tbuckley/cabot-search huggingface dataset:
MicroRNAs in the development and pathobiology of uterine leiomyomata: does evidence support future strategies for clinical intervention?
Authors: Anatte E. Karmon, Eden R. Cardozo, Bo R. Rueda, Aaron K. Styer
Journal: Human Reproduction Update (2014)

BACKGROUNDHuman leiomyomata (fibroids) are benign tumors of the uterus, represent the most common neoplasms of reproductive-aged women and have a prevalence of ∼70% in the general population. This disorder conveys a significant degree of morbidity and remains the leading indication for hysterectomy in the USA. Prior investigations of aberrant microRNA (miRNA) expression in various malignancies have provided invaluable insight into the role of this class of small non-coding RNAs in tumor growth. Evidence of irregular miRNA expression in uterine fibroids has garnered recent interest for diagnostic and therapeutic applications. Since miRNA gene targets modulate several processes implicated in the genesis of uterine fibroids, more focused investigation has the potential to elucidate the functional significance of miRNA in the genesis and pathology of the disease.
Binding of the P2Y <sub>2</sub> Nucleotide Receptor to Filamin A Regulates Migration of Vascular Smooth Muscle Cells
Authors: Ningpu Yu, Laurie Erb, Rikka Shivaji, Gary A. Weisman, Cheikh I. Seye
Journal: Circulation Research (2008)

The functional expression of the G protein-coupled P2Y(2) nucleotide receptor (P2Y(2)R) has been associated with proliferation and migration of vascular smooth muscle cells (SMCs), two processes involved in atherosclerosis and restenosis. Activation of the P2Y(2)R causes dynamic reorganization of the actin cytoskeleton, which transmits biochemical signals and forces necessary for cell locomotion, suggesting that P2Y(2)Rs may be linked to the actin cytoskeleton. Here, we identified filamin A (FLNa) as a P2Y(2)R-interacting protein using a yeast 2-hybrid system screen with the C-terminal region of the P2Y(2)R as bait. The FLNa binding site in the P2Y(2)R is localized between amino acids 322 and 333. Deletion of this region led to selective loss of FLNa binding to the P2Y(2)R and abolished Tyr phosphorylation of FLNa induced by the P2Y(2)R agonist UTP. Using both time-lapse microscopy and the Transwell cell migration assay, we showed that UTP significantly increased SMC spreading on collagen I (6.8 fold; P < or = 0.01) and migration (3.6 fold; P < or = 0.01) of aortic SMCs isolated from wild-type mice, as compared with unstimulated SMCs. UTP-induced spreading and migration of aortic SMCs did not occur with cells isolated from P2Y(2)R knockout mice. Expression of the full-length P2Y(2)R in SMCs isolated from P2Y(2)R knockout mice restored both UTP-induced spreading and migration. In contrast, UTP-induced spreading and migration did not occur in SMCs isolated from P2Y(2)R knockout mice transfected with a mutant P2Y(2)R that does not bind FLNa. Furthermore, ex vivo studies showed that both ATP and UTP (10 micromol/L) promoted migration of SMCs out of aortic explants isolated from wild-type but not P2Y(2)R knockout mice. Thus, this study demonstrates that P2Y(2)R/FLNa interaction selectively regulates spreading and migration of vascular SMCs.
Importance of concomitant local and systemic eosinophilia in uncontrolled asthma
Authors: F. N. Schleich, A. Chevremont, V. Paulus, M. Henket, M. Manise, L. Seidel, R. Louis
Journal: European Respiratory Journal (2014)

