tbuckley/cabot-search huggingface dataset:
Maternal Smoking Leads to Increased Cord Serum IgG3
Authors: C. G. M. Magnusson, S. G. O. Johansson
Journal: Allergy (1986)

IgG subclass levels in cord serum of unselected European newborns were studied in relation to parental smoking. Cord IgG3 was significantly ( P &lt; 0.01) higher in newborns of smoking mothers ( n = 18; geom.mean = 87.0%) compared to those of non‐smoking mothers ( n = 66; geom.mean = 61.0%). Maternal smoking did not influence ( P &gt; 0.10) cord IgG2 or cord IgG4. Paternal smoking did not affect any of the three immunoglobulins in cord serum ( P &gt; 0.10). These data suggest that tobacco smoking affects IgG3 synthesis in some direct or indirect way.
ASNA-1 Activity Modulates Sensitivity to Cisplatin
Authors: Oskar Hemmingsson, Gautam Kao, Maria Still, Peter Naredi
Journal: Cancer Research (2010)

Cancer can be cured by platinum-based chemotherapy, but resistance is a major cause of treatment failure. Here we present the nematode Caenorhabditis elegans as a model to study interactions between the platinum drug cisplatin and signaling pathways in vivo. Null mutation in a single gene, asna-1, makes worms hypersensitive to cisplatin. The metalloregulated ATPase ASNA-1 promotes insulin secretion and membrane insertion of tail-anchored proteins. Using structural data from ASNA-1 homologues, we identify specific ASNA-1 mutants that are sensitive to cisplatin while still able to promote insulin signaling. Mutational analysis reveals that hypersensitivity of ASNA-1 mutants to cisplatin remains in absence of CEP-1/p53 or apoptosis. Human ASNA1 can substitute for the worm gene, indicating a conserved function. Cisplatin sensitivity is not affected by decreased insulin signaling in wild-type nematodes or restored insulin signaling in asna-1 mutants. These findings provide a functional insight into ASNA-1, demonstrate that C. elegans can be used to characterize cisplatin resistance mechanisms, and suggest that rationally designed drugs against ASNA-1 can sensitize cancer cells to cisplatin.
Opportunistic screening for chlamydial infection at time of cervical smear testing in general practice: prevalence study
Authors: P. Oakeshott, S. Kerry, S. Hay, P. Hay
Journal: BMJ (1998)

Contact partners of women with C trachomatis infection may be deterred from seeking medical help because of the intimate nature of the infection and because a urethral swab is needed.Urine samples obtained at home provide a non-invasive and less time consuming alternative.A similar procedure for contact tracing of female partners of men infected with C trachomatis should be considered as the organism has been detected in urine samples from women. 5 We thank the participating general practitioners.Contributors: BA coordinated the primary study hypothesis and the core ideas, designed the protocol, obtained approval from the ethics committee, coordinated inclusion of patients, scanned the data, and coordinated the interpretation of results and writing of the paper.LØ discussed the primary hypothesis, core ideas, analysis, and protocol design and participated in the interpretation of results and writing of the paper.JKM discussed the hypothesis and ideas, led the analysis of the samples obtained, participated in the interpretation of results, and edited the paper.FO discussed the hypothesis and core ideas and participated in the protocol design, coordination of contact with the general practitioners, the interpretation of results, and the writing of the paper.FO is the guarantor of the paper.
Rapid Ventricular Induction of Brain Natriuretic Peptide Gene Expression in Experimental Acute Myocardial Infarction
Authors: Norio Hama, Hiroshi Itoh, Gotaro Shirakami, Osamu Nakagawa, Shin-ichi Suga, Yoshihiro Ogawa, Izuru Masuda, Kuniaki Nakanishi, Takaaki Yoshimasa, Yukiya Hashimoto, Masayuki Yamaguchi, Ryouhei Hori, Hirofumi Yasue, Kazuwa Nakao
Journal: Circulation (1995)

