tbuckley/cabot-search huggingface dataset:
Compensatory role for proline-rich tyrosine kinase 2 (Pyk2) during angiogenesis in adult mice lacking endothelial cell focal adhesion kinase (FAK)
Authors: Sara Weis, Ssang-Taek Lim, Kimberly Lutu-Fuga, Leo Barnes, Xiao Lei Chen, Joachim Goethert, Tang-Long Shen, Jun-Lin Guan, David Schlaepfer, David Cheresh
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

5846 

Focal adhesion kinase (FAK) is a cytoplasmic tyrosine kinase that integrates signals from growth factor receptors and integrins leading to changes in cell migration, proliferation, and survival. Pharmacological inhibitors of FAK have shown promising preclinical results as anti-cancer agents potentially via effects on tumor cells. However, FAK also plays a critical role within endothelial cells (EC) during normal development, vascular remodeling, and angiogenesis that can influence tumor progression. Here, we show that pharmacological inhibition of FAK blocks growth factor-induced angiogenesis in adult mice. But surprisingly, tamoxifen-inducible conditional knockout of FAK in adult blood vessels (herein termed ‘i-EC-FAK-KO mice’) produces no vascular phenotype. In fact, these animals are capable of developing robust angiogenic responses to growth factors, serum, or tumors. In contrast to wildtype animals, FAK inhibition does not block the angiogenic response in i-EC-FAK-KO mice, suggesting that adult i-EC-FAK-KO mice develop a compensatory mechanism to bypass the requirement for FAK. Indeed, expression of the FAK-related proline-rich tyrosine kinase 2 (Pyk2) is elevated and/or activated in i-EC-FAK-KO blood vessels, in ECs following FAK knockdown, and in fibroblasts treated with FAK-specific inhibitors . We propose that Pyk2 functionally compensates for the loss of FAK in i-EC-FAK-KO mice, since angiogenesis in these mice can be blocked by either genetic knockdown or pharmacological inhibition of Pyk2. Our studies reveal the adaptive capacity of endothelial cells to switch to Pyk2-dependent signaling following deletion or inhibition of FAK. This work may have implications for the preclinical development of FAK or dual FAK/Pyk2 kinase inhibitors as anti-cancer and/or anti-angiogenic agents.
Smooth pursuit ocular motor dysfunction in schizophrenia: evidence for a major gene
Authors: W M Grove, B A Clementz, W G Iacono, J Katsanis
Journal: American Journal of Psychiatry (1992)

Evidence suggests that poor eye tracking relates to genetically transmitted vulnerability for schizophrenia. The authors tested competing models for the genetic transmission of poor eye tracking in a search for major gene effects.Samples from three studies (conducted in Minneapolis, New York, and Vancouver, B.C.) were pooled. Probands (N = 92) were diagnosed as schizophrenic by DSM-III criteria. Of the comparison subjects (N = 171), Vancouver patients were an epidemiologic first-episode group; at other sites unselected admitted patients were studied. First-degree relatives (N = 146) of 65 probands were also studied. Eye tracking was measured while subjects followed a horizontally moving, sinusoidally driven (0.4 Hz) spot of light on a screen. Performance was quantified by root mean square error. Data analysis was by complex segregation analysis (Bonney's class D regressive models).A single major gene is needed to account for poor eye tracking in schizophrenic patients and their relatives. This gene alone can explain about two-thirds of the variance in eye tracking performance. A single gene alone (regardless of dominance) will, however, not account for the data; polygenic factors are also required.Results support postulation of a single gene for ocular motor dysfunction, which may be a risk factor for schizophrenia. Eye tracking may be useful as a gene carrier test in genetic studies of schizophrenia.
Abstract 152: Site-Specific Protein S-glutathiolation Modulates the Enzymatic Function of Mitochondrial Complex I by Increasing Electron Transfer Activity and Decreasing Electron Leakage for Superoxide Production
Authors: Chwen-Lih Chen, Liwen Zhang, Kari B Green-Church, Jay L Zweier, Yeong-Renn Chen
Journal: Circulation (2006)

The generation of reactive oxygen species in mitochondria acts as a redox signal in triggering cellular events such as apoptosis, proliferation, and senescence. Overproduction of superoxide (O2· −)...
Abstract 4862: ST-Segment Depression in Lead aVR: A Useful Predictor of Impaired Myocardial Reperfusion in Patients With Anterolateral ST-Segment Elevation Acute Myocardial Infarction
Authors: Masami Kosuge, Toshiaki Ebina, Kiyoshi Hibi, Satoshi Morita, Toshiyuki Ishikawa, Kazuaki Uchino, Kengo Tsukahara, Noriaki Iwahashi, Jyun Okuda, Satoshi Umemura, Kazuo Kimura
Journal: Circulation (2009)