Systemic and airway eosinophilia are recognised features of asthma. There are, however, patients who exhibit discordance between local and systemic eosinophilia. In this study, we sought to determine the prevalence and characteristics of patients with concordant and discordant systemic and bronchial eosinophilia. We conducted a retrospective study on 508 asthmatics with successful sputum induction. We assessed the relationship between blood and sputum eosinophils by breaking down the population into four groups according to blood (≥400 cells per mm3) and sputum (≥3%) eosinophils. Then, we prospectively reassessed the link between eosinophils and asthma control (Asthma Control Questionnaire (ACQ)) and exacerbation rate in a new cohort of 250 matched asthmatics. In our retrospective cohort, asthmatics without eosinophilic inflammation were the largest group (49%). The group with isolated sputum eosinophilia (25%) was, compared with noneosinophilic asthma, associated with lower forced expiratory volume in 1 s (FEV1) and FEV1/forced vital capacity ratio and higher bronchial hyperresponsiveness and exhaled nitric oxide fraction (FeNO). Asthmatics exhibiting isolated systemic eosinophilia (7%) had similar characteristics as noneosinophilic asthmatics. The group with concordant systemic and airway eosinophilia (19%) showed remarkable male predominance, and had the lowest airway calibre, asthma control and quality of life, and the highest bronchial hyperresponsiveness, FeNO and exacerbation rate. The prospective cohort confirmed the different subgroup proportions and the higher ACQ and exacerbation rates in cases of diffuse eosinophilia compared with noneosinophilic asthmatics. Concomitant systemic and bronchial eosinophilic inflammation contribute to poor asthma control.
A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva
Authors: Eileen M Shore, Meiqi Xu, George J Feldman, David A Fenstermacher, Tae-Joon Cho, In Ho Choi, J Michael Connor, Patricia Delai, David L Glaser, Martine LeMerrer, Rolf Morhart, John G Rogers, Roger Smith, James T Triffitt, J Andoni Urtizberea, Michael Zasloff, Matthew A Brown, Frederick S Kaplan
Journal: Nature Genetics (2006)
The Proximal Tubule and Albuminuria
Authors: Landon E. Dickson, Mark C. Wagner, Ruben M. Sandoval, Bruce A. Molitoris
Journal: Journal of the American Society of Nephrology (2014)

Recent data highlight the role of the proximal tubule (PT) in reabsorbing, processing, and transcytosing urinary albumin from the glomerular filtrate. Innovative techniques and approaches have provided exciting insights into these processes, and numerous investigators have shown that selective PT cell defects lead to significant albuminuria, even reaching nephrotic range in animal models. Thus, the mechanisms of albumin reabsorption and transcytosis are undergoing intense study. Working in concert with megalin and cubilin, a nonselective multireceptor complex that predominantly directs proteins for lysosomal degradation, the neonatal Fc receptor (FcRn) located at the brush border of the apical membrane has been implicated as the "receptor" mediating albumin transcytosis. The FcRn pathway facilitates reabsorption and mediates transcytosis by its pH-dependent binding affinity in endosomal compartments. This also allows for selective albumin sorting within the PT cell. This reclamation pathway minimizes urinary losses and catabolism of albumin, thus prolonging its serum half-life. It may also serve as a molecular sorter to preserve and reclaim normal albumin while allowing "altered" albumin to be catabolized via lysosomal pathways. Here, we critically review the data supporting this novel mechanism.
Expression of Multidrug Resistance–Associated Proteins Predicts Prognosis in Childhood and Adult Acute Lymphoblastic Leukemia
Authors: Sabine L.A. Plasschaert, Eveline S.J.M. de Bont, Marike Boezen, Dorina M. vander Kolk, Simon M.J.G. Daenen, Klaas Nico Faber, Willem A. Kamps, Elisabeth G.E. de Vries, Edo Vellenga
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Patients with acute lymphoblastic leukemia (ALL) are treated with a variety of chemotherapeutic drugs, which can be transported by six multidrug resistance–associated proteins (MRP). These MRPs have strongly overlapping functional activities. The aim of this study was to investigate the expression levels of MRP1 to MRP6 and study their effect on prognosis. Experimental Design: The mRNA expression levels of MRP1 to MRP6 were analyzed by quantitative real-time PCR in leukemic blasts of 105 de novo ALL patients (adults, n = 49; children, n = 56) including 70% B-lineage and 30% T-lineage ALL patients. Results: Adults showed a higher expressions of MRP1 (P = 0.008), MRP2 (P = 0.026), and MRP3 (P = 0.039) than children. Interestingly, this difference disappeared when patients were categorized based on clinical outcome. Relapsed patients showed a higher expression of all MRP genes, except MRP4. For the total group of ALL patients, the expressions of MRP1, MRP2, MRP3, MRP5, and MRP6 predicted relapse. Moreover, high expression of all MRP genes, except MRP4, was associated with a reduced relapse-free survival in children and adults (MRP1, P = 0.005; MRP2, P = 0.008; MRP3, P = 0.001; MRP5, P = 0.016; MRP6, P = 0.037). Conclusions: The present study shows that a subset of ALL patients with high MRP expression has an unfavorable prognosis independently of age.
Relief of Nocturnal Enuresis by Desmopressin Is Kidney and Vasopressin Type 2 Receptor Independent
Authors: Joris H. Robben, Mozes Sze, Nine V. Knoers, Paul Eggert, Peter Deen, Dominik Mu[Combining Diaeresis]ller
Journal: Journal of the American Society of Nephrology (2007)

