tbuckley/cabot-search huggingface dataset:
Three-Dimensional Geometry of the Tricuspid Annulus in Healthy Subjects and in Patients With Functional Tricuspid Regurgitation
Authors: Shota Fukuda, Giuseppe Saracino, Yoshiki Matsumura, Masao Daimon, Hung Tran, Neil L. Greenberg, Takeshi Hozumi, Junichi Yoshikawa, James D. Thomas, Takahiro Shiota
Journal: Circulation (2006)

Background— Most rings currently used for tricuspid valve annuloplasty are formed in a single plane, whereas the actual tricuspid annulus (TA) may have a nonplanar or 3-dimensional (3D) structure. The purpose of this study was therefore to investigate the 3D geometry of the TA in healthy subjects and in patients with functional tricuspid regurgitation (TR). Methods and Results— This study consisted of 15 healthy subjects and 16 patients with functional TR who had real-time 3D echocardiography. With our customized software, 8 points along the TA were determined with the rotated plane around the axis at 45°intervals. The TA was traced during a cardiac cycle. The distance between diagonals connecting 2 points was measured. The height was defined as the distance from the plane determined by least-squares regression analysis at all 8 points. Both the maximum (7.5±2.1 versus 5.6±1.0 cm 2 /m 2 ) and minimum (5.7±1.3 versus 3.9±0.8 cm 2 /m 2 ) TA areas in patients with TR were larger than those in healthy subjects (both P &lt;0.01). Healthy subjects had a nonplanar-shaped TA with homogeneous contraction. The posteroseptal portion was the lowest toward the apex from the right atrium, and the anteroseptal portion was the highest. In patients with functional TR, the TA was dilated in the septal to lateral direction, resulting in a more circular shape than in healthy subjects. A similar 3D pattern was observed in patients with TR, but it was more planar than that in healthy subjects. Conclusions— Real-time 3D echocardiography showed a complicated 3D structure of the TA, which appeared to be different from the “saddle-shaped” mitral annulus, suggesting an annuloplasty for TR different from that for mitral regurgitation.
Structural Alterations in Subcutaneous Small Arteries of Normotensive and Hypertensive Patients With Non–Insulin-Dependent Diabetes Mellitus
Authors: Damiano Rizzoni, Enzo Porteri, Daniele Guelfi, Maria Lorenza Muiesan, Umberto Valentini, Antonio Cimino, Angela Girelli, Luigi Rodella, Rossella Bianchi, Intissar Sleiman, Enrico Agabiti Rosei
Journal: Circulation (2001)

It is not presently known whether non-insulin-dependent diabetes mellitus (NIDDM) is associated with the presence of structural alterations in small arteries or whether the combination of hypertension and NIDDM may have an additive effect on endothelial dysfunction. Therefore, we investigated subcutaneous small arteries in 12 normotensive subjects (NT group), 18 patients with essential hypertension (EH group), 13 patients with NIDDM, and 11 patients with NIDDM and EH (NIDDM+EH group).Subcutaneous small arteries were evaluated by a micromyographic technique. The internal diameter, the media-to-lumen ratio, remodeling and growth indices, and the collagen-to-elastin ratio were calculated. Concentration-response curves to acetylcholine, bradykinin, the endothelium-independent vasodilator sodium nitroprusside, and endothelin-1 were performed. The media-to-lumen ratio was higher in the EH, NIDDM, and NIDDM+EH groups compared with the NT group. EH patients showed the presence of eutrophic remodeling, whereas NIDDM and NIDDM+EH patients showed 40% to 46% cell growth. The collagen-to-elastin ratio was significantly increased in the EH and NIDDM+EH groups compared with the NT group. The vasodilatation to acetylcholine and bradykinin was similarly reduced in EH, NIDDM, and NIDDM+EH groups compared with the NT group. The contractile responses to endothelin-1 were similarly reduced in EH, NIDDM, and NIDDM+EH patients.Our data suggest that the effects of NIDDM and EH on small artery morphology are quantitatively similar but qualitatively different and that the presence of hypertension in diabetic patients has little additive effect on small artery morphology and none on endothelial dysfunction.
Moxifloxacin in multidrug-resistant tuberculosis: is there any indication for therapeutic drug monitoring?: Table 1–
Authors: Katerina Manika, Kalliopi Chatzika, Konstantinos Zarogoulidis, Ioannis Kioumis
Journal: European Respiratory Journal (2012)

