tbuckley/cabot-search huggingface dataset:
Identification of Two Distinct Carcinoma-Associated Fibroblast Subtypes with Differential Tumor-Promoting Abilities in Oral Squamous Cell Carcinoma
Authors: Daniela Elena Costea, Allison Hills, Amani H. Osman, Johanna Thurlow, Gabriela Kalna, Xiaohong Huang, Claudia Pena Murillo, Himalaya Parajuli, Salwa Suliman, Keerthi K. Kulasekara, Anne Chr. Johannessen, Max Partridge
Journal: Cancer Research (2013)

Abstract Heterogeneity of carcinoma-associated fibroblasts (CAF) has long been recognized, but the functional significance remains poorly understood. Here, we report the distinction of two CAF subtypes in oral squamous cell carcinoma (OSCC) that have differential tumor-promoting capability, one with a transcriptome and secretome closer to normal fibroblasts (CAF-N) and the other with a more divergent expression pattern (CAF-D). Both subtypes supported higher tumor incidence in nonobese diabetic/severe combined immunodeficient (NOD/SCID) Ilγ2(null) mice and deeper invasion of malignant keratinocytes than normal or dysplasia-associated fibroblasts, but CAF-N was more efficient than CAF-D in enhancing tumor incidence. CAF-N included more intrinsically motile fibroblasts maintained by high autocrine production of hyaluronan. Inhibiting CAF-N migration by blocking hyaluronan synthesis or chain elongation impaired invasion of adjacent OSCC cells, pinpointing fibroblast motility as an essential mechanism in this process. In contrast, CAF-D harbored fewer motile fibroblasts but synthesized higher TGF-β1 levels. TGF-β1 did not stimulate CAF-D migration but enhanced invasion and expression of epithelial–mesenchymal transition (EMT) markers in malignant keratinocytes. Inhibiting TGF-β1 in three-dimensional cultures containing CAF-D impaired keratinocyte invasion, suggesting TGF-β1–induced EMT mediates CAF-D–induced carcinoma cell invasion. TGF-β1–pretreated normal fibroblasts also induced invasive properties in transformed oral keratinocytes, indicating that TGF-β1–synthesizing fibroblasts, as well as hyaluronan-synthesizing fibroblasts, are critical for carcinoma invasion. Taken together, these results discern two subtypes of CAF that promote OSCC cell invasion via different mechanisms. Cancer Res; 73(13); 3888–901. ©2013 AACR.
Occurrence of hepatocellular carcinoma and decompensation in western european patients with cirrhosis type B
Authors: Giovanna Fattovich, Giuliano Giustina, Solko W. Schalm, Stephanos Hadziyannis, Josè Sanchez-Tapias, Piero Almasio, Erik Christensen, Kim Krogsgaard, Francoise Degos, Miguel Carneiro De Moura, Antonio Solinas, Franco Noventa, Giuseppe Realdi
Journal: Hepatology (1995)

To examine the morbidity of compensated cirrhosis type B, a cohort of 349 Western European, white patients (86% men; mean age, 44 years) with biopsy-proven cirrhosis was followed up for a mean period of 73 months and was studied for occurrence of hepatocellular carcinoma (HCC) and decompensation. At entry into the study all patients were tested for hepatitis B e antigen (HBeAg; 34% of patients were HBeAg-positive) and antibody to hepatitis delta virus (anti-HDV; 20% of patients were anti-HDV-positive); 48% of 252 patients tested were hepatitis B virus (HBV)-DNA-positive. During follow-up HCC developed in 32 (9%) of the 349 patients and decompensation was observed in 88 (28%) of 317 tumor-free patients. Five years after diagnosis, the probability of decompensation was 23%. After the first episode of decompensation the probability of survival was 35% at 5 years. Cox's regression analysis identified three variables that idependently correlated with HCC: age, serum levels of platelets, and liver firmness on physical examination. HBV (HBeAg or HBV-DNA) and HDV (anti-HDV) markers at presentation had no prognostic value for the development of HCC. In conclusion, a high proportion of patients with HBsAg-positive compensated cirrhosis do not experience worsening of their condition for several years, but once decompensation occurs life expectancy is poor. European, white patients with compensated cirrhosis type B are at consistent risk for HCC. Prognostic factors for HCC reflect an advanced stage of cirrhosis and support the hypothesis that development of a tumor could be the likely consequence of long-standing hepatic disease. (Hepatology 1995;21:77-82).
Dissolution improvement of fenofibrate by melting inclusion in mesoporous silica
Authors: Fumiaki Uejo, Waree Limwikrant, Kunikazu Moribe, Keiji Yamamoto
Journal: Asian Journal of Pharmaceutical Sciences (2013)

