tbuckley/cabot-search huggingface dataset:
The evolution of progesterone receptor ligands
Authors: Kevin P. Madauss, Eugene L. Stewart, Shawn P. Williams
Journal: Medicinal Research Reviews (2006)

Abstract Progesterone is one of the first nuclear receptor hormones to be described functionally and subsequently approached as a drug target. Because progesterone ( 1 ) affects both menstruation and gestation via the progesterone receptor (PR), research aimed at modulating its activity is usually surrounded by controversy. However, ligands for PR were developed into drugs, and their evolution can be crudely divided into three periods: (1) drug‐like steroids that mimic the gestational properties of progesterone; (2) drug‐like steroids with different properties from progesterone and expanded therapeutic applications; and (3) non‐steroidal PR ligands with improved selectivity and modulator properties and further expanded therapeutic applications. Although the latter have yet to see widespread clinical applications, their development is founded on a half century of research, and they represent the future for this drug target. © 2006 Wiley Periodicals, Inc. Med Res Rev, 27, No. 3, 374–400, 2007
Spontaneous unilateral tubal twin pregnancy
Authors: S D Sur
Journal: Journal of the Royal Society of Medicine (2005)

Dysphagia from carotid artery kinks and coils seems very rare.In reported cases the internal carotid artery has usually been responsible.We have found only one case due to common carotid artery tortuosity-in which the redundant part of the artery was surgically resected and the dysphagic symptoms resolved completely. 4Elongation and kinking of the carotid artery are usually due to atherosclerosis or fibromuscular dysplasia, 5 but the unusual location of the proximal common carotid artery coil in this patient is most likely congenital rather than atherosclerotic.In a fitter patient the treatment of choice would have been a carotid shortening procedure.Dilatation by balloon or stent might provide palliation at the risk of cerebrovascular catastrophe and is contraindicated unless the vessel is known to be occluded.
IgM-rheumatoid factor and anti-cyclic citrullinated peptide decrease by 50% during intensive treatment in early rheumatoid arthritis
Authors: L H D van Tuyl, W F Lems, P J S M Kerstens, A E Voskuyl, B A C Dijkmans, M Boers
Journal: Annals of the Rheumatic Diseases (2009)

Decreases in rheumatoid factor (IgM-RF) during antirheumatic treatment are often reported,1 2 3 4 but the course of anti-cyclic citrullinated peptide (anti-CCP) is less conclusive, with some studies showing decrease,2 5 6 but others finding no change.4 7 8

As anti-CCP antibodies are very specific as a marker for rheumatoid arthritis (RA), decreases in anti-CCP levels on therapy may have prognostic relevance and guide further treatment decisions in patients with early RA.

A total of 21 patients with active, early RA were treated for 40 weeks with intensive conventional disease-modifying antirheumatic drug (DMARD) therapy, comprising hydroxychloroquine, sulfasalazine, methotrexate and tapered high-dose prednisolone (enhanced “COBRA” (Combinatietherapie Bij Reumatoide Artritis trial) schedule, fig 1). On non-response at 8 weeks, methotrexate (MTX)was intensified to 25 mg/week; on non-response at 21 weeks, infliximab was offered to patients on high-dose MTX and MTX was intensified in the remainder. Serum was available for 18 out of 21 patients.



Figure 1 
Top: percentage change of …
Jockey Injuries in the United States
Authors: Anna E. Waller
Journal: JAMA (2000)

In the sport of horse racing, the position of the jockey and speed of the horse predispose the jockey to risk of injury.To estimate rates of medically treated injuries among professional jockeys and identify patterns of injury events.Cross-sectional survey from data compiled by an insurance broker. Information on the cause of injury, location on the track, and body part injured was evaluated.Official races at US professional racing facilities (n = 114) from January 1, 1993, through December 31, 1996.A licensed jockey population of approximately 2700 persons.Annual injury incidence rates per 1000 jockey-years, as well as injury type, cause, and location on the track.A total of 6545 injury events occurred during official races between 1993 and 1996 (606 per 1000 jockey-years). Nearly 1 in 5 injuries (18.8%) was to the jockey's head or neck. Other frequent sites included the leg (15.5%), foot/ankle (10.7%), back (10.7%), arm/hand (11.0%), and shoulder (9.6%). The most frequent location where injuries occurred was entering, within, or leaving the starting gate (35.1%), including 29.5% of head injuries, 39.8% of arm/hand injuries, and 52.0% of injuries to the leg/foot. Most head injuries resulted from being thrown from the horse (41.8%) or struck by the horse's head (23.2%). Being thrown from the horse was the cause of 55.1% of back and 49.6% of chest injuries.Our data suggest that jockeys have a high injury rate. Efforts are needed to reduce the number of potential injury events on the track and to improve protective equipment so events do not lead to injury.
Rapid on-site evaluation of transbronchial aspirates: randomised comparison of two methods
Authors: A. H. Diacon, C. F. N. Koegelenberg, P. Schubert, K. Brundyn, M. Louw, C. A. Wright, C. T. Bolliger
Journal: European Respiratory Journal (2009)

