tbuckley/cabot-search huggingface dataset:
Static Anisotropic Elastic Properties of the Aorta in Living Dogs
Authors: Doli J. Patel, Joseph S. Janicki, Thomas E. Carew
Journal: Circulation Research (1969)

Static anisotropic elasticity was studied in the middle descending thoracic aorta of 14 living dogs. Special transducers were used to measure radius and longitudinal stress at several pressures in situ in an isolated vessel segment. From these data, moduli describing elastic properties of the vessel wall were calculated. Results indicate that (1) at a physiologic pressure of 154 cm H 2 O (extension ratio of 1.52 circumferentially) the mean values for the incremental elastic moduli in the radial, circumferential, and longitudinal directions were 5480, 7510, and 10,100 g/cm 2 , respectively; (2) these moduli increased with an increase in intravascular pressure; and (3) the longitudinal modulus decreased when the vessel was studied in vitro (from the removal of longitudinal tethering).
Point-of-care coagulation monitors calibrated for the international normalized ratio for cirrhosis (INRliver) can help to implement the INRliver for the calculation of the MELD score
Authors: Armando Tripodi, Veena Chantarangkul, Massimo Primignani, Alessandra Dell’Era, Marigrazia Clerici, Francesca Iannuzzi, Alessio Aghemo, Massimo Cazzaniga, Francesco Salerno, Pier Mannuccio Mannucci
Journal: Journal of Hepatology (2009)
Development of a New Tracking Tool for the Human Monomeric Laminin-γ2 Chain <i>In vitro</i> and <i>In vivo</i>
Authors: Naohiko Koshikawa, Tomoko Minegishi, Kazuki Nabeshima, Motoharu Seiki
Journal: Cancer Research (2008)

Abstract Laminin-5 (Ln-5), a heterotrimer composed of three different laminin chains [laminin-α3 (Ln-α3), laminin-β3 (Ln-β3), and laminin-γ2 (Ln-γ2)], is a major component of the basement membrane in most adult tissues. One of the chains, Ln-γ2, is a specific marker of invasive tumors because it is frequently expressed as a monomer in malignant tumors. However, there is no simple and direct method to detect the monomeric form of Ln-γ2 selectively in the presence of Ln-5 because all available antibodies recognize both monomeric and heterotrimeric forms of Ln-γ2. In this study, we developed a new monoclonal antibody (mAb) termed 1H3 that reacts specifically with human Ln-γ2 monomers during immunoprecipitation, ELISA, Western blotting, and immunostaining. Ln-5 was not recognized by mAb 1H3 after denaturation with detergents under nonreducing conditions, but reactivity was recovered when denaturation was done under reducing conditions. The epitope of the antibody was mapped to region on the coiled-coil structure formed between Ln-γ2 and its partner chains Ln-α3 and Ln-β3 in Ln-5, whose structure is further stabilized by disulfide bonds. In normal tissue samples, the basement membrane was stained with conventional antibody against Ln-γ2 but not by mAb 1H3. In contrast, tumor cells in tissue sections could be stained with mAb 1H3 as efficiently as with conventional antibody. Thus, mAb 1H3 holds promise as a powerful tracking tool for the specific detection of monomeric Ln-γ2 in vivo and in vitro and is potentially useful as a diagnostic tool for detecting tumors and as a vehicle for drug delivery to cancer tissues. [Cancer Res 2008;68(2):530–6]
Concatenated Multitype L2 Fusion Proteins as Candidate Prophylactic Pan-Human Papillomavirus Vaccines
Authors: Subhashini Jagu, Balasubramanyam Karanam, Ratish Gambhira, Sudha V. Chivukula, Revathi J. Chaganti, Douglas R. Lowy, John T. Schiller, Richard B. S. Roden
Journal: JNCI Journal of the National Cancer Institute (2009)

