tbuckley/cabot-search huggingface dataset:
Abstract 936: Inhibition of the Endoplasmic Reticulum Calcium ATP-ase Affects the Early Steps of Left-Right Patterning in Zebrafish Embryos.
Authors: Jil A Kreiling, Zaneta L Balantac, Andrew Crawford, Jamal Toure, Alper Celik, Lazaros K Kochilas, Robbert Creton
Journal: Circulation (2007)

Vertebrates develop well defined and conserved left-right (L-R) asymmetries of the heart, gut and brain. Calcium signals play a role in the specification of L-R asymmetry, by translating cilia-dependent fluid flow into asymmetric patterns of gene expression. We aimed to determine the role of early calcium signals on the L-R patterning in zebrafish embryos. Calcium signals were manipulated in zebrafish embryos using thapsigargin, an inhibitor of the endoplasmic reticulum (ER) calcium ATP-ase pump. The embryos were treated with 0.5 μM thapsigargin during early gastrulation (4 – 6 hpf), mid-gastrulation (6 – 8 hpf), late gastrulation (8 –10 hpf) or early somitic stages (10 –12 hpf). The phenotype was analyzed with subtractive imaging, immunolabeling and in situ hybridization (ISH). At 30 hpf, the heart was centralized or reversed in 53% of the early thapsigargin-treated embryos (n=72) vs 5% of the DMSO-treated control embryos (n=75). The embryos were most sensitive to thapsigargin during early and mid-gastrulation with subsequent decrease in heart laterality defects. The incidence of heart laterality defects correlated with decreased or absent no tail expression in the dorsal forerunner cells and disruption of Kupffer’s vesicle formation in 73% of the early treated embryos (n=203), vs 2% of the control embryos (n=198) (p&lt;0.01). Deviation from the normal morphological L-R asymmetry in the habenular nucleus of the diencephalon was found in 54% of the thapsigargin treated embryos (n=17) and in 88% of the embryos with L-looped heart (n=9) vs none control embryos. Analysis of the expression pattern of the “left-sided” marker pitx2 α in the dorsal diencephalon by ISH revealed this to be reversed or bilateral in 56% of the treated embryos (n=97) vs only 10% of the control embryos (p&lt;0.05). In addition 47% of the thapsigargin treated embryo displayed reversed gut-looping (n=49) vs none control embryos. Our data suggest that inhibition of the ER calcium pump by thapsigargin during gastrulation impairs development of the Kupffer’s vesicle and disrupts the concordant heart, brain and gut L-R asymmetry. These results suggest an additional role of calcium in L-R asymmetry determination well before its previously recognized role in sensing fluid flow in the Kupffer’s vesicle.
Abstract 8829: The Disruption of Natural Killer T Cell Exacerbates Cardiac Hypertrophy and Heart Failure Due to Pressure Overload in Mice
Authors: Masashige Takahashi, Arata Fukushima, Tsuneaki Homma, Mochamad A Sobirin, Tadashi Suga, Shingo Takada, Taisuke Ono, Yoshihiro Masaki, Tomoyasu Kadoguchi, Takashi Yokota, Shintaro Kinugawa, Hiroyuki Tsutsui
Journal: Circulation (2011)