Background We have demonstrated that brain natriuretic peptide (BNP) is a cardiac hormone predominantly synthesized in and secreted from the ventricle. We have also reported that, compared with atrial natriuretic peptide (ANP), the plasma concentration of BNP is increased to a greater degree in patients with congestive heart failure and more rapidly in patients with acute myocardial infarction (AMI). Methods and Results To investigate ventricular gene expression of BNP in AMI, we analyzed plasma and ventricular BNP concentrations along with ventricular BNP mRNA in rats with AMI produced by coronary artery ligation. The BNP concentration in the left ventricle increased about 2-fold as early as 12 hours postinfarction and 5-fold 1 day postinfarction compared with sham-operated rats, whereas left ventricular ANP concentration remained unchanged within 1 day. The tissue concentration of BNP increased in the noninfarcted region as well as in the infarcted region. The surviving myocytes in and around the necrotic tissues in the infarcted region were intensely stained with the anti-BNP antiserum, indicating augmented production in the remaining myocytes in the infarcts. The BNP concentration in the right ventricle also increased about 10-fold 12 hours postinfarction, whereas the ANP concentration remained unchanged within 12 hours. Northern blot analysis revealed that BNP mRNA expression was augmented 3-fold in the left ventricle as early as 4 hours postinfarction. In contrast, ANP mRNA expression was unchanged. Reflecting the rapid induction of ventricular BNP production, the plasma BNP concentration rose to about 100 pg/mL 12 hours postinfarction (sham-operated rats, &lt;70 pg/mL). Conclusions These results demonstrate the rapid induction of ventricular BNP gene expression in rats with AMI compared with ANP and suggest that BNP gene expression in the ventricle is regulated distinctively from ANP gene expression against acute ventricular overload. They also suggest that the BNP gene can be one of the acutely responsive cardiac genes for the ventricular overload and suggest a possible pathophysiological role of BNP distinct from ANP in AMI.
Pro- and anti-inflammatory responses in respiratory syncytial virus bronchiolitis
Authors: P.S. McNamara, B.F. Flanagan, A.M. Selby, C.A. Hart, R.L. Smyth
Journal: European Respiratory Journal (2003)

Respiratory syncytial virus (RSV) bronchiolitis is an important cause of severe respiratory disease in infants. This study aimed to characterise changes in pulmonary pro- and anti-inflammatory responses in infants with RSV bronchiolitis over the course of the illness. On the day of intubation (Day 1) and the day of extubation (Day X), nonbronchoscopic bronchoalveolar lavage was performed on term and preterm infants ventilated for RSV bronchiolitis and on control infants on Day 1. Tumour necrosis factor (TNF)‐α, soluble TNF receptor (sTNFR) and interleukin (IL)‐6 messenger ribonucleic acid (mRNA) and protein were measured. Twenty-four infants, born at term and 23 infants born preterm with RSV bronchiolitis and 10 controls were recruited. TNF‐α and IL‐6 mRNA and protein in infants with bronchiolitis were greater than the control group on Day 1. In preterm infants, who were ventilated for longer than term infants, TNF‐α and IL‐6 proteins decreased between Day 1 and Day X. Concentrations of sTNFRs differed between groups on Day 1, but levels did not change between Day 1 and Day X. Large amounts of tumour necrosis factor‐α and interleukin‐6 in the respiratory syncytial virus-infected lung suggest important roles for these cytokines in the pathogenesis of respiratory syncytial virus bronchiolitis. The decrease in tumour necrosis factor‐α and interleukin‐6 protein in preterm infants may reflect the prolonged clinical course seen in these infants.
A Likelihood Framework to Measure Horizontal Gene Transfer
Authors: S. Linz, A. Radtke, A. von Haeseler
Journal: Molecular Biology and Evolution (2007)

We suggest a likelihood-based approach to estimate an overall rate of horizontal gene transfer (HGT) in a simplified setting. To this end, we assume that the number of occurring HGT events within a given time interval follows a Poisson process. To obtain estimates for the rate of HGT, we simulate the distribution of tree topologies for different numbers of HGT events on a clocklike species tree. Using these simulated distributions, we estimate an HGT rate for a collection of gene trees representing a set of taxa. As an illustrative example, we use the “Clusters of Orthologous Groups of proteins” (COGs). We also perform a correction of the estimated rate taking into account the inaccuracies due to gene tree reconstructions. The results suggest a corrected HGT rate of about 0.36 per gene and unit time, in other words 11 HGT events have occurred on average among the 44 taxa of the COG species tree. A software package to estimate an HGT rate is available online (http://www.cibiv.at/software/hgt/).
A new protocol for removal of the endothelium from the perfused rat hind-limb preparation.
Authors: V Ralevic, F Kristek, O Hudlická, G Burnstock
Journal: Circulation Research (1989)

