tbuckley/cabot-search huggingface dataset:
<i>CD74–NRG1</i> Fusions in Lung Adenocarcinoma
Authors: Lynnette Fernandez-Cuesta, Dennis Plenker, Hirotaka Osada, Ruping Sun, Roopika Menon, Frauke Leenders, Sandra Ortiz-Cuaran, Martin Peifer, Marc Bos, Juliane Daßler, Florian Malchers, Jakob Schöttle, Wenzel Vogel, Ilona Dahmen, Mirjam Koker, Roland T. Ullrich, Gavin M. Wright, Prudence A. Russell, Zoe Wainer, Benjamin Solomon, Elisabeth Brambilla, Hélène Nagy-Mignotte, Denis Moro-Sibilot, Christian G. Brambilla, Sylvie Lantuejoul, Janine Altmüller, Christian Becker, Peter Nürnberg, Johannes M. Heuckmann, Erich Stoelben, Iver Petersen, Joachim H. Clement, Jörg Sänger, Lucia A. Muscarella, Annamaria la Torre, Vito M. Fazio, Idoya Lahortiga, Timothy Perera, Souichi Ogata, Marc Parade, Dirk Brehmer, Martin Vingron, Lukas C. Heukamp, Reinhard Buettner, Thomas Zander, Jürgen Wolf, Sven Perner, Sascha Ansén, Stefan A. Haas, Yasushi Yatabe, Roman K. Thomas
Journal: Cancer Discovery (2014)

We discovered a novel somatic gene fusion, CD74-NRG1, by transcriptome sequencing of 25 lung adenocarcinomas of never smokers. By screening 102 lung adenocarcinomas negative for known oncogenic alterations, we found four additional fusion-positive tumors, all of which were of the invasive mucinous subtype. Mechanistically, CD74-NRG1 leads to extracellular expression of the EGF-like domain of NRG1 III-β3, thereby providing the ligand for ERBB2-ERBB3 receptor complexes. Accordingly, ERBB2 and ERBB3 expression was high in the index case, and expression of phospho-ERBB3 was specifically found in tumors bearing the fusion (P < 0.0001). Ectopic expression of CD74-NRG1 in lung cancer cell lines expressing ERBB2 and ERBB3 activated ERBB3 and the PI3K-AKT pathway, and led to increased colony formation in soft agar. Thus, CD74-NRG1 gene fusions are activating genomic alterations in invasive mucinous adenocarcinomas and may offer a therapeutic opportunity for a lung tumor subtype with, so far, no effective treatment.CD74–NRG1 fusions may represent a therapeutic opportunity for invasive mucinous lung adenocarcinomas, a tumor with no effective treatment that frequently presents with multifocal unresectable disease.
Central sensitization following intradermal injection of capsaicin
Authors: William D. Willis
Journal: Behavioral and Brain Sciences (1997)

Intradermal capsaicin in humans causes pain, primary hyperalgesia, and secondary mechanical hyperalgesia and allodynia. Parallel changes occur in the responses of primate spinothalamic tract cells and in rat behavior. Neurotransmitters that trigger secondary mechanical hyperalgesia and allodynia include excitatory amino acids and substance P. Secondary mechanical allodynia is actively maintained by central mechanisms. Our group has investigated mechanisms of central sensitization of nociceptive neurons by examining the responses to intradermal injection of capsaicin. These experiments are pertinent to issues raised by coderre &amp; katz (sect. 2).
Weight loss in obese people has structure-modifying effects on medial but not on lateral knee articular cartilage
Authors: A Anandacoomarasamy, S Leibman, G Smith, I Caterson, B Giuffre, M Fransen, P N Sambrook, L March
Journal: Annals of the Rheumatic Diseases (2011)

