tbuckley/cabot-search huggingface dataset:
COMPARISON OF THE EFFECTS OF PAPAIN AND VITAMIN A ON CARTILAGE
Authors: Honor B. Fell, Lewis Thomas
Journal: The Journal of Experimental Medicine (1960)

The effects of papain protease and of vitamin A on explanted limb bone rudiments from 7- and 13-day chick embryos and fetal mice have been studied and compared. The incubation of cartilaginous rudiments from 7-day chick embryos in a solution containing papain and cysteine resulted in complete loss of the metachromasia of the cartilage matrix within 1 hour; explants treated in this fashion recovered normal metachromatic staining properties when grown in normal medium for 4 days. The incubation of 7-day chick cartilage rudiments in a solution containing papain without cysteine resulted in partial loss of metachromasia from cartilage within 1 hour; the addition of vitamin A to the solution did not enhance the effect of papain during this period. The addition of papain to the culture medium in which 7-day chick embryo cartilage rudiments were grown resulted in uniform loss of the metachromasia of the cartilage matrix; similar explants grown in the presence of excess vitamin A also showed loss of the metachromasia of cartilage, but certain regions of the cartilage were affected earlier and more severely than others. Changes in cartilage cells, including loss of glycogen, occurred when the rudiment was grown in medium containing excess vitamin A, but not when it was grown in the presence of papain. Bone rudiments from 13-day chick embryos showed changes in cartilage similar to those seen in 7-day chick embryo rudiments when grown in the presence of papain or of excess vitamin A; the existing bone was not affected under these conditions. When grown in the presence of papain or excess vitamin A, the cartilage of late fetal mouse bone underwent changes similar to those already described in chick embryo rudiments. In contrast to the chick embryo rudiments, those from the fetal mouse showed rapid resorption of bone when grown in the presence of excess vitamin A. Papain had no effect on bone from either source. The changes seen in cartilage of explants grown in the presence of vitamin A and papain together were greater than those seen with either agent alone. The changes seen in fetal mouse bone grown in the presence of vitamin A were not enhanced by the additional presence of papain. On the basis of these observations, it is suggested that the changes in cartilage seen in experimental hypervitaminosis A may be the result of activation of a proteolytic enzyme or enzymes with properties similar to papain.
Redefining Lamellar Holes and the Vitreomacular Interface: An Ultrahigh-Resolution Optical Coherence Tomography Study
Authors: Andre J. Witkin, Tony H. Ko, James G. Fujimoto, Joel S. Schuman, Caroline R. Baumal, Adam H. Rogers, Elias Reichel, Jay S. Duker
Journal: Ophthalmology (2006)
Gα13 Mediates a Signal That Is Essential for Proliferation and Survival of Thymocyte Progenitors
Authors: V. McNeil Coffield, Whitney S. Helms, Qi Jiang, Lishan Su
Journal: The Journal of Experimental Medicine (2004)

G protein signaling via the Gα12 family (Gα12 and Gα13) has not been well studied in T cells. To investigate whether Gα12 and Gα13 are involved in thymopoiesis, we expressed the regulator of G protein signaling domain of p115RhoGEF to inhibit Gα12 and Gα13 during thymopoiesis. Fetal thymus organ cultures seeded with p115ΔDH-expressing progenitor cells showed impaired thymopoiesis with a block at the CD4−CD8−CD44−CD25+ (DN3) stage. Using Gα13 or Gα12 minigenes, we demonstrated that Gα13, but not Gα12, is required for thymopoiesis. T progenitor cells expressing p115ΔDH showed reduced proliferation and increased cell death. T cell receptor stimulation of the fetal thymus organ cultures did not rescue the block. Overexpression of the antiapoptotic gene Bcl2 rescued the defect in DN3 cells and partially rescued T cell development. Therefore, Gα13-mediated signaling is necessary in early thymocyte proliferation and survival.
Randomized phase III trial of gemcitabine/cisplatin with or without PF-3512676 as first line treatment of advanced non-small cell lung cancer (NSCLC)
Authors: C. Manegold, N. Thatcher, R. J. Benner, D. Readett, N. van Zandwijk
Journal: Journal of Clinical Oncology (2008)