Background: ST-segment depression in lead aVR during ST-segment elevation acute myocardial infarction (STEMI) theoretically represents a reciprocal change in response to an opposite vector resulting from ST-segment elevation in the apical and inferolateral walls. We hypothesized that ST-segment depression in lead aVR during anterolateral STEMI is associated with less successful myocardial reperfusion, because of more extensive area at risk. Methods: We studied 301 patients with a first anterolateral STEMI who underwent coronary recanalization (TIMI grade 3 flow) by fibrinolysis or percutaneous coronary intervention within 6 h after symptom onset. Patients were divided into the 3 groups according to ST-segment deviation in lead aVR on admission ECG: group A, 71 patients with ST-segment elevation of ≥ 0.5 mm; group B, 131 patients without ST-segment deviation; and group C, 99 patients with ST-segment depression of ≥ 0.5 mm. Myocardial blush grade was assessed immediately after recanalization. Results: There were no differences in age, sex, coronary risk factors, time from symptom onset to admission, or multivessel disease among the 3 groups. In groups A, B, and C, the incidence of Killip class ≥ 2 was 6%, 6%, and 15% (p=0.03); the sum of ST-segment elevation in leads I, aVL, and V1– 6 was 20±11, 23±9, and 33±14 mm (p&lt;0.01); the rates of initial TIMI grade 0 or 1 flow was 56%, 70%, and 78% (p=0.01); good collateral circulation was 43%, 39%, and 22% (p=0.03); impaired myocardial reperfusion (defined as myocardial blush grade 0 or 1) was 14%, 23%, and 65% (p&lt;0.01); peak creatine kinase level was 3432±1995, 4045±2144, and 5986±2550 mU/ml (p&lt;0.01); and predischarge left ventricular ejection fraction was 56±13%, 51±11%, 44±12% (p&lt;0.01), respectively. Multivariate analysis showed that ST-segment depression in lead aVR was an independent predictor of impaired myocardial reperfusion (odds ratio 3.31, 95% CI 1.98 to 5.52, p&lt;0.001); but sum of ST-segment elevation in leads I, aVL, and V1– 6 was not. Conclusions: In patients with anterolateral STEMI, ST-segment depression in lead aVR on admission ECG is associated with less successful myocardial reperfusion and larger infarct. Assessment of ST-segment deviation in lead aVR is useful for acute risk stratification.
Abstract 21276: Human Embryonic Stem-cell derived Cardiomyocytes Engulf Apoptotic Cardiomyocytes while Retaining Contractile Function
Authors: Liat Gelernter-Yaniv, Irit Huber, Gil Arbel, Amira Gepstein, Edith Suss Toby, Ofer Shenker, Robert Clancy, Jill P Buyon, Lior Gepstein
Journal: Circulation (2010)
Stimulation by Alcohols of Cyclic AMP Metabolism in Human Leukocytes
Authors: John P. Atkinson, Timothy J. Sullivan, James P. Kelly, Charles W. Parker
Journal: Journal of Clinical Investigation (1977)

In this study ethanol and certain other short-chain aryl (benzyl and phenethyl) and aliphatic (methyl, propyl, butyl, and amyl) alcohols produced up to 10-fold increases in cyclic AMP (cAMP) concentrations in purified human peripheral blood lymphocytes. Ethanol concentrations as low as 80 mg/dl produced significant elevations in lymphocyte cAMP. Significant but less marked augmentation of cAMP in response to alcohols was observed in human platelets, human granulocytes, and rabbit alveolar macrophages. The mechanism of the alcohol-induced cAMP accumulation is probably secondary to membrane perturbation and consequent activation of adenylate cyclase, because ethanol directly stimulated this enzyme in lymphocyte membrane preparations but had no effect on lymphocyte phosphodiesterase activity. Lysosomal enzyme release, by phagocytosing human leukocytes, and aminoisobutyric acid transport in mitogen-stimulated human lymphocytes were shown to be inhibited by ethanol and other alcohols at concentrations which also elevate cAMP. In general, the magnitude of the inhibition of these inflammatory processes correlated with the ability of the alcohol to elevate cAMP concentrations. Lectin-and anti-thymocyte globulin-induced lymphocyte mitogenesis was inhibited or unaffected depending upon both the concentration and type of mitogenic stimulus and the concentration and type of alcohol utilized. Inflammatory mediator release from rat mast cells also was inhibited by ethanol and certain other alcohols, but whole cell cAMP was not increased. Ethanol may alter these inflammatory responses and other biologic processes at least in part by modulating cellular levels of cAMP.
Surveillance of antimicrobial resistance
Authors: D. M Livermore, A. P Macgowan, M. C J Wale
Journal: BMJ (1998)

