tbuckley/cabot-search huggingface dataset:
Abstract 5403: Protein Kinase C-Induced Troponin I Phosphorylation Causes Changes in Cardiac Contractile Function but not the Intracellular Calcium Transient
Authors: Jonathan A Kirk, Stephen H Smith, Guy A MacGowan, Sanjeev G Shroff
Journal: Circulation (2008)

Both intracellular calcium transients ([Ca] i ) and myofilament properties determine cardiac muscle contractile force. Transgenic mouse models created to perturb specific myofilament proteins often cause a compensatory change in [Ca] i , which confounds the assessment of myofilament structure-function relationships. We have created a new transgenic mouse that has all three protein kinase C (PKC) phosphorylation sites on cardiac troponin I (cTnI) mutated to glutamic acid, rendering these sites constitutively pseudo-phosphorylated. Our goal was to determine the effects of this mutation on cardiac muscle contractile function and whether these effects would be concurrent with changes in the [Ca] i . Two sets of studies were conducted: skinned muscle fiber experiments to characterize the steady-state force-pCa relationships at sarcomere lengths of 1.9 and 2.3 μm and right ventricular papillary muscle experiments to characterize the peak developed force (F dev )-muscle length (L) relationships and [Ca] i (fura-5F calcium dye, emission: 510 nm, excitation: 340 and 380 nm, R = [emission fluorescence 340 ]/[emission fluorescence 380 ]). In skinned fibers, there was a significant decrease in maximally activated force (i.e., force at pCa 4.33) in transgenic mice (Wild-Type, WT (n = 7): 64.4± 8.0, Transgenic, TG (n = 6): 42.6±6.8 mN•mm −2 , P = 0.004), without any changes in calcium sensitivity or cooperativity (Hill coefficient). In intact papillary muscles, TG mice showed a decrease in F dev and slowed relaxation for all muscle lengths examined (F dev @ 100% L max , WT (n = 5): 9.3±3.5, TG (n = 6): 4.2±1.6 mN•mm −2 , P = 0.005; dF/dt min @ 100% L max , WT: −136±32, TG: −74±38 mN•mm −2 •s −1 , P = 0.002). In contrast, [Ca] i was unaltered in TG mice at all muscle lengths examined ([Ca] i amplitude as quantified by R systole / R diaastole , WT: 1.62±0.07, TG: 1.48±0.22; [Ca] i relaxation rate d R /dt min , WT: −96±37, TG: −64±30 s −1 ). Thus, PKC-induced TnI phosphorylation affects cardiac muscle contraction (reduced force magnitude and slowed relaxation) via changes in the myofilament properties (activation and/or crossbridge dynamics), and these contractile effects are not related to any changes in the intracellular calcium transient.
Abstract 1007: Platelet Glycoprotein VI (GPVI) Deletion Reduces Myocardial Infarction in Mice
Authors: Haiquan Li, Hisao Takizawa, Xiaoqi Gong, Alice Concepcion, Junichi Kambayashi, Narendra Tandon, Yongge Liu
Journal: Circulation (2007)

Fibrillar collagen, exposed by damage of vascular endothelium, is the most thrombogenic component of the subendothelium, which, in addition to supporting platelet adhesion, is also a potent platelet activator. Platelet glycoprotein VI (GPVI) plays a major role in collagen-induced platelet activation, leading to thrombus formation. Inhibition of GPVI function may be a novel anti-platelet therapy with minimal bleeding risk. Recent evidence in FcRγ-chain-knockout (KO) mice, which also lack GPVI, shows attenuated myocardial infarction after ischemia and reperfusion. Unlike GPVI, which is exclusively expressed in platelets and megakaryocytes, FcRγ-chain also exists in white blood cells and immune cells. Thus, it is unclear whether GPVI deletion is cardioprotective. In this study, we compared myocardial infarction in GPVI-KO and age-matched wild-type (WT) mice. In parallel FcRγ-chain-KO mice were compared with age-matched WT mice. A major branch of left coronary artery was ligated for 30 min followed by reperfusion for 24 hrs. Myocardial infarction was measured by tetrozolium staining. Hemodynamics were not statistically different among the groups. Risk zone sizes were also similar between WT and GPVI-KO mice (0.020 ± 0.004 cm 3 and 0.022 ± 0.005 cm 3 , respectively) (Mean ± SD). However, percentage infarction of the risk zone was significantly smaller in GPVI-KO mice (averaged 22 ± 8 % vs. 45 ± 18 % in WT). Comparable protection was observed in FcRγ-chain-KO mice (12 ± 6 % vs. 46 ± 13 % in WT). Significant exposure of vascular collagen in the ischemia/reperfusion region of myocardium was revealed by FITC-labeled recombinant GPVI protein, injected prior to ischemia, indicating endothelium injury. Furthermore, there was significantly less expression of P-selectin, a marker of activated platelets, in the myocardium from GPVI-KO and FcRγ-KO mice when compared with WT mice. It is concluded that deletion of GPVI reduces myocardial infarction induced by ischemia and reperfusion, likely due to the attenuation of the platelet-collagen interaction. With its known anti-thrombotic effect and minimal risk of bleeding in animals, anti-GPVI therapy may offer a promising novel treatment for cardiovascular diseases.
Abstract 17026: Serum Potassium and Outcomes in Heart Failure: Benefit of Aldosterone Antagonists Independent of Baseline Serum Potassium Levels
Authors: Faiez Zannad, Renaud Fay, Patrick Rossignol, Bertram Pitt
Journal: Circulation (2010)