In this study, using mesoporous silica for the solubility enhancement of poorly water-soluble drug was investigated. Although the incorporating drug into mesoporous silica is generally performed through the solvent method, the new melting method was proposed in the present study. Fenofibrate, a poorly water-soluble drug, was incorporated into mesoporous silica by solvent method and melting method. The obtained samples were observed by SEM and their physicochemical properties were evaluated by PXRD and DSC measurement. The dissolution and supersaturated property were also investigated. The results from SEM, PXRD and DSC measurement showed that drug could be loaded into pore via the melting method as well as by the solvent method. The drug loaded quantity depended on the pore volume. Drug up to 33% could be incorporated into mesoporous silica and existed in amorphous state. When drug was overloaded or difficulty in incorporation into pore was found, recrystallization of drug occurred at the outer surface of mesoporous silica. From the dissolution test, samples prepared by solvent method and melting method gave the supersaturated drug concentration which sample from melting method showed superior dissolution to the one from solvent method. From this study, drug was efficiently incorporated into mesoporous silica by the melting method which is a simple and solvent-free process, and the aqueous solubility enhancement of poorly water-soluble drug was achieved.
Differential Desensitization of Homozygous Haplotypes of the β<sub>2</sub>-Adrenergic Receptor in Lymphocytes
Authors: Jaap Oostendorp, Dirkje S. Postma, Haukeline Volders, Hajo Jongepier, Henk F. Kauffman, H. Marike Boezen, Deborah A. Meyers, Eugene R. Bleecker, S. Adriaan Nelemans, Johan Zaagsma, Herman Meurs
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Single-nucleotide polymorphisms of the β2-adrenergic receptor gene and its 5′ promoter have been associated with differences in receptor function and desensitization. Linkage disequilibrium may account for inconsistencies in reported effects of isolated polymorphisms. Therefore, we have investigated the three most common homozygous haplotypes of the β2-adrenergic receptor (position 19 [Cys/Arg] of the 5′ leader cistron and positions 16 [Arg/Gly] and 27 [Gln/Glu] of the receptor) for putative differences in agonist-induced desensitization. Lymphocytes of well defined nonasthmatic, nonallergic subjects homozygous for the haplotype CysGlyGln, ArgGlyGlu, or CysArgGln were isolated. Desensitization of (−)-isoproterenol–induced cyclic adenosine monophosphate (cAMP) accumulation and β2-adrenergic receptor sequestration and downregulation were measured in relation to β2-adrenergic receptor-mediated inhibition of IFN-γ and interleukin-5 production. We observed that lymphocytes of individuals bearing the CysGlyGln haplotype were more susceptible to desensitization of the β-agonist–induced cAMP response than those of individuals with the ArgGlyGlu or CysArgGln haplotype. The haplotype-dependent desensitization of β-agonist–induced cAMP response was not associated with haplotype-dependent β2-adrenergic receptor sequestration or downregulation. In addition, our data suggest reduced inhibition, in lymphocytes of subjects with the CysGlyGln haplotype, of interleukin-5 production induced by treatment with antibodies to the T-cell receptor–CD3 complex and to costimulatory molecule CD28 (αCD3/αCD28). This is the first study demonstrating haplotype-related differences in agonist-induced β2-adrenergic receptor desensitization in primary human cells. This haplotype-related desensitization of the β2-adrenergic receptor in lymphocytes might have consequences regarding the regulation of helper T-cell type 2 inflammatory responses.
Effects of ventilation, humidity and temperature on airway responsiveness to methacholine in rats
Authors: F.M. Arantes-Costa, S. Zoriki, M.H.C. Santos, C.H.P. Kobata, J.E. Vieira, M.A. Martins
Journal: European Respiratory Journal (2002)

