tbuckley/cabot-search huggingface dataset:
Diagnosis of Creutzfeldt-Jakob disease by measurement of S100 protein in serum: prospective case-control study
Authors: M. Otto, J. Wiltfang, E. Schutz, I. Zerr, A. Otto, A. Pfahlberg, O. Gefeller, M. Uhr, A. Giese, T. Weber, H. A Kretzschmar, S. Poser
Journal: BMJ (1998)

<h3>Abstract</h3> Abstract <b>Objective:</b> To analyse serum concentrations of brain specific S100 protein in patients with Creutzfeldt-Jakob disease and in controls. <b>Design:</b> Prospective case-control study. <b>Setting</b>: National Creutzfeldt-Jakob disease surveillance unit. <b>Subjects:</b> 224 patients referred to the surveillance unit with suspected Creutzfeldt-Jakob disease and 35 control patients without dementia. <b>Main outcome measure:</b> Serum concentration of S100 protein in patients with Creutzfeldt-Jakob disease, in patients with other diseases causing dementia, and in the control group. <b>Results:</b> Of the 224 patients with suspected Creutzfeldt-Jakob disease, 65 were classed as definitely having the disease after neuropathological verification, an additional 6 were classed as definitely having the disease as a result of a genetic mutation, 43 as probably having the disease, 36 as possibly having the disease, and 74 patients were classed as having other disease. In the 108 patients classed as definitely or probably having Creutzfeldt-Jakob disease the median serum concentration of S100 was 395 pg/ml (SD 387 pg/ml). This was significantly higher than concentrations found in the 74 patients classed as having other diseases (median 109 pg/ml; SD 177 pg/ml; P=0.0001). At a cut off point of 213 pg/ml sensitivity for the diagnosis of the disease was 77.8% (95% confidence interval 68.8% to 85.2%) and specificity was 81.1% (70.3% to 89.3%). There was a significant difference in survival at different concentrations of S100 in Kaplan-Meier curves (P=0.023). <b>Conclusion:</b> Measurement of serum concentrations of S100 is a valuable tool which can be used more easily than tests on cerebrospinal fluid in the differential diagnosis of Creutzfeldt-Jakob disease. More studies are needed to determine whether serial testing of serum S100 improves diagnostic accuracy. <h3>Key messages</h3> Creutzfeldt-Jakob disease is a rare, fatal neurodegenerative disease. Diagnosis is made clinically and neuropathologically There is no serum test which allows the diagnosis to be made while the patient is alive In this study raised serum concentrations of S100 protein were found in patients with Creutzfeldt-Jakob disease Serum concentrations of S100 could be used with a sensitivity of 77.8% and a specificity of 81.1% to confirm Creutzfeldt-Jakob disease in the differential diagnosis of diseases that cause dementia Serial measurement of S100 concentrations will enhance diagnostic accuracy
A framework for the interpretation of de novo mutation in human disease
Authors: Kaitlin E Samocha, Elise B Robinson, Stephan J Sanders, Christine Stevens, Aniko Sabo, Lauren M McGrath, Jack A Kosmicki, Karola Rehnström, Swapan Mallick, Andrew Kirby, Dennis P Wall, Daniel G MacArthur, Stacey B Gabriel, Mark DePristo, Shaun M Purcell, Aarno Palotie, Eric Boerwinkle, Joseph D Buxbaum, Edwin H Cook, Richard A Gibbs, Gerard D Schellenberg, James S Sutcliffe, Bernie Devlin, Kathryn Roeder, Benjamin M Neale, Mark J Daly
Journal: Nature Genetics (2014)
The rate of molecular evolution of alpha-fetoprotein approaches that of pseudogenes.
Authors: P P Minghetti, S W Law, A Dugaiczyk
Journal: Molecular Biology and Evolution (1985)

