromorpha) have distinct gene contents, genome organizations, and evolutionary rates. Here, we report the mitochondrial genome of Clathrina clathrus (Calcinea, Clathrinidae), a representative of the fourth poriferan class, the Calcarea, which proves to be the most unusual. Clathrina clathrus mitochondrial DNA (mtDNA) consists of six linear chromosomes 7.6–9.4 kb in size and encodes at least 37 genes: 13 protein codings, 2 ribosomal RNAs (rRNAs), and 24 transfer RNAs (tRNAs). Protein genes include atp9, which has now been found in all major sponge lineages, but no atp8. Our analyses further reveal the presence of a novel genetic code that involves unique reassignments of the UAG codons from termination to tyrosine and of the CGN codons from arginine to glycine. Clathrina clathrus mitochondrial rRNAs are encoded in three (srRNA) and ⩾6 (lrRNA) fragments distributed out of order and on several chromosomes. The encoded tRNAs contain multiple mismatches in the aminoacyl acceptor stems that are repaired posttranscriptionally by 3′-end RNA editing. Although our analysis does not resolve the phylogenetic position of calcareous sponges, likely due to their high rates of mitochondrial sequence evolution, it confirms mtDNA as a promising marker for population studies in this group. The combination of unusual mitochondrial features in C. clathrus redefines the extremes of mtDNA evolution in animals and further argues against the idea of a "typical animal mtDNA."
Chronic intermittent abdominal pain
Authors: J Ockenga
Journal: Gut (2005)

Background: Although previous studies have shown that the hepatic sympathetic nerve controls various physiological functions in the liver, the role of this nerve in liver injury has yet to be clarified.Aims: The purpose of this study was to elucidate the role of this nerve, based on our newly developed technique for selectively removing the activities of the hepatic sympathetic nerve.Subjects and methods: Male C57BL/6 mice were operated on for hepatic sympathetic denervation.Thereafter, mice were intravenously administered 0.25 or 0.35 mg/g weight of the Fas agonist antibody, Jo-2, after which mortality by fulminant hepatitis was evaluated.Apoptosis in the liver was also examined by both terminal deoxynucleotidyl transferase mediated dUTP nick end labelling and caspase-3 assay.Results: Mortality in sympathectomised mice was significantly higher than that in sham operated mice following administration of Jo-2.This result was also supported by apoptosis data in which sympathectomised livers exhibited a significant elevation in the number of apoptotic hepatocytes and caspase-3 activity after Jo-2 treatment compared with sham operated livers.Moreover, pretreatment with norepinephrine dose dependently inhibited the hepatic sympathectomy induced increase in mortality after Jo-2 injection.Antiapoptotic protein levels of FLICE inhibitory protein, Bcl-xL, and Bcl-2 in the liver were significantly lower in sympathectomised mice at one and two hours following Jo-2 treatment than in sham operated animals.In addition, interleukin 6 supplementation dose dependently suppressed the hepatic sympathectomy induced increase in mortality after Jo-2 treatment.Conclusions: These results suggest that norepinephrine released from the hepatic sympathetic nerve plays a critical role in protecting the liver from Fas mediated fulminant hepatitis, possibly via mechanisms including antiapoptotic proteins and interleukin 6.
Childhood peak flow and the Oxford Transport Strategy
Authors: S J MacNeill, F Goddard, R Pitman, S Tharme, P Cullinan
Journal: Thorax (2008)