Vaccination with minor capsid protein L2 induces antibodies that cross-neutralize diverse papillomavirus types. However, neutralizing antibody titers against the papillomavirus type from which the L2 vaccine was derived are generally higher than the titers against heterologous types, which could limit effectiveness against heterologous types. We hypothesized that vaccination with concatenated multitype L2 fusion proteins derived from known cross-protective epitopes of several divergent human papillomavirus (HPV) types might enhance immunity across clinically relevant HPV genotypes.Antibody responses of mice (n = 120) and rabbits (n = 23) to vaccination with HPV-16 amino-terminal L2 polypeptides or multitype L2 fusion proteins, namely, 11-200 x 3 (HPV types 6, 16, 18), 11-88 x 5 (HPV types 1, 5, 6, 16, 18), or 17-36 x 22 (five cutaneous, two mucosal low-risk, and 15 oncogenic types), that were formulated alone or in GPI-0100, alum, or 1018 ISS adjuvants were compared with vaccination with L1 virus-like particles (VLPs), including Gardasil, a licensed quadrivalent HPV L1 vaccine, and a negative control. Mice were challenged with HPV-16 pseudovirions 4 months after vaccination. Statistical tests were two-sided.The HPV-16 L2 polypeptides generated robust HPV-16-neutralizing antibody responses, albeit lower than those to HPV-16 L1 VLPs, and lower responses against other HPVs. In contrast, vaccination with the multitype L2 fusion proteins 11-200 x 3 and 11-88 x 5 induced high serum neutralizing antibody titers against all heterologous HPVs tested. 11-200 x 3 formulated in GPI-0100 adjuvant or alum with 1018 ISS protected mice against HPV-16 challenge (reduction in HPV-16 infection vs phosphate-buffered saline control, P < .001) 4 months after vaccination as well as HPV-16 L1 VLPs, but 11-200 x 3 alone or formulated with either alum or 1018 ISS was less effective (reduction in HPV-16 infection, P < .001).Concatenated multitype L2 proteins in adjuvant have potential as pan-oncogenic HPV vaccines.
P251Elevated levels of circulating CXCR3-agonistic chemokines are associated with left ventricular dysfunction
Authors: R Altara, Y Gu, HAJ Struijker-Boudier, JA Staessen, W M Blankesteijn
Journal: Cardiovascular Research (2014)

Purpose: Heart failure is a condition associated with high morbidity and mortality. Our current pharmacotherapeutic interventions can at best slow down the progression of the disease. At present, a proper molecular characterization of the disease process is lacking. Biomarkers that provides insight into the molecular mechanisms underlying the malfunctioning of the heart could be helpful in this respect. Because inflammation contributes to the symptoms of heart failure, we determined the circulating levels of three related chemokines, CXCL-9, -10 and -11, as well as NT-proBNP in serum from subjects with left ventricular dysfunction (LVD) and controls. Methods: Subjects with either subclinical (n=17) or advanced (N=14) LVD as well as age- and sex-matched controls (n=32), were recruited from the large-scale family-based study on the genetic epidemiology of cardiovascular phenotypes (FLEMENGHO). Mean arterial blood pressure was significantly higher in the subclinical (104.8±8.6 mmHg) and advanced (101.1±11.7 mmHg) LVD groups vs. control (90.5±4.5 mmHg). One-way ANOVA, Odds ratios, Integration Discrimination Improvement and Net Reclassification Improvement were determined using SAS software. Results: Increased serum levels of CXCL-9, -10 and -11 were observed in the LV dysfunction groups (1.5, 1.3 and 1.9-fold in the subclinical LVD and 4.1, 2.3 and 2.7-fold in the advanced LVD group, respectively; p<0.01, <0.001 and <0.01, respectively). NT-proBNP was 1.6 and 2.0-fold higher in the subclinical and advanced LVD groups; p<0.01). Adjustment for sex, age, BMI and mean arterial pressure resulted in a loss of significance for CXCL10 and NT-proBNP, whereas de difference for CXCL9 remained significant (p=0.03) and for CXCL11 a trend towards significance was observed (P=0.06). Doublings of CXCL-9, -10, -11 and NT-proBNP were associated with a 103%, 112%, 113% and 172% higher risk of subclinical and advanced LVD (p<0.019), respectively. Sensitivities were 0.58, 0.65, 0.58 and 0.76 and specificities 0.88, 0.69, 0.84 and 0.69 for CXCL-9, -10 and -11 and NT-proBNP, respectively. When corrected for age and BMI, adding the dichotomized biomarkers significantly enhanced the net reclassification improvement (p<0.006). In conclusion, including CXCL-9, -10 and -11 levels improves the discrimination of risk prediction models for LVD. The results of this study underscore the importance of using a panel of biomarkers to better characterize subjects with LVD.
Skin cancer surveillance in renal transplant recipients: questionnaire survey of current UK practice
Authors: P N Harden, S M Reece, A A Fryer, A G Smith, H M Ramsay
Journal: BMJ (2001)

The risk of non-melanoma skin cancer is increased after organ transplantation, with a prevalence and annual incidence for the United Kingdom reported at 16.5% and 7.1-10.6% respectively. 1 2 Non-melanoma skin cancer presents at an earlier age and spreads more rapidly in people who have received a transplant than in the general population, and it often occurs at more than one site. These factors result in substantial morbidity and a sevenfold increase in mortality from the disease, although absolute death rates are low.3 The high incidence, rapid growth, and increased metastatic potential of non-melanoma skin cancer in transplant recipients justifies a surveillance programme. 1 3 We did a survey to establish current practice in skin cancer surveillance in UK centres managing renal transplant recipients.

