A5041496759- Crystallization and Solubility Studies
- Tissue Engineering and Regenerative Medicine
- Crystallography and molecular interactions
- Pluripotent Stem Cells Research
- Mesenchymal stem cell research
- Mechanical Circulatory Support Devices
- HIV/AIDS drug development and treatment
- Transplantation: Methods and Outcomes
- Computational Drug Discovery Methods
- Virus-based gene therapy research
- X-ray Diffraction in Crystallography
- Aortic Disease and Treatment Approaches
- CRISPR and Genetic Engineering
- Apelin-related biomedical research
- Cardiac Valve Diseases and Treatments
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Drug Solubulity and Delivery Systems
- Cardiac Structural Anomalies and Repair
- Electrospun Nanofibers in Biomedical Applications
- Hepatitis C virus research
- Analytical Chemistry and Chromatography
- Cardiac Imaging and Diagnostics
- Chemical Synthesis and Analysis
- Cardiovascular Function and Risk Factors
- Machine Learning in Materials Science
AbbVie (United States)
2013-2025
Kaiser Permanente San Francisco Medical Center
2018-2024
Kaiser Permanente Santa Clara Medical Center
2024
University of Veterinary and Animal Sciences
2023
AbbVie (Japan)
2022
University of California, San Francisco
2000-2019
Kaiser Permanente
2019
Stanford University
2007-2016
Stanford Health Care
2015
VA Palo Alto Health Care System
2014
Background— Patients with pulmonary arterial hypertension (PAH) have reduced expression of apolipoprotein E (apoE) and peroxisome proliferator–activated receptor-γ in lung tissues, deficiency both has been linked to insulin resistance. ApoE leads enhanced platelet-derived growth factor signaling, which is important the pathobiology PAH. We therefore hypothesized that insulin-resistant apoE-deficient (apoE −/− ) mice would develop PAH could be reversed by a agonist (eg, rosiglitazone)....
Apelin and its cognate G protein–coupled receptor APJ constitute a signaling pathway with positive inotropic effect on cardiac function vasodepressor in the systemic circulation. The apelin-APJ appears to have opposing physiological roles renin-angiotensin system. Here we investigated whether can directly antagonize vascular disease-related Ang II actions. In ApoE-KO mice, exogenous induced atherosclerosis abdominal aortic aneurysm formation; found that coinfusion of apelin abrogated these...
Given their self-renewing and pluripotent capabilities, human embryonic stem cells (hESCs) are well poised as a cellular source for tissue regeneration therapy. However, the host immune response against transplanted hESCs is not characterized. In fact, controversy remains to whether have immune-privileged properties. To address this issue, we used in vivo bioluminescent imaging track fate of stably transduced with double-fusion reporter gene consisting firefly luciferase enhanced GFP. We...
The physicochemical properties of molecular crystals, such as solubility, stability, compactability, melting behaviour and bioavailability, depend on their crystal form1. In silico form selection has recently come much closer to realization because the development accurate affordable free-energy calculations2-4. Here we redefine state art, primarily by improving accuracy calculations, constructing a reliable experimental benchmark for solid-solid differences, quantifying statistical errors...
<h3>Hypothesis</h3> Hyperbaric oxygen (HBO) therapy increases vascular endothelial growth factor (VEGF) levels in wounds. <h3>Design</h3> Wounds were monitored for delivery during HBO treatment, and wound fluids analyzed VEGF lactate on days 2, 5, 10 following wounding. <h3>Setting</h3> Experimental animal model. <h3>Interventions</h3> Rats randomized to control groups. The was administered 90 minutes, twice daily with 100% at 2.1 atmospheres absolute. Treatment 7 <h3>Main Outcome...
Background— Embryonic stem (ES) cells are distinguished by their capacity for self-renewal and pluripotency. Here we characterize the differentiation of ES cell–derived endothelial (ESC-ECs), use molecular imaging techniques to examine survival in vivo, determine therapeutic efficacy ESC-ECs restoration cardiac function after ischemic injury. Methods Results— Murine were transfected with a construct composed vascular cadherin promoter driving enhanced green fluorescence protein...
A comparative analysis of the efficacy different cell candidates for treatment heart disease remains to be described. This study is designed evaluate therapeutic 4 types in a murine model myocardial infarction.Bone marrow mononuclear cells (MN), mesenchymal stem (MSC), skeletal myoblasts (SkMb), and fibroblasts (Fibro) expressing firefly luciferase (Fluc) green fluorescence protein (GFP) were characterized by flow cytometry, bioluminescence imaging (BLI), luminometry. Female FVB mice (n=70)...
Background— Cardiac cell transplantation is limited by poor graft viability. We aimed to enhance the survival of transplanted cardiomyoblasts using growth factor-supplemented collagen matrices. Methods and Results— H9c2 were lentivirally transduced express firefly luciferase green fluorescent protein (GFP). Lewis rats underwent ligation left anterior descending artery (LAD) induce an wall myocardial infarction. Hearts (n=9/group) harvested restored ex vivo with 1×10 6 genetically labeled...