Exercise-induced bronchoconstriction is associated with heat and water loss from the airways. It is not known whether these conditions can influence the response to bronchoactive agonists. The effects of different degrees of alveolar ventilation on the pulmonary response to methacholine and the role of humidity and temperature in this response were evaluated. Wistar rats were anaesthetized, tracheostomized and mechanically ventilated. Increasing doses of methacholine were infused intravenously and respiratory system resistance ( R rs ) and elastance ( E rs ) were measured. The rats were ventilated with dry air at 13°C, dry air at 37°C, humid air at 13°C and humid air at 37°C. These four groups were further divided into three subgroups with a respiratory frequency adjusted to reach a carbon dioxide tension in arterial blood of 30, 40 and 50 mmHg. Temperature, humidity and level of alveolar ventilation did not influence the position of the dose/response curve to methacholine. However, the maximal changes in E rs were significantly lower in the rats ventilated with humid air. In addition, maximal changes in E rs were significantly higher in the rats with lower alveolar ventilation. These differences were not observed for maximal values of R rs . The pulmonary response to methacholine in normal rats is significantly affected by the humidity of inspired air and the level of alveolar ventilation. This influence is more intense in the small airways and/or distal airspaces. This suggests that exercise or hyperventilation can change the behaviour of airway smooth muscle.
Patterns of disease progression and outcomes in a randomized trial testing ABVD alone for patients with limited-stage Hodgkin lymphoma
Authors: D.A. Macdonald, K. Ding, M.K. Gospodarowicz, W.A. Wells, R.G. Pearcey, J.M. Connors, J.N. Winter, S.J. Horning, M.S. Djurfeldt, L.E. Shepherd, R.M. Meyer
Journal: Annals of Oncology (2007)
Tobacco use in relation to COPD and asthma
Authors: M. N. Hylkema, P. J. Sterk, W. I. de Boer, D. S. Postma
Journal: European Respiratory Journal (2007)

Smoking is the leading cause of preventable death worldwide. Hundreds of millions of individuals still smoke, affecting their health as well as that of their peers, family and offspring. Smoking is a well-established prime risk factor for chronic obstructive pulmonary disease and hampers the response to treatment in asthma and chronic obstructive pulmonary disease. In the present paper, new concepts are discussed with respect to pathology, treatment, smoking cessation and tobacco control. Recommendations for future directions are given.
ASSOCIATION OF HIP RANGE OF MOTION AND UPPER EXTREMITY KINETICS IN YOUTH BASEBALL PITCHING
Authors: G Oliver, H Plummer, R Johnson, T Holt, L Henning, W Weimar
Journal: British Journal of Sports Medicine (2014)

Background The overhead throwing motion requires the coordination of efficient segmental actions between the lower and upper extremity. The complexity of the overhead throwing motion, especially in pitching, may be affected by restriction in lower extremity range of motion [ROM]. Objective The purpose of this study was to determine the relationship between lower extremity ROM and upper extremity kinetics during baseball pitching. Design Cross-sectional study. Setting Controlled laboratory setting. Youth sports. Participants 12 baseball pitchers 811.1±1.2 yrs.; 44.0±6.7 kg; 152.3±6.4 cm), free from injury, with 2.4±1.2 years of pitching experience volunteered. Interventions Independent variables were hip internal (IR) and external (ER) ROMs. Dependent variables were shoulder and elbow kinetics. Main outcome measurements Outcome measurements consisted of hip IR and ER ROM, and shoulder and elbow kinetics. Shoulder and elbow kinetics were assessed at maximum shoulder external rotation (MER) and maximum shoulder internal rotation (MIR) of the pitching motion. The relationship between hip ROMs and kinetics were assessed with Person Product Correlation Coefficients (P≤.05). Results A significant negative relationship was evident between left hip IR (r=−0.82, P=.02), right hip ER (r=−0.76, P=.04) and elbow valgus forces at the point of MER. A negative relationship between right hip ER and shoulder distraction forces (r=−0.82, P=.02) at MIR was evident as well. Conclusions These data suggest that there was a complex relationship between hip ROM and upper extremity kinetics during baseball pitching. This may be the first documentation establishing an association between lower extremity ROM and upper extremity kinetics during youth pitching. With elbow and shoulder injuries on the rise in youth baseball, identifying pathomechanics that result in increased joint forces is paramount. Further research is necessary to identify specific mechanisms of injury to the upper extremity associated with lower extremity function.
Thiazolidinediones and Risk of Repeat Target Vessel Revascularization Following Percutaneous Coronary Intervention
Authors: Daniel M. Riche, Rodrigo Valderrama, Nickole N. Henyan
Journal: Diabetes Care (2007)