A new protocol has been developed for selective removal of the endothelium from the arteries of the perfused rat hind-limb preparation. The hind limb was perfused with oxygenated Krebs-Ringer bicarbonate solution with a combination of high flow and timed air bubbles (2 minutes at high flow followed by 5 minutes of air bubbles, followed by a further 2 minutes at high flow). Representative vessels at different diameters of the arterial tree--the femoral artery, the artery supplying the extensor hallucis proprius muscle, and the arteries, arterioles, and capillaries within the hallucis proprius muscle--were taken for examination by transmission and scanning electron microscopy. A graded degree of damage occurred along the length of the hind-limb vasculature, with endothelial cells having been completely removed from the femoral artery, removed from or severely damaged in the artery supplying the hallucis proprius muscle, and partially damaged in arteries within the hallucis proprius muscle. However, no damage occurred to the endothelial cells of the arterioles and capillaries within the hallucis proprius muscle. The integrity of the vascular bed after endothelial removal according to the above protocol was confirmed by the demonstration of no diminution, but in fact an increase, in contractile responses to bolus injections of alpha,beta-methylene ATP, resulting in a shift to the left of the dose-response curve. The viability was further confirmed by the fact that the conductance (flow/perfusion pressure) of the preparation during the periods of high flow was no different before and after removal of the endothelium.(ABSTRACT TRUNCATED AT 250 WORDS)
Prospective evaluation of radiosurgery for hemangioblastomas in von Hippel-Lindau disease
Authors: A. R. Asthagiri, G. U. Mehta, L. Zach, X. Li, J. A. Butman, K. A. Camphausen, R. R. Lonser
Journal: Neuro-Oncology (2009)

To determine the effectiveness of stereotactic radiosurgery (SRS) treatment to central nervous system (CNS) hemangioblastomas in von Hippel–Lindau disease (VHL), we analyzed long-term results in VHL patients treated with SRS. Patients were enrolled in a prospective VHL natural history study, undergoing SRS treatment of CNS hemangioblastomas. Treatment regimens, serial clinical evaluations, and longitudinal imaging data were analyzed. Twenty VHL patients (10 males and 10 females) underwent SRS treatment of 44 CNS hemangioblastomas (39 cerebellar and 5 brainstem). Mean (±SD) age at treatment was 37.5 ± 12.0 years (range: 13–67). Mean follow-up was 8.5 ± 3.2 years (range: 3.0–17.6 years). All patients were alive at last follow-up. Mean treated tumor volume was 0.5 ± 0.7 cm3 (range: 0.01–3.6 cm3). Mean prescription dose was 18.9 Gy (range: 12–24 Gy) at the tumor margin. Local control rate at 2, 5, 10, and 15 years after SRS treatment was 91%, 83%, 61%, and 51%, respectively. Univariate analysis did not identify variables associated (P > .05) with worse tumor control at last follow-up. Thirty-three percent of SRS-treated small (<1.0 cm diameter), asymptomatic tumors progressed over a long-term follow-up. There were no long-term adverse radiation effects. Although SRS treatment of hemangioblastomas in VHL has a low risk for adverse radiation effects, it is associated with diminishing control over a long-term follow-up. These results indicate that SRS should not be used to prophylactically treat asymptomatic tumors and should be reserved for the treatment of tumors that are not surgically resectable.
Effectiveness, training and quality assurance of colonoscopy screening for colorectal cancer
Authors: Douglas J Robertson, Michal F Kaminski, Michael Bretthauer
Journal: Gut (2015)