Studies have shown significant cardiovascular effects of exogenous apelin administration, including the potent activation cardiac contraction. However, role endogenous apelin-APJ pathway is less clear. To study loss signaling, we generated mice lacking either ligand (apelin) or receptor (APJ). Apelin-deficient were viable, fertile, and showed normal development. In contrast, APJ-deficient not born in expected Mendelian ratio, many developmental defects. Under basal conditions, both APJ null...
Signaling by the peptide ligand apelin and its cognate G protein-coupled receptor APJ has a potent inotropic effect on cardiac contractility modulates systemic vascular resistance through nitric oxide-dependent signaling. In addition, there is evidence for counterregulation of angiotensin vasopressin pathways. Regulatory stimuli apelin-APJ pathway are obvious importance but remain to be elucidated. To better understand physiological response disease states such as heart failure elucidate...
Mesenchymal stem cells hold promise for cardiovascular regenerative therapy. Derivation of these from the adipose tissue might be easier compared with bone marrow. However, in vivo fate and function stromal (ASC) infarcted heart has never been directly to marrow-derived mesenchymal (MSC).ASC MSC were isolated transgenic FVB mice a beta-actin promoter driving firefly luciferase green fluorescent protein double fusion reporter gene, they characterized using flow cytometry, microscopy,...
Abstract Bone marrow mononuclear cell (BMMC) therapy shows promise as a treatment for ischemic heart disease. However, the ability to monitor long-term fate remains limited. We hypothesized that molecular imaging could be used track stem homing and survival after myocardial ischemia-reperfusion (I/R) injury. first harvested donor BMMCs from adult male L2G85 transgenic mice constitutively expressing both firefly luciferase (Fluc) enhanced green fluorescence protein reporter gene....
Numerous studies have demonstrated the potential use of stem cells for repair and regeneration injured tissues. However, tracking transplanted cell fate function in vivo remains problematic. To address these issues, murine embryonic (ES) were stably transduced with self-inactivating lentiviral vectors carrying either a triple fusion (TF) or double (DF) reporter gene construct. The TF consisted monomeric red fluorescence protein (mrfp), firefly luciferase (Fluc), herpes simplex virus...
Apelin, a novel peptide with significant cardioactive properties, is upregulated by insulin in adipocytes. However, the mechanism which promotes apelin production unknown. Hypoxia-inducible factor-1 (HIF-1), heterodimeric transcription factor involved angiogenic and metabolic responses to tissue hypoxia, has been shown be activated various settings. We therefore hypothesized that HIF-1 regulates insulin-mediated expression 3T3-L1 cells were differentiated into adipocytes culture. For...
Direct-acting antiviral regimens have transformed therapeutic management of hepatitis C across all prevalent genotypes. Most the chemical matter in these comprises molecules well outside traditional drug development space and presents significant challenges. Herein, implications high conformational flexibility presence a 15-membered macrocyclic ring paritaprevir are studied through combination advanced computational experimental methods with focus on molecular chameleonicity crystal form...
The risk of adverse events from ascending thoracic aorta aneurysm (TAA) is poorly understood but drives clinical decision-making.To evaluate the association TAA size with outcomes in nonsyndromic patients a large non-referral-based health care delivery system.The Kaiser Permanente Thoracic Aortic Aneurysm (KP-TAA) cohort study was retrospective at Northern California, fully integrated system insuring and providing for more than 4.5 million persons. Nonsyndromic regional safety net tracking...
Background— Cell transplantation for myocardial repair is limited by early cell death. Gene therapy with human Bcl-2 (hBcl-2) has been shown to attenuate apoptosis in the experimental setting. Therefore, we studied potential benefit of hBcl-2 transgene expression on survival cardiomyoblast grafts ischemic rat hearts. Methods and Results— H9c2 cardiomyoblasts were genetically modified express both firefly luciferase green fluorescent protein (mH9c2). The cells then transduced adenovirus...
A framework for conceptualization of scalable solution-crystallization processes cocrystals is developed and demonstrated using carbamazepine-nicotinamide as the model system. Calculation intermolecular interactions crystal lattice energy were carried out to understand structure strength binding synthons well predict likely growth morphology overall rate at scale. Experimental measurements solubility behavior pure components, solid form stability domain, speciation in solution effects on...
Pluripotent embryonic stem (ES) cells have the potential to form teratomas composed of derivatives from all three germ layers in animal models. This tumorigenic prevents clinical translation ES cell research. In order understand biology and physiology teratoma formation, we investigated influence undifferentiated number, migration, long-term follow up after transplantation. Murine were stably transduced with a self-inactivating (SIN) lentiviral vector constitutive ubiquitin promoter driving...
Recent analyses establish that heart transplantation is increasing among adults with congenital disease (ACHD), but the effects of pretransplant mechanical circulatory support (MCS) on perioperative and post-transplant outcomes have not been examined in ACHD population.Scientific Registry Transplant Recipients data all adult transplants from September 1987 to 2012 (n = 47 160) were classified based primary diagnosis codes as CHD or non-CHD MCS non-MCS. Demographic, procedural, outcome...
Reversible temperature-mediated solid phase changes, otherwise known as enantiotropic transformations, occur in many molecular crystals. These transformations take place a result of the free-energy stabilization through entropic contributions at finite temperatures and can often have significant implications for properties crystalline solids. As such, understanding predicting these is great importance. In this study, we utilize simulations to elucidate mechanism behind layer-slip...