Background Chronic inflammation has been reported to be involved in the development of cardiac remodeling and failure. Natural killer T (NKT) cells, a subset of T lymphocytes, have capacity to produce various inflammatory cytokines and orchestrate tissue inflammation. Our previous study demonstrated that the pharmacological activation of NKT cells attenuated the development of heart failure (HF), which was mediated by the enhanced expression of interleukin-10. However, no previous studies have examined the pathophysiological role of NKT cells in pressure overload-induced HF. We thus hypothesized that the disruption of NKT cell could exacerbate cardiac hypertrophy and HF after pressure overload in mice. Methods Transverse aortic constriction (TAC) operation was performed in male C57BL/6J wild-type(WT) and NKT cell knockout (KO) mice, and sham operation was also performed; WT+Sham (n=5), KO+sham (n=5), WT+TAC (n=29), and KO+TAC (n=34). After 14 days, echocardiography was performed, and gene expressions in left ventricle (LV) tissues were quantified by RT-PCR. Results Survival rate during 28 days was significantly lower in KO+TAC than WT+TAC (16% vs. 61%, P&lt;0.05), and no mice died in sham groups. NKT cell receptor was increased by 60% in LV from TAC compared to Sham at 14days. LV end-diastolic dimension (4.60±0.14vs3.57±0.08 mm, p&lt;0.05) were greater, and LV fractional shortening (17.1±0.8 vs 30.4±4.3 %, p&lt;0.05) was lower in KO+TAC than in WT+TAC. LV weight and lung weight/body weight were significantly lower in KO+TAC than in WT+TAC. No such changes were observed in either WT+Sham or KO+Sham. In parallel, myocyte cross-sectional area and collagen volume fraction were greater in KO+TAC than in WT+TAC. Interleukin-10 (IL-10) mRNA expression was completely abolished in KO+TAC compared to TAC. Conclusions The disruption of NKT cell exacerbated the development of HF after TAC through the diminished expression of cardioprotective cytokine, IL-10. NKT cells play a critical role in the development of pressure-overload hypertrophy and failure.
Abstract 15495: Ventricular Relaxation Assessment Using Early Diastolic Mitral Annular Velocity in Pediatric Patients
Authors: Satoshi Masutani, Mitsuru Seki, Hirotaka Ishido, Hideaki Senzaki
Journal: Circulation (2010)

Background: Early diastolic mitral annular velocity (e') has been used for non-invasive assessment of ventricular relaxation. However, applicability of this Methods in pediatric population remains ...
Constitutive activation of PI3K-Akt and NF-κB signaling pathway in transgenic adenocarcinoma of the mouse prostate model
Authors: Sanjeev Shukla, Gregory T. Maclennan, Susan R. Marengo, Martin I. Resnick, Sanjay Gupta
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

6072 

Prostate cancer progresses through sequential steps from prostatic intra-epithelial neoplasia (PIN) to locally invasive carcinoma to metastatic disease. Progression through various stages of tumorigenesis presumably requires altered expression of oncogenes and tumor suppressor genes in the initiated cell. These genetic lesions change the cancer cell phenotype through independent growth signals that may lead to increased cell survival and evasion of apoptosis. Phosphatidylinositol 3’-OH kinase (PI3K)-Akt and transcription factor NF-κB are important signaling molecules and key survival factors involved in the control of cell proliferation, apoptosis and oncogenesis. Although PI3K-Akt and NF-κB-IκB have been implicated in the development and progression of prostate cancer, expression of these molecules during progression of autochthonous disease has not been elucidated. Employing transgenic adenocarcinoma of the mouse prostate (TRAMP) model, we examined prostate cancer progression by MRI analysis, studied expression patterns of PI3K-Akt, NF-κB-IκB and associated signaling molecules during different stages of cancer progression and compared with male non-transgenic littermates. Sequential MRI, gross and pathological analysis of prostate gland exhibited increasing prostate volume associated with the development and progression of prostatic adenocarcinoma in TRAMP mice, compared to male non-transgenic littermates. As examined by Western blot analysis, expression of PI3K and phosphorylated-Akt (Ser473) levels were significantly increased during cancer progression in TRAMP mice, compared to male non-transgenic littermates. A progressive increase in the expression of NF-κB/p65, IκBα and its phosphorylation, IKK kinase activity was observed during prostate cancer progression in TRAMP mice as examined by Western blot analysis, electrophoretic-mobility shift assay, ELISA, kinase assay, and immunohistochemistry. Over-expression of these signaling molecules correlated with transcriptional-regulated genes viz . Bcl-2, cyclin D1, matrix metalloproteinase-9, and vascular endothelial growth factor, and cancer progression observed at 24 and 32 weeks TRAMP mice compared to male non-transgenic littermates. Taken together, our results suggest that differential expression pattern of PI3K-Akt and NF-κB-IκB during prostate cancer progression in TRAMP mice represents potential molecular targets for prevention and/or therapeutic intervention. (Supported by USPHS grants NIH RO1 CA108512, RO3 CA094248, RO3 CA099049, and RO3 CA107806 and funds from Cancer Research and Prevention Foundation to SG)
Abstract 2229: CD117 expression and activation in prostate cancer progression
Authors: Bethany Kerr
Journal: Cancer Research (2015)