Introduction: The benefits of aldosterone antagonists (AAs) for patients with heart failure (HF) are well known and have been demonstrated in large outcome trials, the Randomized Aldactone Evaluati...
Revisiting Transitional Hypoglycemia
Authors: Christopher J. D. McKinlay, Jane E. Harding
Journal: JAMA Pediatrics (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Determination of ginsenoside compound K in human plasma by liquid chromatography–tandem mass spectrometry of lithium adducts
Authors: Yunhui Chen, Youming Lu, Yong Yang, Xiaoyan Chen, Liang Zhu, Dafang Zhong
Journal: Acta Pharmaceutica Sinica B (2015)

Ginsenoside compound K (GCK), the main metabolite of protopanaxadiol constituents of Panax ginseng, easily produces alkali metal adduct ions during mass spectrometry particularly with lithium. Accordingly, we have developed a rapid and sensitive liquid chromatography-tandem mass spectrometric method for analysis of GCK in human plasma based on formation of a lithium adduct. The analyte and paclitaxel (internal standard) were extracted from 50 µL human plasma using methyl tert-butyl ether. Chromatographic separation was performed on a Phenomenex Gemini C18 column (50 mm×2.0 mm; 5 μm) using stepwise gradient elution with acetonitrile-water and 0.2 mmol/L lithium carbonate at a flow rate of 0.5 mL/min. Detection was performed in the positive ion mode using multiple reaction monitoring of the transitions at m/z 629→449 for the GCK-lithium adduct and m/z 860→292 for the adduct of paclitaxel. The assay was linear in the concentration range 1.00-1000 ng/mL (r (2)>0.9988) with intra- and inter-day precision of ±8.4% and accuracy in the range of -4.8% to 6.5%. Recovery, stability and matrix effects were all satisfactory. The method was successfully applied to a pharmacokinetic study involving administration of a single GCK 50 mg tablet to healthy Chinese volunteers.
Estradiol regulates the expression of UDP-glucuronosyltransferase 1A10 in normal and malignant human breast cell lines via the estrogen receptor
Authors: Athena Starlard-Davenport, Beverly Lyn-Cook, Anna Radominska-Pandya
Journal: Cancer Research (2007)

4479   It is well established that increased levels of estrogens circulating in the serum and estrogen-targeted cells such as breast cells have a significant impact on breast cancer risk. The local concentration of estrogen in human breast cells is the result of a balance between estrogen synthesis and metabolism. Recently, we have shown that UDP-glucuronosyltransferases (UGTs) are involved in the inactivation of estrogens and facilitate the removal of these compounds from the body potentially preventing accumulation of estrogens in estrogen target cells and tissues. Specifically, human UGT1A10 catalyzes the glucuronidation of all native and hydroxylated estrogens. Here, we show for the first time that treatment of MCF7 (ER-positive) breast cancer cells with estradiol produces a dose-dependent upregulation of mRNA levels for this isoform, followed by a corresponding steady decrease, and that this upregulation can be blocked by the ER-antagonist, ICI182,780. In contrast, estradiol causes a significant decrease of UGT1A10 mRNA in MCF10F non-tumorigenic breast cells and has no effect on MDA-MB-231 (ER-negative) breast cancer cells. Collectively, these results suggest that the induction of UGT1A10 mRNA expression by estradiol is mediated through the ER. We have also characterized UGT1A10 mRNA in a total of 61 normal and malignant human breast tissue samples in from African American and Caucasian women by quantitative real-time PCR analysis in order to further characterize the role of this isoform in estrogen target tissue. Although, these results show wide individual variation in the expression of UGT1A10 mRNA within the normal and malignant tissue samples, the mean expression levels were significantly higher in normal tissues as compared to cancer tissues (252 ± 86 vs. 68.1 ± 25.6, for normal and malignant tissue, respectively; p
Abstract 10649: Upregulation and Adverse Effects of Cardiac Beta3-Adrenoreceptor-Mediated Inducible Nitric Oxide Synthase (iNOS)-Coupled Pathway in Monkeys with Naturally Occurring Type 2 Diabetes
Authors: Heng Jie Cheng, Qun Shao, Li Zhang, Michael F Callahan, Janice D Wagner, Che Ping Cheng
Journal: Circulation (2011)

