tbuckley/cabot-search huggingface dataset:
Uricolysis in Normal and Gouty Individuals
Authors: E. J. Bien, M. Zucker
Journal: Annals of the Rheumatic Diseases (1955)

<b>Introduction:</b> Cough and airway irritation are adverse effects (AEs) associated with inhaled treprostinil (TRE). The site of action causing these AEs is unknown. <b>Aim:</b> Nebulized TRE, at a concentration that causes cough in guinea pigs, was administered to the isolated laryngeal airway of rats and guinea pigs to determine if the actions of TRE involved activation of laryngeal reflexes. <b>Methods:</b> The laryngeal airway was isolated in anesthetized male Sprague Dawley rats and Dunkin Hartley guinea pigs for administration (20 sec) of either nebulized TRE (30 µg/mL), citric acid (CA), hypertonic saline (HS) or phosphate buffered saline (PBS). Pulmonary airflow and expiratory duration (T<sub>E</sub>) were measured with a pneumotachograph connected to a tracheal catheter. The apneic index (T<sub>E</sub> post-challenge/T<sub>E</sub> pre-challenge), mean arterial blood pressure (MAP), heart rate (HR), arterial oxygen saturation (SaO<sub>2</sub>) and the number of swallows were measured before and after drugs. <b>Results:</b> In rats, nebulized CA (0, 0.01, 0.1 and 1 M) increased the apneic index (1, 32, 90, 101, respectively), MAP and swallowing and decreased SaO<sub>2</sub> and HR. Similar effects occurred with nebulized HS (1.5, 3, 5 and 7 %). However, nebulized TRE (30 µg/mL), like nebulized PBS had no effects. In guinea pigs, nebulized CA (0, 0.1 and 1 M) increased the apneic index (2, 3 and 15, respectively) and produced cough and swallowing. Nebulized TRE (30 µg/mL) had no effects. <b>Conclusions:</b> These results demonstrate that nebulization of TRE to the laryngeal airway of rats and guinea pigs does not produce cough and airway irritation and suggest that sites more distal in the tracheobronchial tree and lung are involved.
Some Functions of a Scientific Journal
Authors: JULIUS H. COMROE
Journal: Circulation Research (1966)

Crisis in Communication 1 has divided scientific journals into two classes-those that are primarily newspapers and those that serve as permanent records of scientific achievement.Circulation Research is primarily a journal that presents today and records permanently new achievements in cardiovascular science.Therefore, the first function of Circulation Research is to achieve and maintain excellence in its class.According to Wiggers, 2 "Success or failure of a journal to achieve its ideals ... is determined fundamentally by its contributors."According to Landis, s "The excellence of a journal depends fundamentally on the standards adhered to by each member of the Editorial Board."Both are correct.A scientific journal achieves excellence only when the articles published in it present important new advances in basic understanding in the field.This occurs in two steps.The first is when the editorial board, by its review and priority system, indicates to the scientific community that the board has high standards and will not recommend for acceptance articles that have been published in part or in whole elsewhere, or represent minor variations on a larger theme, or reconfirm well-established knowledge, or are incomplete or not well documented.The second step occurs when scientists consider that the acceptance of their research by this editorial board is at least a minor distinction and consequently submit to it only their very best effort.Dr. Landis (see page 1) and his board, continuing the work of Dr. Carl Wiggers and then of Dr. Carl Schmidt, have brought Circulation Research to this enviable position and have achieved the first function of this journal.My role is to maintain the present excellence and, when possible, to develop other functions of a journal.A second important function of any journal is that it be maximally useful to its readers.This requires identifying what the majority of readers want.Most readers, I believe, agree that certain matters are desirable.Two of these are prompt publication of completed research and saving the readers' time.
A mutation in the leptin receptor is associated with Entamoeba histolytica infection in children
Authors: Priya Duggal, Xiaoti Guo, Rashidul Haque, Kristine M. Peterson, Stacy Ricklefs, Dinesh Mondal, Faisal Alam, Zannatun Noor, Hans P. Verkerke, Chelsea Marie, Charles A. Leduc, Streamson C. Chua, Martin G. Myers, Rudolph L. Leibel, Eric Houpt, Carol A. Gilchrist, Alan Sher, Stephen F. Porcella, William A. Petri
Journal: Journal of Clinical Investigation (2011)

