tbuckley/cabot-search huggingface dataset:
A feed forward mechanism for adenoviral E1A protein-mediated sensitization to apoptosis
Authors: Yong Liao, Y. Y. Zou, W. Xia, Mien-Chie Hung
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

5474 

The adenovirus type-5 E1A was reported originally as an oncogene, which could cooperate with other viral and cellular oncogenes to transform primary culture cells, however, E1A has not been associated with human malignancies despite extensive studies trying to identify such a link. Instead, the type-5 E1A gene was shown to suppress tumorigenicity and experimental metastasis and expression of the E1A protein has also been shown to increase sensitivity to a variety of apoptotic stimuli-induced apoptosis. However, the molecular mechanisms underlying E1A-mediated sensitization to apoptosis are still not completely defined. Earlier studies suggested that E1A-mediated sensitization to apoptosis dependens on the expression of functional p53 and p19ARF in normal fibroblast cells or through downregulation of Her-2/neu overexpression in human cancer cells. In other studies, E1A was reported to mediate sensitization to anti-cancer drugs in a p53- and Her-2/neu-independent manner. Similarly, there is no correlation between p53 protein level and sensitivity of DNA-damaging agents in keratinocytes carrying adenovirus E1A. Additional critical molecules was also proposed to be involved in E1A-induced chemosensitization, such as the pro-apoptotic protein Apaf-1, Bax, a few procaspases. However, none of the above molecules or pathways can really serve as a general cellular mechanism for E1A-mediated sensitization to apoptosis in a diverse cellular context. To clarify this issue, we established E1A-expressing stable cells of low-Her-2/neu-expressing human breast cancer cells with or without wide-type p53. Sensitization to anti-cancer drug-induced apoptosis of E1A-expressing cells was observed in cell culture in vitro and in orthotopic animal models in vivo. However, we did not observe a consistent upregulation of procaspases or Bax protein in different E1A-stable cell lines established in human cancer. Instead, we found that E1A by upregulating the catalytic subunit of PP2A downregulated Akt activity and upregulated p38 activity. We demonstrate that Akt and p38 can regulate each other through PP2A phosphatase and that PP2A dephosphorylated and inactivated Akt, which could stimulate p38 activity, likely through activation of ASK1, by increasing phosphorylation of p38. Since p38 is known to upregulate PP2A activity, the increased p38 activity can enhance PP2A activity and then further inactivate Akt. Thus, PP2A phosphatase, Akt, ASK1 and p38 kinases form a signal loop that can enhance pro-apoptotic signaling in a feedforward manner.
Survival After Endovascular vs Open Aortic Aneurysm Repairs
Authors: David C. Chang, Ralitza P. Parina, Samuel E. Wilson
Journal: JAMA Surgery (2015)

<h3>Importance</h3> To our knowledge, long-term outcomes of open and endovascular (EVAR) repairs of abdominal aortic aneurysms (AAAs) have not been studied on a population level outside a controlled trial setting. <h3>Objective</h3> To determine long-term outcomes of EVAR vs open repair on a population level. <h3>Design, Setting, and Participants</h3> Analysis of the longitudinally linked California Office of Statewide Health Planning and Development inpatient database from 2001 to 2009. Median follow-up was 3.3 years. <h3>Exposures</h3> Endovascular vs open repairs. <h3>Main Outcomes and Measures</h3> Mortality and complications at 30 days, as well as long-term mortality and complications up to 9 years. <h3>Results</h3> In this observational study, a total of 23 670 patients were studied, with 52% receiving EVAR. Endovascular repair was associated with improved 30-day outcomes (all-cause mortality, readmission, surgical site infection, pneumonia, and sepsis), as well as significantly improved survival until 3 years postoperatively. After 3 years, mortality was higher for patients who underwent an EVAR repair. No significant difference in long-term mortality was observed for the entire cohort on adjusted analysis (hazard ratio, 0.99; 95% CI, 0.94-1.04;<i>P</i> = .64). Endovascular repair was found to be associated with a significantly higher rate of reinterventions and AAA late ruptures. <h3>Conclusions and Relevance</h3> The survival advantage for EVAR repair in a statewide population is maintained for 3 years. After 3 years, EVAR repair was associated with higher mortality; however, these mortality differences did not reach statistical significance over the entire study period. Reintervention and late AAA rupture rates are higher after EVAR repair.
Selenite-Releasing Bone Mineral Nanoparticles Retard Bone Tumor Growth and Improve Healthy Tissue Functions In Vivo
Authors: Yanhua Wang, Hang Hao, Haoming Liu, Yifan Wang, Yan Li, Gaojie Yang, Jun Ma, Chuanbin Mao, Shengmin Zhang
Journal: Advanced Healthcare Materials (2015)

