tbuckley/cabot-search huggingface dataset:
Abstract 14921: Influence of Primary PCI on the Mortality of Very Old Patients With ST-segment Elevation Myocardial Infarction
Authors: Robert Zabrocki, Stefanie Bünger, Andreas Fach, Eduard Fiehn, Johannes Schmucker, Harm Wienbergen, Daniela Garstka, Rainer Hambrecht
Journal: Circulation (2014)

Introduction:  ST-segment elevation myocardial infarction (STEMI) is a life threatening acute event with impaired long - term prognosis in particular in elderly patients (pts). Until now there is only limited information about the effectiveness and the impact on short - and long - term survival of primary PCI in very old patients.   Methods:  Since 2006 all patients with STEMI from the metropolitan area of Bremen (Germany) were admitted to the Bremen heart center and documented in the Bremen STEMI-registry (BSR). The study population comprised 5263 pts and was divided by age into three groups (G): G1:  89 years. The outcome of pts treated with primary PCI was analysed regarding inhospital mortality (IM) and mortality after one year (1yM). Furthermore bleeding rates, use of glycoprotein IIb/IIIa inhibitors (GPI), Killip class and signs of cardiogenic shock were assessed during initial hospital stay.   Results:  A total of 5263 pts admitted from January 2006 until May 2013 were included in this analysis. A higher overall mortality was associated with higher age. In each subgroup (G1-3) the 1yM was almost twice as high compared to the corresponding IM. Killip class and signs of cardiogenic shock were highest in G2 suggesting a preselection before admittance within the pts >89 years (G3). Despite treatment with GPI was less frequently observed in elderly pts (G2 and G3), bleedings appeared to occur more often in these subgroups.   Conclusions:  Even very old patients with STEMI can be treated successfully with primary PCI. Despite an initially successful PCI, lower application rate of GPI, and preselection before admittance, very old patients demonstrate a higher rate of bleeding events as well as short - and long - term mortality. Every second very old patient affected by a STEMI and successfully treated by primary PCI did not survive the first year.
Neurotoxicity of Radiation Therapy and Chemotherapy
Authors: Eudocia Quant Lee
Journal: Neuro-Oncology (2012)

Oncology patients are living longer because of earlier cancer detection and better treatments. Unfortunately, neurotoxicity from radiation and chemotherapy remains an important source of morbidity and may play a part in limiting potential therapies. Acute, subacute, and chronic syndromes may affect the central and peripheral nervous systems. Because treatments for therapy-induced neurotoxicity are limited, awareness of common neurologic complications is important to prevent permanent damage. This chapter discusses common neurotoxicites associated with anticancer therapies.
1016. Novel Chimeric Adenovirus Vaccine Vectors
Authors: Soumitra Roy, Yan Zhi, David Clawson, Guangping Gao, Gary P. Kobinger, James M. Wilson
Journal: Molecular Therapy (2004)