8017 Background: Gemcitabine/cisplatin (GC) is standard first line therapy for patients (pts) with Stage IIIB/IV NSCLC. PF- 3512676 (PF-676) is an oligodeoxynucleotide toll-like receptor 9 (TLR9) agonist. In a randomized phase 2 trial, addition of PF-676 to first line taxane/platinum chemotherapy produced a higher objective response rate and a trend toward improved overall survival (OS) in pts with advanced NSCLC. Confirmatory phase 3 trials were subsequently conducted. Methods: Chemotherapy naïve pts with Stage IIIB (pleural effusion) or Stage IV NSCLC, ECOG PS 0 or 1, measurable disease, adequate bone marrow, renal and hepatic function, no pre- existing autoimmune disease, no brain metastases and no chronic systemic corticosteroid therapy were included. All pts received G (1250 mg/m2) on D1 and 8 and C (75mg/m2) on D1 of each 21 day cycle (max 6 cycles). In the investigational arm pts also received PF-676 (0.2 mg/kg) SC on D 8 and 15 of each chemotherapy cycle and weekly thereafter until progression. The primary endpoint was OS. Results: 839 pts were randomized (416 GC + PF-676, 423 GC) from Nov '05 to Dec '06. Interim data reviewed by an external DSMC is reported. No increment in OS (120 deaths on GC + PF-676, 118 on GC [HR 0.978, 95 % CI 0.74, 1.29]) or PFS (Median 4.9 mos on GC+PF-676, 5.1 mos on GC) was noted for addition of PF-676. Many pts in the PF-676 arm experienced mild/moderate injection site reactions (62% [8 % G3/4]) or flu-like symptoms (37% [4% G3/4]). G3/4/5 thrombocytopenia and neutropenia and transfusions were reported more commonly in pts receiving PF-676 (61% vs 33%, 69% vs 47%, 19% vs 10%). The DSMC recommended termination of the trial due to lack of incremental efficacy and added toxicity. PF-676 administration was discontinued in all pts but collection of follow-up data continues. Updated results will be reported. Conclusions: Addition of PF-676 to GC did not improve the outcome of pts with advanced NSCLC. Alternative development opportunities are being explored for TLR9 agonists in the treatment of cancer. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pfizer Pfizer Pfizer Pfizer
Can changes of ryanodine receptor expression affect cardiac contractility?
Authors: M Díaz
Journal: Cardiovascular Research (2000)

Yamamoto et al. [1] have shown in their recent article that the expression of cardiac ryanodine receptors is decreased in dogs subjected to heart failure induced by rapid-pacing. This agrees with previous work showing that in some models of failure down regulation of the RyR is observed [2,3]. As well as a decrease in the number of RyRs, it has also been suggested that there may be a decrease in the functional coupling between Ca entry into the cell and the opening of the RyR [4,5]. The purpose of this letter is to question the idea that changes in the expression or properties of the RyR are involved in changes of contractility observed in cardiac hypertrophy or failure. The argument below is based on both experimental and theoretical considerations [6].

We have examined the effects of manoeuvres which alter the open probability of the RyR. For example caffeine …
Diagnostic Ultrasound Combined With Glycoprotein IIb/IIIa–Targeted Microbubbles Improves Microvascular Recovery After Acute Coronary Thrombotic Occlusions
Authors: Feng Xie, John Lof, Terry Matsunaga, Reena Zutshi, Thomas R. Porter
Journal: Circulation (2009)

The high mechanical index (MI) impulses from a diagnostic ultrasound transducer may be a method of recanalizing acutely thrombosed vessels if the impulses are applied only when microbubbles are channeling through the thrombus.In 45 pigs with acute left anterior descending thrombotic occlusions, a low-MI pulse sequence scheme (contrast pulse sequencing) was used to image the myocardium and guide the delivery of high-MI (1.9 MI) impulses during infusion of either intravenous platelet-targeted microbubbles or nontargeted microbubbles. A third group received no diagnostic ultrasound and microbubbles. All groups received half-dose recombinant prourokinase, heparin, and aspirin. Contrast pulse sequencing examined replenishment of contrast within the central portion of the risk area and guided the application of high-MI impulses. Angiographic recanalization rates, resolution of ST-segment elevation on ECG, and wall thickening were analyzed. Pigs receiving platelet-targeted microbubbles had more rapid replenishment of the central portion of the risk area (80% versus 40% for nontargeted microbubbles; P=0.03) and higher epicardial recanalization rates (53% versus 7% for prourokinase alone; P=0.01). Replenishment of contrast within the risk area (whether with platelet-targeted microbubbles or nontargeted microbubbles) was associated with both higher recanalization rates and even higher rates of ST-segment resolution (82% versus 21% for prourokinase alone; P=0.006). ST-segment resolution occurred in 6 pigs (40%) treated with microbubbles who did not have epicardial recanalization, of which 5 had recovery of wall thickening.Intravenous platelet-targeted microbubbles combined with brief high-MI diagnostic ultrasound impulses guided by contrast pulse sequencing improve both epicardial recanalization rates and microvascular recovery.
Chronic hepcidin induction causes hyposideremia and alters the pattern of cellular iron accumulation in hemochromatotic mice
Authors: Lydie Viatte, Gaël Nicolas, Dan-Qing Lou, Myriam Bennoun, Jeanne-Claire Lesbordes-Brion, François Canonne-Hergaux, Kai Schönig, Hermann Bujard, Axel Kahn, Nancy C. Andrews, Sophie Vaulont
Journal: Blood (2005)
Traumatic carotid and vertebral artery dissection in a professional jockey: a cautionary tale.
Authors: J Fletcher, P T Davies, T Lewis, M J Campbell
Journal: British Journal of Sports Medicine (1995)