Background. Recent evidence links altered cardiac β-adrenergic receptor (AR) signaling to the pathology of diabetic cardiomyopathy (DCM). Although the β3-AR-mediated inhibitory pathway is increasin...
Protriptyline: an effective agent in the treatment of the narcolepsy- cataplexy syndrome and hypersomnia
Authors: H S Schmidt, R W Clark, P R Hyman
Journal: American Journal of Psychiatry (1977)

The authors present five case reports illustrating that 10-20 mg of protriptyline in a single dose at bedtime can effectively control arousal dysfunction (sleep drunkenness and hypersomnia) and the narcolepsycataplexy syndrome without the apparent development of tolerance and without the side effects that are frequent complications of treatment with other agents. Although protriptyline was efficacious in controlling symptoms, it was found to have relatively poor REM sleep-suppressing properties.
Abstract 5564: Sequencial Activation of VEGF/Flk-1/MKK2/NFkappaB Signaling in Ischemic Preconditioning Induced Neovascularization: A Study with Flk-1+/− and MKK2−/− Knockout Mice
Authors: Mahesh Thirunavukkarasu, Yozu Akita, Samson Mathews Samuel, Lijun Zhan, Chi-Kuang Huang, Matthias Gaestel, Nilanjana Maulik
Journal: Circulation (2008)

Ischemic preconditioning mediated activation of VEGF-FLK-1-MKK2/NFkappaB pathway identifies these components as a critical regulator of myocardial angiogenesis in an infarcted myocardium. In the present study we used Flk-1+/− and MKK2−/− knockout mice in an attempt to address and prove this important clinical issue by identifying potential downstream candidates of VEGF signaling through Flk-1 receptor that trigger angiogenic signal during ischemic preconditioning (IP). Both wild type (WT) and Flk1+/− mice were subjected to either permanent LAD ligation (MI) or Ischemic preconditioning (IP) followed by MI. Flk-1+/− mouse hearts displayed significant increase in infarct size in Flk-1+/−PCMI (46%) group as compared to WTPCMI (33%) groups. Immunohistochemical analysis demonstrated decreased capillary and arteriolar density in both Flk-1+/−MI and Flk-1+/−PCMI groups as compared to WTMI and WTPCMI. Echocardiography demonstrated significant decrease in fractional shortening ( 21% vs 28%) and ejection fraction (42% vs 54%) following 4 weeks of myocardial infarction in Flk-1+/−PCMI group as compared with WTPCMI. As expected we found Flk-1+/− resulted in disruption of the cardioprotective effect by IP compared to WT. IP induced phosphorylation of p38MAPK, MKK2 was found to be inhibited (1.8 and 2 folds) significantly in both the Flk-1+/−MI and Flk-1+/−PCMI groups by Western blot analysis. Similarly Gelshift analysis showed down regulation of transcription factor NFkappaB (2 fold) in the Flk-1+/− mice as compared to WT. We further extended our experiments to validate our data in MKK2−/− mice. Hearts were subjected to LAD ligation. After 4-days of MI BSL-lectin infusion demonstrated significant disruption of neovascularization (capillary density) in the MKK2−/−PCMI (1520 counts/mm2) group compared to the WTPCMI ( 1850 counts/mm2). Gel-shift analysis in MKK2−/−PCMI group documented reduced NFkappaB activity (1.5 fold) compared to WTPCMI (2.4 fold). Taken together, this study validated for the first time that NFkappaB is a novel downstream mediator of VEGF/FLK-1/p38MAPK-MKK2 signaling and it induces IP mediated cardioprotection and angiogenesis via MKK2 signaling.
Resveratrol inhibits insulin-like growth factor-1 mediated migration and invasion of human breast cancer cells
Authors: Feng-Yao Tang, Hsin-Ju Cho, Hui-Shan Hsieh
Journal: Cancer Research (2008)