Background Obesity is an important risk factor for knee osteoarthritis (OA), Weight loss can reduce the symptoms of knee OA. No prospective studies assessing the impact of weight loss on knee cartilage structure and composition have been performed. Objectives To assess the impact of weight loss on knee cartilage thickness and composition. Methods 111 obese adults were recruited from either laparoscopic adjustable gastric banding or exercise and diet weight loss programmes from two tertiary centres. MRI was performed at baseline and 12-month follow-up to assess cartilage thickness. 78 eligible subjects also underwent delayed gadolinium-enhanced MRI of cartilage (dGEMRIC), an estimate of proteoglycan content. The associations between cartilage outcomes (cartilage thickness and dGEMRIC index) and weight loss were adjusted for age, gender, body mass index (BMI) and presence of clinical knee OA. Results Mean age was 51.7±11.8 years and mean BMI was 36.6±5.8 kg/m 2 ; 32% had clinical knee OA. Mean weight loss was 9.3±11.9%. Percentage weight loss was negatively associated with cartilage thickness loss in the medial femoral compartment in multiple regression analysis (β=0.006, r 2 =0.19, p=0.029). This association was not detected in the lateral compartment (r 2 =0.12, p=0.745). Percentage weight loss was associated with an increase in medial dGEMRIC in multiple regression analysis (β=3.9, r 2 =0.26; p=0.008) but not the lateral compartment (r 2 =0.14, p=0.34). For every 10% weight loss there was a gain in the medial dGEMRIC index of 39 ms (r 2 =0.28; p=0.014). The lowest weight loss cut-off associated with reduced medial femoral cartilage thickness loss and improved medial dGEMRIC index was 7%. Conclusions Weight loss is associated with improvements in the quality (increased proteoglycan content) and quantity (reduced cartilage thickness losses) of medial articular cartilage. This was not observed in the lateral compartment. This could ultimately lead to a reduced need for total joint replacements and is thus a finding with important public health implications.
Medial necrosis and acute alterations in aortic distensibility following removal of the vasa vasorum of canine ascending aorta
Authors: C. I Stefanadis, P. E Karayannacos, H. K Boudoulas, C. G Stratos, C. V Vlachopoulos, I. A Dontas, P. K Toutouzas
Journal: Cardiovascular Research (1993)

It is known that the outer layers of the thoracic aorta receive substantial blood flow through vasa vasorum. This study was undertaken to test the hypothesis that removal of vasa vasorum flow will alter the elastic properties of the ascending aorta.Distensibility of the ascending aorta was determined before and 30 min after careful removal of the periaortic fat network which contains the vasa vasorum in 10 acutely instrumented dogs (experimental group) and the results were compared with those obtained from six weight matched sham operated control dogs. Aortic distensibility was measured using the formula: distensibility = 2 x pulsatile changes in aortic diameter divided by (diastolic aortic diameter x pulse pressure). Aortic pressures were measured directly from the ascending aorta by a pressure gauge. Aortic diameters were simultaneously determined by an elastic air filled ring connected to a transducer. The efficacy of the technique for the interruption of vasa vasorum blood supply to the aortic wall was proved in six additional animals by histology of transverse blocks of aortic wall from the area of interest. Histology was performed before vasa vasorum removal in two animals, 30 min after vasa vasorum removal in another two, and 15 d after vasa vasorum removal in the remainder.At baseline, there was no difference in the measured variables between the two groups. Aortic distensibility decreased significantly in the experimental group after vasa vasorum removal by 0.90(SEM 0.17) 10(-6).cm2.dyn-1 (p < 0.001), while it remained unchanged in the control group during the experiment. Complete removal of vasa vasorum of the ascending aorta was found in experimental group animals which were killed 30 min after operation, while ischaemic medial necrosis was observed in those killed 15 d after operation.Vasa vasorum removal led to an acute decrease in the distensibility of the ascending aorta. Lack of blood supply to the outer part of the aortic wall is most likely to have accounted for these findings.
Timely diagnosis and therapy for suspected lung cancer patients in a 2 day rapid outpatient diagnostic program with integrated FGD-PET and diagnostic CT
Authors: Pepijn Brocken, Berni Kiers, Monika Looijen-Salamon, Richard Dekhuijzen, Chantal Smits-van der Graaf, Liesbeth Peters-Bax, Lioe-Fee De Geus-Oei, Hendrikus Van Der Heijden
Journal: European Respiratory Journal (2012)