The value of different staining methods for rapid analysis of transbronchial needle aspirates during bronchoscopy has not been explored. In the present study, we compared a Papanicolaou-based rapid stain, prepared by a technologist and read by a cytopathologist, and a Wright-Giemsa-based rapid stain, prepared and read by a cytopathologist alone. Gold standard was the final laboratory report issued on each aspirate. We harvested 827 aspirates from 218 target sites in 126 consecutive patients. At least one positive aspirate was found in 99 (79%) patients. In those 99 patients, 288 of 574 (50%) aspirates were positive for neoplastic (83%) or non-neoplastic (17%) disease. False-negative aspirates and target sites were more frequent with the rapid Wright-Giemsa than with the rapid Papanicolaou stain (14.2 versus 7.3%, p = 0.008, and 13.7 versus 3.6%, p = 0.021, respectively). The sensitivity of the Wright-Giemsa-based and Papanicolaou-based rapid stains for detecting diagnostic material was 93 and 100% in patients, 83.1 and 95.5% in target sites, and 72.8 and 84.9% in aspirates, respectively. Specificity was 100% for both methods in patients and target sites, and 90.4 and 95% in aspirates. We concluded that a Papanicolaou-based stain has superior yield and accuracy to a Wright-Giemsa-based stain for rapid on-site evaluation of transbronchial needle aspirates.
Helicobacter pylori and Atrophic Gastritis: Importance of the cagA Status
Authors: E. J. Kuipers, G. I. Perez-Perez, S. G. M. Meuwissen, M. J. Blaser
Journal: JNCI Journal of the National Cancer Institute (1995)

Background : Infection with Helicobacter pylori is a major risk factor for the development of atrophic gastritis and gastric cancer. H. pylori strains can differ with respect to the presence of cagA (cytotoxin-associated gene A), a gene encoding a high-molecular-weight immunodominant antigen. H. pylori strains possessing cagA have been associated with enhanced induction of acute gastric inflammation. Purpose : We investigated the relationship between cagA status and the development of atrophic gastritis in a cohort of subjects infected with H. pylori . Methods : Gastrointestinal endoscopy with biopsy sampling was used to study the natural history of gastritis in 58 subjects infected with H. pylori . Biopsy specimens were obtained before and after a mean follow-up period of Hi years (range, 10–13 years). The cagA status of each individual was determined at the follow-up visit with the use of an enzyme-linked immunosorbent assay designed to detect the presence of serum immunoglobulin G directed against the CagA protein. Two-sided Fisher's exact tests, McNemar's tests, Student's t tests, and Wilcoxon sum rank tests were used to analyze the data. Results : Twenty-four (41%) of the 58 evaluated subjects had serum antibodies against CagA (i.e., they were cagA positive), and 34 subjects were cagA negative. At the initial visit, moderate to severe atrophic gastritis was observed in eight (33%) of the cagA-positive subjects and in six (18%) of the cagA-negative subjects. At that time, positive cagA status and gastric atrophy were not significantly related ( P =.22; Fisher's exact test; odds ratio [OR] 2.33; 95% confidence interval [CI] = 0.58–9.65). During follow-up, 16 (36%) of the 44 initially atrophy-negative subjects developed atrophic gastritis (eight [50%] of 16 cagA-positive subjects versus eight [29%] of 28 cagA-negative subjects; P =.20, Fisher's exact test; relative risk [RR] = 1.75; 95% CI = 0.82–3.76). In six of these 16 subjects (five cagA positive versus one cagA negative), atrophic gastritis was accompanied by the development of intestinal metaplasia (i.e., a change in the type of specialized cells present) ( P =.02; Fisher's exact test; RR = 9.06; 95% CI = 1.16–71.0). One of the initially atrophy-negative, cagA-positive subjects developed early gastric cancer. Four (29%) of the 14 subjects initially diagnosed with atrophic gastritis showed regression of atrophy during follow-up (one cagA positive and three cagA negative). Therefore, at the end of follow-up, 15 (62%) of the 24 cagA-positive subjects had atrophic gastritis compared with 11 (32%) of the 34 cagA-negative subjects (P =.02; Fisher's exact test; OR = 3.48; 95% CI = 1.02–12.18). Conclusion : Infection with cagA-positive H. pylori strains is associated with an increased risk for the eventual development of atrophic gastritis and intestinal metaplasia.
Disease severity and the effect of fluticasone propionate on chronic obstructive pulmonary disease exacerbations
Authors: P.W. Jones, L.R. Willits, P.S. Burge, P.M.A. Calverley
Journal: European Respiratory Journal (2003)