Selenite-doped bone mineral nanoparticles can retard the growth of osteosarcoma in a nude mice model, through sustained release of selenite ions. The selenite ions released from the nanoparticles through a degradation-mediated fashion inhibit tumor metastasis. Blood routine analysis indicates that selenite ions can also improve the functions of liver, kidney, and heart.
Alcohol and aldehyde dehydrogenase polymorphisms and the risk for alcoholism
Authors: S Higuchi, S Matsushita, M Murayama, S Takagi, M Hayashida
Journal: American Journal of Psychiatry (1995)

The authors studied a large number of Japanese alcoholic patients and comparison subjects to establish the genotype frequencies of alcohol dehydrogenase-2 (ADH2) and mitochondrial aldehyde dehydrogenase (ALDH2) and to quantify the relative risk for alcoholism from the results.The subjects were 655 alcoholic patients and 461 comparison subjects. ADH2 and ALDH2 were genotyped by the combination of polymerase chain reaction and hybridization methods.Active ALDH2 and usual ADH2 were significantly more frequent in the alcoholic patients. Inactive ALDH2 was not always associated with a low risk of alcoholism, and active ALDH2 was not always associated with high risk. In individuals with heterozygous inactive ALDH2 and usual ADH2, the odds ratio for alcoholism was high.The risk for alcoholism in Japanese has been accurately estimated on the basis of the genotype frequencies of ADH2 and ALDH2. Many Japanese may be protected from alcoholism by inactive ALDH2 and by higher frequencies of atypical ADH2.
A simple prediction score for estimating the risk of candidaemia caused by fluconazole non-susceptible strains
Authors: G. Cuervo, M. Puig-Asensio, C. Garcia-Vidal, M. Fernández-Ruiz, J. Pemán, M. Nucci, J.M. Aguado, M. Salavert, F. González-Romo, J. Guinea, O. Zaragoza, C. Gudiol, J. Carratalà, B. Almirante
Journal: Clinical Microbiology and Infection (2015)
Molecular profiling of circulating tumor cells in the peripheral blood of patients with primary and metastatic breast cancer
Authors: N. Fersis, V. Deckwart, A. Leitz, M. Weber, J. Rom, O. Böcher, W. H. Albert, G. Bastert, C. Sohn, S. Kaul
Journal: Journal of Clinical Oncology (2006)