We conducted the present study in an attempt to correlate function with the rate of molecular evolution for serum albumin and alpha-fetoprotein. We found a high rate of silent substitution (between 5 X 10(-9) and 7 X 10(-9)/site/year) for both the albumin and alpha-fetoprotein genes, perhaps the highest so far reported for an expressed nuclear gene. The rates of effective substitution and amino acid changes were also very high, but in contrast to silent substitutions, they are higher for alpha-fetoprotein than for albumin by approximately 70%. For alpha-fetoprotein, the rate of effective substitution (1.5 X 10(-9)/site/year) may be approaching that for nonfunctional pseudogenes (about 3 X 10(-9)/site/year). Evolutionary divergence was also estimated at the amino acid level. It was found that the rate of change of alpha-fetoprotein (55% amino acids replaced in 100 Myr) approaches that of the fastest-evolving fibrinopeptides (92% amino acids replaced in 100 Myr). This high rate may indicate that alpha-fetoprotein can tolerate a great deal of molecular variation without its function being impaired in the process. Albumin evolves at a slower rate (39% amino acids replaced in 100 Myr), although still faster than either hemoglobin (17% amino acids replaced in 100 Myr) or cytochrome c (5% amino acids replaced in 100 Myr). The slower evolutionary rate may indicate that albumin has more refined functional specifications and hence can tolerate fewer mutational changes. The latter conclusion remains, however, to be reconciled with the condition of inherited analbuminemia, where a virtually complete absence of albumin produces surprisingly few symptoms.
Reduced dose salbutamol in comparison with standard dosage for symptom relief in asthma
Authors: DH Yates, MJ Peters, V Keatings, PS Thomas, PJ Barnes
Journal: European Respiratory Journal (1995)

Regular treatment with beta 2-agonists has been reported to be associated with an increase in risk of asthma death or near death, and with a deterioration in asthma symptom control. Low-dose beta 2-agonists provide effective bronchodilatation and bronchoprotection, even though maximal bronchodilatation is not achieved, and they may offer a better safety profile. In a double-blind, randomized,, cross-over study, we evaluated the efficacy of low-dose salbutamol metered-dose inhaler (50 micrograms.puff-1), used over a period of 2 weeks, compared with a standard dose (100 micrograms.puff-1) in control of asthma symptoms in 20 moderately severe asthmatic subjects using inhaled glucocorticosteroid therapy. Asthma control was assessed by symptom scores, peak flow rates, spirometry, inhaler usage and, where possible, by bronchial responsiveness to methacholine. Despite a 46% reduction in mean weekly salbutamol dosage, mean forced expiratory volume in one second (FEV1), morning and evening peak expiratory flow (PEF), PEF variability, dose of methacholine provoking a 20% decrease in FEV1 (PC20) (n=9), and symptom scores showed no difference between low-dose and standard inhaler treatment periods. Low-dose inhaler administration resulted in a small but significant increase in number of inhaler actuations. Low-dose salbutamol metered-dose inhaler may, thus, be useful for control of symptoms in moderately severe asthma. This strategy could be used to achieve a reduction in total beta 2-agonist usage, which may minimize any potential for adverse effects.
Once-Daily Fluticasone Furoate∗ Nasal Spray (FFNS) 110mcg Improves Quality of Life (QoL) in Subjects with Seasonal Allergic Rhinitis (SAR) during the ragweed season ∗USAN approved name
Authors: J. Given, T. Toler, A. Ellsworth, R. Stanford, E. Philpot
Journal: Journal of Allergy and Clinical Immunology (2007)
A Phase 0 Trial of Riluzole in Patients with Resectable Stage III and IV Melanoma
Authors: Dana Yip, Maithao N. Le, Joseph L.-K. Chan, Jonathan H. Lee, Janice A. Mehnert, Anthony Yudd, Jeffery Kempf, Weichung J. Shih, Suzie Chen, James S. Goydos
Journal: Clinical Cancer Research (2009)

Ectopic expression of GRM1 in murine melanocytes results in transformation into a form of melanoma, and more than 60% of human melanoma samples tested ectopically express GRM1. Stimulation of this receptor in vitro results in up-regulation of activated extracellular signal-regulated kinase (ERK). Furthermore, a xenograft model of melanoma treated with riluzole, an oral GRM1 blocking agent, showed decreased tumor growth compared with the untreated controls. We have now completed a phase 0 trial of riluzole in patients with melanoma.Patients enrolled on this trial underwent a pretreatment biopsy, took 200 mg of oral riluzole per day for 14 days, and then underwent resection of their remaining tumor. We compared the levels of pERK and pAKT in the pretreatment and post-treatment samples and assessed the metabolic activity of pretreatment and post-treatment tumors using fluorodeoxyglucose positron emission tomography (FDG-PET) scanning.We accrued 12 patients and all expressed GRM1. We found a significant decrease in pAKT and/or pERK in post-treatment tumor samples as compared with pretreatment samples in 4 (34%) patients. These four patients had a significant decrease in FDG-PET intensity post-treatment as well. Two other patients had a clinical response with no corresponding metabolic response; five patients had similar pretreatment and post-treatment FDG-PET scan findings; and one patient had progressive disease.Our data show that glutamate blockade with riluzole can inhibit signaling through the mitogen-activated protein kinase and phosphatidylinositol 3-kinase/AKT pathways and suppress the metabolic activity of melanoma. The ectopic expression of metabotropic glutamate receptors may be important in the pathogenesis of human melanoma, and targeting this pathway may be an effective therapy.
Degraded conditions: Confounds in the study of decision making
Authors: Louise Antony
Journal: Behavioral and Brain Sciences (2014)