The presence of circulating antibodies to adenovirus capsid proteins is a barrier to the use of adenovirus vectors for gene therapy. The prevalence of antibodies against subgroup C adenoviruses is generally high in human populations and this fact is likely to greatly limit the effectiveness of gene therapy vectors based on serotypes such as Ad5. One approach to overcoming this problem is to use adenovirus vectors that rarely cause human infections or to use adenoviruses from non-human sources, because antibodies capable of neutralizing these viruses are likely to be absent in most humans. However therapies that require multiple vector administrations will probably require a different serotype for each treatment. This will therefore necessitate the construction of adenovirus vectors based on several unrelated serotypes, which may require the construction of the appropriate complementing cell line suitable for its manufacture. In view of the above, we have investigated whether it may be possible to construct chimeric adenoviruses where most structural proteins, including the capsid, are derived from an adenovirus of one serotype, preserving the majority of the protein-protein interactions that are involved in capsid assembly, whereas the early genes encoded by the E1 and E4 regions that are responsible for transcription regulation and regulation of the host cell cycle, are retained from a different serotype that is known to result in high titer virus generation in the commonly used cell types such as HEK 293 which supplies the Ad5 E1 proteins in trans. One of the first vectors we have constructed in this way is chimeric between the chimpanzee adenoviruses Pan 5 (Simian adenovirus 22, subgroup E) and C1 (Simian adenovirus 21, subgroup B) expressing the Ebola virus (Zaire) glycoprotein (C5C1-CMVGP). In order to test the efficacy of the vector C5C1-CMVGP as a vaccine candidate, we have compared it to the Ad5 based vector (H5-CMVGP). Compared to H5-CMVGP, the C5C1-CMVGP vector yielded only a slightly decreased level of GP expression in transduced A549 cells. We evaluated GP-specific T cell and B cell responses elicited in B10BR mice vaccinated with either H5-CMVGP or C5C1-CMVGP vectors. The C5C1-CMVGP vector appeared to induce lower frequencies of gamma interferon producing CD8+ T cells with kinetics slower than the H5-CMVGP vector as determined by intracellular cytokine staining using an H-2k restricted GP-specific peptide as stimulant. The total IgG response to GP, measured by ELISA, was similar in sera from mice vaccinated with the C5C1-CMVGP or the H5-CMVGP vectors. However, the C5C1-CMVGP vector induced a more potent Th1 type response while the H5-CMVGP vector stimulated a more balanced Th1/Th2 type response. We have shown that a single administration of the H5-CMVGP vector can protect mice against a lethal challenge with a mouse-adapted strain of the Ebola Zaire virus. We are currently investigating the efficacy of the C5C1-CMVGP vector in this model.
Genistein, but not estradiol, inhibits MMP-9 secretion by mammary cancer cells
Authors: Mona Hdeib, Jimmy D. Browning, Ruth S. MacDonald
Journal: Cancer Research (2004)

3895  Evidence suggests Asian women who consume diets rich in soy have lower incidence of metastatic breast cancer. Soy provides several bioactive compounds including the isoflavones that are structurally similar to estradiol. Extracellular matrix (ECM) digesting enzymes, such as the matrix metalloproteinases (MMPs), that are secreted by tumor cells attack the basement membrane and other ECM components to allow cancer invasion into neighboring tissues and organs thereby leading to metastasis. We hypothesize that genistein, the primary isoflavone in soy, reduced mammary cancer metastasis by inhibiting secretion of MMP-9. To test this hypothesis we used MCF-7 mammary tumor cells stimulated with 12-O-tetradecanoylphorbol 13-acetate (TPA), and quantified MMP-9 (92 kDa) in conditioned media by gelatin zymography. We empirically determined that our MCF-7 cells expressed estrogen receptors and cell proliferation was increased by estradiol added to estrogen-depleted media. Cells were plated in media containing 10% serum and incubated until near confluence. After washing, cells were incubated overnight in serum-free media without phenol red. They were then incubated in the same media containing 162 nM TPA with 0, 0.1, 1, 10, 25, or 50 μM genistein or 0, 0.001, 0.010, 0.100, 1 or 10 nM estradiol. Conditioned media were collected after 12-24 hours and analyzed by zymography. The results were verified by Western immunoblot using an antibody specific for MMP-9. Cells not exposed to TPA did not secrete MMP-9. Incubation of cells with genistein resulted in a dose-dependent inhibition of MMP-9 secretion. Estradiol however did not inhibit MMP-9 secretion at any concentration. These results suggest the estrogen receptor is not involved in MMP-9 secretion in MCF-7 mammary tumor cells. Genistein was a potent inhibitor of MMP-9 secretion in these cells however, suggesting an estrogen-receptor independent mechanism. We are currently investigating other cellular pathways through which genistein may regulate MMP-9 secretion. If genistein proves to be an effective inhibitor MMP-9 secretion, this may lead to a novel approach to reduce mammary cancer metastasis.
197. Do Bone Marrow-Derived Progenitor Cells Contribute to VEGF-Induced Post-Natal Neovascularization?
Authors: Lorena Zentilin, Sabrina Tafuro, Nikola Arsic, Serena Zacchigna, Milena Sinigaglia, Sara Tomasi, Lucia Pattarini, Marina Dapas, Mauro Giacca
Journal: Molecular Therapy (2004)