Antibiotic resistance is increasing and significant public health problems are feared. Actions to mitigate the problem include development of new antimicrobials, better infection control, and greater conservation of existing agents. One pressing problem is the paucity of data to measure the impact of resistance on public health or the effect of interventions to prevent its emergence and spread. Moreover, other factors besides clinical prescribing may drive resistance — failure of infection control; institutionalisation of care for the very young and elderly; changing population age structures; agricultural use of antibiotics; and the spread of strains that are effective colonists and which, coincidentally, are resistant.1 Better surveillance of resistance is needed to understand this interplay as well as to advise on empirical therapy. 2 3 Once relations between use and resistance have been established surveillance data then can serve as “information for action” for initiatives to decrease unnecessary prescribing and prolong the usefulness of existing antibiotics.

Establishing such surveillance presents several problems. 2 3 It is easiest to count resistance rates of bacteria received at laboratories, but these organisms form a biased sample because (a) laboratory requesting varies greatly among clinicians; (b) some diseases (such as chronic obstructive airways disease) are more likely to generate laboratory specimens than others (such as pneumonia); (c) some age groups, particularly the elderly, are more likely to have specimens taken than others; and (d) primary care specimens are usually sent only from patients who have failed to respond to empirical treatment or who have comorbidities. Ideally resistance should have a clinical denominator (number of infected patients) not a laboratory one (number of isolates), but this is not easy except in uncommon diseases such …
Abstract 18029: Left Ventricular Systolic Strain in Older Subjects with No Known Cardiac Disease
Authors: Bhaskar Purushottam, Morris N Kotler, Vincent M Figueredo
Journal: Circulation (2011)

Introduction: It is known that with increasing age impaired myocardial relaxation increases, while systolic function is preserved. We hypothesize that there is, in fact, subclinical left ventricular (LV) systolic dysfunction in older subjects. We test this hypothesis by assessing LV systolic strain using velocity vector imaging in older subjects with no known cardiac disease. Methods: One-hundred and ninety consecutive subjects with no known cardiac disease had their echocardiograms analyzed by VVI after excluding patients with a left ventricular ejection fraction(LVEF) &lt;55%, grade 2 and above diastolic dysfunction and QRS duration &gt; 120ms. Subjects were divided into 2 groups based on age; older (&gt; 60 years) and younger (&lt; 60 years). Demographic, clinical and echocardiographic data were collected. Time to peak longitudinal and circumferential strain were calculated from apical 4-chamber, 2-chamber and short axis views. The above collected data were compared between groups. Results: The final cohort consisted of 136 subjects (46 were older). Mean age was 55 + 16 years, 32% were female and mean LVEF was 60 + 8%. The older group had a higher LVEF (63 + 9% vs. 59 + 6%; p=0.03), smaller LV diastolic dimension (4.4 + 0.5cm vs. 4.7 + 0.5cm; p&lt;0.01) and higher occurrences of diastolic dysfunction (84% vs. 59%; p&lt;0.01) and hypertension (85% vs. 63%; p=0.02), when compared to the younger group. There were no significant differences in the longitudinal and circumferential strain (even with cut-off ages of 50 or 75 years). Conclusions: Contrary to our hypothesis, older subjects with no known cardiac disease had a better LVEF than their younger counterparts. There were no significant differences in the longitudinal and circumferential myocardial strain between the older and younger groups. Therefore, impaired myocardial relaxation does not appear to have a direct influence on the myocardial contractility or systolic function in older subjects.
HIV/AIDS surveillance in Europe: update 2007
Authors: M J van de Laar, G Likatavicius, A R Stengaard, M C Donoghoe
Journal: Eurosurveillance (2008)

