tbuckley/cabot-search huggingface dataset:
Induced sputum cell profiles in lung transplant recipients with or without chronic rejection: correlation with lung function
Authors: K M Beeh
Journal: Thorax (2001)

Background-Sputum induction is a noninvasive procedure for measuring inflammatory processes of the lower respiratory tract.The aim of this study was to establish sputum cell counts and diVerentials in patients after lung transplantation (LTx), with or without chronic transplant rejection.Methods-Sputum induction was performed in 41 LTx patients (25 single LTx (sLTx), 16 double LTx (dLTx) and 15 healthy non-smoking volunteers.Sputum was processed according to standard protocols.Total cell count was calculated as mean (SE) cells × 10 6 /ml sputum and cell diVerential (%) was evaluated after staining.Cellular profiles were correlated with lung function.Results-Total sputum cell counts were increased in sLTx (9 (1.9) cells × 10 6 /ml, p=0.01) and dLTx patients (7.2 (1.5) × 10 6 / ml, p=0.01) compared with healthy controls (2.6 (0.6) × 10 6 /ml).There was also a marked sputum neutrophilia in both patient groups (59 (6)% and 62 (6)%, respectively, p<0.001 v controls).Moreover, in both sLTx and dLTx patients with chronic transplant rejection there was an increased number of sputum neutrophils compared with patients with normal graft function (p<0.05 both comparisons), and neutrophils were inversely correlated with lung function (forced expiratory volume in one second (FEV 1 ) % predicted): sLTx, r=-0.61,p=0.001; dLTx, r=-0.75, p=0.001, respectively).Sputum lymphocytes and eosinophils were similar in both groups.No relevant side eVects occurred during sputum induction.Conclusions-Sputum induction is a safe and non-invasive tool for monitoring lower respiratory tract inflammation in LTx patients.Both sLTx and dLTx patients with chronic rejection had increased sputum neutrophils compared with patients with normal transplant function.These data support findings of other authors highlighting a possible role for neutrophils in the pathogenesis of chronic transplant rejection.
Feasibility of a Novel Blood Noise Reduction Algorithm to Enhance Reproducibility of Ultra–High-Frequency Intravascular Ultrasound Images
Authors: Kiyoshi Hibi, Atsushi Takagi, Xiangmin Zhang, Tat-Jin Teo, Heidi N. Bonneau, Paul G. Yock, Peter J. Fitzgerald
Journal: Circulation (2000)

Background —Ultra–high-frequency (40- to 50-MHz) intravascular ultrasound (IVUS) improves image quality compared with conventional 20- to 30-MHz IVUS. However, as the frequency of IVUS increases, high-intensity backscatter from blood components may cause visual difficulties in discrimination between the lumen and arterial wall structure. The purpose of this study was to evaluate the effect of a novel blood noise reduction algorithm (BNR) on quantitative coronary ultrasound measurements. Methods and Results —IVUS studies using a 40-MHz transducer were performed in 35 patients with coronary artery disease. A total of 620 gray-scale images (310 pairs) were processed with and without the BNR, and lumen cross-sectional area (CSA) was determined by 2 independent observers. With the BNR, the intraobserver and interobserver correlation coefficients for lumen CSA were significantly improved (0.85 to 0.99 and 0.80 to 0.98, respectively). In the 270 images (135 pairs) in which vessel wall measurements were possible, the BNR significantly improved the intraobserver and interobserver correlation coefficients for plaque plus media CSA (0.83 to 0.99 and 0.76 to 0.97, respectively), whereas no influence was observed for external elastic membrane CSA (1.00 to 1.00 and 0.99 to 0.99, respectively). Conclusions —This study demonstrates the feasibility of this novel algorithm to reduce blood noise, thereby enabling accurate lumen border delineation and providing reproducible measurements of both the lumen and plaque plus media CSAs. Incorporating a digital BNR may serve as an important adjunct to ultra–high-frequency IVUS imaging for improving accurate quantitative evaluation of vessel dimensions.
Restoration of Resting Sarcomere Length After Uniaxial Static Strain Is Regulated by Protein Kinase Cε and Focal Adhesion Kinase
Authors: Haytham Mansour, Pieter P. de Tombe, Allen M. Samarel, Brenda Russell
Journal: Circulation Research (2004)