Introduction:    Delays in the diagnosis of lung cancer are under debate and may affect outcome. The objectives of this study were to compare delays in a rapid outpatient diagnostic program (RODP) for suspected lung cancer patients with those described in literature and guideline recommendations, to investigate the effects of referral route and symptoms on delays, and to establish whether delays were related to disease stage and outcome.   Methods:    We performed a retrospective chart study of all patients with suspected lung cancer, referred to the RODP of our tertiary care university clinic between 1999 and 2009. Patient characteristics, tumor stage and different delays were analyzed.   Results:   Of 565 patients with available data, 290 were diagnosed with lung cancer, 48 with another type of malignancy, and 111 patients with a non-malignant lesion. In 112 patients no immediate definite diagnosis was obtained, and in 82 of these the proposed follow-up strategy confirmed a benign outcome. The median first line, patient, referral, diagnostic, curative and palliative therapeutic delays were 54, 19, 7, 2, 18 and 21.5 days, respectively. The RODP care was generally far more timely compared to literature and published guidelines, except for both referral and palliative therapeutic delay. No specific delay was significantly related to disease stage or survival.   Conclusion:    An RODP results in a timely diagnosis well within guideline recommendations. Patient and first line delay account for most of total patient delay. Within the limitations of this retrospective study, we found no association with disease stage or survival.
Personal and Relationship Challenges of Adults With Type 1 Diabetes
Authors: Paula M. Trief, Jonathan G. Sandberg, Jacqueline A. Dimmock, Patricia J. Forken, Ruth S. Weinstock
Journal: Diabetes Care (2013)

OBJECTIVE Little is known about the psychosocial challenges of adults living with type 1 diabetes or its impact on partner relationships. This qualitative study was undertaken to gain better understanding of these issues. RESEARCH DESIGN AND METHODS Four focus groups were held, two with adult type 1 diabetic patients (n = 16) and two with partners (n = 14). Two broad questions were posed: “What are the emotional and interpersonal challenges you have experienced because you have (your partner has) type 1 diabetes?” and “How does the fact that you have (your partner has) type 1 diabetes affect your relationship with your partner, positively and/or negatively?” Sessions were recorded and transcribed, and analyzed by a team of four researchers, using constant comparative methods to identify core domains and concepts. RESULTS Four main domains were identified: 1) impact of diabetes on the relationship, including level of partner involvement, emotional impact of diabetes on the relationship, and concerns about child-rearing; 2) understanding the impact of hypoglycemia; 3) stress of potential complications; and 4) benefits of technology. Themes suggest that, although partner involvement varies (very little to significant), there exists significant anxiety about hypoglycemia and future complications and sources of conflict that may increase relationship stress. Partner support is highly valued, and technology has a positive influence. CONCLUSIONS Adults with type 1 diabetes face unique emotional and interpersonal challenges. Future research should focus on gaining a better understanding of how they cope and the effect of psychosocial stressors and coping on adherence, quality of life, and glycemic control.
Occult hepatitis B infection and HBV replicative activity in patients with cryptogenic cause of hepatocellular carcinoma
Authors: Danny Ka Ho Wong, Fung Yu Huang, Ching Lung Lai, Ronnie Tung Ping Poon, Wai Kay Seto, James Fung, Ivan Fan Ngai Hung, Man Fung Yuen
Journal: Hepatology (2011)

We aimed to investigate the incidence of occult hepatitis B infection (OBI) in patients with "cryptogenic" hepatocellular carcinoma (HCC) and to study the HBV replicative activity in these patients. Tumorous and adjacent nontumorous liver tissues were obtained from 33 cryptogenic HCC patients and 28 HCC patients with identifiable causes (13 with chronic hepatitis B [CHB], six with chronic hepatitis C, and nine alcohol-related). OBI was identified by nested polymerase chain reaction (PCR). Intrahepatic HBV DNA, covalently closed circular DNA (cccDNA), and pregenomic RNA (pgRNA) were quantified by real-time PCR and reverse-transcription PCR (RT-PCR), respectively. OBI was identified in 24 (73%) cryptogenic HCC patients, one (17%) HCC patient with HCV, and five (56%) patients with alcohol-related HCC. In HCC patients with OBI, HBV DNA were detected in ≥2 HBV genomic regions more often in nontumorous tissues than in tumorous tissues (90% versus 57%, respectively; P = 0.007). Cryptogenic HCC patients with OBI had lower intrahepatic total HBV DNA levels than HCC patients with CHB (median: 0.010 versus 3.19 copies/cell, respectively; P < 0.0001). Only six (26%) cryptogenic HCC patients with OBI had detectable cccDNA (median: <0.0002 copies/cell), which was significantly lower than that of the CHB patients (median: 0.005 copies/cell; P < 0.0001). HBV pgRNA were detectable in 12 (52%) cryptogenic HCC patients with OBI (median: 0.0001 copies/cell), which was significantly lower than that of the CHB patients (median: 2.90 copies/cell; P < 0.001).73% of patients with apparently unidentifiable causes for HCC were HBV-related. The detection rate was higher in nontumorous tissues than tumorous tissues. The low intrahepatic HBV DNA and pgRNA levels indicated that persistent viral replication and possibly HBV integration are the likely causes of HCC in OBI patients.
A functional role of prostate-specific membrane antigen in prostate cancer metastasis
Authors: Sharron X. Lin, Vincent Navarro, He Liu, Neil H. Bander
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4373 