20033 Background: The purpose of this study was detection and expression profiling of circulating tumor cells (CTC) in breast cancer patients. Methods: Two separate probes of 5 mL peripheral EDTA-blood from patients with primary breast cancer (n=167) and metastatic disease (n=111) were used for immunomagnetic tumor cell selection. Targets for preanalytical enrichment were the antigens EpCAM and MUC-1. Separated cells were lysed and used for mRNA isolation and c-DNA synthesis. The breast carcinoma-associated transcripts EpCAM, MUC-1, HER-2, claudin7, cytokeratin 19, mammaglobin 1, prostate-specific ets factor (PSE) and survivin were amplified by three separate multiplex RT-PCR reactions. Amplicons were analysed by capillary electrophoresis with the Agilent Bioanalyzer 2100. Specificity of the RT-PCR was confirmed by examination of blood of healthy donors. Results: Sensitivity for every single transcript was adjusted to 2 tumor cells per 5 ml blood. Tumor-associated transcripts were detected in 31 of of 167 (18.5%) patients with primary breast cancer and in 46 of 111 (41%) patients with metastatic disease. The marker with the highest incidence in both groups was MUC-1, with a positivity rate of 81%. Tumor-associated transcripts were heterogenouosly expressed, however multiple markers were identified in more than 50% of the positive samples. Conclusion: Using a combination of preanalytical immunomagnetic tumor cell enrichment followed by a multigen RT-PCR approach we describe a sensitive detection system for breast carcinoma cells. In this study a panel of 8 genes overexpressed at high levels in metastatic breast cancer was selected for the identification of disseminated tumor cells in the peripheral blood of breast cancer patients. HER-2, survivin as a unique member of the inhibitor of apotosis protein family, as well as PSE identified in circulating breast cancer cells may serve as prognostic indicators of tumor progression and could represent valid targets for new individualized therapeutic interventions. No significant financial relationships to disclose.
Cross-bridge dynamics in human ventricular myocardium. Regulation of contractility in the failing heart.
Authors: R J Hajjar, J K Gwathmey
Journal: Circulation (1992)

BACKGROUND To investigate whether altered cross-bridge kinetics contribute to the contractile abnormalities observed in heart failure, we determined the mechanical properties of cardiac muscles from control and myopathic hearts. METHODS AND RESULTS Muscle fibers from normal (n = 5) and dilated cardiomyopathy (n = 6) hearts were obtained and chemically skinned with saponin. The muscles were then maximally activated at saturating calcium concentrations. Unloaded shortening velocities (V0) were determined in both groups. V0 in control was 0.72 +/- 0.09 Lmax/sec, whereas in myopathic muscles, V0 was 0.41 +/- 0.06 Lmax/sec at 22 degrees C. The muscles were also sinusoidally oscillated at frequencies ranging between 0.01 and 100 Hz. The dynamic stiffness of the muscles was calculated from the ratio of force response amplitude to length oscillation amplitude. At low frequencies (&lt; 0.2 Hz) the stiffness was constant but was larger in myopathic muscles. In the range of 0.2-1 Hz, there was a drop in the magnitude of dynamic stiffness to approximately one quarter of the low-frequency baseline. This range reflects cross-bridge turnover kinetics. In control muscles, the frequency of minimum stiffness was 0.78 +/- 0.06 Hz, whereas it was 0.42 +/- 0.07 Hz in myopathic muscles. At higher frequencies, the dynamic stiffness increased and reached a plateau at 30 Hz. There were no differences in the plateau reached between control and myopathic muscles. CONCLUSIONS Because myopathic hearts have a markedly diminished energy reserve, the slowing of the cross-bridge cycling rate plays an important adaptational role in the observed contractility changes in human heart failure. Although the potential to generate maximal Ca(2+)-activated force is similar in normal and myopathic hearts, alterations in contractile protein composition could explain the diminished cross-bridge cycling rate in failing hearts.
Abstract 3023: Symptom Differences Among Patients With and Without an Acute Coronary Syndrome Diagnosis
Authors: Michele M Pelter, Barbara Riegel, Debra Moser, Hendrika Meischke, Sharon McKinley, Lynn V Doering, Kathleen Dracup
Journal: Circulation (2007)

Background: In patients with acute coronary syndrome (ACS), prompt and accurate recognition of symptoms can lead to timely treatment. Clinicians treating patients with ACS also rely on symptoms for identifying high risk patients who may benefit from reperfusion therapies. Similar symptoms, however, may also occur with non-ACS diagnoses. Objectives: In this study, common ACS symptoms are compared in patients presenting to the emergency department (ED) for presumed ACS and subsequently diagnosed with and without confirmed ACS. Methods: Data were obtained from patients, with coronary artery disease, enrolled in a multi-site randomized clinical trial evaluating a nursing educational intervention aimed at reducing pre-hospital delay in patients at risk for ACS. During a two year follow-up period, data related to ED visits for symptoms suggestive of ACS were obtained from patients and medical record review. Results: A total of 3522 patients were enrolled in the parent study and 565 (16%) presented to the ED for...
Abstract 5490: Cathepsin K Deficiency does not Affect Murine Aneurysm Formation However it Reduces Macrophage-Rich Neointima Formation in Apoe−/−Mice
Authors: Lili Bai, Suzanne Lutgens, Veronica Herias, Paul Saftig, Mat Daemen, Kitty Cleutjens, Erik Biessen, Sylvia Heeneman
Journal: Circulation (2008)