Physiological or pathological stresses and strains produce longer or wider muscle cells, but resting sarcomere length remains constant. Our goal was to investigate the cellular mechanisms for controlling this optimal, resting sarcomere length. To do so, we cultured neonatal rat cardiomyocytes on microfabricated peg-and-groove, laminin-coated silicone surfaces and applied a uniaxial static strain of 10%. Sarcomere length was accurately measured by fast Fourier transform analysis of images before, within 5 minutes of, and 4 to 6 hours after imposition of the strain. Sarcomere length of aligned cardiomyocytes (1.94+/-0.07 microm) was lengthened acutely (2.06+/-0.06 microm), and recovered (1.95+/-0.07 microm) by 4 hours. Puromycin, an mRNA translational inhibitor, prevented recovery of resting sarcomere length by 4 hours, thus indicating a requirement for new protein synthesis in the recovery process. Furthermore, activation of protein kinase Cepsilon (PKCepsilon) was necessary for length recovery, as nonselective PKC inhibitors [staurosporine (5 micromol/L) and chelerythrine chloride (10 micromol/L)], and a replication-defective adenovirus (Adv) encoding a dominant-negative mutant of PKCepsilon prevented the restoration of sarcomere length. To assess the importance of focal adhesion complexes, cardiomyocytes were infected with an Adv encoding a dominant-negative inhibitor of focal adhesion kinase (FAK) (Adv-GFP-FRNK). Adv-GFP-FRNK also prevented resting sarcomere length recovery, whereas a control Adv encoding only GFP did not. In conclusion, using our novel culture system, we provide evidence indicating that the length remodeling process requires new protein synthesis, PKCepsilon and FAK.
Creatinine Excretion Rate and Mortality in Type 2 Diabetes and Nephropathy
Authors: Steef J. Sinkeler, Arjan J. Kwakernaak, Stephan J.L. Bakker, Shahnaz Shahinfar, Enric Esmatjes, Dick de Zeeuw, Gerjan Navis, Hiddo J. Lambers Heerspink
Journal: Diabetes Care (2013)

The creatinine excretion rate (CER) is inversely associated with mortality in the general and renal transplant population. The CER is a marker for muscle mass. It is unknown whether the CER is associated with outcome in diabetes. We therefore investigated whether the CER is a determinant of all-cause mortality in diabetic patients.
Quadratus femoris tendinitis as a cause of groin pain.
Authors: P Klinkert, R J Porte, T P de Rooij, A C de Vries
Journal: British Journal of Sports Medicine (1997)

Groin pain can be very disabling and is often difficult to diagnose.There are many possible causes for chronic groin pain.'5In this case report we describe a patient with quadratus femoris tendinitis, causing disabling groin pain.
Implementing guidance on hip fracture: Advice is misleading
Authors: G Keith Ions
Journal: BMJ (2004)

EDITOR—Dr Foster's case notes by Bottle et al quote the Scottish Intercollegiate Guidelines Network (SIGN) recommendation that patients with fractured neck of femur are operated on as soon as possible, ideally within 48 hours after admission.1

Patients with femoral neck fracture who are fit on admission are usually operated on early. …
Sarcolemmal Ca2+-ATPase ability to transport Ca2+ gradually diminishes after myocardial infarction in the rat
Authors: U. Mackiewicz, M. Maczewski, A. Konior, J. O. Tellez, D. Nowis, H. Dobrzynski, M. R. Boyett, B. Lewartowski
Journal: Cardiovascular Research (2008)

