A5038864826- Pharmacogenetics and Drug Metabolism
- Platelet Disorders and Treatments
- Cell Adhesion Molecules Research
- Drug Transport and Resistance Mechanisms
- Hemophilia Treatment and Research
- Cellular Mechanics and Interactions
- Metabolism and Genetic Disorders
- Protein Kinase Regulation and GTPase Signaling
- Cytokine Signaling Pathways and Interactions
- Estrogen and related hormone effects
- Hormonal Regulation and Hypertension
- Biochemical Analysis and Sensing Techniques
- Immunodeficiency and Autoimmune Disorders
- Birth, Development, and Health
- Prenatal Substance Exposure Effects
- Folate and B Vitamins Research
- Blood groups and transfusion
- Reproductive System and Pregnancy
- Asthma and respiratory diseases
- Virus-based gene therapy research
- Microbial bioremediation and biosurfactants
- Blood properties and coagulation
- Ion channel regulation and function
- Angiogenesis and VEGF in Cancer
- Blood disorders and treatments
Medical College of Wisconsin
2003-2025
Children's Hospital of Wisconsin
2008-2025
Wayne State University
2005
University of Alabama at Birmingham
2005
University of Crete
1994-1999
University Hospital of Heraklion
1996
The human cytochrome P4503A forms show expression patterns subject to developmental influence. CYP3A7 and CYP3A4 are generally classified as the major fetal adult liver forms, respectively. However, characterization of CYP3A4, -3A5, -3A7 has historically been confounded by lack CYP3A isoform-specific antibodies or marker enzyme activities. Therefore, objective this study was characterize hepatic from early gestation 18 years age using up 212 pediatric samples. Based on immunoquantitation,...
The CYP2C subfamily is responsible for metabolizing many important drugs and accounts about 20% of the cytochrome P450 in adult liver. To determine developmental expression patterns, liver microsomal CYP2C9 -2C19 were measured (<i>n</i> = 237; ages, 8 weeks gestation-18 years) by Western blotting with diclofenac or mephenytoin, respectively, as probe substrates. CYP2C9-specific content catalytic activity consistent at 1 to 2% mature values (i.e., specific content, 18.3 pmol/mg protein...
It is essential to improve therapies for controlling excessive bleeding in patients with haemorrhagic disorders. As activated blood platelets mediate the primary response vascular injury, we hypothesize that storage of coagulation Factor VIII within may provide a locally inducible treatment maintain haemostasis haemophilia A. Here show haematopoietic stem cell gene therapy can prevent occurrence severe episodes dogs A at least 2.5 years after transplantation. We employ clinically relevant...
Human hepatic <i>CYP2E1</i> expression developmental changes likely have an impact on the effects of xenobiotics metabolized by encoded enzyme. To resolve previous conflicting results, CYP2E1 content was determined in human microsomes from samples spanning fetal (<i>n</i> = 73, 8–37 weeks) and postnatal 165, 1 day–18 years) ages. Measurable immunodetectable seen 18 49 second-trimester (93–186 gestational days) 12 15 third-trimester (>186 (medians 0.35 6.7 pmol/mg microsomal protein,...
In glomerulonephritis, there is intraglomerular activation of inducible nitric oxide synthase (iNOS) leading to high output production (NO). This can result in supraphysiologic amounts NO and cause oxidative injury. It unknown whether mechanisms cellular defense against NO-mediated injury exist. Induction the heme catabolizing enzyme oxygenase-1 (HO-1), which generates biliverdin, carbon monoxide (CO), iron (Fe), may provide such a mechanism, as CO Fe are two negative modulators iNOS...
Human hepatic <i>CYP2E1</i> expression developmental changes likely have an impact on the effects of xenobiotics metabolized by encoded enzyme. To resolve previous conflicting results, CYP2E1 content was determined in human microsomes from samples spanning fetal (<i>n</i> = 73, 8–37 weeks) and postnatal 165, 1 day–18 years) ages. Measurable immunodetectable seen 18 49 second-trimester (93–186 gestational days) 12 15 third-trimester (>186 (medians 0.35 6.7 pmol/mg microsomal protein,...