Screening for colorectal cancer has been proven to be effective in reducing colorectal cancer incidence and mortality. While the precise benefit of screening exclusively by colonoscopy is not yet known, unarguably, the exam is central to the success of any screening programme. The test affords the opportunity to detect and resect neoplasia across the entire large bowel and is the definitive examination when other screening tests are positive. However, colonoscopy is invasive and often requires sedation as well as extensive bowel preparation, all of which puts the patient at risk. Furthermore, the test can technically be demanding and, unarguably, there is variation in how it is performed. This variation in performance has now been definitively linked to important outcome measures. For example, interval cancers are more common in low adenoma detectors as compared with high adenoma detectors. This review outlines the most current thinking regarding the effectiveness of colonoscopy as a screening tool. It also outlines key concepts to optimise its performance through robust quality assurance programmes and high-quality training.
Oral terbinafine in the treatment of toenail onychomycosis: North American multicenter trial
Authors: L A Drake, N H Shear, J P Arlette, R Cloutier, F W Danby, B E Elewski, S Garnis-Jones, J M Giroux, D Gratton, W Gulliver, P Hull, H E Jones, M Journet, A L Krol, J J Leyden, S C Maddin, J B Ross, R C Savin, R K Scher, G R Sibbald, N H Tawfik, N Zaias, M Tolpin, S Evans, J E Birnbaum
Journal: Journal of the American Academy of Dermatology (1997)
Strategy for Safe Performance of Extrathoracic Magnetic Resonance Imaging at 1.5 Tesla in the Presence of Cardiac Pacemakers in Non–Pacemaker-Dependent Patients
Authors: Torsten Sommer, Claas P. Naehle, Alexander Yang, Volkert Zeijlemaker, Matthias Hackenbroch, Alexandra Schmiedel, Carsten Meyer, Katharina Strach, Dirk Skowasch, Christian Vahlhaus, Harold Litt, Hans Schild
Journal: Circulation (2006)

The purpose of the present study was to evaluate a strategy for safe performance of extrathoracic magnetic resonance imaging (MRI) in non-pacemaker-dependent patients with cardiac pacemakers.Inclusion criteria were presence of a cardiac pacemaker and urgent clinical need for an MRI examination. Pacemaker-dependent patients and those requiring examinations of the thoracic region were excluded. The study group consisted of 82 pacemaker patients who underwent a total of 115 MRI examinations at 1.5T. To minimize radiofrequency-related lead heating, the specific absorption rate was limited to 1.5 W/kg. All pacemakers were reprogrammed before MRI: If heart rate was <60 bpm, the asynchronous mode was programmed to avoid magnetic resonance (MR)-induced inhibition; if heart rate was >60 bpm, sense-only mode was used to avoid MR-induced competitive pacing and potential proarrhythmia. Patients were monitored with ECG and pulse oximetry. All pacemakers were interrogated immediately before and after the MRI examination and after 3 months, including measurement of pacing capture threshold (PCT) and serum troponin I levels. All MR examinations were completed safely. Inhibition of pacemaker output or induction of arrhythmias was not observed. PCT increased significantly from pre- to post-MRI (P=0.017). In 2 of 195 leads, an increase in PCT was only detected at follow-up. In 4 of 114 examinations, troponin increased from a normal baseline value to above normal after MRI, and in 1 case (troponin pre-MRI 0.02 ng/mL, post-MRI 0.16 ng/mL), this increase was associated with a significant increase in PCT.Extrathoracic MRI of non-pacemaker-dependent patients can be performed with an acceptable risk-benefit ratio under controlled conditions and by taking both MR- and pacemaker-related precautions.
Thrombosis and Neointima Formation in Vein Grafts Are Inhibited by Locally Applied Aspirin Through Endothelial Protection
Authors: Evelyn Torsney, Ursula Mayr, Yiping Zou, W. Douglas Thompson, Yanhua Hu, Qingbo Xu
Journal: Circulation Research (2004)

Vein graft failure within the first month after bypass surgery is largely because of thrombosis. However, systemic study of thrombus formation in vein grafts is still lacking, and few effective techniques are available to prevent this event. Herein, we analyzed the kinetics of thrombosis and tested the effectiveness of locally applied aspirin on prevention of the disease in a mouse model. En face analysis of vein grafts revealed that 67±12% and 54±17% of the surface areas were covered by microthrombi at 1 and 3 days, respectively. Thrombus generation was also identified by labeling of platelets and fibrin, which occurred in 35 grafts examined at 1 and 3 days and 1, 2, 4, and 8 weeks. In a fifth of grafts, the thrombus occluded the vessel lumen by ≥1/4. Furthermore, a significant loss of endothelial cells was evidenced by β-gal staining for vein grafts in transgenic mice expressing LacZ gene controlled by TIE2-endothelial specific gene promoter. Following thrombosis, neointimal lesions were significantly increased by 4-fold 2 weeks after the operation. When vein grafts were treated locally with aspirin in pluronic gel-127, the thrombus area was significantly reduced ( P &lt;0.005) at 1, 4, and 8 weeks. Interestingly, neointimal lesions were markedly reduced in the local, but not oral, aspirin-treated group at 4 and 8 weeks by 50% to 70% ( P &lt;0.005). The mechanism of reduced lesions by locally applied aspirin involved the protection of vein graft endothelium. Thus, we provide strong evidence that thrombus formation occurs before the development of neointimal lesions in vein grafts and that local aspirin treatment successfully reduces vein graft arteriosclerosis through endothelial protection, resulting in reduction of thrombosis.
Social governance: a necessary third pillar of healthcare governance
Authors: Chris Bem
Journal: Journal of the Royal Society of Medicine (2010)