Thiazolidinediones (TZDs) (rosiglitazone and pioglitazone) are a class of antidiabetes agents that have a high affinity for peroxisome proliferator-activated receptor-gamma. TZDs initiate a multitude of physiologic processes that may elicit benefits as systemic agents for the prevention of restenosis requiring revascularization following percutaneous coronary intervention (PCI). Numerous trials have evaluated the impact of TZDs on repeat target vessel revascularization (TVR) in patients following PCI; however, several limitations (small sample size, inconclusive results, and risk factor stratification) complicate definitive conclusions. A meta-analysis was performed to evaluate the impact of TZDs on repeat TVR following PCI.Included trials met the following criteria: 1) prospective, randomized controlled trials evaluating available TZDs versus standards of care; 2) well-described protocol; 3) minimum of 6 months of follow-up; and 4) data provided on repeat TVR. Data are presented as relative risks (RRs) with 95% CIs.Seven clinical trials (n = 608) met the inclusion criteria. Upon meta-analysis, the risk of repeat TVR was significantly reduced in patients who received TZD therapy compared with standards of care (RR 0.35 [95% CI 0.22-0.57]). In studies using rosiglitazone (0.45 [0.25-0.83]) and pioglitazone (0.24 [0.11-0.51]), risk of repeat TVR was significantly reduced. Risk of repeat TVR was also significantly reduced among patients with (0.34 [0.19-0.63]) and without (0.37 [0.18-0.77]) diabetes.Results from this meta-analysis suggest that TZDs effectively reduce the risk of repeat TVR following PCI.
Brucella arthritis: a study of 96 cases in Kuwait.
Authors: M I Khateeb, G F Araj, S A Majeed, A R Lulu
Journal: Annals of the Rheumatic Diseases (1990)

Of 400 patients with brucellosis, 104 (26%) had arthritis, of whom 96 could be followed up. The systemic disease in the 96 patients was acute in 54 (56%), subacute in 24 (25%), and chronic in 18 (19%). The main presenting symptoms were joint pain, fever, sweating, and easy fatigability. The joints most commonly affected were the sacroiliac joint (26%) and knee (25%) followed by hip (18%) and spine (8%). There was no particular pattern of joint affection in relation to age. Joint effusion occurred in 32/104 (30%) of cases, predominantly (94%) in the acute group. Culture of synovial fluid was negative in all, and analysis of synovial fluid for cellular profile, glucose, and protein content was not particularly helpful in diagnosis. Plain radiographs did not show major pathological changes. Among the laboratory tests, including haematological and liver function tests, the brucella enzyme linked immunosorbent assay (ELISA) was the most reliable in the diagnosis of disease, using serum and synovial fluid specimens. Treatment with a combination of streptomycin plus tetracyclines or rifampicin resulted in an excellent cure rate and resolution of arthritis without sequelae or mortality. Thus brucellosis should be considered in the differential diagnosis of arthritis, especially in areas in which the disease is endemic.
Alanine Aminotransferase and Directly Measured Insulin Sensitivity in a Multiethnic Cohort
Authors: Anthony J.G. Hanley, Lynne E. Wagenknecht, Andreas Festa, Ralph B. D'Agostino, Steven M. Haffner
Journal: Diabetes Care (2007)

OBJECTIVE— The objective of the present analysis was to evaluate the association of alanine aminotransferase (ALT) with directly measured insulin sensitivity (Si) in a large, multiethnic cohort of U.S. adults and to determine whether ALT adds to existing metabolic risk definitions in identifying subjects with insulin resistance. RESEARCH DESIGN AND METHODS— Si was directly measured from frequently sampled intravenous glucose tolerance tests among 999 nondiabetic African-American, Hispanic, and non-Hispanic white subjects aged 40–69 years who were participating in the Insulin Resistance Atherosclerosis Study. Subjects also received an oral glucose tolerance test, and fasting insulin, ALT, and alcohol intake were determined. RESULTS— ALT was associated with Si after adjustment for age, sex, ethnicity, impaired fasting glucose, triglycerides, HDL, blood pressure, and waist (clinical model) (P &amp;lt; 0.0001). The association remained significant after further adjustment for fasting insulin and impaired glucose tolerance (P = 0.004). In logistic regression analysis, elevated ALT (upper quartile) was associated with insulin resistance (lowest quartile of Si) after adjustment for age, sex, and ethnicity (odds ratio 3.0 [95% CI 2.2–4.1]). Elevated ALT was independently associated with insulin resistance when included in models with waist circumference, National Cholesterol Education Program criteria for metabolic syndrome, hypertriglyceridemic waist, elevated triglyceride-to-HDL ratio, or homeostasis model assessment of insulin resistance (HOMA-IR) (all P &amp;lt; 0.01). Finally, the addition of elevated ALT improved classification of insulin resistance by area under the receiver operating characteristic curve criteria for all models except HOMA-IR. CONCLUSIONS— ALT was associated with insulin resistance independently of conventional and more detailed metabolic measures. These findings suggest that the addition of ALT to existing clinically based metabolic risk definitions is an inexpensive way to improve the identification of subjects with insulin resistance.
STIM2 protects hippocampal mushroom spines from amyloid synaptotoxicity
Authors: Elena Popugaeva, Ekaterina Pchitskaya, Anastasiya Speshilova, Sergey Alexandrov, Hua Zhang, Olga Vlasova, Ilya Bezprozvanny
Journal: Molecular Neurodegeneration (2015)