Proteolytic arterial remodelling is a key process in various vasculopathies including restenosis and aortic aneurysm formation. One of the candidate effector proteases in both processes, may be cathepsin K (CatK), a potent lysosomal cysteine protease. We therefore hypothesized that a deficiency of this cystein protease could protect against these vascular pathologies. Firstly, we studied the effect of CatK deficiency on the intimal hyperplasia under normo-lipidemic (CatK−/− vs WT) and hyperlipidemic conditions (CatK−/−//ApoE−/− vs ApoE−/−) as induced by permanent ligation of the right carotid artery. Average neointima formation in hyperlipidemic CatK−/−//ApoE mice was significantly reduced compared to ApoE−/− mice (64%, p=0.02). Total vessel area was also significantly reduced in CatK−/−//ApoE−/− mice (46%, p=0.008 ). In contrast, catK deficiency did not affect SMC-rich neointima formation in normolipidemic mice as there was no difference in neointima size between CatK−/− mice and WT mice of C57BL/6 background. Secondly, we investigated the effect of CatK deficiency on angiotensin II-induced aneurysm formation in ApoE−/− mice. Contrary to our expectations, CatK deficiency did not protect against murine aneurysm formation. Strikingly, despite the similar aneurysm area, collagen content of aneurism lesions was 6-fold higher in CatK−/−//ApoE mice (p=0.04). Furthermore, we noticed a compensatory 71% and 90% increase, respectively, in the percentage of cathepsin S and cathepsin C positive cells in adventitia of CatK−/−//ApoE versus ApoE−/− mice (p=0.007 and 0.013, respectively). Taken these observations together, CatK deficiency appears to have divergent effects on restenosis and aneurysm formation only conferring protecting macrophage rich neointima formation in CatK−/−//ApoE−/− mice. Despite enhancing collagen content, CatK deficiency did not reduce aneurysm formation, which may be related to compensatory activation of other cathepsins in CatK deficiency. This also suggests that novel inhibitors selectively targeting CatK to intervene in pathogenic remodelling responses should be applied with caution.
Tissue inhibitor of metalloproteinases (TIMP)‐1 creates a premetastatic niche in the liver through SDF‐1/CXCR4‐dependent neutrophil recruitment in mice
Authors: Bastian Seubert, Barbara Grünwald, Julia Kobuch, Haissi Cui, Florian Schelter, Susanne Schaten, Jens T. Siveke, Ngee H. Lim, Hideaki Nagase, Nicole Simonavicius, Mathias Heikenwalder, Thomas Reinheckel, Jonathan P. Sleeman, Klaus‐Peter Janssen, Percy A. Knolle, Achim Krüger
Journal: Hepatology (2014)