Plasmalemmal Ca(2+)-ATPase (PMCA) is involved in Ca(2+) handling and the regulation of intracellular signalling pathways in the heart. However, there is no information on its functioning in heart hypertrophy and failure. We aimed to investigate the Ca(2+)-transporting ability of PMCA, Na(+)/Ca(2+) exchanger (NCX), and sarcoplasmic reticulum (SR) Ca(2+)-ATPase (SERCA2a), as well as the amplitude of Ca(2+) transients and cell shortening in myocytes isolated from rat hearts at various time intervals after myocardial infarction (MI).The rate of Ca(2+) transport by PMCA, NCX, and SERCA2a was estimated from the rate constants of decay of electrically and caffeine-evoked Ca(2+) transients in left ventricular myocytes isolated 1 week, 1 month, and 3 months after MI. One week, 1 month, and 3 months after MI, the transporting function of PMCA decreased by 27, 41, and 67%, respectively, compared with that in time-matched sham animals. This was accompanied by increased amplitude of Ca(2+) transients, cell shortening, and SR Ca(2+) content. Carboxyeosin, a blocker of PMCA, increased the amplitude of shortening in cells extracted from control hearts. This effect was absent 1 and 3 months after MI. PMCA1, 2, and 4 mRNAs were unchanged in the ventricular muscle 3 months after MI when compared with time-matched sham animals. The transporting function of NCX was increased by 65% only 3 months after MI, whereas that of SERCA2a was decreased by approximately 18% at all three time points after MI.The ability of PMCA to transport Ca(2+) progressively decreases over 3 months after MI. This decrease may contribute to the increase in amplitude of Ca(2+) transients and myocyte shortening.
Transient Activation of Hedgehog Pathway Rescued Irradiation-Induced Hyposalivation by Preserving Salivary Stem/Progenitor Cells and Parasympathetic Innervation
Authors: Bo Hai, Lizheng Qin, Zhenhua Yang, Qingguo Zhao, Lei Shangguan, Xinyu Ti, Yanqiu Zhao, Sangroh Kim, Dharanipathy Rangaraj, Fei Liu
Journal: Clinical Cancer Research (2013)

To examine the effects and mechanisms of transient activation of the Hedgehog pathway on rescuing radiotherapy-induced hyposalivation in survivors of head and neck cancer.Mouse salivary glands and cultured human salivary epithelial cells were irradiated by a single 15-Gy dose. The Hedgehog pathway was transiently activated in mouse salivary glands, by briefly overexpressing the Sonic hedgehog (Shh) transgene or administrating smoothened agonist, and in human salivary epithelial cells, by infecting with adenovirus encoding Gli1. The activity of Hedgehog signaling was examined by the expression of the Ptch1-lacZ reporter and endogenous Hedgehog target genes. The salivary flow rate was measured following pilocarpine stimulation. Salivary stem/progenitor cells (SSPC), parasympathetic innervation, and expression of related genes were examined by flow cytometry, salisphere assay, immunohistochemistry, quantitative reverse transcription PCR, Western blotting, and ELISA.Irradiation does not activate Hedgehog signaling in mouse salivary glands. Transient Shh overexpression activated the Hedgehog pathway in ductal epithelia and, after irradiation, rescued salivary function in male mice, which is related with preservation of functional SSPCs and parasympathetic innervation. The preservation of SSPCs was likely mediated by the rescue of signaling activities of the Bmi1 and Chrm1-HB-EGF pathways. The preservation of parasympathetic innervation was associated with the rescue of the expression of neurotrophic factors such as Bdnf and Nrtn. The expression of genes related with maintenance of SSPCs and parasympathetic innervation in female salivary glands and cultured human salivary epithelial cells was similarly affected by irradiation and transient Hedgehog activation.These findings suggest that transient activation of the Hedgehog pathway has the potential to restore salivary gland function after irradiation-induced dysfunction.
Clonal relationship between langerhans cell histiocytosis and myeloid sarcoma
Authors: A H Schmitt-Graeff, H Duerkop, B Vollmer-Kary, S Haxelmans, R Nitschke, P Fisch, U Germing, H Stein
Journal: Leukemia (2012)