Malnutrition substantially increases susceptibility to Entamoeba histolytica in children. Leptin is a hormone produced by adipocytes that inhibits food intake, influences the immune system, and is suppressed in malnourished children. Therefore we hypothesized that diminished leptin function may increase susceptibility to E. histolytica infection. We prospectively observed a cohort of children, beginning at preschool age, for infection by the parasite E. histolytica every other day over 9 years and evaluated them for genetic variants in leptin (LEP) and the leptin receptor (LEPR). We found increased susceptibility to intestinal infection by this parasite associated with an amino acid substitution in the cytokine receptor homology domain 1 of LEPR. Children carrying the allele for arginine (223R) were nearly 4 times more likely to have an infection compared with those homozygous for the ancestral glutamine allele (223Q). An association of this allele with amebic liver abscess was also determined in an independent cohort of adult patients. In addition, mice carrying at least 1 copy of the R allele of Lepr were more susceptible to infection and exhibited greater levels of mucosal destruction and intestinal epithelial apoptosis after amebic infection. These findings suggest that leptin signaling is important in mucosal defense against amebiasis and that polymorphisms in the leptin receptor explain differences in susceptibility of children in the Bangladesh cohort to amebiasis.
Acute sports injuries in Oslo: a one-year study.
Authors: S. Maehlum, O. A. Daljord
Journal: British Journal of Sports Medicine (1984)

All sport injuries treated at the Emergency Department, Ullevål Hospital in Oslo (OKL) were registered for one year. They accounted for 6.3% of the total number of patients treated at OKL in that period. 4673 patients were seen; 3292 males and 1381 females. The women were younger than the men, 55% were below 20 years of age; 41% of the males (p less than 0.05). Most of the men (64%) were injured in connection with competitive sports, but 52% of the women sustained their injury pursuing recreational sports. Football and skiing accounted for 49% of the total number of injuries. In males football caused most injuries--35%. In females handball accounted for most injuries--18%. Nearly 3/4 of the injuries affected the extremities; the most common injury being the ankle sprain (16%). Almost 1/4 of the patients had a fracture, and 218 patients (4.7%) were admitted to hospital, the rest being treated as outpatients. In all, the sports injuries required 7658 consultations.
Early and Vigorous Fluid Resuscitation Prevents Acute Renal Failure in the Crush Victims of Catastrophic Earthquakes
Authors: Ali Ihsan Gunal, Huseyin Celiker, Ayhan Dogukan, Goksel Ozalp, Ercan Kirciman, Huseyin Simsekli, Izzettin Gunay, Mustafa Demircin, Oktay Belhan, Mustafa A Yildirim, Mehmet S Sever
Journal: Journal of the American Society of Nephrology (2004)

This study analyzes the effects of fluid resuscitation in the crush victims of the Bingol earthquake, which occurred in May 2003 in southeastern Turkey. Questionnaires asking about demographic, clinical, laboratory, and therapeutic features of 16 crush victims were filled in retrospectively. Mean duration under the rubble was 10.3 +/- 7 h, and all patients had severe rhabdomyolysis. Fourteen patients were receiving isotonic saline at admission, which was followed by mannitol-alkaline fluid resuscitation. All but two patients were polyuric. Admission serum creatinine level was lower than and higher than 1.5 mg/dl in 11 and 5 patients, respectively. Marked elevations were noted in muscle enzymes in all patients. During the clinical course, hypokalemia was observed in nine patients, all of whom needed energetic potassium chloride replacement. Four (25%) of 16 victims required hemodialysis. Duration between rescue and initiation of fluids was significantly longer in the dialyzed victims as compared with nondialyzed ones (9.3 +/- 1.7 versus 3.7 +/- 3.3 h, P < 0.03). Sixteen fasciotomies were performed in 11 patients (68%), nine of which were complicated by wound infections. All patients survived and were discharged from the hospital with good renal function. Early and vigorous fluid resuscitation followed by mannitol-alkaline diuresis prevents acute renal failure in crush victims, resulting in a more favorable outcome.
No significant improvement in the outcome of patients with Waldenström's macroglobulinemia treated over the last 25 years
Authors: Efstathios Kastritis, Marie‐Christine Kyrtsonis, Evdoxia Hatjiharissi, Argiris Symeonidis, Eurydiki Michalis, Panagiotis Repoussis, Konstantinos Tsatalas, Michael Michael, Anastasia Sioni, Zafiris Kartasis, Ekaterini Stefanoudaki, Michael Voulgarelis, Sosana Delimpasi, Maria Gavriatopoulou, Efstathios Koulieris, Dimitra Gika, Elissavet Vervesou, Konstantinos Konstantopoulos, Garyfalia Kokkini, Athanasios Zomas, Paraskevi Roussou, Nikolaos Anagnostopoulos, Theofanis Economopoulos, Evangelos Terpos, Konstantinos Zervas, Meletios A. Dimopoulos
Journal: American Journal of Hematology (2011)