<h3>Background:</h3> Studies of the health effects of traffic interventions are rare. The Oxford Transport Strategy (OTS), implemented in June 1999, involved a wide range of permanent changes designed to reduce congestion in the city centre of Oxford, UK. The impact of the OTS on peak expiratory flow (PEF) and respiratory symptoms among schoolchildren in the city is reported. <h3>Methods:</h3> A dynamic cohort of 1389 children aged 6–10 years attending first schools in Oxford was studied. Schools were visited 2–3 times a year for 5-day periods between 1998 and 2000. On each day of each visit children had their PEF measured and were asked about their respiratory symptoms. <h3>Results:</h3> Changes in traffic varied across the city. In the whole population, regression analysis of daily PEF adjusting for potential confounders showed statistically significant improvements post-OTS (β = 5.52 l/min, 95% CI 3.08 to 7.97), but there was no consistent evidence that these improvements varied by changes in traffic exposure. In post-hoc analyses, children currently receiving treatment for asthma tended to experience a greater increase in PEF post-OTS as did children from less affluent homes, although these differences did not reach statistical significance. In each of these groups, greater benefits were observed among those living near roads where traffic levels fell post-OTS. <h3>Conclusions:</h3> These findings suggest that traffic management may lead to small localised improvements in childhood respiratory health and that such benefits are limited to children with pre-existing respiratory problems and those from less affluent backgrounds.
DNA-Dependent Protein Kinase Is a Molecular Target for the Development of Noncytotoxic Radiation–Sensitizing Drugs
Authors: Eric T. Shinohara, Ling Geng, Jiahui Tan, Heidi Chen, Yu Shir, Eric Edwards, James Halbrook, Edward A. Kesicki, Adam Kashishian, Dennis E. Hallahan
Journal: Cancer Research (2005)

DNA-dependent protein kinase (DNA-PK)-defective severe combined immunodeficient (SCID) mice have a greater sensitivity to ionizing radiation compared with wild-type mice due to deficient repair of DNA double-strand break. SCID cells were therefore studied to determine whether radiosensitization by the specific inhibitor of DNA-PK, IC87361, is eliminated in the absence of functional DNA-PK. IC87361 enhanced radiation sensitivity in wild-type C57BL6 endothelial cells but not in SCID cells. The tumor vascular window model was used to assess IC87361-induced radiosensitization of SCID and wild-type tumor microvasculature. Vascular density was 5% in irradiated SCID host compared with 50% in C57BL6 mice (P < 0.05). IC87361 induced radiosensitization of tumor microvasculature in wild-type mice that resembled the radiosensitive phenotype of tumor vessels in SCID mice. Radiosensitization by IC87361 was eliminated in SCID tumor vasculature, which lack functional DNA-PK. Irradiated LLC and B16F0 tumors implanted into SCID mice showed greater tumor growth delay compared with tumors implanted into either wild-type C57BL6 or nude mice. Furthermore, LLC tumors treated with radiation and IC87361 showed tumor growth delay that was significantly greater than tumors treated with radiation alone (P < 0.01 for 3 Gy alone versus 3 Gy + IC87361). DNA-PK inhibitors induced no cytotoxicity and no toxicity in mouse normal tissues. Mouse models deficient in enzyme activity are useful to assess the specificity of novel kinase inhibitors. DNA-PK is an important target for the development of novel radiation-sensitizing drugs that have little intrinsic cytotoxicity.
Tumor-Cell DNA Content Predicts Outcome in Children and Adolescents With Clinical Group III Embryonal Rhabdomyosarcoma
Authors: Alberto S. Pappo, William M. Crist, John Kuttesch, Susan Rowe, Richard A. Ashmun, Harold M. Maurer, William A. Newton, Lina Asmar, Xiaolong Luo
Journal: Journal of Clinical Oncology (1994)

The legend for Fig 1 in the report entitled "Tumor-Cell DNA Content Predicts Outcome in Children and Adolescents With Clinical Group III Embryonal Rhabdomyosarcoma" by Pappo et al (J Clin Oncol 11:1901–1905, 1993) incorrectly identified parts A and B. The legend is reprinted here correctly in its entirety with the figure. Please see the PDF for Figure.
S55 Mir-181: a potential biomarker of acute muscle wasting?
Authors: SAA Bloch, PR Kemp, MJD Griffiths, MI Polkey
Journal: Thorax (2013)