Exacerbations of chronic obstructive pulmonary disease (COPD) are associated with worse health and increased healthcare utilisation. The Inhaled Steroids in Obstructive Lung Disease in Europe (ISOLDE) study in COPD showed a 26% reduction in the yearly rate of exacerbations in patients treated with fluticasone propionate (FP) compared to placebo, but did not indicate which patients showed greatest benefit. In this study the patients were stratified into mild and moderate‐to‐severe COPD using the American Thoracic Society criterion of forced expiratory volume in one second (FEV 1 ) 50% predicted, and the total number of exacerbations and those requiring treatment with oral corticosteroids were examined. There were 391 (195 FP) patients with mild COPD and 359 (180 FP) patients with moderate‐to‐severe disease. The exacerbation rate was highly skewed in mild disease, but more normally distributed in moderate‐to‐severe disease. FP reduced the overall exacerbation rate in moderate‐to‐severe disease (FP median rate 1.47 yr −1 , placebo 1.75 yr −1 ), but not in mild disease (FP 0.67 yr −1 , placebo 0.92 yr −1 ). FP use was associated with fewer patients with ≥1 exacerbation·yr −1 being treated with oral corticosteroids (mild: FP 8%, placebo 16%; moderate‐to‐severe: FP 17%, placebo 30%). Effects of fluticasone propionate on exacerbations were seen predominantly in patients with a postbronchodilator forced expiratory volume in one second &lt;50% predicted. These data support recommendations in the Global Initiative for Chronic Obstructive Disease treatment guidelines that inhaled corticosteroids should be considered in patients with moderate‐to‐severe chronic obstructive pulmonary disease who experience recurrent exacerbations.
Novel cytokine peptide‐based vaccines: an interleukin‐4 vaccine suppresses airway allergic responses in mice
Authors: Y. Ma, K. T. Hayglass, A. B. Becker, A. J. Halayko, S. Basu, F. E. R. Simons, Z. Peng
Journal: Allergy (2007)

Monoclonal antibodies or soluble receptors have been used to block over-produced endogenous cytokines. However, they have disadvantages of short half-lives, high costs, and possible adverse effects. Using interleukin (IL)-4 as a model target, we sought to develop a novel therapeutic strategy by constructing an IL-4 peptide-based vaccine for blocking IL-4 on a persistent basis, and to evaluate its efficacy in a mouse model of asthma.A peptide was selected by antigenic prediction and structure analysis of IL-4/receptor complex. The vaccine was constructed by employing truncated hepatitis B core antigen as carrier with the peptide inserted using gene engineering methods. It was then expressed, purified and identified. Prior to intraperitoneal sensitization and intranasal challenge with ovalbumin, mice were subcutaneously immunized three times with the vaccine, or the carrier or saline as controls. Serum antibodies, inflammatory cells in bronchoalveolar lavage fluids (BALF), lung histology, and responsiveness to inhaled methacholine were analyzed.The vaccine presented as virus-like particles and reacted to polyclonal anti-IL-4 in Western blotting. Vaccinated mice produced high titers of IgG to IL-4. Serum ovalbumin-specific IgE, eosinophil accumulation in BALF, goblet cell hyperplasia, tissue inflammation and methacoline-induced respiratory responses were markedly suppressed in vaccinated mice with statistical significance, as compared with those in the control groups.Administration of this novel IL-4 vaccine led to an overall decrease in the development of airway allergic inflammatory responses. The results indicate that cytokine peptide-based vaccines hold potential for treatment of asthma and, by extension, other diseases where over-expressed cytokines play a pivotal role in pathogenesis.
Rituximab-Induced Depletion of Anti-PLA2R Autoantibodies Predicts Response in Membranous Nephropathy
Authors: Laurence H. Beck, Fernando C. Fervenza, David M. Beck, Ramon G.B. Bonegio, Fahim A. Malik, Stephen B. Erickson, Fernando G. Cosio, Daniel C. Cattran, David J. Salant
Journal: Journal of the American Society of Nephrology (2011)