Primary nocturnal enuresis (PNE) is a common problem in childhood and adolescence. Although various treatments are highly effective, a common underlying hypothesis on the pathogenesis is lacking. The success of desmopressin, a synthetic analogue of the antidiuretic hormone vasopressin, has been attributed to increased renal water reabsorption that is mediated by activation of the renal vasopressin V2 receptor (V2R). However, this effect does not explain other symptoms of PNE, such as the failure to arouse upon bladder distension. This study identified a family in which one child displayed PNE and coexisting nephrogenic diabetes insipidus, as a result of a novel nonsense mutation in the V2R gene (C358X). Cell-biologic investigations revealed that V2R-C358X is retained in the endoplasmic reticulum and is unstable, which explains his nephrogenic diabetes insipidus. Consistently, extrarenal V2R-mediated responses were absent in the patient who was treated with desmopressin. Administration of desmopressin, however, changed his PNE into nocturia, because he now still voided unchanged high urinary volumes at night but woke up and went to the bathroom. Withdrawal of desmopressin was accompanied by bedwetting, whereas reintroduction again relieved the symptoms. Therefore, these data indicate that neither a functioning renal concentration system nor a functional V2R is needed for the therapeutic benefit of desmopressin in PNE. Rather, it suggests that another vasopressin receptor and other organ(s) is the target for desmopressin to relieve PNE.
Expression and Antitumor Effects of TRAIL in Human Cholangiocarcinoma
Authors: Shinji Tanaka, Keishi Sugimachi, Ken Shirabe, Mitsuo Shimada, Jack R. Wands, Keizo Sugimachi
Journal: Hepatology (2000)

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)/Apo2L has been recently identified as important in promoting programmed cell death in breast and colon adenocarcinomas. In this study, we investigated the expression and therapeutic potential of TRAIL in cholangiocarcinoma, one of the most devastating human hepatic malignancies. Expression of TRAIL receptors was determined in 13 patients with resectable intrahepatic cholangiocarcinoma. Cellular effects of TRAIL in promoting apoptosis of human cholangiocarcinoma cells were analyzed after exposure to recombinant protein, as well as following transfection with a cDNA expression construct. In vivo effects of TRAIL on tumor growth were investigated after subcutaneous injection of cholangiocarcinoma cells into nude mice. Analysis of 13 clinical and tissue samples revealed that TRAIL receptors containing the death domain were present in all cholangiocarcinomas as well as paired normal hepatic tissues derived from surgically resected margins. In contrast, 7 tumors did not express the TRAIL decoy receptors lacking the death domain; such receptors were detectable in all of the normal hepatic tissue counterparts. Recombinant TRAIL induced extensive programmed cell death in cholangiocarcinoma cell lines lacking decoy receptor expression. Transfection of the ectodomain of TRAIL also induced cellular apoptosis; this effect was abolished by introduction of the generalized lymphoproliferative disease-like mutation in the TRAIL protein. Finally, in vivo administration of recombinant TRAIL substantially inhibited subcutaneous tumor growth of human cholangiocarcinoma cells. Induction of apoptosis in tumor cells is possible with a biologically active TRAIL, and suggests that this cytokine is a promising antitumor agent against human cholangiocarcinoma.
Does Low Bone Mineral Density Start in Post-Teenage Years in Women With Type 1 Diabetes?
Authors: Emily Y. Liu, Jean Wactawski-Wende, Richard P. Donahue, Jacek Dmochowski, Kathleen M. Hovey, Teresa Quattrin
Journal: Diabetes Care (2003)

