A5068740794- Drug-Induced Hepatotoxicity and Protection
- Metabolism, Diabetes, and Cancer
- Immune Response and Inflammation
- Protein Kinase Regulation and GTPase Signaling
- Pancreatic function and diabetes
- Sulfur Compounds in Biology
- Congenital heart defects research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Pesticide Exposure and Toxicity
- Receptor Mechanisms and Signaling
- Growth Hormone and Insulin-like Growth Factors
- Single-cell and spatial transcriptomics
- Sepsis Diagnosis and Treatment
- S100 Proteins and Annexins
- Monoclonal and Polyclonal Antibodies Research
- Liver physiology and pathology
- Pulmonary Hypertension Research and Treatments
- Viral Infectious Diseases and Gene Expression in Insects
- Alcoholism and Thiamine Deficiency
- Eicosanoids and Hypertension Pharmacology
- Drug Transport and Resistance Mechanisms
- Angiogenesis and VEGF in Cancer
- Molecular Biology Techniques and Applications
- Metabolism and Genetic Disorders
- Cardiomyopathy and Myosin Studies
Stanford University
1976-2021
Colorado College
2018
Michigan State University
1991-2016
University of Graz
2007
Memorial Sloan Kettering Cancer Center
2006
University of Pennsylvania
1962-2006
Karolinska University Hospital
1999
Freie Universität Berlin
1995
Eunice Kennedy Shriver National Institute of Child Health and Human Development
1993
National Institutes of Health
1993
To identify potential signaling molecules involved in mediating insulin-induced biological responses, a yeast two-hybrid screen was performed with the cytoplasmic domain of human insulin receptor (IR) as bait to trap high-affinity interacting proteins encoded by liver or HeLa cDNA libraries. A SH2-domain-containing protein identified that binds high affinity vitro autophosphorylated IR. The mRNA for this found Northern blot analyses be highest skeletal muscle and also detected fat PCR. study...
Maturation of the insulin proreceptor in a late Golgi compartment requires cleavage at an Arg-Lys-Arg-Arg processing site, suggesting involvement furin, transmembrane serine protease Kex2 family enzymes. A genetically engineered secreted, soluble form human furin (ss-furin), expressed by infection insect cells with recombinant baculovirus, was purified to near homogeneity. ss-Furin exhibited rapid and efficient both isoforms solubilized extracts cultured mammalian expressing preproreceptor...
We have placed human insulin receptor cDNA into a vector under the control of simian virus 40 (SV40) early promoter and tested its function by transient expression in microinjected Xenopus oocytes stably transformed CHO cells. The precursor alpha beta subunits were detected immunoprecipitation from extracts these expressed cells specifically binds 125I-labeled but not insulin-like growth factor I, displays insulin-stimulated autophosphorylation subunit, mediates 2-deoxyglucose uptake....
Antibodies to the insulin receptor were prepared in BALB/c mice by immunization with IM-9 human lymphocytes, a cell type that has large number of plasma membrane receptors. The spleens these then removed, and their lymphocytes fused mouse myeloma line, FO cells. After screening over 1,200 resulting hybrids, one stable hybrid was obtained produced IgG1 antibodies directed towards receptor. This antibody blocked 125I-labeled binding its more than 90% three tissues: cultured freshly isolated...
Abstract Aims Non-compaction cardiomyopathy is a devastating genetic disease caused by insufficient consolidation of ventricular wall muscle that can result in inadequate cardiac performance. Despite being the third most common cardiomyopathy, mechanisms underlying disease, including cell types involved, are poorly understood. We have previously shown endothelial cell-specific deletion chromatin remodeller gene Ino80 results defective coronary vessel development leads to non-compaction...
[Figure: see text].
Autophosphorylation of the insulin receptor has been previously documented to activate phosphotransferase activity from 20-to 200-fold.Biochemical studies have correlated activation kinase with autophosphorylation tyrosines residues 1158,1162, and 1163.To further assess role these 3 in process, we studied effect their substitution either neutral amino acids phenylalanine or alanine o r negatively charged aspartate glutamate.In several other proteins, it shown that phosphorylated can mimic...
Chinese hamster ovary (CHO) cells were transfected with a cDNA encoding protein kinase C alpha (PKC) and cell line (CHO-PKC alpha) expressing approximately 7-fold greater amounts of PKC as the parental isolated. Activation by 12-O-tetradecanoylphorbol-13-acetate in CHO-PKC inhibited 75% the: 1) insulin-stimulated increase antiphosphotyrosine precipitable phosphatidylinositol 3-kinase activity these cells; 2) PI associated insulin receptor substrate-1; 3) tyrosine phosphorylation endogenous...