3064   Metastasis is the primary cause of death from breast cancer. Cell migration and invasion play important roles in neoplastic metastasis. The insulin like growth factor (IGF-1) stimulated cell migration through activation of PI3K/Akt signaling pathway. IGF-1 induces the tumorigenicity of many types of cancer cells and is critical for metastatic cell spread in estrogen receptor (ER)-negative breast cancer cells. Matrix metalloproteinase-2 (MMP-2) is a key enzyme in the degradation of extracellular matrices, and its expression has been dysregulated in breast cancer invasion and metastasis. Resveratrol exhibited potential anticarcinogenic activities in several studies. However, the inhibitory effects of resveratrol on the expression of MMP-2, migration and invasion of breast cancer cell have not been demonstrated yet. In the present study, we investigated the anti-invasive mechanism of resveratrol in human breast cancer MDA-MB 435cells. Here we showed that IGF-1 is a potent stimulant for the migration of ER-negative human breast cancer cells. Resveratrol could inhibit IGF-1 mediated cell migration of MDA-MB 435  in vitro.  The inhibitory effect of resveratrol was mediated in part through the suppression of the activation of PI-3K/Akt signaling pathway. Furthermore, IGF-1 mediated expression of MMP-2 was significantly inhibited by resveratrol in concomitance with alteration of cell invasion.
Hyperprolactinaemia caused by antipsychotic drugs
Authors: O. Howes
Journal: BMJ (2002)

Editor—Wieck and Haddad highlight the fact that hyperprolactinaemia is a common side effect of antipsychotic treatment, but they do not indicate just how often it occurs.1

We have found that three quarters of women and one third of men taking typical antipsychotics have prolactin concentrations above the upper limit of the normal range, and there is a highly significant relation between the dose of antipsychotic treatment and prolactin concentrations.2 Oestradiol and progesterone concentrations were below the lower limit of the normal range in 85% of the women.

This evidence supports the authors' suggestion that antipsychotic induced hyperprolactinaemia is linked to clinically important hypogonadism. Furthermore, preliminary results indicate that over 40% of patients taking prolactin raising antipsychotics show osteopenia associated with hypogonadism (A Meaney et al, proceedings of the British Association of Psychopharmacology, Harrogate, 2001). We are currently measuring bone mineral density in patients taking prolactin sparing antipsychotics, and we hope that this study will address some of the evidence needs raised by Wieck and Haddad.

The authors point out that prolactin sparing atypical antipsychotics offer a new management strategy for antipsychotic induced hyperprolactinaemia. However, there are risks associated with reversing hyperprolactinaemia and hypogonadism, as indicated by reports of unplanned pregnancies after patients changed to prolactin sparing antipsychotics.3 Many of these patients also experienced a relapse of their psychotic illness after the pregnancy. It is important that patients are counselled about the change in fertility associated with changing to a prolactin sparing atypical and given contraceptive advice.

The national service framework has emphasised that patients with severe mental illness have increased physical morbidity and that assessment should include their physical health.4 Wieck and Haddad point to the contribution that endocrine antipsychotic side effects may make to the increased physical morbidity, and these side effects should be monitored.

We recently helped to develop a drug review model that provides patients receiving long term antipsychotic treatment with systematic and periodic assessment of psychopathology, quality of life, and side effects. It is an alternative to the traditional depot clinic style of practice, which often meant that patients took antipsychotics for many years while receiving only ad hoc and limited review. The model represents a move in line with the national service framework towards more proactive patient centred care, and a management approach to the adverse effects of antipsychotics, including the frequently neglected endocrine effects.
Abstract 17373: MicroRNA-155 Over-expression Inhibits Angiogenesis Of Lin-/cd34+ Cells From Human CAD Patients and HUVECs
Authors: Jennipher N Adi, Nikhil C Adi, Keith A Webster
Journal: Circulation (2011)

Introduction: In the cellular hypothesis of atherosclerosis, bone marrow (BM) derived EPCs contribute to vascular repair and regeneration, and defects in number and/or function of EPCs may contribu...
Abstract #LB-303: Advances in Proteomic Characterization of Extracellular Matrix Samples: ECM Profile Influences Mammary Cell Phenotype
Authors: Kirk Hansen, Lauren Kiemele, Ori Maller, Jenean Obrien, Jaime Fornetti, Pepper Schedin
Journal: Cancer Research (2009)