Abstract We have demonstrated that CD117/c-kit expression on circulating tumor cells and in primary tumors correlates with advanced disease in prostate cancer patients. In addition, the ligand for CD117, stem cell factor (SCF) is increased in high-grade prostate cancer patients. To examine the effects of CD117 activation and expression on prostate cancer progression, we sorted CD117 positive and negative RM1 murine prostate cancer cells and LNCaP-C4-2 human prostate cancer cells. Sorted cells were then examined for tumorigenicity, proliferation, cell signaling, cell migration, angiogenesis and epithelial-mesenchymal transition. A xenograft model demonstrated that CD117 positive LNCaP-C4-2 tumors generate larger tumors characterized by increased vascularization and proliferation. In vitro, SCF induced CD117 activation results in altered cell signaling, migration and epithelial-to-mesenchymal transition. In addition, in vivo imaging of tumor growth demonstrated changes in tumor cell organization between CD117 positive and negative cell populations. In summary, CD117 expression and activation enhances prostate cancer progression. Citation Format: Bethany Kerr. CD117 expression and activation in prostate cancer progression. [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 2229. doi:10.1158/1538-7445.AM2015-2229
Abstract 17135: Serum 25-Hydroxyvitamin D Deficiency Increases Risk of Myocardial Infarction: Results From the Prospective Monica/Kora Augsburg Case-Cohort Study
Authors: Mahir Karakas, Barbara Thorand, Astrid Zierer, Cornelia Huth, Christa Meisinger, Michael Roden, Wolfgang Rottbauer, Annette Peters, Wolfgang Koenig, Christian Herder
Journal: Circulation (2011)

Background: A growing body of evidence suggests that vitamin D deficiency may adversely affect the cardiovascular system, but data from longitudinal studies are lacking. Circulating 25-hydroxyvitamin D3 (25[OH]D), the most commonly used index of vitamin D status, is converted to the active hormone 1,25-dihydroxyvitamin D3 (1,25[OH]2D), which, operating through the vitamin D receptor, inhibits in vitro cell proliferation, induces differentiation and apoptosis, and may protect against coronary heart disease (CHD). Therefore, the aim was to prospectively assess the association between serum (25[OH]D) concentrations and incident CHD. Methods: Using a case-cohort design, serum levels of (25[OH]D) were measured in 1,783 subjects (964 men, 819 women) selected from a source population of 9,300 middle-aged participants in the population-based MONICA/KORA Augsburg studies. Results: A total of 298 CHD cases (225 male, 73 female) were identified over an 11-year average follow-up period. We found a significant interaction of the effects of vitamin D with sex. After adjustment for age, survey, and season of blood sampling, the hazard ratio (HR) and 95% confidence interval (CI) comparing tertile extremes of serum levels of (25[OH]D) was 0.32 (0.16-0.65) (p for trend=0.001) in women, and 0.56 (0.38-0.82) (p-trend=0.005) in men. Further adjustment for standard cardiovascular risk factors (including BMI, smoking, physical activity, alcohol, systolic blood pressure, total cholesterol/HDL-cholesterol ratio, and parental history) slightly attenuated the association in women (HR: 0.39 [0.18-0.84] p-trend=0.013, and strongly in men (HR: 0.76 [0.49-1.17] p-trend=0.215). After additional adjustment for C-reactive protein, interleukin-6, ICAM-1, and IP-10, the effect remained significant in women (HR: 0.42 [0.19-0.93] p-trend=0.028) while it was further reduced in men (HR: 0.84 [0.52-1.35] p-trend=0.461). Conclusions: Our findings suggest that higher vitamin D status is associated with decreased risk of CHD. This effect seems to be particularly pronounced in women. Further clinical and experimental studies are needed to investigate the sex differences and whether or not correction of vitamin D deficiency could contribute to the prevention of CHD.
Reducing the risk of diabetes:
Authors: Tahseen Ahmad Chowdhury, Rupal Shah
Journal: BMJ (2015)

#### The bottom line

A 45 year old white man comes to see you to discuss his blood glucose result. This was measured because he had an elevated QDiabetes risk score of 15%,1 as well as a brother with diabetes. His glycated haemoglobin (HbA1c) is 43 mmol/mol (6.1%).