Moxifloxacin in multidrug-resistant tuberculosis: is there any indication for therapeutic drug monitoring?To the Editors:Fluoroquinolones are rapidly emerging as important drugs in the treatment of tuberculosis (TB) worldwide [1].In drugsusceptible TB, their use is currently under investigation and, according to the American Thoracic Society/Centers for Disease Control guidelines, fluoroquinolones are indicated only in patients receiving the conventional regimen who present severe adverse reactions [2].However, in drug-resistant (DR) and, more specifically, in multidrug-resistant (MDR)-TB, the role of fluoroquinolones is much better established.Later-generation fluoroquinolones are included even in extensively drug resistant (XDR)-TB regimens since they may have some efficacy against ofloxacin-resistant strains [3].
A Urokinase Receptor–Bim Signaling Axis Emerges during EGFR Inhibitor Resistance in Mutant EGFR Glioblastoma
Authors: Jill Wykosky, Jingjing Hu, German G. Gomez, Tiffany Taylor, Genaro R. Villa, Donald Pizzo, Scott R. VandenBerg, Amy Haseley Thorne, Clark C. Chen, Paul S. Mischel, Steven L. Gonias, Webster K. Cavenee, Frank B. Furnari
Journal: Cancer Research (2014)

Abstract EGFR is the most common genetically altered oncogene in glioblastoma (GBM), but small-molecule EGFR tyrosine kinase inhibitors (TKI) have failed to yield durable clinical benefit. Here, we show that in two novel model systems of acquired resistance to EGFR TKIs, elevated expression of urokinase plasminogen activator (uPA) drives signaling through the MAPK pathway, which results in suppression of the proapoptotic BCL2-family member protein BIM (BCL2L11). In patient-derived GBM cells and genetic GBM models, uPA is shown to suppress BIM levels through ERK1/2 phosphorylation, which can be reversed by siRNA-mediated knockdown of uPA. TKI-resistant GBMs are resensitized to EGFR TKIs by pharmacologic inhibition of MEK or a BH3 mimetic drug to replace BIM function. A link between the uPA–uPAR–ERK1/2 pathway and BIM has not been previously demonstrated in GBM, and involvement of this signaling axis in resistance provides rationale for a new strategy to target EGFR TKI-resistant GBM. Cancer Res; 75(2); 394–404. ©2014 AACR.
An Intensive Surveillance Program Detected a High Incidence of Hepatocellular Carcinoma Among Hepatitis B Virus Carriers With Abnormal Alpha-Fetoprotein Levels or Abdominal Ultrasonography Results
Authors: Tony S.K. Mok, Winnie Yeo, Simon Yu, Paul Lai, Henry L.Y. Chan, Anthony T.C. Chan, Joseph W.Y. Lau, Herman Wong, Nancy Leung, Edwin P. Hui, Joseph Sung, Jane Koh, Frankie Mo, Benny Zee, Philip J. Johnson
Journal: Journal of Clinical Oncology (2005)

To study the incidence and treatment outcomes of hepatocellular carcinoma (HCC) detected in an intensive surveillance program (ISP) of hepatitis B virus (HBV) carriers.We screened 1,018 HBV carriers by serum alpha-fetoprotein (AFP) measurement and abdominal ultrasonography (AUS). Patients with an abnormal AFP level or AUS result were enrolled in an ISP that included Lipiodol computed tomography followed by AFP measurement/AUS every 3 months for 2 years and then every 6 months thereafter. The rest were on routine surveillance for 2 years.A total of 9,849 serum AFP measurements and 3,053 AUSs were performed. After a median follow-up of 4.12 years, we diagnosed 24 HCCs among 78 patients with abnormal screening test results at enrollment (group A); 23 HCCs among 93 patients with only abnormal surveillance test results during follow-up (group B); and nine HCCs among 847 patients with 2 years of normal surveillance (group C). Annual incidence of HCC in the ISP was 760.2 (95% CI, 538.4 to 1,073.7) per 100,000. Mean tumor sizes were 3.02, 2.91, and 4.82 cm in groups A, B, and C, respectively (P = .01). Tumor resection rate of the ISP was 36.2%, although another 29.8% of the patients were eligible for locoregional ablative therapy.This study illustrated that a high incidence of relatively small HCCs may be detected by using intensive surveillance of high-risk HBV carriers. However, the surgical resection rate was low, and we were not able to demonstrate clinical benefit with the early detection. Future surveillance studies should consider incorporation of therapy aimed at long-term control of small-sized tumors.
Clinical and epidemiological characteristics of a fatal case of avian influenza A H10N8 virus infection: a descriptive study
Authors: HaiYing Chen, Hui Yuan, Rongbao Gao, Jinxiang Zhang, Dayan Wang, Ying Xiong, GuoYin Fan, Fan Yang, Xiaodan Li, Jianfang Zhou, Shumei Zou, Lei Yang, Tao Chen, Libo Dong, Hong Bo, Xiang Zhao, Ye Zhang, Yu Lan, Tian Bai, Jie Dong, Qun Li, ShiWen Wang, YanPing Zhang, Hui Li, Tian Gong, Yong Shi, Xiansheng Ni, Jianxiong Li, Jun Zhou, Jiyi Fan, Jingwen Wu, Xianfeng Zhou, Maohong Hu, Jianguo Wan, WeiZhong Yang, DeXin Li, Guizhen Wu, ZiJian Feng, George F Gao, Yu Wang, Qi Jin, Mingbin Liu, Yuelong Shu
Journal: The Lancet (2014)
alpha2-Macroglobulin on human vascular endothelium.
Authors: C G Becker, P C Harpel
Journal: The Journal of Experimental Medicine (1976)