Autoantibodies to the M-type phospholipase A(2) receptor (PLA(2)R) are sensitive and specific for idiopathic membranous nephropathy. The anti-B cell agent rituximab is a promising therapy for this disease, but biomarkers of early response to treatment currently do not exist. Here, we investigated whether levels of anti-PLA(2)R correlate with the immunological activity of membranous nephropathy, potentially exhibiting a more rapid response to treatment than clinical parameters such as proteinuria. We measured the amount of anti-PLA(2)R using Western blot immunoassay in serial serum samples from a total of 35 patients treated with rituximab for membranous nephropathy in two distinct cohorts. Pretreatment samples from 25 of 35 (71%) patients contained anti-PLA(2)R, and these autoantibodies declined or disappeared in 17 (68%) of these patients within 12 months after rituximab. Those who demonstrated this immunologic response fared better clinically: 59% and 88% attained complete or partial remission by 12 and 24 months, respectively, compared with 0% and 33% among those with persistent anti-PLA(2)R levels. Changes in antibody levels preceded changes in proteinuria. One subject who relapsed during follow-up had a concomitant return of anti-PLA(2)R. In summary, measuring anti-PLA(2)R levels by immunoassay may be a method to follow and predict response to treatment with rituximab in membranous nephropathy.
Mutations of Gonadotropins and Gonadotropin Receptors: Elucidating the Physiology and Pathophysiology of Pituitary-Gonadal Function
Authors: Axel P. N. Themmen, Ilpo T. Huhtaniemi
Journal: Endocrine Reviews (2000)

The recent unraveling of structures of genes for the gonadotropin subunits and gonadotropin receptors has provided reproductive endocrinologists with new tools to study normal and pathological functions of the hypothalamic-pituitary-gonadal axis. Rare inactivating mutations that produce distinctive phenotypes of isolated LH or FSH deficiency have been discovered in gonadotropin subunit genes. In addition, there is a common polymorphism in the LHβ subunit gene with possible clinical significance as a contributing factor to pathologies of LH-dependent gonadal functions. Both activating and inactivating mutations have been detected in the gonadotropin receptor genes, a larger number in the LH receptor gene, but so far only a few in the gene for the FSH receptor. These mutations corroborate and extend our knowledge of clinical consequences of gonadotropin resistance and inappropriate gonadotropin action. The information obtained from human mutations has been complemented by animal models with disrupted or inappropriately activated gonadotropin ligand or receptor genes. These clinical and experimental genetic disease models form a powerful tool for exploring the physiology and pathophysiology of gonadotropin function and provide an excellent example of the power of molecular biological approaches in the study of pathogenesis of diseases.
Fasting glucose and treatment outcome in breast and colorectal cancer patients treated with targeted agents: results from a historic cohort
Authors: M. Barba, F. Sperati, S. Stranges, C. Carlomagno, G. Nasti, V. Iaffaioli, G. Caolo, M. Mottolese, G. Botti, I. Terrenato, P. Vici, D. Serpico, A. Giordano, G. D’Aiuto, A. Crispo, M. Montella, G. Capurso, G. Delle Fave, B. Fuhrman, C. Botti, S. De Placido
Journal: Annals of Oncology (2011)
Identity of the elusive IgM Fc receptor (FcμR) in humans
Authors: Hiromi Kubagawa, Satoshi Oka, Yoshiki Kubagawa, Ikuko Torii, Eiji Takayama, Dong-Won Kang, G. Larry Gartland, Luigi F. Bertoli, Hiromi Mori, Hiroyuki Takatsu, Toshio Kitamura, Hiroshi Ohno, Ji-Yang Wang
Journal: The Journal of Experimental Medicine (2009)

Although Fc receptors (FcRs) for switched immunoglobulin (Ig) isotypes have been extensively characterized, FcR for IgM (FcμR) has defied identification. By retroviral expression and functional cloning, we have identified a complementary DNA (cDNA) encoding a bona fide FcμR in human B-lineage cDNA libraries. FcμR is defined as a transmembrane sialoglycoprotein of ∼60 kD, which contains an extracellular Ig-like domain homologous to two other IgM-binding receptors (polymeric Ig receptor and Fcα/μR) but exhibits an exclusive Fcμ-binding specificity. The cytoplasmic tail of FcμR contains conserved Ser and Tyr residues, but none of the Tyr residues match the immunoreceptor tyrosine-based activation, inhibitory, or switch motifs. Unlike other FcRs, the major cell types expressing FcμR are adaptive immune cells, including B and T lymphocytes. After antigen-receptor ligation or phorbol myristate acetate stimulation, FcμR expression was up-regulated on B cells but was down-modulated on T cells, suggesting differential regulation of FcμR expression during B and T cell activation. Although this receptor was initially designated as Fas apoptotic inhibitory molecule 3, or TOSO, our results indicate that FcμR per se has no inhibitory activity in Fas-mediated apoptosis and that such inhibition is only achieved when anti-Fas antibody of an IgM but not IgG isotype is used for inducing apoptosis.
Randomized Comparison of Gemcitabine, Dexamethasone, and Cisplatin Versus Dexamethasone, Cytarabine, and Cisplatin Chemotherapy Before Autologous Stem-Cell Transplantation for Relapsed and Refractory Aggressive Lymphomas: NCIC-CTG LY.12
Authors: Michael Crump, John Kuruvilla, Stephen Couban, David A. MacDonald, Vishal Kukreti, C. Tom Kouroukis, Morel Rubinger, Rena Buckstein, Kevin R. Imrie, Massimo Federico, Nicola Di Renzo, Kang Howson-Jan, Tara Baetz, Leonard Kaizer, Michael Voralia, Harold J. Olney, A. Robert Turner, Jonathan Sussman, Annette E. Hay, Marina S. Djurfeldt, Ralph M. Meyer, Bingshu E. Chen, Lois E. Shepherd
Journal: Journal of Clinical Oncology (2014)