<h3>Introduction and Objectives</h3> Acute muscle wasting in the critically ill is common and associated with significant morbidity and mortality. Although some aetiological risk factors are recognised it is difficult to predict those who will develop muscle wasting. The ability to predict who will go on to develop muscle wasting or to detect muscle wasting prior to it becoming clinically significant would provide the opportunity to intervene at an early stage with strength training or anabolic agents. MicroRNAs are small non coding RNA that are thought to modulate post transcriptional regulation of translation. Since we have previously found that microRNA expression in skeletal muscle relates to muscle weakness in COPD (<i>Thorax </i>2012;67:26–34) and in blood are associated with skeletal muscle phenotype (<i>Thorax</i> in press PMID 23814167) we hypothesised that plasma microRNAs could be biomarkers of ICU acquired muscle weakness. <h3>Methods</h3> In a prospective observational study (<i>Crit Care Med</i> 2013;41:982–989) of 42 patients undergoing elective high-risk cardiothoracic surgery plasma levels of selected microRNAs were assayed pre-operatively and over the first week post operatively. Those who developed muscle wasting were identified by ultrasound. <h3>Main Results</h3> 55% (23 of the 42) of patients developed muscle atrophy. Rise in mir-181 was significantly higher at day 2 post surgery in those who developed muscle wasting compared to those who did not (p = 0.03, Figure 1). A rise in mir-181 of greater than 1.7 times baseline at day 2 post surgery has a 90% specificity for muscle wasting, (with 55% sensitivity). Other microRNAs did not show significant differences between the groups. <h3>Conclusion</h3> Mir-181 has been shown to be involved in both regulation of inflammation and muscle regeneration and differentiation. Mir-181 provides a potential biomarker of developing muscle wasting and with further development in the future may prove to be useful in directing treatment. <h3>Funding</h3> This work is funded by an MRC Clinical fellowship to Dr Bloch and supported by the NIHR Respiratory BRU at the Royal Brompton and Harefiled NHS Trust and Imperial College who part fund the salries of MIP and MG
House Dust Mite–induced Airway Changes in hu-SCID Mice
Authors: CATHERINE DUEZ, JOHAN KIPS, JOËL PESTEL, KURT TOURNOY, ANDRÉ-BERNARD TONNEL, ROMAIN PAUWELS
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

SCID (severe combined immunodeficiency) mice reconstituted with peripheral blood mononuclear cells (PBMC) from Dermatophagoides pteronissynus (Dpt)-sensitive patients and exposed to Dpt aerosol (allergic hu-SCID mice) develop human IgE and pulmonary inflammation. The present study investigated concomitant changes in airway hyperresponsiveness (AHR). No significant difference in baseline airway responsiveness was seen between nonreconstituted SCID mice exposed or not to Dpt aerosol at Day 35. Allergic hu-SCID mice developed AHR (provocative dose of carbachol causing a 50% increase in lung resistance [PD50 Rl] = 96.33 ± 16.88 μ g/kg) compared with nonallergic hu-SCID mice (PD50 Rl = 242.03 ± 37.84 μ g/kg) and nonreconstituted SCID mice (PD50 Rl = 297.60 ± 45.60 μ g/kg) exposed to Dpt aerosol. An inverse correlation was observed between PD50 Rl (Day 35) and total human IgE at Day 7 (r = − 0.58) and Day 15 (r = − 0.64). However, no correlation existed between PD50 Rl and human cell number in the lungs of allergic hu-SCID mice. Moreover, despite the absence of eosinophils, the bronchoalveolar lavage fluid (BALF) of allergic hu-SCID mice had more human interleukin-5 (IL-5) (3.28 ± 0.40 pg/ml, n = 13) than nonallergic hu-SCID mice ( < 0.5 pg/ml) which inversely correlated with the PD50 Rl (r = − 0.61). No tumor necrosis factor-alpha (TNF- α ), IL-6, or IL-4 was detected. These observations indicate that humanized allergic hu-SCID mice may develop AHR after exposure to the relevant allergen, suggesting that this model may improve our understanding of AHR, one characteristic feature of allergic asthma. Duez C, Kips J, Pestel J, Tournoy K, Tonnel A-B, Pauwels R. House dust mite–induced airway changes in hu-SCID mice.
Long-term survival results of a randomized phase III trial of vinflunine plus best supportive care versus best supportive care alone in advanced urothelial carcinoma patients after failure of platinum-based chemotherapy
Authors: J. Bellmunt, R. Fougeray, J.E. Rosenberg, H. von der Maase, F.A. Schutz, Y. Salhi, S. Culine, T.K. Choueiri
Journal: Annals of Oncology (2013)
Developing a Prediction Rule From Automated Clinical Databases to Identify High-Risk Patients in a Large Population With Diabetes
Authors: Joe V. Selby, Andrew J. Karter, Lynn M. Ackerson, Assiamira Ferrara, Jennifer Liu
Journal: Diabetes Care (2001)