The treatment of Waldenström's macroglobulinemia (WM) has changed over the last decades, mainly because of the introduction of nucleoside analogues and of rituximab while novel agents such as bortezomib have been recently introduced. We performed an analysis to investigate whether the outcome of patients with WM has improved over the last years, compared to that of patients who started treatment before new drugs became widely available, especially as part of the frontline treatment. We analyzed 345 symptomatic patients with WM: 130 who initiated treatment before and 215 who started treatment after January 1, 2000. Patients who started treatment in the latter group were older and had more often elevated beta2-microglobulin but the other characteristics were similar between the two groups. Most patients who started treatment before January 1, 2000 were treated upfront with alkylating agent-based regimens and most patients who started treatment after January 1, 2000 received rituximab-based regimens as initial treatment. Objective response (63 and 59%, respectively) and median overall survival, OS, (106.5 months for Group A and is estimated at 94 months for Group B, P = 0.327) were similar. There was also no difference regarding OS or cause specific survival (CSS) in each risk group according to IPSSWM. Our observation may be explained by the indolent course of WM in several patients and by the lack of profound cytoreduction in patients with high-risk disease. Possible differences in the 15- or 20-year survival rate between the two groups may be detected with further follow-up of these patients.
N-acetylcysteine prevents cigarette smoke induced small airways alterations in rats
Authors: M.L. Rubio, M.V. Sanchez-Cifuentes, M. Ortega, G. Peces-Barba, J.D. Escolar, S. Verbanck, M Paiva, N Gonzalez Mangado
Journal: European Respiratory Journal (2000)

This study investigated the effect of cigarette smoke exposure and the potential protection N-acetylcysteine (NAC) in rat lungs. Forty-eight rats were exposed to cigarette smoke (CS) for 10 weeks, without (CS group) or with (CS+NAC group) oral intake of NAC 200 mg x rat(-1) x day(-1), or to fresh air (Control). All rat lungs were assessed in terms of lung function, ventilation distribution (nitrogen, helium and sulphur hexafluoride phase III slopes), and morphometry (airway wall thickening of small, medium and large bronchi). The small bronchi, defined as the airways with an internal perimeter &lt;1,000 microm showed significantly thicker airway walls in the CS than in the Control group. By contrast, no airway wall thickening was observed in the CS+NAC group with respect to Control. Except for decreased lung volumes and compliance in CS and CS+NAC groups, which were entirely attributable to smaller body weight gain, lung function was indistinguishable from Control. Phase III slopes were significantly increased only in the CS group. In conclusion, smoke-induced alterations in the rat lungs were reflected in wall thickening of the small bronchi and increased ventilation maldistribution. These smoke-induced morphometric and ventilation distribution alterations were prevented by N-acetylcysteine.
Liver-Enriched Transcription Factors in Liver Function and Development. Part II: the C/EBPs and D Site-Binding Protein in Cell Cycle Control, Carcinogenesis, Circadian Gene Regulation, Liver Regeneration, Apoptosis, and Liver-Specific Gene Regulation
Authors: Harald Schrem, Jürgen Klempnauer, Jürgen Borlak
Journal: Pharmacological Reviews (2004)