Type 1 diabetes has been associated with decreased bone mineral density (BMD). However, the natural history and etiopathogenesis of osteoporosis in type 1 diabetes are not clear. The aims of this study were to assess BMD in a cohort of young women with type 1 diabetes compared with nondiabetic control subjects and to evaluate the possible association of BMD with diabetes duration, HbA(1c), and biomarkers of bone metabolism.BMD was measured by dual-energy X-ray absortiometry scan in 39 teenage (age 13-19 years) and 33 post-teenage females (age 20-37 years) with type 1 diabetes and 91 female age-matched control subjects. Serum osteocalcin, IGF-I, IGF binding protein-3 (IGFBP-3), HbA(1c), and urine N-telopeptides were measured.After adjustment for age and BMI, BMD values were significantly lower at the femoral neck and lateral spine in women with type 1 diabetes older than age 20 years compared with control subjects but not in the case subjects younger than age 20 years, nor at the anterio-posterior spine, wrist, or whole body. No association was found between BMD and diabetes duration or glycemic control. IGF-I, IGFBP-3, osteocalcin, and N-telopeptides were similar in diabetic subjects and control subjects.This study indicates that women with type 1 diabetes exhibit BMD differences early in life with significant differences already present in the post-teenage years. Lower hip BMD in these young women may explain, in part, the higher incidence of hip fracture experienced in postmenopausal women with type 1 diabetes.
Ambulatory Blood Pressure Monitoring Could Unmask Hypertension in Patients with Psoriasis Vulgaris
Authors: Ahmet Bacaksız, Ercan Erdogan, Osman Sonmez, Emrah Sevgili, Abdurrahman Tasal, Nahide Onsun, Bugce Topukcu, Beytullah Kulac, Omer Uysal, Omer Goktekin
Journal: Journal of the American College of Cardiology (2013)
Trainee GP who posted photos of patients online is told his fitness to practise is impaired
Authors: C. Dyer
Journal: BMJ (2014)

A trainee GP who posted photographs of three patients’ injuries on Instagram along with demeaning comments has escaped sanction despite a finding of impaired fitness to practise by the Medical Practitioners Tribunal Service.

Cemal Kavasogullari, who qualified in Turkey in 2008, asked permission from his patients to photograph their injuries with his mobile phone, to consult with colleagues. But after deleting them on his phone he later found that they had been uploaded to an online storage service, and he posted them to his Instagram account without the patients’ consent. The patients …
Greater peak rearfoot eversion predicts foot orthoses efficacy in individuals with patellofemoral pain syndrome
Authors: C J Barton, H B Menz, P Levinger, K E Webster, K M Crossley
Journal: British Journal of Sports Medicine (2010)

Objective There is growing evidence for the provision of foot orthoses when treating individuals with patellofemoral pain syndrome (PFPS), and prescription is frequently based on the assessment of foot posture/function. However, evaluation of the link between abnormal foot posture/function and foot orthoses outcomes has previously been limited to static alignment measures and has produced inconsistent findings. In this study, the ability of baseline foot kinematics associated with pronation to predict marked improvement 12 weeks following foot orthoses prescription in individuals with PFPS was evaluated. Methods 26 individuals with PFPS were issued with prefabricated foot orthoses, and patient-reported level of improvement was documented at 12 weeks. Potential predictors of marked improvement at 12 weeks were measured during walking at baseline and included forefoot dorsiflexion and abduction, and rearfoot eversion. Results Of the 25 participants who completed the study, seven (28%) reported marked improvement with the foot orthoses after 12 weeks. Discriminant function analysis revealed a greater peak rearfoot eversion to be the only significant independent predictor of marked improvement. Conclusion These findings provide preliminary evidence that greater peak rearfoot eversion is predictive of marked improvement 12 weeks following prefabricated foot orthoses prescription in individuals with PFPS. Therefore, foot orthoses may be most effective in the subgroup of people with PFPS and increased dynamic foot pronation.
Clinical Significance of Sphingosine Kinase-1 Expression in Human Astrocytomas Progression and Overall Patient Survival
Authors: Jun Li, Hong-Yu Guan, Li-Yun Gong, Li-Bing Song, Nu Zhang, Jueheng Wu, Jie Yuan, Yi-Jie Zheng, Zheng-Song Huang, Mengfeng Li
Journal: Clinical Cancer Research (2008)