Despite the consistent finding of upregulated prostate specific membrane antigen (PSMA) with increased prostate cancer (PCa) aggressiveness, the functional role of PSMA in PCa is unknown. Recently, it was reported that suppression of PSMA expression increases invasiveness, and expression of inactivating PSMA mutants reduces invasiveness. In this study, using in vitro cell model systems and live-cell imaging methods, we characterized the role of PSMA in cell motility and adhesion. We demonstrated, using wound-healing assay, that PSMA expression reduces cell motility when compared with control PSMA-negative PCa cells. Six hours after wounding, significant numbers of PSMA-negative cells migrating into the wounded area could be observed. In contrast, limited migration was observed in cells expressing PSMA. We also found enhanced PCa cell motility in cells when the PSMA enzymatic activity was inhibited by a specific anti-PSMA antibody. When live cell motility was recorded, the number of PSMA-positive LNCaP cells migrating into the wounded area was almost 2-fold higher in the presence of the inhibitory antibody than control LNCaP cells in the absence of the antibody. No difference in the number of the PSMA-negative PC3 cell migration was observed with or without the application of the inhibitory antibody. More interestingly, we found that expression of PSMA results in morphologically better-spreading PCa cells with redistributed F-actin filaments that regulate cell adhesion and motility. Since the progression of PCa is a multi-stage process that requires repeated adhesion to and detachment from the extracellular matrix microenvironment, our results suggest that PSMA may play a role in PCa adhesion and migration during PCa metastasis.
Effect of secondhand smoke on asthma control among black and Latino children
Authors: Sam S. Oh, Haig Tcheurekdjian, Lindsey A. Roth, Elizabeth A. Nguyen, Saunak Sen, Joshua M. Galanter, Adam Davis, Harold J. Farber, Frank D. Gilliland, Rajesh Kumar, Pedro C. Avila, Emerita Brigino-Buenaventura, Rocio Chapela, Jean G. Ford, Michael A. LeNoir, Fred Lurmann, Kelley Meade, Denise Serebrisky, Shannon Thyne, William Rodriguez-Cintron, Jose R. Rodriguez-Santana, L. Keoki Williams, Luisa N. Borrell, Esteban G. Burchard
Journal: Journal of Allergy and Clinical Immunology (2012)
Idiopathic cholestasis of pregnancy in a large kindred.
Authors: H Reyes, J Ribalta, M Gonzalez-Ceron
Journal: Gut (1976)

A past history of idiopathic cholestasis of pregnancy (ICP) was detected in 10 out of the 32 multiparous women in the last two generations of a large kindred. The affected women are distributed in five family units, sharing Chilean-born great-grandparents. The connection between the ICP-affected women and the common trunk is given both by male and female parents. Five cases are concentrated in one family unit, where the mother and all her daughters have been affected by the disease. The role of genetic factors in the pathogenesis of ICP is supported by this study. It is proposed that the disease may be transmitted as a predisposing trait by individuals of either sex and that non-genetic factors may influence its expressivity. A reliable test to identify all the genetic carriers seems indispensable to define the pattern of inheritance in this disease.
Increased Risk of Fracture and Postfracture Adverse Events in Patients With Diabetes: Two Nationwide Population-Based Retrospective Cohort Studies
Authors: Chien-Chang Liao, Chao-Shun Lin, Chun-Chuan Shih, Chun-Chieh Yeh, Yi-Cheng Chang, Yuan-Wen Lee, Ta-Liang Chen
Journal: Diabetes Care (2014)