In the first part of our review (see <i>Pharmacol Rev</i> 2002;54:129-158), we discussed the basic principles of gene transcription and the complex interactions within the network of hepatocyte nuclear factors, coactivators, ligands, and corepressors in targeted liver-specific gene expression. Now we summarize the role of basic region/leucine zipper protein family members and particularly the albumin D site-binding protein (DBP) and the CAAT/enhancer-binding proteins (C/EBPs) for their importance in liver-specific gene expression and their role in liver function and development. Specifically, regulatory networks and molecular interactions were examined in detail, and the experimental findings summarized in this review point to pivotal roles of DBP and C/EBPs in cell cycle control, carcinogenesis, circadian gene regulation, liver regeneration, apoptosis, and liver-specific gene regulation. These regulatory proteins are therefore of great importance in liver physiology, liver disease, and liver development. Furthermore, interpretation of the vast data generated by novel genomic platform technologies requires a thorough understanding of regulatory networks and particularly the hierarchies that govern transcription and translation of proteins as well as intracellular protein modifications. Thus, this review aims to stimulate discussions on directions of future research and particularly the identification of molecular targets for pharmacological intervention of liver disease.
Continuous positive airway pressure does not reduce blood pressure in nonsleepy hypertensive OSA patients
Authors: G. V. Robinson
Journal: European Respiratory Journal (2006)

Obstructive sleep apnoea (OSA) is associated with high cardiovascular morbidity and mortality. Several randomised controlled trials have shown that continuous positive airway pressure (CPAP) treatment of OSA reduces blood pressure (BP). This randomised, sham-placebo controlled crossover trial assesses whether CPAP produces a similar clinically significant fall in BP in hypertensive OSA patients, but without hypersomnolence. Thirty-five, nonsleepy, hypertensive patients with OSA were treated with CPAP for 1 month, randomised first to either therapeutic or sham-placebo (subtherapeutic CPAP, about 1 cmH<sub>2</sub>O pressure). The second months9 alternative treatment followed a 2-week washout period. BP was measured over 24 h, before and at the end of the two treatment periods: mean 24-h BP was the primary outcome variable. There was no overall significant difference in mean 24-h BP: the change in mean 24-h BP on therapeutic CPAP was -2.1 mmHg (sd 8.1), and -1.1 mmHg (sd 8.1) on subtherapeutic CPAP, with a difference of 0.7 mmHg (95% confidence interval (CI) +2.9– -4.4). There was a small significant fall in Epworth Sleepiness Score, therapeutic (-1.4) <i>versus</i> sham (-0.3), and difference -1.2 (95% CI -2.0– -0.4), but no change in objective sleepiness. In nonhypersomnolent hypertensive patients with obstructive sleep apnoea, there is no significant fall in mean 24-h blood pressure with continuous positive airway pressure, in contrast to the fall seen in hypersomnolent patients with obstructive sleep apnoea.
A–Z of nutritional supplements: dietary supplements, sports nutrition foods and ergogenic aids for health and performance–Part 20
Authors: K Currell, W Derave, I Everaert, L McNaughton, G Slater, L M Burke, S J Stear, L M Castell
Journal: British Journal of Sports Medicine (2011)

As usual, the alphabet throws together a mixture of supplements with different levels of popularity and scientific support. Part 20 covers some rarely reported, studied and/or little used supplements in sport: glycine, histidine and inosine. The majority of human studies of supplementation with the essential amino acid histidine has involved clinical work. In terms of athletic performance, there is current interest in supplementation strategies to increase muscle content of the histidine-containing dipeptide (HCD), carnosine. Despite some interest in the use of a chicken breast extract (CBEX) described in this article, most of the focus in this area involves β-alanine supplementation (covered in part 5). There was some interest in inosine as an ergogenic aid in the 1990s but it appears not to have been studied since then. Meanwhile, there appears little role for glycine supplementation in sport although some interest in glycine-containing compounds is possible. β-Hydroxymethyl β-butyrate (HMB) is much more well known, with marketing usually targeting bodybuilders.

### K Currell

Glycine is the smallest amino acid; it is non-essential and can be synthesised from serine. Glycine is present in most proteins and is particularly highly concentrated in collagen. Consequently, one of the highest food sources of glycine is gelatin. Glycine is also one of the three amino acid components of glutathione, which is a key component of the body's defences against oxidative stress; however, it is thought that glycine availability is not the limiting step in glutathione synthesis. Glycine ingestion increases plasma concentrations of insulin in a similar way to other amino acids.1 Glycine is also an inhibitory neurotransmitter.