Abstract Purpose: To characterize the expression of sphingosine kinase-1 (SPHK1) in human astrocytomas and to investigate the association between SPHK1 expression and progression of astrocytomas. Experimental Design: The expression of SPHK1 in normal human astrocytes, astrocytoma cell lines, and four pairs of matched astrocytoma tissues and their adjacent normal brain tissues were detected by quantitative reverse transcription-PCR and Western blot. In addition, SPHK1 protein expression was examined in 243 cases of histologically characterized astrocytomas by immunohistochemistry. Statistical analyses were applied to test for prognostic and diagnostic associations. Results: SPHK1 in astrocytoma cell lines was elevated at both mRNA and protein levels, and the SPHK1 mRNA and protein were significantly up-regulated by up to 6.8- and 40-fold, respectively, in primary astrocytomas compared with those in the adjacent noncancerous brain tissues. Immunohistochemical analysis showed that 100 of 243 (41.2%) paraffin-embedded archival astrocytoma biopsies exhibited high expression of SPHK1. Statistical analysis suggested that the up-regulation of SPHK1 was significantly correlated with the histologic grade of astrocytoma (P = 0.000) and that patients with high SPHK1 level exhibited shorter survival time (P &amp;lt; 0.001). Multivariate analysis revealed that SPHK1 up-regulation might be an independent prognostic indicator for the survival of patients with astrocytoma. Conclusions: SPHK1 might represent a novel and useful prognostic marker for astrocytoma and play a role during the development and progression of the disease.
Replication and meta-analysis of the gene-environment interaction between body mass index and the interleukin-6 promoter polymorphism with higher insulin resistance
Authors: Patricia C. Underwood, Bindu Chamarthi, Jonathan S. Williams, Bei Sun, Anand Vaidya, Benjamin A. Raby, Jessica Lasky-Su, Paul N. Hopkins, Gail K. Adler, Gordon H. Williams
Journal: Metabolism (2011)
Cervical pessary in pregnant women with a short cervix (PECEP): an open-label randomised controlled trial
Authors: Maria Goya, Laia Pratcorona, Carme Merced, Carlota Rodó, Leonor Valle, Azahar Romero, Miquel Juan, Alberto Rodríguez, Begoña Muñoz, Belén Santacruz, Juan Carlos Bello-Muñoz, Elisa Llurba, Teresa Higueras, Luis Cabero, Elena Carreras
Journal: The Lancet (2012)
Vitreous Levels of Bevacizumab and Vascular Endothelial Growth Factor-A in Patients with Choroidal Neovascularization
Authors: Qi Zhu, Focke Ziemssen, Sigrid Henke-Fahle, Olcay Tatar, Peter Szurman, Sabine Aisenbrey, Nicole Schneiderhan-Marra, Xun Xu, Salvatore Grisanti
Journal: Ophthalmology (2008)
THE EFFECT OF CHEMICAL AND PHYSICAL AGENTS ON THE PHAGE RECEPTOR OF PHASE II SHIGELLA SONNEI
Authors: Guy T. Barry, Walther F. Goebel
Journal: The Journal of Experimental Medicine (1951)

A study has been made of the effect of bactericidal agents on the phage adsorption properties of Phase II. Sh. sonnei. The ability of this microorganism to adsorb T(3), T(4), and T(7) phages can be altered by treating the bacteria with chemical and physical agents.
Progressive left ventricular remodeling in patients with hypertrophic cardiomyopathy and severe left ventricular hypertrophy
Authors: Rajesh Thaman, Juan R. Gimeno, Sebastian Reith, Maria T.Tome Esteban, Giuseppe Limongelli, Ross T. Murphy, Bryan Mist, William J. McKenna, Perry M. Elliott
Journal: Journal of the American College of Cardiology (2004)
Diabetes risk factors in low-income Mexican-American children.
Authors: R P Treviño, R M Marshall, D E Hale, R Rodriguez, G Baker, J Gomez
Journal: Diabetes Care (1999)

OBJECTIVE: To learn if Mexican-American children from low income neighborhoods have excess diabetes risk factors. RESEARCH DESIGN AND METHODS: The study involved 173 Mexican-American children aged 9 years. This is the age before type 2 diabetes usually develops in youths and where the disparity in body fat between Mexican-American and non-Hispanic white children is evident. The study also targets poor children because diabetes and being overweight are more common in Mexican-American adults from a lower than from a higher socioeconomic status. The diabetes risk factors measured were percent body fat, dietary fat intake, daily fruit and vegetable intake, and physical fitness. Body fat was measured by bioelectric impedance, dietary intake was measured by three 24-h dietary recalls, and physical fitness was measured by a modified Harvard step test. RESULTS: According to self-reported dietary recalls, Mexican-American children ate higher than recommended fat servings and had higher percent energy from fat and saturated fat. On the other hand, their reported daily fruit and vegetable intake was half of that recommended by national dietary guidelines. A large percentage of these children were at unacceptable physical fitness levels. Percent body fat was higher in these Mexican-American children than that reported for non-Hispanic white children. Finally, 60% of the children had a first- or second-degree relative with diabetes. CONCLUSIONS: Because diabetes is highly prevalent in Mexican-American adults, type 2 diabetes in increasing in Mexican-American youths, and diabetes risk factors are more common in Mexican-American children, a prudent measure would be to explore early-age diabetes risk factor prevention programs in this population.