The relationship between diabetes and fracture is not completely understood. This study evaluated fracture risk and postfracture mortality in patients with diabetes.We identified 32,471 adults newly diagnosed with diabetes in 2000-2003 using Taiwan's National Health Insurance Research Database. A comparison cohort of 64,942 adults without diabetes was randomly selected from the same dataset, with frequency matched by age and sex. Fracture events in 2000-2008 were ascertained from medical claims. Adjusted hazard ratios (HRs) and 95% CIs of fracture associated with diabetes were calculated. A nested cohort study of 17,002 patients with fracture receiving repair surgeries between 2004 and 2010 calculated adjusted odds ratios (ORs) and 95% CIs of adverse events after fracture in patients with and without diabetes.During 652,530 person-years of follow-up, there were 12,772 newly diagnosed fracture cases. The incidences of fracture for people with diabetes and without were 24.2 and 17.1 per 1,000 person-years, respectively (P < 0.0001). Compared with people without diabetes, the adjusted HR of fracture was 1.66 (95% CI 1.60-1.72) for people with diabetes. The ORs of postfracture deep wound infection, septicemia, and mortality associated with diabetes were 1.34 (95% CI 1.06-1.71), 1.42 (95% CI 1.23-1.64), and 1.27 (95% CI 1.02-1.60), respectively.Diabetes was associated with fracture. Patients with diabetes had more adverse events and subsequent mortality after fracture. Prevention of fracture and postfracture adverse events is needed in this susceptible population.
In vitro and in vivo evaluation of gastroretentive floating drug delivery system of ofloxacin
Authors: Rajani Shakya, Panna Thapa, Ranendra N. Saha
Journal: Asian Journal of Pharmaceutical Sciences (2013)

This study aimed to develop hydrophilic matrix based controlled release gastroretentive drug delivery system of ofloxacin and conducting its in vitro and in vivo evaluations. Effervescent floating gastroretentive drug delivery system of ofloxacin was prepared utilizing Box–Behnken statistical design with 3 factors, 3 levels and 15 experimental trials. Formulation optimization was done by setting targets on selected responses. In vivo studies were carried out for the optimized formulation with 12 healthy human volunteers and obtained pharmacokinetic parameters were compared with the marketed once daily formulation, "Zanocin OD". Optimized formulation showed satisfactory controlled in vitro drug release for more than 12 h with excellent buoyancy properties (floating lag time <1 min, floating duration >16 h). Optimized and marketed formulations were found to have similar in vitro release profile (f2 = 79.22) and also were found to be bioequivalent. Serum ofloxacin concentration was well maintained above its reported minimum inhibitory concentrations for most of the pathogens for sufficiently longer duration. Cmax and AUC values of optimized formulation were found to be significantly higher than of marketed product despite their bioequivalence. Bettertherapeutic effect can be expected since ofloxacin exhibits concentration dependent killing. Hence, gastroretention can be a promising approach to enhance bioavailability of ofloxacin with narrow absorption window in upper GIT.
Clinicoimmunologic studies on <i>Phoenix sylvestris</i> Roxb. pollen: an aeroallergen from Calcutta, India
Authors: P. Chakraborty, I. Chowdhury, S. Gupta‐bhattacharya, S. Chanda, S. Gupta, D.N. Sengupta
Journal: Allergy (1999)

Background: This study highlights the allergenicity and allergenic components of the pollen of Phoenix sylvestris Roxb. (PS), or date sugar palm, which is predominantly airborne in the air of Greater Calcutta. Methods: A 2‐year aerobiologic survey was performed by Burkard sampler. PS pollen extract was used in skin tests of allergic patients, fractionated by (NH 4 ) 2 SO 4 and the SephacrylS‐200 column. The allergenicity of each fraction was checked by skin test and IgE ELISA inhibition. The principal allergenic fraction, Fr.IIa, was separated in 11% SDS–PAGE, and its allergenicity was confirmed by IgE ELISA inhibition and immunoblotting. Results: PS pollen grains were found to be prevalent in the air of the suburban zone of Calcutta from January to March with a peak in February. The pollen extract showed high (44.07%) positive skin reaction on 540 respiratory allergic patients. Among the (NH 4 ) 2 SO 4 cut fractions, Fr.II was the most active one, and it was resolved into four subfractions in the Sephacryl S‐200 column. Fr.IIa was the principal allergenic fraction, showing the presence of two components of 33 and 66 kDa in SDS–PAGE. In IgE immunoblotting, both of the components were found to be allergenic. Conclusions: The PS pollen grain is an important aeroallergen from Calcutta, India. The 33‐ and 66‐kDa components are the major allergens present in the relevant pollen extract.