Bone marrow-derived cells have been recently proposed to participate in the development of new blood vessels during physiological and pathological angiogenesis in adult organisms.
863. Expression and Secretion of Human Glucocerebrosidase Mediated by Recombinant Lentivirus Vectors In Vitro and In Vivo
Authors: Eun Young Kim, Young Bin Hong, Zhennan Lai, Roscoe O. Brady, Sung-Chul Jung
Journal: Molecular Therapy (2004)

Gaucher disease is a lysosomal storage disorder resulting from a deficiency of glucocerebrosidase (GC). Most research on gene therapy for Gaucher disease has centered on ex vivo transduction of hematopoietic stem cells by retroviral vectors. In this study, we showed that vascular and hepatic delivery of a HIV-1 based recombinant lentivirus vector encoding human GC cDNA produced therapeutic levels of GC protein.Human cell lines and Gaucher fibroblasts were transduced at 10-50 multiplicity of infection (MOI) of lenti-EF-GC or lenti-CMV-GC. In vivo experiments were carried out in C57BL/6J mice by intravenous and intraportal injection with 1-5 107 transducing unit (TU) of lenti-EF-GC. Cells and tissues were assayed for GC activity. A high level of expression of GC was produced in cultured fibroblasts derived from patients with Gaucher disease by transducing the cells with lentivirus vectors. GC secreted by transduced fibroblasts was taken up by adjacent GC-deficient cells by endocytosis. Intraportal administration of recombinant lenti-EF-GC vector was resulted in efficient transduction of hepatic cells and expression of the GC. Vascular delivery of vector resulted in high levels of GC expression in liver, spleen, heart, lung, and bone marrow cells in mice that persisted in most organs over the four months. No significant abnormalities were found attributable to recombinant lentivirus vectors in any of the tissues examined. Recombinant lentivirus vector-mediated gene transfer appears to be effective and safe. This study represents an initial step toward gene transfer using recombinant lentivirus vectors for treatment of Gaucher disease.
Assessment of left atrial volume in resistant hypertension by cardiac magnetic resonance imaging
Authors: Cecilia Corros, Krishna Gaddam, Steven G. Lloyd, Monique Pratt-Ubunama, Eduardo Pimenta, Louis J. Dell’Italia, David A. Calhoun, Himanshu Gupta
Journal: Circulation (2006)

Introduction: Increased left atrial (LA) volumes are associated with impaired diastolic properties of the left ventricle (LV) and have been shown to predict cardiovascular events in a wide spectrum of patients. A relation between LA volume and aldosterone has been reported in idiopathic dilated cardiomyopathy, but this relationship has not been evaluated in resistant hypertensive subjects. Hypothesis: We hypothesized that patients with elevated plasma aldosterone concentration (PAC) have greater LA volumes. We compared LA volumes in normal subjects and mildly hypertensive patients (Controls) and patients with resistant hypertension. Methods: 71 patients (55 resistant hypertensive (51% male, age 57±12 y) and 16 Controls (62% men, age 54±11 y, p=ns) were studied. Clinic blood pressure (BP), plasma levels of B-type natriuretic peptide (BNP), PAC, plasma renin activity (PRA), serum cortisol, and 24 hour urinary aldosterone and sodium excretion were determined. Cardiac magnetic resonance imaging was performed in all patients and LA volumes were measured using a biplane length-area method and indexed for the body surface area. Results: Results are summarized in the Table. Resistant hypertensives had significantly higher systolic and diastolic BP compared to Controls. There was a trend towards higher PAC in hypertensives that did not reach statistical significance. BNP levels also were not different between the groups but we found a relationship between BNP and LA volume index (r=0.43, p=0.003). Hypertensives also exhibited increased LV mass and LA volume index compared to Controls. No relation between LA volume index and PAC was found. PRA, cortisol, and 24 hour urinary aldosterone and sodium excretion also had no relation to LA volume index. Conclusions: LA volume index is higher in resistant hypertension and shows positive correlation with BNP levels in all subjects but is not related to PAC in either the Control or Resistant hypertension groups.
Identifying Patients at Risk of Recurrent Venous Thromboembolism
Authors: Daniel J. Brotman
Journal: JAMA (2003)