Despite the important role that the ECM plays in cell function and survival very few proteomic studies have been reported. Proteomic analyses of ECM proteins have been hindered by the insoluble and digestion resistance nature of this type of sample. Here we explore the utility of combining rapid ultrasonication and surfactant assisted digestion for the detailed proteomic analysis of ECM samples. When we compared this method to traditional overnight digestion, or surfactant assisted digestion alone, this optimized method dramatically improved the sequence coverage for collagen I and allowed for the detailed characterization of two in vivo derived matrices. We applied the method to characterize the EHS tumor derived sample Matrigel. Despite being the matrix of choice for 2D and 3D cell culture experiments the composition of this sample has not been reported in more detail than the presence of about two dozen proteins. Our analysis revealed the presence of hundreds of previously unidentified proteins. We then analyzed and identified a protein profile for ECM isolated from rat mammary glands that was substantially different to that found in Matrigel. Finally we tested the functional significance of the two in vivo matrices in a 3D culture assay to investigate epithelial cell-ECM interactions. Mammary epithelial cells were found to undergo extensive branching morphogenesis when plated with mammary-derived matrix in comparison to Matrigel. Cumulatively, these data highlight the tissue-specific nature of ECM composition and function, and underscore the need for optimized techniques for the proteomic characterization of ECM samples.   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr LB-303.
Phosphodiesterase Isoform Regulation of Cell Proliferation and Fluid Secretion in Autosomal Dominant Polycystic Kidney Disease
Authors: Cibele S. Pinto, Archana Raman, Gail A. Reif, Brenda S. Magenheimer, Corey White, James P. Calvet, Darren P. Wallace
Journal: Journal of the American Society of Nephrology (2015)

cAMP stimulates cell proliferation and Cl–-dependent fluid secretion, promoting the progressive enlargement of renal cysts in autosomal dominant polycystic kidney disease (ADPKD). Intracellular cAMP levels are determined by the balance of cAMP synthesis by adenylyl cyclases and degradation by phosphodiesterases (PDEs). Therefore, PDE isoform expression and activity strongly influence global and compartmentalized cAMP levels. We report here that PDE3 and PDE4 expression levels are lower in human ADPKD tissue and cells compared with those of normal human kidneys (NHKs), whereas PDE1 levels are not significantly different. Inhibition of PDE4 caused a greater increase in basal and vasopressin (AVP)-stimulated cAMP levels and Cl– secretion by ADPKD cells than inhibition of PDE1, and inhibition of PDE4 induced cyst-like dilations in cultured mouse Pkd1−/− embryonic kidneys. In contrast, inhibition of PDE1 caused greater stimulation of extracellular signal–regulated kinase (ERK) and proliferation of ADPKD cells than inhibition of PDE4, and inhibition of PDE1 enhanced AVP-induced ERK activation. Notably, inhibition of PDE1, the only family of Ca2+-regulated PDEs, also induced a mitogenic response to AVP in NHK cells, similar to the effect of restricting intracellular Ca2+. PDE1 coimmunoprecipitated with B-Raf and A-kinase anchoring protein 79, and AVP increased this interaction in ADPKD but not NHK cells. These data suggest that whereas PDE4 is the major PDE isoform involved in the regulation of global intracellular cAMP and Cl– secretion, PDE1 specifically affects the cAMP signal to the B-Raf/MEK/ERK pathway and regulates AVP-induced proliferation of ADPKD cells.
Immunoglobulin Fc-fused, neuropilin-1-specific peptide shows efficient tumor tissue penetration and inhibits tumor growth via anti-angiogenesis
Authors: Ye-Jin Kim, Jeomil Bae, Tae-Hwan Shin, Se Hun Kang, Moonkyoung Jeong, Yunho Han, Ji-Ho Park, Seok-Ki Kim, Yong-Sung Kim
Journal: Journal of Controlled Release (2015)
Limited Superiority Of Recombinant Thrombomodulin For Disseminated Intravascular Coagulation; A Comparative Analysis In 41 Children
Authors: Eri Nishikawa, Hiroshi Yagasaki, Katsuyoshi Shimozawa, Hirotsugu Okuma, Maiko Hirai, Maiko Kato, Hiroyuki Shichino, Motoaki Chin, Shouri Takahashi, Hideo Mugishima
Journal: Blood (2013)