Abstract I raise a consideration complementary to those raised in the target article. Many of the most widely cited studies on decision making involve introspection in degraded conditions, namely, conditions in which agents have no reason for the decisions they reach. But the fact that confabulation occurs in degraded conditions does not impugn the reliability of introspection in non-degraded conditions, that is, in cases in which a subject actually does make a choice for a reason.
STUDIES ON THE PHYSIOLOGY OF THE PARATHYROID GLANDS
Authors: Fuller Albright, Read Ellsworth
Journal: Journal of Clinical Investigation (1929)

In order to determine, if possible, the exact train of events which lead to a rise in the serum calcium following the injection of a potent parathyroid extract, we undertook the present series of investigations. The subject of this study was an Italian boy on whom the diagnosis of idiopathic hypoparathyroidism was made. The criteria on which such a diagnosis can be based will be discussed below. The injection of a potent parathyroid extract results in four wellestablished changes and any theory as to the action of a parathyroid extract will have to take cognizance of these four cardinal points. They are: a. Rise in serum calcium (1). b. Rise in urinary calcium excretion (2) (3) (4). c. Fall in serum phosphorus (5). d. Rise in urinary phosphorus excretion (2) (3). Removal of the parathyroid glands results in the converse changes, i.e., a. Fall in the serum calcium. b. Fall in the urinary calcium excretion. c. Rise in the serum phosphorus. d. Fall in urinary phosphorus excretion. In addition Albright, Bauer, Ropes, and Aub (3) emphasize the fact that on administration of parathormone, the increase in urinary phosphorus excretion tends to precede the increase in calcium excretion. They further point out that the increased phosphorus appearing in
Suppression of ventricular arrhythmias in man by d-propranolol independent of beta-adrenergic receptor blockade.
Authors: K T Murray, C Reilly, R P Koshakji, D M Roden, M D Lineberry, A J Wood, L A Siddoway, J T Barbey, R L Woosley
Journal: Journal of Clinical Investigation (1990)

To investigate the mechanisms of ventricular arrhythmia suppression by propranolol, we determined the antiarrhythmic efficacy of d-propranolol in 10 patients with frequent ventricular ectopic depolarizations (VEDs) and nonsustained ventricular tachycardia. After an initial placebo phase, 40 mg d-propranolol was administered orally every 6 h with dosage increased every 2 d until arrhythmia suppression (greater than or equal to 80% VED reduction), intolerable side effects, or a maximal dosage (1,280 mg/d) was reached. Response was verified by documenting return of arrhythmia during a final placebo phase. Arrhythmia suppression occurred in six patients while two more had partial responses. Effective dosages were 320-1,280 mg/d (mean 920 +/- 360, SD) of d-propranolol with corresponding plasma concentrations of 60-2,280 ng/ml (mean 858 +/- 681). For the entire group, the QTc interval shortened by 4 +/- 4% (P = 0.03). Arrhythmia suppression was accompanied by a reduction in peak heart rate during exercise of 0-29%. To determine whether arrhythmia suppression could be attributed to beta-blockade, racemic propranolol was then administered in dosages producing the same or greater depression of exercise heart rate. In 3/8 patients, arrhythmias were not suppressed by racemic propranolol indicating that d-propranolol was effective via a non-beta-mediated action. By contrast, in 5/8 patients racemic propranolol also suppressed VEDs. We conclude that propranolol suppresses ventricular arrhythmias by both beta- and non-beta-adrenergic receptor-mediated effects.
Dissecting the Molecular Relationship Among Various Cardiogenic Progenitor Cells
Authors: Devaveena Dey, Leng Han, Michael Bauer, Fumihiro Sanada, Angelos Oikonomopoulos, Toru Hosoda, Kazumasa Unno, Patricia De Almeida, Annarosa Leri, Joseph C. Wu
Journal: Circulation Research (2013)