Due to its ability to inhibit prometastatic matrix metalloproteinases, tissue inhibitor of metalloproteinases (TIMP)-1 has been thought to suppress tumor metastasis. However, elevated systemic levels of TIMP-1 correlate with poor prognosis in cancer patients, suggesting a metastasis-stimulating role of TIMP-1. In colorectal cancer patients, tumor as well as plasma TIMP-1 levels were correlated with synchronous liver metastasis or distant metastasis-associated disease relapse. In mice, high systemic TIMP-1 levels increased the liver susceptibility towards metastasis by triggering the formation of a premetastatic niche. This promoted hepatic metastasis independent of origin or intrinsic metastatic potential of tumor cells. High systemic TIMP-1 led to increased hepatic SDF-1 levels, which in turn promoted recruitment of neutrophils to the liver. Both inhibition of SDF-1-mediated neutrophil recruitment and systemic depletion of neutrophils reduced TIMP-1-induced increased liver susceptibility towards metastasis. This indicates a crucial functional role of neutrophils in the TIMP-1-induced premetastatic niche.Our results identify TIMP-1 as an essential promoter of hepatic premetastatic niche formation.
Biogeographical origin and varicella risk in the adult immigration population in Catalonia, Spain (2004-2006)
Authors: L Valerio, J M Escribà, J Fernández-Vázquez, C Roca, J Milozzi, L Solsona, I Molina
Journal: Eurosurveillance (2009)

Immigrants to the European Union may have a higher susceptibility to varicella-zoster virus primo-infection than the indigenous population. There is no evidence as yet that this is caused by genetic or social factors. Therefore, susceptibility could be due to a lesser transmission of the virus in their ecosystems of origin. A multicentre observational study was performed from July 2004 to June 2006 in four primary healthcare centres in Catalonia, Spain, monitoring varicella incidences and comparing standardised incidence rates and standardised rate ratios among different populations classified according to their biogeographical origin (holarctic, Asian paleotropical, African paleotropical or neotropical). Overall, 516 varicella cases were recorded. The standardised incidence rates per 1,000 inhabitants per year were: holarctic: 2.17 (95% confidence interval (CI): 1.95-2.39); autochthonous 2.26 (95% CI: 2.03-2.49); immigrants 3.59 (95% CI: 2.92-4.26); neotropical 4.50 (95% CI: 3.28-5.71); non-holarctic 5.38 (95% CI: 4.27-6.14); Asian paleotropical 7.03 (95% CI: 4.77-9.28); and African paleotropical 7.05 (95% CI: 1.12-23.58). The difference to the autochthonous population was greatest in immigrants of neotropical origin (standardised rate ratio = 2.07 (95% CI: 1.61-2.64) or 4.5 excess cases per 1,000 inhabitants per year) and Asian paleotropical origin (standardised rate ratio = 3.24 (95% CI: 2.47-4.11) or 9.6 excess cases per 1,000 inhabitants per year). Biogeographical origin may therefore account for the vulnerability of certain immigrant populations to varicella, in particular those from Asian paleotropical (Indostan and Southest Asia) and neotropical (South America and the Caribbean) ecosystems. Vaccination of immigrants at high risk (fertile women, healthcare workers) could be recommendable.
Anxiety disorders linked to gene abnormality
Authors: Xavier Bosch
Journal: BMJ (2001)

People with anxiety disorders such as panic attacks and agoraphobia may have a genetic mutation that makes them susceptible to these conditions, a Spanish study has found ( Cell 2001;106:367-79).

The research, led by geneticist Xavier Estivill of the Medical and Molecular Genetic Center and psychiatrist Antoni Bulbena of the Hospital del Mar, both in Barcelona, was based on an earlier observation of a clinical association between anxiety disorders and laxity of the joints, which involved …
Secondary prevention in acute myocardial infarction
Authors: Michael Leslie Burr
Journal: BMJ (1998)

Acute myocardial infarction affects hundreds of thousands of people each year.Around a quarter die, half of them before reaching a hospital.Survivors are at increased risk of recurrent myocardial infarctions or cardiac death, with a 10% death rate in the first year after discharge and a subsequent annual death rate of 5%-six times that in people of the same age who do not have coronary artery disease.Whereas aggressive management of the acute infarction has been enthusiastically adopted, far less attention has been given to preventive strategies.Though most doctors agree with the importance of secondary prevention, the results of studies suggest that many patients are currently not being given optimal preventive care.Since most patients after acute myocardial infarction are routinely followed up in primary care, general practitioners must be fully informed and participate in treatment strategies designed for the secondary prevention of coronary artery disease. MethodsWe conducted a Medline search for all articles on acute myocardial infarction dating from January 1980 to August 1997, with particular emphasis on secondary prevention in acute myocardial infarction.We scanned all of these reports, which numbered more than 3000.In this review we have also incorporated current standard practice at the University of Michigan, Ann Arbor, for managing myocardial infarction.
Psychiatrists' judgments of dangerousness in patients on an acute care unit
Authors: Paul D. Werner, Terrence L. Rose, Jerome A. Yesavage, Kenneth Seeman
Journal: American Journal of Psychiatry (1984)