This man is at high risk of developing diabetes. Guidance from the UK National Institute for Health and Care Excellence (NICE) suggests that risk of diabetes should be determined by using a computer based risk assessment tool such as the QDiabetes risk calculator (http://qdiabetes.org/), Cambridge diabetes risk score, or Leicester practice score.2 If the risk assessment tool suggests elevated risk (for example >10% over 10 years), a fasting plasma glucose or HbA1c test should be offered. Fasting plasma glucose of 5.5-6.9 mmol/L or HbA1c between …
Abstract 9309: Benefit of Prasugrel in ST-Elevation Myocardial Infarction According to Timing of Percutaneous Coronary Intervention: Insight from the TRITON-TIMI 38 Study
Authors: Jacob A Udell, Eugene Braunwald, Elliot M Antman, Sabina A Murphy, Gilles Montalescot, Stephen D Wiviott, None TRITON-TIMI 38 Investigators
Journal: Circulation (2011)

Background: Prasugrel is approved as an alternative to clopidogrel in STEMI. Treatment strategies and outcomes for primary PCI (&lt;12 hours from onset [PPCI]) versus secondary PCI (&gt;12 hours from onset or initial medical therapy [SecPCI]) may differ. Methods: We performed a pre-specified analysis within the 3534 STEMI patients in TRITON-TIMI 38. Patients were randomized to prasugrel or clopidogrel on presentation if PPCI was intended or at the time of SecPCI. Since the clinical importance of procedural MI remains controversial, we performed sensitivity analyses excluding these events from the primary endpoint. Results: 2340 (68%) STEMI patients underwent PPCI. As previously reported, the reduction in the primary endpoint (CV death, MI, or stroke) with prasugrel versus clopidogrel was significant in STEMI patients at 30 days (30d) and 15 months (15m). Efficacy appeared consistent among PPCI patients (30d HR 0.81 [95% CI 0.60-1.09]; 15m HR 0.89 [0.69-1.13]) and SecPCI patients (30d HR 0.51 [0.34-0.76]; 15m HR 0.65 [0.46-0.93]; Figure 1+2). There was no interaction between timing of PCI and randomized treatment with respect to outcome at 30d or 15m (p-interaction&gt;0.05 for both). Reduction in CV death/spontaneous MI/stroke with prasugrel remained consistent among PPCI and SecPCI patients (Figure 1+2) with no interaction with timing of PCI and treatment (p-interaction&gt;0.05 for both). Trends in reduction of spontaneous MI were observed in PPCI (30d HR 0.53 [0.28-1.01]; 15m HR 0.72 [0.48-1.10]) and SecPCI (30d HR 0.26 [0.09-0.80] and 15m HR 0.57 [0.29-1.14]). TIMI major bleeding events were infrequent, however bleeding associated with prasugrel as compared to clopidogrel was consistent in the STEMI cohort, and either PCI subgroup, with the overall trial result (PPCI 15m HR 1.52 [0.87-2.65]; SecPCI 15m HR 0.39 [0.14-1.11]). Conclusion: In patients with STEMI, the efficacy and safety of prasugrel as compared to clopidogrel is consistent irrespective of the timing of PCI.
Abstract 1838: MUC1 serves as metabolic regulator in triple negative breast cancer
Authors: Gennifer D. Goode
Journal: Cancer Research (2015)

Abstract Breast cancer, the second leading cause of cancer deaths in women, is the most common cancer among North American women, accounting for nearly 1 in 3 cancer cases diagnosed in the U.S. women. Triple negative breast cancer (TNBC) subtype accounts for approximately 15-25% of all breast cancer cases and has an increased incidence of metastasis, high recurrence within 1-3 years and a high mortality rate. Therefore, identifying factors that facilitate tumor growth and metastases have the potential to serve as novel molecular targets for breast cancer therapy. Mucin1 (MUC1), a glycoprotein associated with chemoresistance, is aberrantly overexpressed in TNBC and facilitates growth and metastasis of TNBC cells. This occurrence can be partially attributed to MUC1 interaction with hypoxia-inducible factor alpha (HIF1α), a key regulator of glycolysis. In the present study we examined the effect of MUC1 expression on cancer cell metabolism of TNBC cell lines under normoxic (20% Oxygen) and hypoxic (1% Oxygen) conditions. MUC1 was ectopically overexpressed in the MDA-MB-231 cell line and stably knocked down in the MDA-MB-468 cell line. Results indicate that MUC1 interacts with HIF1α and the interaction is further enhanced under hypoxic conditions. In addition, MUC1 expression enhanced glucose and glutamine uptake, enhanced lactate secretion and altered the expression of several metabolic genes. Furthermore, untargeted global metabolomic profiling identified metabolite alterations in which MUC1 expression modulates cancer cell metabolism to facilitate growth properties of TNBC cells. Thus our results support the notion that MUC1 serves as a metabolic regulator in TNBC, facilitating metabolic reprogramming that influences growth of TNBC. Citation Format: Gennifer D. Goode. MUC1 serves as metabolic regulator in triple negative breast cancer. [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 1838. doi:10.1158/1538-7445.AM2015-1838
Simple schizophrenia: past, present, and future
Authors: D W Black, T J Boffeli
Journal: American Journal of Psychiatry (1989)