Langerhans cells (LCs) represent the main antigen capturing, processing and presenting dentritic cells (DCs) resident in epithelial surfaces including the skin or the oral mucosa, thus leading to either the induction of immune responses or tolerance. They are classically considered as myeloid-derived DCs sharing initial steps of their differentiation with monocytes. LC histiocytosis (LCH) and the more aggressive variant LC sarcoma (LCS) are considered as the neoplastic counterparts of this DC cell type. The immunoreactivity for macrophage-associated antigens in conjunction with CD1a, S-100 protein and langerin (CD207) represents a useful tool to establish the diagnosis of LCH in paraffin-embedded material.1 Rare cases of neoplasms with LC differentiation features developing in patients previously diagnosed with follicular lymphoma or acute lymphoblastic lymphoma/leukaemia (ALL) of T- and B-cell lineage have been reported. In these cases, identical clonal IgH- or TCRγ-gene rearrangements were detected in the H/DC neoplasms and the lymphomas consistent with a common clonal origin.2, 3, 4, 5 The development of the histiocytic dentritic/cell (H/DC) neoplasm was associated with progressive disease in most of these cases. Thus, it has been suggested that these tumours may represent a part of the clonal evolution of the underlying lymphomas.4 The development of a LCS in a patient with an acute B-ALL in complete remission for 9 years has been attributed to a transcription factor-induced transdifferentiation.5 Both neoplasms showed an identical IgH rearrangement, but different expressions of PAX5 and ID2.5
Evolution of Clonality and Polyploidy in a Weevil System
Authors: P. Stenberg
Journal: Molecular Biology and Evolution (2003)

The increased interest in asexual organisms calls for in-depth studies of asexual complexes that actively give rise to new clones. We present an extensive molecular study of the Otiorhynchus scaber (Coleoptera, Curculionidae) weevil system. Three forms have traditionally been recognized: diploid sexuals, triploid, and tetraploid parthenogens. All forms coexist in a small central area, but only the polyploid parthenogens have colonized marginal areas. Analyzing the phylogenetic relationship, based on three partial mitochondrial genes, of 95 individuals from 19 populations, we find that parthenogenesis and polyploidy have originated at least three times from different diploid lineages. We observe two major mitochondrial lineages, with over 2.5% sequence divergence between the most basal groups within them, and find that current distribution and phylogenetic relationships are weakly correlated. Quite unexpectedly, we also discover diploid clones that coexist with, and are morphologically indistinguishable from, the diploid sexual females. Our results support that these diploid clones are derived directly from the diploid sexuals. We also find that it is mainly an increase in ploidy level and not the benefits of asexual reproduction that confers to polyploid parthenogens the advantage over their diploid sexual relatives.
A historical perspective on the discovery of the accessory duct of the pancreas, the ampulla 'of Vater' and pancreas divisum.
Authors: C D Stern
Journal: Gut (1986)

The discovery of the accessory duct of the pancreas is usually ascribed to Giovanni Domenico Santorini (1681-1737), after whom this structure is named. The papilla duodeni (ampulla 9of Vater9, or papilla 9of Santorini9) is named after Abraham Vater (1684-1751) or after GD Santorini. Pancreas divisum, a persistence through non-fusion of the embryonic dorsal and ventral pancreas is a relatively common clinical condition, the discovery of which is usually ascribed to Joseph Hyrtl (1810-1894). In this review I report that pancreas divisum, the accessory duct and the papilla duodeni (ampulla 9of Vater9) had all been observed and the observations published during the 17th century by at least seven anatomists before Santorini, Vater, and Hyrtl. I further suggest, in the light of frequent anatomical misattributions in common usage, that anatomical structures be referred to only by their proper anatomical names.
Disruption of the fibroblast growth factor-2 gene results in decreased bone mass and bone formation
Authors: Aldemar Montero, Yosuke Okada, Masato Tomita, Masako Ito, Hiroshi Tsurukami, Toshitaka Nakamura, Thomas Doetschman, J. Douglas Coffin, Marja M. Hurley
Journal: Journal of Clinical Investigation (2000)