Multiple progenitors derived from the heart and bone marrow (BM) have been used for cardiac repair. Despite this, not much is known about the molecular identity and relationship among these progenitors. To develop a robust stem cell therapy for the heart, it is critical to understand the molecular identity of the multiple cardiogenic progenitor cells.This study is the first report of high-throughput transcriptional profiling of cardiogenic progenitor cells carried out on an identical platform.Microarray-based transcriptional profiling was carried out for 3 cardiac (ckit(+), Sca1(+), and side population) and 2 BM (ckit(+) and mesenchymal stem cell) progenitors, obtained from age- and sex-matched wild-type C57BL/6 mice. Analysis indicated that cardiac-derived ckit(+) population was very distinct from Sca1(+) and side population cells in the downregulation of genes encoding for cell-cell and cell-matrix adhesion proteins, and in the upregulation of developmental genes. Significant enrichment of transcripts involved in DNA replication and repair was observed in BM-derived progenitors. The BM ckit(+) cells seemed to have the least correlation with the other progenitors, with enrichment of immature neutrophil-specific molecules.Our study indicates that cardiac ckit(+) cells represent the most primitive population in the rodent heart. Primitive cells of cardiac versus BM origin differ significantly with respect to stemness and cardiac lineage-specific genes, and molecules involved in DNA replication and repair. The detailed molecular profile of progenitors reported here will serve as a useful reference to determine the molecular identity of progenitors used in future preclinical and clinical studies.
Genes regulating lymphangiogenesis control venous valve formation and maintenance in mice
Authors: Eleni Bazigou, Oliver T.A. Lyons, Alberto Smith, Graham E. Venn, Celia Cope, Nigel A. Brown, Taija Makinen
Journal: Journal of Clinical Investigation (2011)

Chronic venous disease and venous hypertension are common consequences of valve insufficiency, yet the molecular mechanisms regulating the formation and maintenance of venous valves have not been studied. Here, we provide what we believe to be the first description of venous valve morphogenesis and identify signaling pathways required for the process. The initial stages of valve development were found to involve induction of ephrin-B2, a key marker of arterial identity, by venous endothelial cells. Intriguingly, developing and mature venous valves also expressed a repertoire of proteins, including prospero-related homeobox 1 (Prox1), Vegfr3, and integrin-α9, previously characterized as specific and critical regulators of lymphangiogenesis. Using global and venous valve-selective knockout mice, we further demonstrate the requirement of ephrin-B2 and integrin-α9 signaling for the development and maintenance of venous valves. Our findings therefore identified molecular regulators of venous valve development and maintenance and highlighted the involvement of common morphogenetic processes and signaling pathways in controlling valve formation in veins and lymphatic vessels. Unexpectedly, we found that venous valve endothelial cells closely resemble lymphatic (valve) endothelia at the molecular level, suggesting plasticity in the ability of a terminally differentiated endothelial cell to take on a different phenotypic identity.
Taking an 'ethics history' * Authors' reply
Authors: G. M Sayers
Journal: Journal of the Royal Society of Medicine (2005)

Examining the potential impact of the proposed two-year cut in otology training, Jaydip Ray and colleagues conclude that intensification of training would be necessary to eradicate the significant difference in specialist surgical experience between current year-four and year-six otology trainees (June 2005 JRSM 1 ).In our opinion their article misses the point regarding the changes.The proposed model of four years' general training followed by two years of specialist training will not require future year-four trainees to have comparable operative experience to today's year-six trainees, as implied.The Specialist Advisory Committee for Otolaryngology has set stage-specific criteria of required operative competencies for higher surgical trainees. 2Georgalas et al., 3 in a recent survey of otolaryngology trainees, concluded that all stage-specific criteria were currently being met, and that training standards were satisfactory across the UK.They concluded that current training is adequate and that a system of twotier trainees, with four years of general training and two years devoted to the subspecialties, would be an adequate option for the vast majority of specialist registrars, provided that current standards are maintained. 2 Training in specialist otological surgery will not be offered or assessed in the new four-year 'generalist' higher surgical rotations, since specialist experience will be gained in accredited otology fellowships for prospective otologists.
Implementation of NCCN Distress Management Guidelines by Member Institutions
Authors: Paul B. Jacobsen, Sean Ransom
Journal: Journal of the National Comprehensive Cancer Network (2007)