View this table:

Skin cancer surveillance and education of transplant recipients followed up in 61 surgical and nephrology centres. Values are numbers (percentages) of centres unless stated otherwise



We sent a questionnaire to …
Loss of Gata5 in mice leads to bicuspid aortic valve
Authors: Brigitte Laforest, Gregor Andelfinger, Mona Nemer
Journal: Journal of Clinical Investigation (2011)

Bicuspid aortic valve (BAV), the leading congenital heart disease, occurs in 1%-2% of the population. Genetic studies suggest that BAV is an autosomal-dominant disease with reduced penetrance. However, only 1 gene, NOTCH1, has been linked to cases of BAV. Here, we show that targeted deletion of Gata5 in mice leads to hypoplastic hearts and partially penetrant BAV formation. Endocardial cell-specific inactivation of Gata5 led to BAV, similar to that observed in Gata5-/- mice. In all cases, the observed BAVs resulted from fusion of the right-coronary and noncoronary leaflets, the subtype associated with the more severe valve dysfunction in humans. Neither endocardial cell proliferation nor cushion formation was altered in the absence of Gata5. Rather, defective endocardial cell differentiation, resulting from the deregulation of several components of the Notch pathway and other important endocardial cell regulators, may be the underlying mechanism of disease. The results unravel a critical cell-autonomous role for endocardial Gata5 in aortic valve formation and identify GATA5 as a potential gene responsible for congenital heart disease in humans. Mice with mutated Gata5 alleles represent unique models to dissect the mechanisms underlying degenerative aortic valve disease and to develop much-needed preventive and therapeutic interventions.
Effectiveness and Harms of Recombinant Human Bone Morphogenetic Protein-2 in Spine Fusion
Authors: Rongwei Fu, Shelley Selph, Marian McDonagh, Kimberly Peterson, Arpita Tiwari, Roger Chou, Mark Helfand
Journal: Annals of Internal Medicine (2013)

Background: Recombinant human bone morphogenetic protein-2 (rhBMP-2) is used as a bone graft substitute in spinal fusion, which unites (fuses) bones in the spine. The accuracy and completeness of journal publications of industry-sponsored trials on the effectiveness and harms of rhBMP-2 has been called into question. Purpose: To independently assess the effectiveness and harms of rhBMP-2 in spinal fusion and reporting bias in industry-sponsored journal publications. Data Sources: Individual-patient data (IPD) from 17 industry-sponsored studies; related internal documents; and searches of MEDLINE (1996 to August 2012), other databases, and reference lists. Study Selection: Randomized, controlled trials (RCTs) and cohort studies of rhBMP-2 versus any control and uncontrolled studies of harms. Data Extraction: Effectiveness outcomes in IPD were recalculated using consistent definitions. Study characteristics and results were abstracted by 1 investigator and confirmed by another. Two investigators independently assessed quality using predefined criteria. Data Synthesis: Thirteen RCTs and 31 cohort studies were included. For lumbar spine fusion, rhBMP-2 and iliac crest bone graft were similar in overall success, fusion, and other effectiveness measures and in risk for any adverse event, although rates were high across interventions (77% to 93% at 24 months from surgery). For anterior lumbar interbody fusion, rhBMP-2 was associated with nonsignificantly increased risk for retrograde ejaculation and urogenital problems. For anterior cervical spine fusion, rhBMP-2 was associated with increased risk for wound complications and dysphagia. At 24 months, the cancer risk was increased with rhBMP-2 (risk ratio, 3.45 [95% CI, 1.98 to 6.00]), but event rates were low and cancer was heterogeneous. Early journal publications misrepresented the effectiveness and harms through selective reporting, duplicate publication, and underreporting. Limitations: Outcome assessment was not blinded, and ascertainment of harms in trials was poor. No trials were truly independent of industry sponsorship. Conclusion: In spinal fusion, rhBMP-2 has no proven clinical advantage over bone graft and may be associated with important harms, making it difficult to identify clear indications for rhBMP-2. Earlier disclosure of all relevant data would have better informed clinicians and the public than the initial published trial reports did. Primary Funding Source: Yale University and Medtronic.
BMA drops plans for further industrial action over pensions
Authors: A. O'Dowd
Journal: BMJ (2012)

Doctors’ leaders have backed away from taking a second day of industrial action to protest over pension reform following a face to face meeting with health secretary Andrew Lansley.