Basic fibroblast growth factor (FGF-2), an important modulator of cartilage and bone growth and differentiation, is expressed and regulated in osteoblastic cells. To investigate the role of FGF-2 in bone, we examined mice with a disruption of the Fgf2 gene. Measurement of trabecular bone architecture of the femoral metaphysis of Fgf2+/+ and Fgf2–/– adult mice by micro-CT revealed that the platelike trabecular structures were markedly reduced and many of the connecting rods of trabecular bone were lost in the Fgf2–/– mice. Dynamic histomorphometry confirmed a significant decrease in trabecular bone volume, mineral apposition, and bone formation rates. In addition, there was a profound decreased mineralization of bone marrow stromal cultures from Fgf2–/– mice. This study provides strong evidence that FGF-2 helps determine bone mass as well as bone formation.
Endogenous Interleukin-10 Regulates Hemodynamic Parameters, Leukocyte-Endothelial Cell Interactions, and Microvascular Permeability During Endotoxemia
Authors: Michael J. Hickey, Andrew C. Issekutz, Paul H. Reinhardt, Richard N. Fedorak, Paul Kubes
Journal: Circulation Research (1998)

Abstract —The objective of this study was to determine whether endogenous IL-10 is capable of regulating hemodynamic parameters, leukocyte recruitment, and microvascular permeability in response to endotoxin. Intravital microscopy was used to examine hemodynamic parameters, leukocyte rolling and adhesion, and microvascular permeability in cremasteric postcapillary venules in wild-type mice and in IL-10–deficient (IL-10 −/− ) mice exposed to lipopolysaccharide (LPS). Doses of LPS (3 or 30 μg/kg, IV), which did not reduce blood pressure and minimally altered microvascular hemodynamic factors in wild-type mice, caused significant reductions in these parameters in IL-10 −/− mice, demonstrating at least a 10-fold increased sensitivity in IL-10 −/− mice to LPS-induced hemodynamic alterations. Furthermore, in response to LPS (30 μg/kg, IV), leukocyte rolling, adhesion, and fluorescein isothiocyanate–albumin extravasation were increased in the IL-10 −/− mice. Antibody blockade experiments showed that in both types of mice, leukocyte rolling was mediated by E-selectin and P-selectin. Leukocyte accumulation into other tissues, such as lung, also was enhanced greatly in IL-10 −/− mice. This was specific to endotoxin, because acute chemotactic stimuli including N-formyl-methionyl-leucyl-phenylalanine elicited similar responses in IL-10 −/− and wild-type mice. These results suggest that endogenous IL-10 may be a homeostatic regulator of hemodynamic parameters, leukocyte-endothelial cell interactions, and microvascular dysfunction in response to endotoxin and provide potential mechanisms to explain the protective effect of IL-10 against LPS-induced mortality.
Fibroblast Growth Factor 23 Is a Counter-Regulatory Phosphaturic Hormone for Vitamin D
Authors: Shiguang Liu, Wen Tang, Jianping Zhou, Jason R. Stubbs, Qiang Luo, Min Pi, L. Darryl Quarles
Journal: Journal of the American Society of Nephrology (2006)