Chimeric receptors containing different portions of the homologous human insulin receptor, insulin-like growth factor I and receptor-related receptor were utilized to identify epitopes recognized by various anti-insulin antibodies. The antibodies studied included 12 monoclonal extracellular domain as well 15 patients' sera with autoimmune All all 8 that inhibit binding found recognize an epitope contained within residues 450-601 alpha subunit receptor. In contrast, 2 do not cysteine-rich...
Human exposure to Gram-negative bacterial lipopolysaccharide (LPS) is common and may have an important influence on chemical toxicity. LPS has been shown previously enhance synergistically the toxicity of trichothecene mycotoxins. Because either these toxin groups alone characteristically target lymphoid organs at high doses, we evaluated effects coexposure subthreshold doses Salmonella typhimurium vomitoxin (VT) administered by intraperitoneal injection oral gavage B6C3F1 mice,...
To determine whether defects in the insulin signal transduction pathway to glucose transport occur a muscle fiber type-specific manner, post-receptor insulin-signaling events were assessed oxidative (soleus) and glycolytic (extensor digitorum longus [EDL]) skeletal from Wistar or diabetic GK rats. In soleus rats, maximal insulin-stimulated (120 nmol/l) was significantly decreased, compared with that of EDL normal, while submaximal response reduced We next treated rats phlorizin for 4 weeks...
Other SectionsABSTRACTINTRODUCTIONHISTORY AND DEVELOPMENT OF SINGLE-CELL-RNA TRANSCRIPTOMICS SEQUENCING ANALYSISMAJOR USE ScRNA-SEQ ON CARDIOVASCULAR DISEASELIMITATIONS FUTURE PERSPECTIVESACKNOWLEDGEMENTSCONFLICTS INTERESTREFERENCES
Airway obstruction and hyperreactivity are characteristics off human asthma of “heaves,” a naturally occurring respiratory disorder horses ponies. To document the role cyclooxygenase products arachidonic acid metabolism in pathogenesis heaves, we measured plasma bronchoalveolar lavage (BAL) fluid concentrations metabolites thromboxane (TX)A2 prostaglandins (PG) I2 D2 five affected ponies their age- gender-matched controls prior to during acute airway precipitated by housing barn exposing...
Insulin is a member of family structurally related hormones with diverse physiological functions. The basic structure these molecules present even in isolated from invertebrates (Thorpe and Duve 1988). In humans, the best-characterized members this include insulin, insulin-like growth factor (IGF)-I, IGF-II. role insulin primarily to regulate rapid anabolic responses, such as glucose uptake into muscle fat cells (Rosen 1987). IGF-I, on other hand, appears be involved regulating long-term...
The response of cerebral arteries to norepinephrine was examined in vivo six dated preterm fetal (94-121 days gestation), eight term (127-141 five newborn (7-14 days), and adult sheep, anesthetized equipped with a closed cranial window. Norepinephrine (10(-8)-10(-4) M cerebrospinal fluid) caused dose-dependent decrease pial arteriolar diameter lambs; however, fetuses were 7- 14-fold more sensitive than lambs, respectively. effective concentration inducing 15% (EC15) 4.6 +/- 1.8, 33 11, 64 23...
Cellular radiosensitivity parameters of the track structure theory Katz and co-workers (see Nucl. Instrum. Meth., vol.111, p.93 (1973)), are evaluated from a sum squares minimizing computer program for nonlinear models. Based on these observations, suggestions presented efficient experiment design determination track-segment bombardments high LET radiations.
The acute hepatotoxicity induced by alpha-naphthylisothiocyanate (ANIT) in rats is manifested as neutrophil-dependent necrosis of bile duct epithelial cells (BDECs) and hepatic parenchymal cells. This mirrors that drug-induced cholangiolitic hepatitis humans. Since BDECs are primary targets ANIT-induced toxicity, we hypothesized after exposure to ANIT, produce a factor(s) causes neutrophil chemotaxis hepatocellular injury. To test this hypothesis were isolated from male Sprague Dawley...
The insulin receptor-related receptor (IRR) demonstrates striking structural homology to the (IR) and insulin-like growth factor-I (IGFR), suggesting that IRR is a member of IR family. However, endogenous ligand biological role for this "orphan" are unknown. To identify potential sites action IRR, in situ hybridization was employed reveal cellular patterns gene expression developing adult rat human kidney. From embryonic days 15-20, mRNA most abundant sensory neurons trigeminal dorsal root...