A decision was taken at a meeting of the full BMA Council on 18 July to pursue other options on the issue of pension reform, namely, to join further talks with other health unions.

The BMA, however, said it would increase its campaigning to achieve improvements in the longer term and was not ruling out more industrial action at a later date.

The government plans to reform the NHS pension scheme, meaning that doctors and other NHS staff would have to pay more, work longer, and get less …
IOC handbook of sports medicine &amp; science: swimming, 2nd edn
Authors: M Mountjoy
Journal: British Journal of Sports Medicine (2007)

Edited by Joel Stager, David Tanner. Oxford, UK: Blackwell Publishing, 2005, £24.95, US$46.98 (approx), €36.58 (approx), pp 149 (softcover). ISBN 0632059141

The IOC handbook of sports medicine & science: swimming 2nd edn: does it sink or swim? Is this the book of champions, or will it be left to drown in the pool of sports science epic textbooks? As the chairman of the FINA Sports Medicine Committee, it was with great interest that I reviewed this handbook.

One of the greatest criticisms of sports science textbooks is their lack of practical applicability. What good is the latest in technical scientific research if it has no applicability or benefit for the athlete in the pool? As I work closely with doctors, coaches, and athletes, I am most interested in evaluating the effectiveness of the authors in creating …
Feasibility and Tolerability of Sequential Doxorubicin/Paclitaxel Followed by Cyclophosphamide, Methotrexate, and Fluorouracil and Its Effects on Tumor Response as Preoperative Therapy
Authors: Luca Gianni, José Baselga, Wolfgang Eiermann, Vicente Guillem Porta, Vladimir Semiglazov, Aña Lluch, Milvia Zambetti, Dolores Sabadell, Günther Raab, Antonio Llombart Cussac, Alla Bozhok, Angel Martinez-Agulló, Marco Greco, Mikhail Byakhov, Juan Josè Lopez Lopez, Mauro Mansutti, Pinuccia Valagussa, Gianni Bonadonna
Journal: Clinical Cancer Research (2005)

The European Cooperative Trial in Operable breast cancer (ECTO) randomly tested whether efficacy of adjuvant doxorubicin followed by i.v. cyclophosphamide, methotrexate, and fluorouracil (CMF; doxorubicin-->CMF, arm A) could be improved by adding paclitaxel (doxorubicin/paclitaxel-->CMF) as adjuvant (arm B) or primary systemic therapy (PST, arm C). We report here feasibility, tolerability, locoregional antitumor activity, and breast conservation rate.A total of 1,355 women entered the study. Feasibility and safety were compared in arm A versus arms B plus C. Surgical findings were compared in arms A plus B versus arm C.Grade 3 or 4 National Cancer Institute toxicities were low (<5%) in all arms. Neuropathy was more frequent in the paclitaxel-containing arms (grade 2, 20.5% versus 5.0%; grade 3, 1.3% versus 0.2%). At 31 months of follow-up, asymptomatic drop of left ventricular ejection fraction was similar in all arms, whereas symptomatic cardiotoxicity was recorded in three patients (0.5%) in A and in three patients (0.3%) in B plus C. PST induced clinical complete plus partial remission in 78%, with an in-breast pathologic complete response rate of 23% and an in-breast plus axilla pathologic complete response rate of 20%. In the multivariate analysis, only estrogen receptor (ER) status was significantly associated with pathologic complete response (odds ratio for ER negative, 5.77; 95% confidence interval, 3.49-9.52; P<0.0001). PTS induced a significant axillary downstaging (P<0.001), and breast sparing surgery was feasible in 65% versus 34% (P<0.001).Doxorubicin/paclitaxel-->CMF is feasible, safe, and well tolerated. Given as PST, it is markedly active, allowing for breast-sparing surgery in a large fraction of patients.
The effects of diet induced obesity on breast cancer associated pathways in mice deficient in SFRP1
Authors: Kelly J Gauger, Lotfi M Bassa, Elizabeth M Henchey, Josephine Wyman, Jennifer Ser-Dolansky, Akihiko Shimono, Sallie S Schneider
Journal: Molecular Cancer (2014)