alpha2-Macroglobulin (alpha2M) has been identified on the luminal surface of endothelial cells in sections of normal human arteries, veins, and lymphatics by the indirect immunofluorescent technique. The specificity of the immunofluorescent reaction was confirmed by immunoabsorption studies. Prior absorption of the anti-alpha2M antiserum by purified alpha2M at equivalence completely inhibited endothelial surface as well as hepatic parenchymal cell staining. Endothelial cells in blood vessels were not stained when sections were treated with rabbit antisera toward alpha1-antitrypsin, antithrombin III, IgG, IgA, IgM, C3, or fibrinogen. The location of alpha2M at the surface of the vessel wall suggests that this protease inhibitor may protect the vascular endothelium from potentially injurious intravascular proteases.
Dietary folate, alcohol and B vitamins in relation to LINE-1 hypomethylation in colon cancer
Authors: E. S. Schernhammer, E. Giovannucci, T. Kawasaki, B. Rosner, C. S. Fuchs, S. Ogino
Journal: Gut (2009)

<h3>Background and aims</h3> Although critical for methylation reactions, how dietary folate and B vitamins affect global DNA methylation level in colorectal cancers is currently unknown. Long interspersed nucleotide element-1 (LINE-1) is an emerging indicator of genome-wide DNA methylation level that has previously been linked to colon cancer survival. <h3>Methods</h3> We examined the association between dietary intake of folate, alcohol and B vitamins and LINE-1 hypomethylation in 609 incident colon cancers, utilising the database of two independent prospective cohort studies. <h3>Results</h3> Participants with ≥400 μg folate intake per day were significantly less likely to develop LINE-1 hypomethylated colon cancers than those reporting &lt;200 μg of folate intake per day (RR=0.57, 95% CI=0.36 to 0.91 for &lt;55% LINE-1 methylated colon tumours; RR=0.74, 95% CI=0.51 to 1.06 for 55–64% LINE-1 methylated colon tumours; and RR=1.08, 95% CI=0.66 to 1.75 for ≥65% LINE-1 methylated tumours; P<sub>interaction</sub>=0.01). By contrast, high alcohol consumption conferred a higher risk of LINE-1 hypomethylated cancers (≥15 g alcohol per day versus none, RR=1.67, 95% CI=1.04 to 2.67 for &lt;55% LINE1 methylated tumours; and RR=1.55, 95% CI=1.10 to 2.18 for 55–64% LINE-1 methylated tumours) but had no association with ≥65% LINE-1 methylated tumours (RR=1.06, 95% CI=0.69 to 1.62). High intakes of vitamin B<sub>6</sub>, B<sub>12</sub> or methionine were not significantly associated with colon cancers, regardless of LINE-1 methylation level. <h3>Conclusion</h3> The influence of dietary folate intake and alcohol consumption on colon cancer risk differs significantly according to tumoral LINE-1 methylation level.
Carotid artery stenting increased risk for stroke more than carotid endarterectomy in severe symptomatic stenosis
Authors: Mark J.W. Koelemay
Journal: Annals of Internal Medicine (2009)

Source Citation Mas JL, Trinquart L, Leys D, et al. Endarterectomy Versus Angioplasty in Patients with Symptomatic Severe Carotid Stenosis (EVA-3S) trial: results up to 4 years from a randomised, multicentre trial. Lancet Neurol. 2008;7:885-92. 18774745
Activation of Akt pathway by transcription-independent mechanisms of retinoic acid promotes survival and invasion in lung cancer cells
Authors: Alejandro García-Regalado, Miguel Vargas, Alejandro García-Carrancá, Elena Aréchaga-Ocampo, Claudia Haydée González-De la Rosa
Journal: Molecular Cancer (2013)