Purpose For patients with relapsed or refractory aggressive lymphoma, we hypothesized that gemcitabine-based therapy before autologous stem-cell transplantation (ASCT) is as effective as and less toxic than standard treatment. Patients and Methods We randomly assigned 619 patients with relapsed/refractory aggressive lymphoma to treatment with gemcitabine, dexamethasone, and cisplatin (GDP) or to dexamethasone, cytarabine, and cisplatin (DHAP). Patients with B-cell lymphoma also received rituximab. Responding patients proceeded to stem-cell collection and ASCT. Coprimary end points were response rate after two treatment cycles and transplantation rate. The noninferiority margin for the response rate to GDP relative to DHAP was set at 10%. Secondary end points included event-free and overall survival, treatment toxicity, and quality of life. Results For the intention-to-treat population, the response rate with GDP was 45.2%; with DHAP the response rate was 44.0% (95% CI for difference, −9.0% to 6.7%), meeting protocol-defined criteria for noninferiority of GDP (P = .005). Similar results were obtained in a per-protocol analysis. The transplantation rates were 52.1% with GDP and 49.3% with DHAP (P = .44). At a median follow-up of 53 months, no differences were detected in event-free survival (HR, 0.99; stratified log-rank P = .95) or overall survival (HR, 1.03; P = .78) between GDP and DHAP. Treatment with GDP was associated with less toxicity (P &lt; .001) and need for hospitalization (P &lt; .001), and preserved quality of life (P = .04). Conclusion For patients with relapsed or refractory aggressive lymphoma, in comparison with DHAP, treatment with GDP is associated with a noninferior response rate, similar transplantation rate, event-free survival, and overall survival, less toxicity and hospitalization, and superior quality of life.
FURTHER CHARACTERIZATION OF THE HUMAN SERUM D 1.063-1.21, α1-LIPOPROTEIN*
Authors: Angelo Scanu, Walter L. Hughes
Journal: Journal of Clinical Investigation (1962)

The high density lipoprotein class floating at a solvent density between 1.063 and 1.21 g per ml can be fractionated by flotation in solvents of in- termediate density into two major subfractions (1, 2), which according to Shore (3) have a protein moiety with identical amino acid composition and Cand N-terminal amino acids.Homogeneity of the D 1.063-1.21lipoprotein in terms of protein moiety has also been indicated by immunochemical studies (4).It would appear, therefore, that the human serum high density lipoprotein of D 1.063- 1.21 constitutes a group of molecules identi- cal as to protein moiety and possibly differing only in lipid complement.The experiments reported below were designed to test this hypothesis.The serum D 1.063-1.21lipoprotein was arbitrarily fractionated into three fractions floating respectively at solvent densities of D 1.063-1.125,1.125-1.168,and 1.168-1.21.The results dealing with some of the physicochemical and bio- logical properties of these lipoprotein subfractions form the object of this report. MATERIAL AND METHODSThe source of the lipoproteins was pooled sera from healthy human male subjects, fasted for at least 12 hours.All separations of lipoproteins were performed in a Spinco model L ultracentrifuge, 30.2 rotor, at 79,420 G and 16°C for 24 hours.Sera were first adjusted to D 1.063 by addition of solid NaCl.After ultracentrifugation, the top fractions, containing lipoproteins of densi- ties between 1.006 and 1.063, were discarded and the re- mainder adjusted to D 1.125 by addition of solid KBr.After ultracentrifugation, the top fractions were collected (lipoproteins of D 1.063-1.125),the remainder adjusted to D 1.168 by adding solid KBr and ultracentrifuged.