Secreted frizzled-related proteins (SFRPs) are a family of proteins that block the Wnt signaling pathway and loss of Sfrp1 expression is observed in breast cancer. The molecular mechanisms by which obesity contributes to breast tumorigenesis are not well defined, but involve increased inflammation. Mice deficient in Sfrp1 show enhanced mammary gland inflammation in response to diet induced obesity (DIO). Furthermore, mammary glands from Sfrp1 −/− mice exhibit increased Wnt signaling, decreased cell death responses, and excessive hyper branching. The work described here was initiated to investigate whether obesity exacerbates the aforementioned pathways, as they each play a key roles in the development of breast cancer. Wnt signaling is significantly affected by DIO and Sfrp1 −/− loss as revealed by analysis of Myc mRNA expression and active β-catenin protein expression. Furthermore, Sfrp1 −/− mice fed a high fat diet (HFD) exhibit an increase in mammary cell proliferation. The death response is also impaired in the mammary gland of Sfrp1 −/− mice fed a normal diet (ND) as well as a HFD. In response to γ-irradiation, mammary glands from Sfrp1−/− mice express significantly less Bax and Bbc3 mRNA, caspase-3 positive cells, and p53 protein. The expression of Wnt4 and Tnfs11 are critical for normal progesterone mediated mammary gland development and in response to obesity, Sfrp1−/− mice express significantly more Wnt4 and Tnfs11 mRNA expression. Evaluation of progesterone receptor (PR) expression showed that DIO increases the number of PR positive cells. Our data indicate that the expression of Sfrp1 is a critical factor required for maintaining appropriate cellular homeostasis in response to the onset of obesity.
Effect of coronary artery bypass graft surgery on survival: overview of 10-year results from randomised trials by the Coronary Artery Bypass Graft Surgery Trialists Collaboration
Authors: S Yusuf, D Zucker, E Passamani, P Peduzzi, T Takaro, L.D Fisher, J.W Kennedy, K Davis, T Killip, R Norris, C Morris, V Mathur, E Varnauskas, T.C Chalmers
Journal: The Lancet (1994)
Involvement of p40phox in activation of phagocyte NADPH oxidase through association of its carboxyl-terminal, but not its amino-terminal, with p67phox.
Authors: S Tsunawaki, S Kagara, K Yoshikawa, L S Yoshida, T Kuratsuji, H Namiki
Journal: The Journal of Experimental Medicine (1996)

Phagocyte NADPH oxidase, dormant in resting cells, is activated upon cell stimulation to produce superoxide anion, a precursor of microbicidal oxidants. Active NADPH oxidase is found on the membrane as an enzyme complex, composed of membrane-integrated cytochrome b558 (gp91phox and p22phox subunits) and two cytosolic factors (p47phox and p67phox), each of the latter containing two src homology 3 (SH3) domains. Recently, we radioactively identified a third cytosolic factor, p40phox, as a molecule that associates with p67phox in human neutrophils. Although it has been found that this p40phox protein is defective in patients with chronic granulomatous disease (CGD) who lack p67phox, evidence to functionally relate it to the NADPH oxidase system has hitherto been lacking. In this study, we raised separate antibodies against both the COOH- and NH2-terminal polypeptides of p40phox as well as against the COOH-terminal polypeptide of p67phox to examine the mode of interaction between p40phox and p67phox in a complex. The antibody against the COOH terminus of p67phox was able to communoprecipitate p40phox in conjunction with p67phox itself as was expected. Very interestingly, however, the antibody against the COOH terminus of p40phox completely dissociated the p67phox molecule from the p40phox-p67phox complex unit without any detectable coimmunoprecipitation of p67phox, despite their tight association, whereas that against the NH2 terminus of p40phox had absolutely no dissociation effect. Similar results were found regarding their effects on the O2-generating ability of cytosol in a cell-free activation system, i.e., inhibition was noted with the COOH terminus antibody but not with that for the NH2 terminus of p40phox. However, this dissociation did not affect the translocation of the cytosolic components including p47phox to the membrane. Once the NADPH oxidase was activated, the antibody for the COOH terminus did not show any inhibitory effect on catalysis by the activated enzyme. The stimulators of NADPH oxidase, MA and SDS, did not dissociate the p40phox-p67phox complex. These results provide the first demonstration that p40phox is practically involved in the activation of NADPH oxidase through the association of its COOH-terminal, but not its NH2-terminal, with p67phox.