The regulation of the phosphaturic factor fibroblast growth factor 23 (FGF23) is not well understood. It was found that administration of 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) to mice rapidly increased serum FGF23 concentrations from a basal level of 90.6 ± 8.1 to 213.8 ± 14.6 pg/ml at 8 h (mean ± SEM; P < 0.01) and resulted in a four-fold increase in FGF23 transcripts in bone, the predominate site of FGF23 expression. In the Hyp-mouse homologue of X-linked hypophosphatemic rickets, administration of 1,25(OH)2D3 further increased circulating FGF23 levels. In Gcm2 null mice, low 1,25(OH)2D3 levels were associated with a three-fold reduction in FGF23 levels that were increased by administration of 1,25(OH)2D3. In osteoblast cell cultures, 1,25(OH)2D3 but not calcium, phosphate, or parathyroid hormone stimulated FGF23 mRNA levels and resulted in a dose-dependent increase in FGF23 promoter activity. Overexpression of a dominant negative vitamin D receptor inhibited 1,25(OH)2D3 stimulation of FGF23 promoter activity, and mutagenesis of the FGF23 promoter identified a vitamin D-responsive element (−1180 GGAACTcagTAACCT −1156) that is responsible for the vitamin D effects. These data suggest that 1,25(OH)2D3 is an important regulator of FGF23 production by osteoblasts in bone. The physiologic role of FGF23 may be to act as a counterregulatory phosphaturic hormone to maintain phosphate homeostasis in response to vitamin D.
Antitumor Activity and Safety of Tivozanib (AV-951) in a Phase II Randomized Discontinuation Trial in Patients With Renal Cell Carcinoma
Authors: Dmitry A. Nosov, Brooke Esteves, Oleg N. Lipatov, Alexei A. Lyulko, A. A. Anischenko, Raju T. Chacko, Dinesh C. Doval, Andrew Strahs, William J. Slichenmyer, Pankaj Bhargava
Journal: Journal of Clinical Oncology (2012)

The antitumor activity and safety of tivozanib, which is a potent and selective vascular endothelial growth factor receptor-1, -2, and -3 inhibitor, was assessed in patients with advanced/metastatic renal cell carcinoma (RCC).In this phase II, randomized discontinuation trial, 272 patients received open-label tivozanib 1.5 mg/d (one cycle equaled three treatment weeks followed by a 1-week break) orally for 16 weeks. Thereafter, 78 patients who demonstrated ≥ 25% tumor shrinkage continued to take tivozanib, and 118 patients with less than 25% tumor change were randomly assigned to receive tivozanib or a placebo in a double-blind manner; patients with ≥ 25% tumor growth were discontinued. Primary end points included safety, the objective response rate (ORR) at 16 weeks, and the percentage of randomly assigned patients who remained progression free after 12 weeks of double-blind treatment; secondary end points included progression-free survival (PFS).Of 272 patients enrolled onto the study, 83% of patients had clear-cell histology, 73% of patients had undergone nephrectomy, and 54% of patients were treatment naive. The ORR after 16 weeks of tivozanib treatment was 18% (95% CI, 14% to 23%). Of the 118 randomized patients, significantly more patients who were randomly assigned to receive double-blind tivozanib remained progression free after 12 weeks versus patients who received the placebo (49% v 21%; P = .001). Throughout the study, the ORR was 24% (95% CI, 19% to 30%), and the median PFS was 11.7 months (95% CI, 8.3 to 14.3 months) in the overall study population. The most common grade 3 and 4 treatment-related adverse event was hypertension (12%).Tivozanib was active and well tolerated in patients with advanced RCC. These data support additional development of tivozanib in advanced RCC.
Use of Forensic Methods Under Exigent Circumstances Without Full Validation
Authors: Steven E. Schutzer, Paul Keim, Ken Czerwinski, Bruce Budowle
Journal: Science Translational Medicine (2009)

Forensic science can be instrumental in providing investigative leads or clues to help identify the perpetrators, and those who are innocent, of a chemical, biological, radiological, or nuclear terrorist attack, as well as identify leads during infectious outbreaks or other public health threats. Because of a need to react quickly in exigent circumstances during which the threat of continued attack persists, methods may be used that are not fully validated. A preliminary validation should be performed to evaluate the acquisition of limited test data to ensure that the interpretation of results remains within the limitations of known performance of the method. If results from a preliminarily validated method are used beyond developing an investigative lead, further validation should be considered to support its reliability for adjudication purposes.