Human immunodeficiency virus (HIV) infection remains of major public health importance in Europe, with evidence of increasing transmission of HIV in several countries. This article provides an overview of HIV and acquired immunodeficiency syndrome (AIDS) surveillance data, and indicates that since 2000 the rate of newly reported cases of HIV per million population has almost doubled in Europe. In 2007, a total of 48,892 cases of HIV infection were reported from 49 of 53 countries in the Region, with the highest rates in Estonia, Ukraine, Portugal and the Republic of Moldova. In the European Union (EU) and European Free Trade Association (EFTA) countries, the predominant mode of transmission for HIV infection is sex between men followed by heterosexual contact. Injecting drug use is still the main mode of transmission in the eastern part of the WHO European region, while in the central part heterosexual contact is the predominant mode of transmission. In 2007, the reported number of AIDS cases diagnosed decreased in the Region overall, except in the eastern part. HIV/AIDS surveillance data are vital to monitor the trends of the HIV epidemic and evaluate public health responses.
Whole-Body Visualization of Ectopic Bone Formation of Arteries and Skin in Pseudoxanthoma Elasticum
Authors: Sytse F. Oudkerk, Pim A. de Jong, Björn A. Blomberg, Asbjørn M. Scholtens, Willem P.Th.M. Mali, Wilko Spiering
Journal: JACC. Cardiovascular imaging (2015)
Gene expression of paired abdominal adipose AQP7 and liver AQP9 in patients with morbid obesity
Authors: Merce Miranda, Victòria Ceperuelo-Mallafré, Albert Lecube, Cristina Hernandez, Matilde R. Chacon, Jose M. Fort, Lluís Gallart, Juan A. Baena-Fustegueras, Rafael Simó, Joan Vendrell
Journal: Metabolism (2009)
Testing should be in all women
Authors: N. J Wald, A. Kennard, H. Watt, J. E Haddow, G. E Palomaki, G. J Knight, J. A Canick
Journal: BMJ (1995)

EDITOR,--The paper by J Fletcher and colleagues1 was incorrect to conclude that restricting serum screening for Down's syndrome to women aged 30 or over is preferable to screening all women. Firstly, using a 58% detection rate and a 5% false positive rate for all pregnant women instead of estimates applicable to women aged 30 or over (72% and 12%2 3), and, secondly, not comparing screening policies appropriately introduces important errors.

Screening tests involve a trade off between detection rate and false positive rate. To compare screening policies, cut off levels must be set such that among all pregnancies in …
Proximal Endovascular Occlusion for Carotid Artery Stenting
Authors: Eugenio Stabile, Luigi Salemme, Giovanni Sorropago, Tullio Tesorio, Wail Nammas, Marianna Miranda, Grigore Popusoi, Angelo Cioppa, Vittorio Ambrosini, Linda Cota, Giampaolo Petroni, Giovanni Della Pietra, Angelo Ausania, Arturo Fontanelli, Giancarlo Biamino, Paolo Rubino
Journal: Journal of the American College of Cardiology (2010)
Expression of programmed cell death ligand 1 is associated with poor overall survival in patients with diffuse large B-cell lymphoma
Authors: Junichi Kiyasu, Hiroaki Miyoshi, Akie Hirata, Fumiko Arakawa, Ayako Ichikawa, Daisuke Niino, Yasuo Sugita, Yuji Yufu, Ilseung Choi, Yasunobu Abe, Naokuni Uike, Koji Nagafuji, Takashi Okamura, Koichi Akashi, Ryoichi Takayanagi, Motoaki Shiratsuchi, Koichi Ohshima
Journal: Blood (2015)
A Phase II, Single-Center, Open-Label Study Of Oral Panobinostat In Combination With Lenalidomide and Weekly Dexamethasone In Patients With Multiple Myeloma
Authors: Noa Biran, Samira Shahnaz, Sundar Jagannath, Hearn J. Cho, Keren Osman, Samir Parekh, Danielle Choi, Katarzyna Garcia, Donna Catamero, Lisa La, Jude Gullie, Elaine Chan, Ajai Chari
Journal: Blood (2013)
Nanotechnology approaches for inhalation treatment of lung diseases
Authors: Andriy Kuzmov, Tamara Minko
Journal: Journal of Controlled Release (2015)