Jockeys accept bony fractures and soft tissue injuries as occupational hazards. An average National Hunt jockey falls once in ten races with an injury rate of 4.25%. Head injury is a common cause of morbidity and the benefit of helmets is well recognized. Neck injuries are also common and usually musculoskeletal. Although rare, trauma to the neck arteries may go unnoticed yet have catastrophic consequences. Internal tears can allow arterial blood to dissect the layers of the arterial wall and obstruct the lumen. Severe obstruction may lead to cerebral ischaemia and infarction. An appreciation of the early clinical signs caused by this process may allow effective intervention. We report a case which illustrates these points.
Double-blind randomised trial of very-low-dose warfarin for prevention of thromboembolism in stage IV breast cancer
Authors: M. Levine, J. Hirsh, A. Arnold, M. Gent, M. Levine, A. Arnold, V. Bramwell, K.I. Pritchard, D. Stewart, D. Warr, P. Goodwin, M. Samosh, A. Falanga
Journal: The Lancet (1994)
Serum Circulating Human mRNA Profiling and Its Utility for Oral Cancer Detection
Authors: Yang Li, David Elashoff, Myungshin Oh, Uttam Sinha, Maie A.R. St John, Xiaofeng Zhou, Elliot Abemayor, David T. Wong
Journal: Journal of Clinical Oncology (2006)

Purpose The purpose of this study is to explore the presence of informative RNA biomarkers from human serum transcriptome, and evaluate the serum transcriptome diagnostics for disease detection. Oral squamous cell carcinoma (OSCC) was selected as the proof-of-concept disease. Patients and Methods Blood samples were collected from patients (n = 32) with primary T1/T2 OSCC and matched healthy patients (n = 35). Circulating RNA was isolated from serum and linearly amplified using T7 polymerase. Microarrays were applied for profiling transcriptome in serum from 10 cancer patients and controls. The differential gene expression was analyzed by combining the present calls, t tests, and fold-change statistics. Quantitative polymerase chain reaction (PCR) was used to validate the selected candidate RNA markers identified by microarray. Receiver operating characteristic curve and classification models were exploited to evaluate the diagnostic power of these markers for OSCC. Results Human serum circulating mRNAs were presented by reverse transcriptase PCR. Microarray identified 2,623 ± 868 probes assigned present calls in OSCC (n = 10) versus 1,792 ± 165 in healthy patients (n = 10), indicating a higher complexity of serum transciptome in OSCC patients (P = .002, Wilcoxon test). Three hundred thirty-five serum RNAs exhibited significantly differential expression level between the two groups (P &lt; .05, t test; fold ≥ 2). Five cancer-related gene transcripts were consistently validated by quantitative PCR on serum from OSCC patients (n = 32) and controls (n = 35). The best combination of biomarkers yielded a receiver operating characteristic curve value of 88%, sensitivity (91%), and specificity (71%) in distinguishing OSCC. Conclusion The utility of serum transcriptome diagnostics is successfully demonstrated for OSCC detection. This novel concept could be developed as an adjunctive tool for disease diagnosis.
A Genome Scan to Detect Candidate Regions Influenced by Local Natural Selection in Human Populations
Authors: Manfred Kayser, Silke Brauer, Mark Stoneking
Journal: Molecular Biology and Evolution (2003)