Alzheimer disease (AD) is a disease of lost memories. Mushroom postsynaptic spines play a key role in memory storage, and loss of mushroom spines has been proposed to be linked to memory loss in AD. Generation of amyloidogenic peptides and accumulation of amyloid plaques is one of the pathological hallmarks of AD. It is important to evaluate effects of amyloid on stability of mushroom spines.In this study we used in vitro and in vivo models of amyloid synaptotoxicity to investigate effects of amyloid peptides on hippocampal mushroom spines. We discovered that application of Aβ42 oligomers to hippocampal cultures or injection of Aβ42 oligomers directly into hippocampal region resulted in reduction of mushroom spines and activity of synaptic calcium-calmodulin-dependent kinase II (CaMKII). We further discovered that expression of STIM2 protein rescued CaMKII activity and protected mushroom spines from amyloid toxicity in vitro and in vivo.Obtained results suggest that downregulation of STIM2-dependent stability of mushroom spines and reduction in activity of synaptic CaMKII is a mechanism of hippocampal synaptic loss in AD model of amyloid synaptotoxicity and that modulators/activators of this pathway may have a potential therapeutic value for treatment of AD.
Mutation of SHOC2 promotes aberrant protein N-myristoylation and causes Noonan-like syndrome with loose anagen hair
Authors: Viviana Cordeddu, Elia Di Schiavi, Len A. Pennacchio, Avi Ma’ayan, Anna Sarkozy, Valentina Fodale, Serena Cecchetti, Alessio Cardinale, Joel Martin, Wendy S. Schackwitz, Anna Lipzen, Giuseppe Zampino, Laura Mazzanti, Maria C Digilio, Simone Martinelli, Elisabetta Flex, Francesca Romana Lepri, Deborah Bartholdi, Kerstin Kutsche, Giovanni B Ferrero, Cecilia Anichini, Angelo Selicorni, Cesare Rossi, Romano Tenconi, Martin Zenker, Daniela Merlo, Bruno Dallapiccola, Ravi Iyengar, Paolo Bazzicalupo, Bruce D. Gelb, Marco Tartaglia
Journal: Nature Genetics (2009)
Polymers and inflammation: disease mechanisms of the serpinopathies
Authors: Bibek Gooptu, David A. Lomas
Journal: The Journal of Experimental Medicine (2008)

Members of the serpin (serine proteinase inhibitor) superfamily play a central role in the control of inflammatory, coagulation, and fibrinolytic cascades. Point mutations that cause abnormal conformational transitions in these proteins can trigger disease. Recent work has defined three pathways by which these conformers cause tissue damage. Here, we describe how these three mechanisms can be integrated into a new model of the pathogenesis of emphysema caused by mutations in the serpin α1-antitrypsin.
Legislation and teenage sex
Authors: G. E Robinson, G. E Forster, J R W Harris
Journal: BMJ (1984)

ControlsCarriers Patients Males Females (Females)Steroid sulphatase activity in 31 healthy controls (15 males aged 9 to 68 years and 16 females aged 4 to 62 years, one of whom was seven months pregnant), 18 healthy obligate carriers (aged 10 to 47 years), and 10 patients with X-linked ichthyosis (aged 0-80 years).Determination of activity was based on the hydrolysis of 3H-dehydroepiandrosterone sulphate2 expressed in pmol 3H-dehydroepiandrosterone sulphate/h/ml homogenate of leucocytes.Differential expression seems to be consistent with our results and those of others,8 which show a steroid sulphatase activity ratio of about 15 between normal female and male controls.In case of complete inactivation a ratio of 10 would be expected and in case of non-inactivation a ratio of 2 0 would have been observed.
New approach for bone marrow transplantation in patients with class 3 thalassemia aged younger than 17 years
Authors: Pietro Sodani, David Gaziev, Paola Polchi, Buket Erer, Claudio Giardini, Emanuele Angelucci, Donatella Baronciani, Marco Andreani, Marisa Manna, Sonia Nesci, Barbarella Lucarelli, Reginald A. Clift, Guido Lucarelli
Journal: Blood (2004)