OBJECTIVE—To develop and validate a prediction rule for identifying diabetic patients at high short-term risk of complications using automated data in a large managed care organization. RESEARCH DESIGN AND METHODS—Retrospective cohort analyses were performed in 57,722 diabetic members of Kaiser Permanente, Northern California, aged ≥19 years. Data from 1994 to 1995 were used to model risk for macro- and microvascular complications (n = 3,977), infectious complications (n = 1,580), and metabolic complications (n = 316) during 1996. Candidate predictors (n = 36) included prior inpatient and outpatient diagnoses, laboratory records, pharmacy records, utilization records, and survey data. Using split-sample validation, the risk scores derived from logistic regression models in half of the population were evaluated in the second half. Sensitivity, positive predictive value, and receiver operating characteristics curves were used to compare scores obtained from full models to those derived using simpler approaches. RESULTS—History of prior complications or related outpatient diagnoses were the strongest predictors in each complications set. For patients without previous events, treatment with insulin alone, serum creatinine ≥1.3 mg/dl, use of two or more antihypertensive medications, HbA1c &amp;gt;10%, and albuminuria/microalbuminuria were independent predictors of two or all three complications. Several risk scores derived from multivariate models were more efficient than simply targeting patients with elevated HbA1c levels for identifying high-risk patients. CONCLUSIONS—Simple prediction rules based on automated clinical data are useful in planning care management for populations with diabetes.
Differential activation of transcription versus recombination of transgenic T cell receptor beta variable region gene segments in B and T lineage cells.
Authors: A Okada, M Mendelsohn, F Alt
Journal: The Journal of Experimental Medicine (1994)

We have tested the ability of the T cell receptor beta (TCR-beta) transcriptional enhancer (E beta) to confer transcriptional activation and tissue-specific V(D)J recombination of TCR-beta V, D, and J segments in a transgenic minilocus recombination substrate. We find that the minimal E beta element, as previously shown for a DNA segment that contained the E mu element, promotes a high level of substrate D to J beta rearrangement in both B and T cells, but only promotes V beta to DJ beta rearrangement in T cells. Thus, both the E mu and E beta elements similarly direct V(D)J recombination of this substrate in vivo, supporting a general role for transcriptional enhancers in the normal regulation of this rearrangement process. Surprisingly, however, we found that both the V beta and DJ beta portion of the constructs were transcribed in an enhancer-dependent fashion (conferred by either E mu or E beta) in both B and T lineage cells, including normal precursor B cells propagated in culture. These findings indicate that, at least in some contexts, transcriptional activation, per se, is not sufficient to confer V(D)J recombinational accessibility to a substrate V gene segment.
Points from Letters: Size of Promotional Literature
Authors: W. N. Kingsbury
Journal: BMJ (1970)

refers I did not comment directly on the case for or against a large increase in number, but was concerned with the evi- dence indicating that the Royal Commission had failed to understand the mathematical basis on which they proposed an exponential expansion, and had thus reached a wholly unjustifiable conclusion about the number of doctors necessary.I also drew attention to the implications of an error of this magnitude, which could require perhaps the provision of 10,000 unnecessary doctors in 10 years, a number equivalent to the output of five new medical schools.As this appears a serious matter, one would expect the mathematical errors in this section of the report to have been ac- knowledged and corrected before now, since it must surely be necessary to prepare a new estimate based on less indefensible grounds.If, however, my conclusions are unjustified, it should be an easy matter to refute them.-Iam, etc.,