As human populations dispersed throughout the world, they were subjected to new selective forces, which must have led to local adaptation via natural selection and hence altered patterns of genetic variation. Yet, there are very few examples known in which such local selection has clearly influenced human genetic variation. A potential approach for detecting local selection is to screen random loci across the genome; those loci that exhibit unusually large genetic distances between human populations are then potential markers of genomic regions under local selection. We investigated this approach by genotyping 332 short tandem repeat (STR) loci in Africans and Europeans and calculating the genetic differentiation for each locus. Patterns of genetic diversity at these loci were consistent with greater variation in Africa and with local selection operating on populations as they moved out of Africa. For 11 loci exhibiting the largest genetic differences, we genotyped an additional STR locus located nearby; the genetic distances for these nearby loci were significantly larger than average. These genomic regions therefore reproducibly exhibit larger genetic distances between populations than the "average" genomic region, consistent with local selection. Our results demonstrate that genome scans are a promising means of identifying candidate regions that have been subjected to local selection.
The dinucleotide repeat polymorphism in the 3'UTR of the CD154 gene has a functional role on protein expression and is associated with systemic lupus erythematosus
Authors: M J Citores
Journal: Annals of the Rheumatic Diseases (2004)

To investigate the association of the (CA)n dinucleotide repeat in the 3' untranslated region (3'UTR) of the CD154 gene with systemic lupus erythematosus (SLE), and its functional role in protein expression.The allelic and genotypic distributions of the polymorphism were compared in 80 patients with SLE and 80 controls. A complete clinical and analytical database was recorded in each patient in order to correlate the clinical manifestations in SLE with different alleles. To investigate the functional role of the polymorphism, the CD154 protein expression on activated lymphocytes from healthy homozygous controls was evaluated by flow cytometry.The 24 CA allele was the most represented in controls (p = 0.029), whereas the alleles containing >24 CA repeats were found in patients (p = 0.0043). Furthermore, when only homozygous women were considered, most controls carried two 24 CA alleles (p = 0.041), whereas most patients carried two alleles containing >24 CA repeats (p = 0.032). Also, patients carrying at least one 24 CA allele had less neurological involvement (p = 0.034), and carriers of at least one allele with fewer than 24 CA repeats presented more livedo reticularis (p = 0.006) and anti-Sm (p = 0.01) and anti-RNP (p = 0.038) autoantibodies. CD154 maximum expression in activated lymphocytes from all controls was reached after 54 hours, but it was more prolonged in controls carrying two alleles with >24 CA repeats (p = 0.0068).The CD154 3'UTR microsatellite is associated with SLE, and the most represented alleles in patients were accompanied by a more prolonged protein expression in activated lymphocytes from controls.
Pitx2 impairs calcium handling in a dose-dependent manner by modulating Wnt signalling
Authors: Estefanía Lozano-Velasco, Francisco Hernández-Torres, Houria Daimi, Selma A. Serra, Adela Herraiz, Leif Hove-Madsen, Amelia Aránega, Diego Franco
Journal: Cardiovascular Research (2015)

Atrial fibrillation (AF) is the most common type of arrhythmia in humans, yet the genetic cause of AF remains elusive. Genome-wide association studies (GWASs) have reported risk variants in four distinct genetic loci, and more recently, a meta-GWAS has further implicated six new loci in AF. However, the functional role of these AF GWAS-related genes in AF and their inter-relationship remain elusive. To get further insights into the molecular mechanisms driven by Pitx2, calcium handling and novel AF GWAS-associated gene expression were analysed in two distinct Pitx2 loss-of-function models with distinct basal electrophysiological defects; a novel Pitx2 conditional mouse line, Sox2CrePitx2, and our previously reported atrial-specific NppaCrePitx2 line. Molecular analyses of the left atrial appendage in NppaCrePitx2+/− and NppaCrePitx2−/− adult mice demonstrate that AF GWAS-associated genes such as Zfhx3, Kcnn3, and Wnt8a are severely impaired but not Cav1, Synpo2l, nor Prrx1. In addition, multiple calcium-handling genes such as Atp2a2, Casq2, and Plb are severely altered in atrial-specific NppaCrePitx2 mice in a dose-dependent manner. Functional assessment of calcium homeostasis further underscores these findings. In addition, multiple AF-related microRNAs are also impaired. In vitro over-expression of Wnt8, but not Zfhx3, impairs calcium handling and modulates microRNA expression signature identified in Pitx2 loss-of-function models. Our data demonstrate a dose-dependent relation between Pitx2 expression and the expression of AF susceptibility genes, calcium handling, and microRNAs and identify a complex regulatory network orchestrated by Pitx2 with large impact on atrial arrhythmogenesis susceptibility.
Stenotrophomonas maltophilia and achromobacter xylosoxidans in cystic fibrosis patients
Authors: Silvia Gartner, Marta Mumany, Adelaida Ferrer, Carlos Martin, Sandra Rovira, Alba Torrent, Ines de Mir, Antonio Moreno
Journal: European Respiratory Journal (2011)

Introduction: In recent years there has been an increasing number of recognized emerging pathogens like Stenotrophomonas maltophilia (SM) and Achromobacter xylosoxidans (AX) but their effect in CF lung disease is yet unknown.