There are at present two pillars of governance in healthcare delivery today. These are financial governance and clinical governance. Health, however, has social, cultural, economic and environmental parameters,1,2 which at present play little substantive part in the theory and governance of healthcare delivery. Health services are also an important part of the economy. The economy gives structure to society, and so healthcare organization has an important influence on the values, relationships, security and aspirations of a society. I, therefore, propose that a third system of governance is introduced into healthcare, namely that of social governance.
Insulin receptor degradation is accelerated in cultured lymphocytes from patients with genetic syndromes of extreme insulin resistance.
Authors: A McElduff, J A Hedo, S I Taylor, J Roth, P Gorden
Journal: Journal of Clinical Investigation (1984)

Previous studies of the insulin receptor in disease states have utilized primarily techniques of equilibrium binding and, to a limited extent structural, analysis. Though techniques have been developed to study receptor degradation in normal cells, they have not been applied to disease states. In the present study we have examined insulin receptor degradation rate in B lymphocytes that were obtained from peripheral blood of normal subjects and patients with several syndromes of extreme insulin resistance. B lymphocytes were established in culture from each patient's peripheral cells by transformation with Epstein-Barr virus. The insulin receptors were surface labeled using Na125I/lactoperoxidase and the cells were returned to incubate in growth media. After varying periods of incubation, aliquots of cells were solubilized and the cell content of labeled receptor subunits were measured by immunoprecipitation with anti-receptor antibodies and NaDodSO4/polyacrylamide gel electrophoresis. The fall in 125I-insulin receptor content approximated a single exponential and was quantitated as receptor subunit half-life (t1/2). In cell lines from four patients in whom the number of insulin receptors was reduced by greater than 90%, the rate of receptor loss was greater than normal (t1/2 equals 3.8 +/- 0.9 h vs. 6.5 +/- 1.2 h; mean +/- SD, P less than 0.01). However, a similar acceleration in receptor degradation was seen in cells from five patients with extreme insulin resistance but low-normal insulin receptor concentration (t1/2 equals 4.4 +/- 0.9 h). This group included cells from one patient with a qualitatively abnormal receptor. Thus, all the patients with genetic syndromes of insulin resistance had accelerated receptor degradation, regardless of their receptor concentration. By contrast, insulin receptors on cultured lymphocytes that were obtained from patients with extreme insulin resistance secondary to autoantibodies to the insulin receptor had normal receptor degradation (t1/2 equals 6.1 +/- 1.9 h). We conclude that (a) accelerated insulin receptor degradation is an additional feature of cells from patients with genetic forms of insulin resistance; (b) that accelerated insulin receptor degradation may explain the low-normal receptor concentrations that were seen in some patients with extreme insulin resistance; and (c) that accelerated degradation does not explain the decreased receptor concentration in patients with very low insulin receptor binding and, therefore, by inference, a defect in receptor synthesis must be present in this subgroup.
British psychiatry and its discontents
Authors: Brian Cooper
Journal: Journal of the Royal Society of Medicine (2010)

Summary Psychiatry in the UK is currently faced with serious difficulties arising from failure in recruiting British doctors and a high rate of early retirement from the specialty. To diagnose the underlying causes, account must be taken of government policies affecting the NHS in general and mental health services in particular. The latter include an excessive run-down of acute hospital beds, as well as projects aimed at changing the clinical role of psychiatrists and promoting mass treatment of milder mental disorders by non-medical personnel. Psychiatrists have reacted to these developments with anger and dismay, but have as yet reached no consensus with regard to either causal factors or appropriate response. Their uncertainty reflects the need for a firmer grasp of the historical background. Modern British psychiatry was effectively created and moulded as an integral part of the NHS. It flourished as long as the public service framework remained intact, but has suffered a decline since the whole structure began to buckle under the pressure of sustained political assaults. A clearer understanding of this vital connection would help to raise psychiatrists' morale and encourage them to establish common ground with medical colleagues and other healthcare professionals.