Statistical analyses suggest that psychiatrists emphasize hostility, agitation, previous assaultiveness, and suspiciousness as factors predictive of violence in psychiatric inpatients. When the actual correlates of violence in these patients are evaluated, a different picture of the assaultive inpatient emerges. Examination of differences between the cues emphasized by clinicians to make their predictions and the empirical correlates of violence suggests ways of improving the accuracy of clinical judgments of inpatients' dangerousness.
Abstract 8895: Clinical Outcomes of Mutation Carriers in Pulmonary Arterial Hypertension in Children
Authors: Ayako Chida, Masaki Shintani, Hisato Yagi, Maya Fujiwara, Yasuko Kojima, Hiroki Sato, Shinichiro Imamura, Tomotaka Nakayama, Takahiro Ishiwata, Yoshiyuki Furutani, Kei Inai, Tsutomu Saji, Rumiko Matsuoka, Shigeaki Nonoyama, Toshio Nakanishi
Journal: Circulation (2012)

Background: In heritable pulmonary arterial hypertension (HPAH) and idiopathic pulmonary arterial hypertension (IPAH), mutations have previously been described in genes for the bone morphogenetic protein receptor type 2 ( BMPR2 ) and the activin receptor-like kinase 1 ( ALK1 ). It is, however, not known, especially in childhood, how these mutations relate to the clinical characteristics. Methods: Sixty four childhood patients whose onset of IPAH/HPAH was under 16 years old were selected. Mutations were monitored by direct sequencing and multiplex ligation-dependent probe amplification in BMPR2, ALK1, endoglin, SMAD1, SMAD2, SMAD3, SMAD4, SMAD5, SMAD6, SMAD7, SMAD8 , BMPR1A and BMPR1B genes. One SMAD8 mutation carrier and 2 BMPR1B mutation carriers were excluded from the present analysis because of minority of cases. Functional characteristics, hemodynamic parameters, and clinical outcomes were compared among BMPR2 mutation group, ALK1 mutation group, and noncarrier group. Results: Among these 61 childhood IPAH/HPAH patients, 18 had BMPR2 mutation and 7 had ALK1 mutation. At the time of diagnosis, age, WHO functional class, mean pulmonary artery pressure, pulmonary resistance, serum brain natriuretic peptide level, and 6-minute walking distance were similar among 3 groups. Medications including bosentan and sildenafil were also similar among 3 groups. Among 61 patients, 5-year and 10-year survival were 77% and 74%, respectively. Despite targeted therapy, 5-year survival in the BMPR2 mutation group (55%) was lowest among these 3 groups. The 5-year survival in the ALK1 mutation group (64%) tended to be lower than that in the noncarrier group (91%). Intravenous epoprostenol therapy strongly ameliorated the WHO functional class in all groups. Especially in the ALK1 mutation group, pulmonary vasodilator therapies were not effective except for intravenous epoprostenol. Conclusions: Prognosis of IPAH/HPAH in children with BMPR2 and ALK1 mutation is poor. Aggressive treatment including intravenous epoprostenol may be warranted in those children.
L-Selectin–Dependent Leukocyte Adhesion to Microvascular But Not to Macrovascular Endothelial Cells of the Human Coronary System
Authors: A. Zakrzewicz, M. Gräfe, D. Terbeek, M. Bongrazio, W. Auch-Schwelk, B. Walzog, K. Graf, E. Fleck, K. Ley, P. Gaehtgens
Journal: Blood (1997)