Local administration of therapeutics by inhalation for treatment of lung diseases has the ability to deliver drugs, nucleic acids and peptides specifically to the site of their action and therefore enhance the efficacy of the treatment, limit the penetration of nebulized therapeutic agent(s) into the bloodstream and consequently decrease adverse systemic side effects of the treatment. Nanotechnology allows for a further enhancement of the treatment efficiency. The present review analyzes modern therapeutic approaches of inhaled nanoscale-based pharmaceutics for the detection and treatment of various lung diseases.
Abstract 821: Human mammary tumor virus(HMTV) is deeply involved in breast cancer and metastasis
Authors: James F. Holland, Stella Melana, Shabnam Jaffer, Polly Etkind, Teiko Nartey, Tina Lee, Beatriz G.T. Pogo
Journal: Cancer Research (2015)

Abstract Human Mammary Tumor Virus (HMTV), a betaretrovirus 90-95% homologous to Mouse Mammary Tumor Virus (MMTV), present in 40% of American women's breast cancers, but not in the normal tissue from the same breast indicates an infection (Cancer Res 1995, 55:5173-79). Absence of murine intracisternal particles and murine cyclo-oxygenase 2 by PCR and nanoString excludes contemporaneous mouse DNA, and thus MMTV contamination (Proc AACR 2014 #1595). We have detected the entire 9.9 kb proviral sequence. Proviral DNA is visible in nuclei by FISH, and budding virus was observed by EM. HMTV in cells is present in the milk of 8% of unselected American women, but in 21% if they had had a prior biopsy based upon clinical or radiologic suspicion of a mass. (Infectious Agents and Cancer 2014, 9:20). HMTV has been found in cells of 30 of 32 (94%) metastatic breast cancer effusions (MSSM cells). HMTV protein and virion RNA were detected in MSSM cells but not in normal human mammary epithelium. (J Virol Methods 2010,163:157-61). HMTV isolated from MSSM cells is infectious for B and T lymphocytes, MCF10A andF and human mammary epithelial cells (HMEC). Infection led to proviral insertion sites with different flanking sequences. Epithelial-mesenchymal transition was observed with upregulation of vimentin and downregulation of E-cadherin. Restriction factors including the cytidine deaminase APOBEC G and F, TRIM 5, 21 and 25 and Tetherin were also increased after in vitro HMTV infection. Epidemiologically, breast cancer is less frequent in 5 countries of Central and East and Asia (28-43/100,000/y. World Cancer Report 2014) where HMTV positivity in breast cancers ranges from 0 to 20%, compared to 7 countries of Western Europe and its former colonies in North and South America and Australia (47-92/100,000/y op.cit.) where 30 to 60% are positive. This correlates with indigenous mouse species, Mus musclus and M.castaneus in the East, and M. domesticus with much more HMTV in its genome in the West. HMTV positive lymphomas have been reported in patients with HMTV positive breast cancers (Clin Cancer Res 2004 10:56565-64). The parallel with MMTV behavior in the mouse with respect to breast cancer and lymphomas is striking. These composite data support a significant role of HMTV in human breast cancer and its metastatic process. Citation Format: James F. Holland, Stella Melana, Shabnam Jaffer, Polly Etkind, Teiko Nartey, Tina Lee, Beatriz G.T. Pogo. Human mammary tumor virus(HMTV) is deeply involved in breast cancer and metastasis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 821. doi:10.1158/1538-7445.AM2015-821
Abstract 3903: IGF-1, Angiotensin II and Human Cardiac Progenitor Cell Function
Authors: Silvana Bardelli, Claudia Bearzi, Adriana Bastos Carvalho, Cynthia Carrillo-Infante, Silvia Maestroni, Domenico D'Amario, Arantxa Gonzalez, Hanqiao Zheng, Federico Quaini, Roberto Bolli, David A. D'Alessandro, Robert E. Michler, Jan Kajstura, Tiziano Moccetti, Piero Anversa
Journal: Circulation (2008)

The objective of this work was to characterize the molecular properties of functionally competent c-kit-positive human cardiac progenitor cells (hCPCs) which are critical for their clinical impleme...
A Profound Decrease in FoxP3+Helios+CD4+ T Cells in a Subset of Patients with Acquired Aplastic Anemia and Pure Red Cell Aplasia: A Common Mechanism Underlying a Dependency on Cyclosporine
Authors: An T. T. Dao, Kohei Hosokawa, Chiharu Sugimori, Luis J. Espinoza, Kana Maruyama, Yoshitaka Zaimoku, Hiroyuki Maruyama, Takamasa Katagiri, Hirohito Yamazaki, Hiroyuki Takamatsu, Chizuru Saito, Noriko Iwaki, Shinji Nakao
Journal: Blood (2014)