Abstract Background All- trans retinoic acid (ATRA) is currently being used in clinical trials for cancer treatment. The use of ATRA is limited because some cancers, such as lung cancer, show resistance to treatment. However, little is known about the molecular mechanisms that regulate resistance to ATRA treatment. Akt is a kinase that plays a key role in cell survival and cell invasion. Akt is often activated in lung cancer, suggesting its participation in resistance to chemotherapy. In this study, we explored the hypothesis that activation of the Akt pathway promotes resistance to ATRA treatment at the inhibition of cell survival and invasion in lung cancer. We aimed to provide guidelines for the proper use of ATRA in clinical trials and to elucidate basic biological mechanisms of resistance. Results We performed experiments using the A549 human lung adenocarcinoma cell line. We found that ATRA treatment promotes PI3k-Akt pathway activation through transcription-independent mechanisms. Interestingly, ATRA treatment induces the translocation of RARα to the plasma membrane, where it colocalizes with Akt. Immunoprecipitation assays showed that ATRA promotes Akt activation mediated by RARα-Akt interaction. Activation of the PI3k-Akt pathway by ATRA promotes invasion through Rac-GTPase, whereas pretreatment with 15e (PI3k inhibitor) or over-expression of the inactive form of Akt blocks ATRA-induced invasion. We also found that treatment with ATRA induces cell survival, which is inhibited by 15e or over-expression of an inactive form of Akt, through a subsequent increase in the levels of the active form of caspase-3. Finally, we showed that over-expression of the active form of Akt significantly decreases expression levels of the tumor suppressors RARβ2 and p53. In contrast, over-expression of the inactive form of Akt restores RARβ2 expression in cells treated with ATRA, indicating that activation of the PI3k-Akt pathway inhibits the expression of ATRA target genes. Conclusion Our results demonstrate that rapid activation of Akt blocks transcription-dependent mechanism of ATRA, promotes invasion and cell survival and confers resistance to retinoic acid treatment in lung cancer cells. These findings provide an incentive for the design and clinical testing of treatment regimens that combine ATRA and PI3k inhibitors for lung cancer treatment.
Molecular Evolution and Functional Diversification of Fatty Acid Desaturases after Recurrent Gene Duplication in Drosophila
Authors: S. Fang, C.-T. Ting, C.-R. Lee, K.-H. Chu, C.-C. Wang, S.-C. Tsaur
Journal: Molecular Biology and Evolution (2009)

Frequent gene duplications in the genome incessantly supply new genetic materials for functional innovation presumably driven by positive Darwinian selection. This mechanism in the desaturase gene family has been proposed to be important in triggering the pheromonal diversification in insects. With the recent completion of a dozen Drosophila genomes, a genome-wide perspective is possible. In this study, we first identified homologs of desaturase genes in 12 Drosophila species and noted that while gene duplication events are relatively frequent, gene losses are not scarce, especially in the desat1–desat2–desatF clade. By reconciling the gene tree with species phylogeny and the chromosomal synteny of the sequenced Drosophila genomes, at least one gene loss in desat2 and a minimum of six gene gains (resulting in seven desatF homologs, α-η), three gene losses and one relocation in desatF were inferred. Upon branching off the ancestral desat1 lineage, both desat2 and desatF gained novel functions through accelerating protein evolution. The amino acid residues under positive selection located near the catalytic sites and the C-terminal region might be responsible for altered substrate selectivity between closely related species. The association between the expression pattern of desatF-α and the chemical composition of cuticular hydrocarbons implies that the ancestral function of desatF-α is the second desaturation at the four carbons after the first double bond in diene synthesis, and the shift from bisexual to female-specific expression in desatF-α occurred in the ancestral lineage of Drosophila melanogaster subgroup. A relationship between the number of expressed desatF homologs and the diene diversification has also been observed. These results suggest that the molecular diversification of fatty acid desaturases after recurrent gene duplication plays an important role in pheromonal diversity in Drosophila.
Response to ‘pervasive sequence patents cover the entire human genome’ - authors’ reply
Authors: Jeffrey Rosenfeld, Christopher Mason
Journal: Genome Medicine (2014)

An author reply to the Letter to the Editor from Tu et al. regarding Pervasive sequence patents cover the entire human genome by J Rosenfeld and C Mason. Genome Med 2013, 5:27. See related Correspondence by Rosenfeld and Mason, http://genomemedicine.com/content/5/3/27, and related letter by Tu et al., http://genomemedicine.com/content/6/2/14.
Presidential Address: Our Patients' Future in a Changing World: The Imperative for Psychiatric Involvement in Public Policy
Authors: JOHN A. TALBOTT
Journal: American Journal of Psychiatry (1985)