Aims: 1) to assess the prevalence of SM and AX and 2) to compare the lung function, clinical symptoms at first isolation, CT scan and colonization with Pseudomonas aeruginosa (PA) between the two groups.

Methods: Retrospective cohort study using the CF Database of the CF Center of Catalonia (Spain). Data were collected at first isolation and after one year.

Results: 130 patients were included in this study, 44 of whom (33,8%) had a positive culture to SM and 11 (8.4%) to AX at some time. Mean age at acquisition of SM was 6±4.6 years and of AX was 6.5±3 years. In the SM group 36% of patients were under 4 years in comparison with 9% in the AX group. No significant difference in symptoms at acquisition (56% and 63% respectively), FEV1 (75% and 84%), bronchiectasis (47% and 36%) and PA colonization (79% and 91%) were found between the SM and AX groups. After specific ATB therapy, chronic colonization was higher in AX (36%) in comparison with the SM group (9%).

Conclusions: The prevalence of SM colonisation was higher than AX. Patients colonized with SM were younger but chronic infection was more associated with AX.
In vivo assessment in sheep of thromboresistant materials by determination of platelet survival.
Authors: J N Lindon, R E Collins, N P Coe, A Jagoda, D Brier-Russell, E W Merrill, E W Salzman
Journal: Circulation Research (1980)

The thromboresistance of 13 potentially blood-compatible polymers was assessed in sheep by determining survival of 51Cr-labeled platelets. Polymer tubing (120-150 cm x 2.0-2.3 mm i.d.) coiled around the neck was incorporated into the circulation through silicone rubber connectors as a carotid artery-external jugular vein shunt. The mean platelet half-life in control animals ("shunt control") was 78.2 +/- 2.8 (SEM) hours. Eleven of the 13 polymers tested significantly shortened platelet half-life. Polyvinyl chloride (T1/2 = 45.4 +/- 3.0 hours), polyperfluoro ethylene (T1/2 = 47.0 +/-1.6 hours), and a polymethylacrylate (PMA)/acrilonitrile copolymer (T1/2 = 50.7 +/- 7.0 hours) produced the greatest shortening. Only silica-free polydimethyl siloxane (T1/2 = 74.7 +/- 4.9 hours) and PMA (T1/2 = 81.5 +/- 3.4 hours) were indistinguishable from shunt controls. Pretreatment of PMA tubing with autologous plasma in a paired trial significantly increased platelet half-life (P less than 0.05 vs. untreated PMA). This system offers an economical, reproducible, sensitive, and biologically relevant method for assessment of the reactivity of artificial surfaces with platelets.
Genetics and developing countries
Authors: B. R Bloom
Journal: BMJ (2001)

With the publication of the sequence of the human genome, we can now approach our history as human beings in a way never previously possible—a history that has been written in only 30 000 or so genes. There is a completely different way of looking at history and genetics, however—one that should never be forgotten by clinicians.

Take a real case history: a 27 year old woman presents for a routine examination with a small lump on her breast. She had been seen by doctors who ignored the lump and took neither a biopsy nor an adequate history. The latest doctor to see her asked whether members of her family had had breast cancer. Both her mother and maternal grandmother died before the age of 40 from breast cancer. Whether their malignancies were caused by mutations in BRCA1 or 2, the p53, or other genes is unimportant: an adequate history would have revealed a great deal about her genetic susceptibility to disease. Classic papers, 1 2 largely but not entirely forgotten,3 point out that 70% of diagnoses can be revealed in clinical histories, with laboratory diagnosis accounting for only about 10% additional information. For clinicians in developing countries, without access to advanced diagnostic facilities but with knowledge of genetic research, a careful history can reveal much of what modern genetics and high technology can teach that is important …
Bariatric surgery in severely obese adolescents improves major comorbidities including hyperuricemia
Authors: Andreas Oberbach, Jochen Neuhaus, Thomas Inge, Katharina Kirsch, Nadine Schlichting, Susann Blüher, Yvonne Kullnick, Joachim Kugler, Sven Baumann, Holger Till
Journal: Metabolism (2013)
Prevalence of abuse and intimate partner violence surgical evaluation (PRAISE) in orthopaedic fracture clinics: a multinational prevalence study
Authors: Sheila Sprague, Mohit Bhandari, Gregory J Della Rocca, J Carel Goslings, Rudolf W Poolman, Kim Madden, Nicole Simunovic, Sonia Dosanjh, Emil H Schemitsch
Journal: The Lancet (2013)