The diagnostic category called simple schizophrenia has disappeared from official American nosology but has been retained in ICD-9. The diagnosis has a long history, was one of the traditional schizophrenic subtypes identified by Bleuler, and was later accepted by Kraepelin. The authors provide a historical overview of the concept, review its modern successors, and provide recommendations for its inclusion in DSM-IV as a proposed diagnostic category needing further study.
Abstract 13630: Cathepsin K Knockout Mitigates High Fat Diet-Induced Cardiac Dysfunction
Authors: Yinan Hua, Julia Dolence, Jun Ren, Guo-Ping Shi, Sreejayan Nair
Journal: Circulation (2011)

Cathepsin K (catK) is a lysosomal cysteine proteinase with elastolytic and collagenolytic activities. Recent studies have implicated a role of catK in obesity associated-insulin resistance. However...
Highly increased levels of IgE antibodies to vaccine components in children with influenza vaccine–associated anaphylaxis
Authors: Mizuho Nagao, Takao Fujisawa, Toshiaki Ihara, Yoichiro Kino
Journal: Journal of Allergy and Clinical Immunology (2015)

Influenza vaccines produced in embryonated eggs might pose a risk to patients with egg allergy. However, patients experiencing influenza vaccine-associated anaphylaxis (IVA) do not always have egg allergy. In the 2011-2012 season, an unusually high incidence of IVA was reported in Japan.We sought to identify the cause of the increase in anaphylactic events in 2011-2012 in Japan.We collected blood specimens from patients with IVA from all areas of Japan. We analyzed 19 patients with confirmed IVA and 25 age-matched control subjects, including 10 with egg allergy who had no adverse events after corresponding vaccination. ELISA was used to measure specific IgE levels to the trivalent vaccines of several manufacturers and hemagglutinin proteins derived from both egg and cell cultures. Antigen-induced basophil activation was evaluated by measuring CD203c expression by means of flow cytometry. Vaccine excipients were also examined for effects on CD203c expression.None of the patients with IVA had severe egg allergy. Levels of specific IgE antibodies to influenza vaccine antigens, whole-vaccine products from different manufacturers, and hemagglutinin proteins (A H1, H3, and B) derived from both egg and cell cultures were significantly increased in patients with IVA compared with those in control subjects. Influenza vaccine-induced CD203c expression in basophils was also highly enhanced in patients with IVA but not in control subjects. Because IVA was most frequent in patients who received 2-phenoxyethanol (2-PE)-containing vaccine, the effect of this preservative on basophil activation was examined, and the activation was slightly enhanced by 2-PE but not thimerosal.The 2011-2012 IVA spike in Japan was caused by specific IgE antibodies to influenza vaccine components. Excipients could not be implicated, except for a modest effect of 2-PE.
Abstract 14021: Similar Patterns and Proportions of Ventricular Tachycardia Initiation With Pacing in Patients With CRT-D versus ICD
Authors: Karin K Chia, Nate Myall, Amin Al-Ahmad, Wojciech Zareba, Arthur J Moss, Paul J Wang
Journal: Circulation (2011)

Introduction: Pacing for bradycardia in ICDs has been suggested to be potentially proarrhythmic by facilitating short-long-short (SLS) sequences. CRT-D with its high volume pacing may be similarly ...
Abstract 20985: The Aortic Isthmus-Ductal Angle, a Novel Predictor of Coarctation of the Aorta in the Fetus
Authors: Julene S Carvalho, Alison Groves, Adam Jacobs, Edwin Quarello
Journal: Circulation (2010)

Background: Neonatal coarctation of the aorta is common. Reducing false positive rates in the fetus has been difficult and remains an important challenge in prenatal diagnosis. We studied diagnosti...