Patients who had reconstructive breast surgery at the time of mastectomy (immediate) or within 1 year (early) had significantly less recalled distress about their mastectomy than those who had it more than 1 year later (delayed). Women who had immediate or delayed reconstructive surgery had similar levels of psychological symptoms, which were slightly lower than those reported by women in the early reconstructive group. The wish to wear a wider range of clothes and the wish to be rid of the external prosthesis were common motivations for reconstructive surgery. The desire to improve sexual relations or one's marital state was less common and should be viewed with caution when presented as the primary motivation for this procedure.
Intensity of Resistance Exercise Determines Adipokine and Resting Energy Expenditure Responses in Overweight Elderly Individuals
Authors: Ioannis G. Fatouros, Athanasios Chatzinikolaou, Symeon Tournis, Michalis G. Nikolaidis, Athanasios Z. Jamurtas, Ioannis I. Douroudos, Ioannis Papassotiriou, Petros M. Thomakos, Kyriakos Taxildaris, George Mastorakos, Asimina Mitrakou
Journal: Diabetes Care (2009)

OBJECTIVE To evaluate the time course of leptin, adiponectin, and resting energy expenditure (REE) responses in overweight elderly males after acute resistance exercise protocols of various intensity configurations. RESEARCH DESIGN AND METHODS Forty inactive men (65–82 years) were randomly assigned to one of four groups (n = 10/group): control, low-intensity resistance exercise, moderate-intensity resistance exercise, and high-intensity resistance exercise. Exercise energy cost, REE, leptin, adiponectin, cortisol, insulin, lactate, glucose, nonesterified fatty acids (NEFAs), and glycerol were determined at baseline, immediately after exercise, and during a 72-h recovery period. RESULTS Exercise energy cost was lower in high-intensity than in low-intensity and moderate-intensity groups (221.6 ± 8.8 vs. 295.6 ± 10.7 and 281.6 ± 9.8 kcal, P &amp;lt; 0.001). Lactate, glucose, NEFAs, and glycerol concentrations increased (P &amp;lt; 0.001) after exercise and returned to baseline thereafter in all groups. REE increased (P &amp;lt; 0.001) in all groups at 12 h in an intensity-dependent manner (P &amp;lt; 0.05). REE reached baseline after 48 h in the low- and moderate-intensity groups and after 72 h in the high-intensity group. Cortisol peaked in all active groups after exercise (P &amp;lt; 0.001) and remained elevated (P &amp;lt; 0.001) for 12 h. After adjustment for plasma volume shifts, leptin remained unaltered. Adiponectin concentration increased after 12 h and remained elevated for 24 h only in the high-intensity group (P &amp;lt; 0.001). CONCLUSIONS Resistance exercise does not alter circulating leptin concentration but does increase REE and adiponectin in an intensity-dependent manner for as long as 48 and 24 h, respectively, in overweight elderly individuals. It appears that resistance exercise may represent an effective approach for weight management and metabolic control in overweight elderly individuals.
A Gata6-Wnt pathway required for epithelial stem cell development and airway regeneration
Authors: Yuzhen Zhang, Ashley M Goss, Ethan David Cohen, Rachel Kadzik, John J Lepore, Karthika Muthukumaraswamy, Jifu Yang, Francesco J DeMayo, Jeffrey A Whitsett, Michael S Parmacek, Edward E Morrisey
Journal: Nature Genetics (2008)
Global Alliance against Chronic Respiratory Diseases
Authors: J. Bousquet, R. Dahl, N. Khaltaev
Journal: European Respiratory Journal (2006)

Hundreds of millions of people of all ages suffer from chronic respiratory diseases which include asthma and respiratory allergies, chronic obstructive pulmonary disease, occupational lung diseases and pulmonary hypertension. More than 500 million patients live in developing countries or in deprived populations. Chronic respiratory diseases are increasing in prevalence. Although the cost of inaction is clear and unacceptable, chronic respiratory diseases and their risk factors receive insufficient attention from the healthcare community, government officials, media, patients and families. The Fifty-Third World Health Assembly recognised the enormous human suffering caused by chronic diseases and requested the World Health Organization (WHO) Director General to give priority to the prevention and control of chronic diseases, with special emphasis on developing countries. This led to the formation of the WHO Global Alliance against Chronic Respiratory Diseases (GARD). GARD is a voluntary alliance of organisations, institutions and agencies working towards a common vision to improve global lung health according to local needs. GARD is developed in a stepwise approach using the following three planning steps: estimate population need and advocate action; formulate and adopt policy; and identify policy implementation steps.