There is little research on supplementation with glycine. Research has looked at its potential role in decreasing inflammation.2 Sport specific research has focused on combining glycine with other nutrients. Glycine-propionyl-L-carnitine (GPLC) has been shown to influence exercise performance,3 decrease oxidative …
Thin Basement Membrane Nephropathy
Authors: Karl Tryggvason, Jaakko Patrakka
Journal: Journal of the American Society of Nephrology (2006)

Thin basement membrane nephropathy (TBMN) is the most common cause of persistent hematuria in children and adults, the other main causes being IgA nephropathy and Alport syndrome ([1][1]–[3][2]). In addition to hematuria, patients with TBMN usually have minimal proteinuria, normal renal function,
Disruption of Scaffold Attachment Factor B1 Leads to TBX2 Up-regulation, Lack of p19ARF Induction, Lack of Senescence, and Cell Immortalization
Authors: Klaudia M. Dobrzycka, Kaiyan Kang, Shiming Jiang, Rene Meyer, Pulivarthi H. Rao, Adrian V. Lee, Steffi Oesterreich
Journal: Cancer Research (2006)

Scaffold attachment factor B1 (SAFB1) is a multifunctional protein, which has previously been implicated in breast cancer. Here, we show that genetic deletion of SAFB1 in mouse embryonic fibroblasts (MEF) leads to spontaneous immortalization and altered expression of two proteins involved in immortalization and escape from senescence: low levels of p19(ARF) and high levels of TBX2. Inactivation of TBX2 using a dominant-negative TBX2 resulted in up-regulation of p19(ARF) in SAFB1 knockout MEFs. SAFB1 loss also caused lack of contact inhibition, increased foci formation, and increased oncogene-induced anchorage-independent growth. These findings suggest that SAFB1 is a novel player in cellular immortalization and transformation.
Clinical Outcome of the ACCORD 12/0405 PRODIGE 2 Randomized Trial in Rectal Cancer
Authors: Jean-Pierre Gérard, David Azria, Sophie Gourgou-Bourgade, Isabelle Martel-Lafay, Christophe Hennequin, Pierre-Luc Etienne, Véronique Vendrely, Eric François, Guy de La Roche, Olivier Bouché, Xavier Mirabel, Bernard Denis, Laurent Mineur, Jean-François Berdah, Marc-André Mahé, Yves Bécouarn, Olivier Dupuis, Gérard Lledo, Jean-François Seitz, Laurent Bedenne, Béata Juzyna, Thierry Conroy
Journal: Journal of Clinical Oncology (2012)

The ACCORD 12 trial investigated the value of two different preoperative chemoradiotherapy (CT-RT) regimens in T3-4 Nx M0 resectable rectal cancer. Clinical results are reported after follow-up of 3 years.Between November 2005 and July 2008, a total of 598 patients were randomly assigned to preoperative CT-RT with CAP45 (45-Gy RT for 5 weeks with concurrent capecitabine) or CAPOX50 (50-Gy RT for 5 weeks with concurrent capecitabine and oxaliplatin). Total mesorectal excision was planned 6 weeks after CT-RT. The primary end point was sterilization of the operative specimen, which was achieved in 13.9% versus 19.2% of patients, respectively (P = .09). Clinical results were analyzed for all randomly assigned patients according to the intention-to-treat principle.At 3 years, there was no significant difference between CAP45 and CAPOX50 (cumulative incidence of local recurrence, 6.1% v 4.4%; overall survival, 87.6% v 88.3%; disease-free survival, 67.9% v 72.7%). Grade 3 to 4 toxicity was reported in four patients in the CAP45 group and in two patients in the CAPOX50 group. Bowel continence, erectile dysfunction, and social life disturbance were not different between groups. In multivariate analysis, the sterilization rate (Dworak score) of the operative specimen was the main significant prognostic factor (hazard ratio, 0.32; 95% CI, 0.21 to 0.50).At 3 years, no significant difference in clinical outcome was achieved with the intensified CAPOX regimen. When compared with other recent randomized trials, these results indicate that concurrent administration of oxaliplatin and RT is not recommended.