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Abstract 1208: Plaque Components in Coronary Artery Disease Increase at Different Rates: A Virtual Histology Intravascular Ultrasound Report from the Global VH-IVUS Registry
Authors: Raimund Erbel, Hector Garcia-Garcia, Jeffrey Moses, Micheal Pieper, Roseann White, Koichi Sano, Gary S Mintz, Patrick W Serruys, VH Registry Investigators
Journal: Circulation (2006)
Abstract P162: The Baseline Ankle Brachial Index (ABI), but Not Change in the ABI, is Associated With 11-Year Change in the SF-36: The San Diego Population Study (SDPS)
Authors: Christina L Wassel, Matthew A Allison, Joachim H Ix, Julie O Denenberg, Dena E Rifkin, Michael H Criqui
Journal: Circulation (2015)

Background: Lower extremity peripheral artery disease (PAD) affects approximately 9 million people in the US. Less well-recognized is that PAD, even when asymptomatic, is associated with decreased functional status and quality of life. Previous studies have largely examined associations of the ankle brachial index (ABI) and quality of life in participants with PAD. To our knowledge no studies have examined the impact of ABI and change in ABI on change in quality of life in a population-based setting. Methods: The SDPS is a population-based prospective study that evaluated non-Hispanic White, African-American, Hispanic and Asian men and women for lower extremity PAD at two examinations approximately 11 years apart. Participants completed the SF-36 questionnaire, and 802 participants had ABI and SF-36 data available at both examinations. Analyses were restricted to these participants who also had a baseline ABI&lt;1.4. Growth curve models were used to assess the associations of baseline ABI and change in the ABI with change in the SF-36 physical component score (PCS) and mental component score (MCS) over time. Change in the ABI was defined as (follow-up ABI - baseline ABI)/baseline ABI. Results: Participants were on average 57±9 years of age at baseline, and 69±9 at follow-up. At baseline, nearly 2 percent had ABI≤0.90, and the mean±SD ABI was 1.12±0.10. After adjustment for age, sex, race/ethnicity, BMI, ever smoking, physical activity, hypertension, diabetes, and dyslipidemia, each SD lower baseline ABI was significantly associated with an average change of -0.63 points (95% CI (-0.10, -1.17), p=0.02) on the PCS. This association was marginally significant for the MCS (-0.54 points (0.14, 1.22), p=0.12). Lower baseline ABI was also associated with negative change in two SF-36 subscales, physical functioning (p=0.02) and vitality (p=0.01). Change in the ABI over 11 years was not associated with change in the MCS (p=0.97) or PCS (p=0.41). Results were similar when excluding participants with ABI≤0.90. Conclusions: A lower ABI at baseline is associated with a significantly worse physical functioning quality of life approximately 11 years later. However change in the ABI was not significantly associated with change in quality of life over this time period. Additional studies are warranted in larger samples, especially to confirm the lack of findings for change in ABI.
Genome-wide interaction study of gene-by-occupational exposure and effects on FEV1 levels
Authors: Kim de Jong, Judith M. Vonk, Wim Timens, Yohan Bossé, Don D. Sin, Ke Hao, Hans Kromhout, Roel Vermeulen, Dirkje S. Postma, H. Marike Boezen
Journal: Journal of Allergy and Clinical Immunology (2015)
Id-1 destabilizes HBX protein through the proteasome-mediated protein degradation pathway
Authors: Ming Tat Ling, Maggie Fung, Xianghong Wang, Yc Wong
Journal: Cancer Research (2006)