Up to half of all adults with cancer experience clinically significant psychological distress and much of this distress goes unrecognized and untreated. As part of an effort to improve the care of cancer patients, the National Comprehensive Cancer Network (NCCN) has developed clinical practice guidelines for distress management that include recommendations about the evaluation and treatment of distress. These authors conducted a study to evaluate the implementation of these distress management guidelines by NCCN member institutions. The NCCN member institutions that treat adults were asked in April and May 2005 to describe their distress management practices, and 15 (83%) provided responses. Of these, 8 (53%) conduct routine distress screening for at least some patient groups, with 4 additional institutions (27%) pilot-testing screening strategies. However, only 20% of surveyed member institutions screened all patients as the guidelines recommend. In addition, whether institutions that conduct routine distress screening do so through standardized assessment methods is unclear, because 37.5% of institutions that conduct screening rely only on interviews to identify distressed patients. Findings suggest that most institutions consider screening patients' mental health concerns important and worthwhile, but that greater implementation of guideline recommendations is needed.
Effects of St. John's Wort on Irinotecan Metabolism
Authors: R. H. J. Mathijssen
Journal: JNCI Journal of the National Cancer Institute (2002)

St. John's wort (SJW), a widely used herbal product, has been implicated in drug interactions resulting from the induced expression of the cytochrome P450 CYP3A4 isoform. In this study, we determined the effect of SJW on the metabolism of irinotecan, a pro-drug of SN-38 and a known substrate for CYP3A4. Five cancer patients were treated with irinotecan (350 mg/m2, intravenously) in the presence and absence of SJW (900 mg daily, orally for 18 days) in an unblinded, randomized crossover study design. The plasma levels of the active metabolite SN-38 decreased by 42% (95% confidence interval [CI] = 14% to 70%) following SJW cotreatment with 1.0 μM × h (95% CI = 0.34 μM × h to 1.7 μM × h) versus 1.7 μM × h (95% CI = 0.83 μM × h to 2.6 μM × h) (P = .033, two-sided paired Student's t test). Consequently, the degree of myelosuppression was substantially worse in the absence of SJW. These findings indicate that patients on irinotecan treatment should refrain from taking SJW because plasma levels of SN-38 were dramatically reduced, which may have a deleterious impact on treatment outcome.
Bronchiectasis caused by pulmonary tuberculosis: The epidemiology, clinical presentations and the differences from non-tuberculosis-caused bronchiectasis
Authors: Jin-Fu Xu, Xiao-Bing Ji, Hui-Ping Li, Hai-Wen Lu, Ke Fei, Li-Hong Fan, Jie-Ming Qu
Journal: European Respiratory Journal (2013)

RATIONALE  Because of the highest absolute numbers of tuberculosis (TB) patients (Lange C, et al. Eur Respir J. 2010;36:714), the number of hospitalization of bronchiectasis patients caused by TB was growing fast in China.  METHODS  We retrospectively reviewed the records of 6977 patients with bronchiectasis in 17 years in the largest single center. Follow-up have done only on patients from 2009 to 2011.  RESULTS  Adult patients who diagnosed as bronchiectasis at the hospital between 1995 and 2011 were recruited to this study. The amount of hospitalized patients with bronchiectasis in 2011 was 9.3 fold of that in 1995. The number was increase very fast during the seventeen years. The data tallied with the situation of pulmonary TB in China. 69.21% (4892 in 6977) patients were original from countryside. The main causes of bronchiectasis were pulmonary TB (31.17%), bacterial infection and pertussis. The peak age ranges of post-TB bronchiectasis were 30 to 39 and 60 to 69. Patients with post-TB bronchiectasis prone to have haemoptysis but less sputum. The X ray of patients with post-TB bronchiectasis represented upper lobes injury of the lung. Less pseudomonas aeruginosa culture positive and less acute exacerbation were recorded in post-TB bronchiectasis patients from the data of available follow-up patients.  CONCLUSIONS  The main cause of bronchiectasis in China was pulmonary TB, possiblely because of the grim pulmonary TB epidemic situation. Post-TB bronchiectasis patients have marked different clinical features and prognosis, compared with non-TB bronchiectasis.