1742  Background/Aims: Kruppel-like factor 4 (KLF4) is a transcription factor that controls the expression of several genes that are known markers of the terminal differentiation of colonic stem cells, such as intestinal alkaline phosphatase and mucin. Furthermore, KLF4 is a tumor suppressor in the gut, inhibiting the expression of genes controlling the cell cycle, such as Cyclin E and Cyclin D1, and simultaneously induces expression of the cell cycle inhibitor p21Cip1/WAF1. Since KLF4 interacts with p300 and recruitment of co-activators to the transcriptional apparatus is a common method transcription factors use to activate gene expression, we decided to study what effect KLF4/p300 interaction would have upon expression of known KLF4 target genes. Results: Via GST-labeled pull-down assays, we confirmed that KLF4 and p300 do indeed interact. We then made several luciferase reporter constructs containing the full-length reporter sequence of various KLF4 target genes and tested the ability of p300 to synergize with KLF4 in transactivating these reporters. With some of these reporter constructs, p300 further increased KLF4-mediated transactivation, suggesting a synergistic interaction. To identify the KLF4 binding site, we made a panel of deletion mutants for each promoter. These binding sites were then confirmed using chromatin immunoprecipitation using a novel KLF4 antibody developed in our laboratory. Since KLF4 appears to recruit p300, a histone acetyltransferase, we decided to investigate the effect of KLF4 binding to its binding element on chromatin remodeling. We tested this using chromatin immunoprecipitation against acetylated histones. Conclusions: We confirmed that KLF4 and p300 interact and found that this interaction results in a synergistic activation of several known KLF4 target genes. Furthermore, we were able to identify the binding element for KLF4 on these target genes. Finally, we found that KLF4 plays a role in chromatin remodeling via recruiting p300 to the promoter, suggesting that acetylation is important for KLF4-mediated transactivation.
Abstract #5547: Enhancement of decitabine cytotoxicity by methoxyamine via inhibition of base excision repair
Authors: Alina Bulgar, Yanling Miao, Ernest Borden, Stanton Gerson, Lili Liu
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

Decitabine (5aza-2\#8217;deoxycytidine) is a nucleoside analog used for the treatment of hematological malignancies. Previously, it was shown that the cytotoxic effect of low dose decitabine treatment is due to incorporation of its active metabolite, 5aza-2\#8217;deoxycytidine triphosphate, into DNA leading to inhibition of DNA methylation by binding irreversibly to DNA methyltransferases. We hypothesized that incorporated 5aza-2\#8217;deoxycytidine (or its deaminated analog, 5aza-2\#8217;deoxuridine) into DNA is also recognized and processed by the base excision repair (BER) pathway. In this case, inhibition of BER by methoxyamine (MX) would potentiate the cytotoxicity of decitabine. We evaluated role of BER in decitabine cytotoxicity in colon cancer, melanoma cells, and primary acute myelogenos leukemia (AML) cells. Decitabine-induced abasic sites (AP-sites) were increased proportionally with dose and duration of exposure. MX reduced the number of available AP-sites up to 80% indicating formation of stable MX-bound AP-sites that have the potential to interrupt BER pathway. A similar correlation between decitabine dose and the AP-sites formed was observed after in vitro exposure of primary AML cells to increase concentrations of decitabine. MX was able to bind a significant percentage (up to 60%) of these AP sites. Decitabine cytotoxicity was potentiated by MX. Cell survival assays demonstrate a 4-fold decrease in the IC50for decitabine when cells were co-treated with MX (IC50 dec = 4 \#956;M and IC50 Dec+ MX = 1 \#956;M). Apoptotic cell death measurements using Annexin V staining showed a 5-fold increase in cell death following decitabine and MX treatments. These events were accompanied by a concomitant increase in cleavage of PARP, and in \#947;H2AX. Moreover, MX enhanced decitabine-induced antitumor effect in mice bearing A375 human melanoma xenografts, as measured by tumor growth delay: 7 days (0.5 mg/kg decitabine) versus 14 days (0.5 mg/kg decitabine plus 2 mg/kg MX).These studies not only suggests for the first time the role of BER in the processing of incorporated decitabine, but they also provide insights into a new and promising cancer therapeutic strategy of combining decitabine with MX to block BER.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 5547.
Pelvic Tuberculosis
Authors: A. Kouyoumdjian
Journal: BMJ (1955)

substances makes it more and more apparent that genetic homogeneity is essential to most physiological work, and that genetic variety between strains provides an array of valuable tools for particular types of physiological experiments. SummaryThe use of inbred strains in biological research is essential for fixation of either phenotype, average grade, relative rank, or reaction to conditions.Examples are presented of each type of strain differences in mice, gleaned from 1951-3 literature and from research in the Inbred Nucleus of the Jackson Laboratory.These include differences in disease susceptibility, nature of disease produced by a given pathogen, survival time of infected individuals; capacity for antibody production, cold tolerance, reaction to specific toxins; sensitivity to and content of various hormones and reaction to endocrine extirpation; and differences in normal blood-cell levels, life-expectancy, and pathology pattern.