Aryl- (SULT1A1), estrogen- (SULT1E1), and hydroxysteroid- (SULT2A1) sulfotransferases (SULTs) are active determinants of xenobiotic detoxication hormone metabolism in the adult human liver. To investigate role these conjugating enzymes developing liver, ontogeny immunoreactive SULT1A1, SULT1E1, SULT2A1 expression was characterized a series 235 pre- postnatal liver cytosols ranging age from early gestation to 18 years. Interindividual variability levels apparent for all three SULTs samples....
Transient receptor potential vanilloid 4 (TRPV4) is a Ca2+-permeable channel activated by diverse physical and chemical stimuli, including mechanical stress endogenous lipid arachidonic acid (AA) its metabolites. Phosphorylation of TRPV4 protein kinase A (PKA) C (PKC) predominant mechanism for regulation, especially in the cytoplasmic domains due to their importance assembly, channelopathies. However, studies corresponding phosphorylation sites these kinases remain incomplete. We...
Flavin-containing monooxygenases (FMOs) are important for the disposition of many therapeutics, environmental toxicants, and nutrients. FMO3, major adult hepatic FMO enzyme, exhibits significant interindividual variation. Eighteen <i>FMO3</i> single-nucleotide polymorphism (SNP) frequencies were determined in 202 Hispanics (Mexican descent), 201 African Americans, 200 non-Latino whites. Using expressed recombinant enzyme with methimazole, trimethylamine, sulindac, ethylenethiourea, novel...
Activated blood platelets mediate the primary response to vascular injury. Although molecular abnormalities of platelet proteins occur infrequently, taken collectively, an inherited defect accounts for a bleeding diathesis in ≈1:20,000 individuals. One rare example disorder, Glanzmann thrombasthenia (GT), is characterized by life-long morbidity and mortality due major adhesion receptor, integrin αIIbβ3. Transfusion therapy frequently inadequate because patients often generate antibodies...
Glucocorticoids, in addition to their well characterized effects on the genome, may affect cell function a manner not involving genomic pathways. The mechanisms by which latter is achieved are yet clear. A possible means for this action involve actin cytoskeleton, since dynamic equilibrium of polymerization changes rapidly following exposure several stimuli, including hormones. aim present work was find out if glucocorticoids exert rapid, nongenomic Ishikawa human endometrial cells,...
The flavin-containing monooxygenases (FMOs) are important for xenobiotic metabolism. FMO3, the predominant FMO enzyme in human adult liver, exhibits significant interindividual variation that is poorly understood. This study was designed to identify common <i>FMO3</i> genetic variants and determine their potential contributing differences expression. single nucleotide polymorphism (SNP) discovery accomplished by resequencing DNA samples from Coriell Polymorphism Discovery Resource....
Arylamine compounds, such as sulfamethoxazole (SMX) and dapsone (DDS), are metabolized in epidermal keratinocytes to arylhydroxylamine metabolites that auto-oxidize arylnitroso derivatives, which turn bind cellular proteins can act antigens/immunogens. Previous studies have demonstrated neither cytochromes P450 nor cyclooxygenases mediate this bioactivation normal human (NHEKs). In investigation, we methimazole (MMZ), a prototypical substrate of the flavin-containing monooxygenases (FMOs),...
Abstract The state of polymerization actin and the organization filaments is widely believed to be related cellular transformation. Since intracellular monomer (G) filamentous (F) content reflects microfilament polymerization, we measured G/total ratio in primary cultures normal malignant human keratinocytes. In keratinocytes mean value this was 0·30 ± 0·03 (mean SE, n = 15), while basal cell carcinoma (BCC) it 0·49 ( 8) squamous (SCC) 0·5 0·07 4), indicating a 1·7‐fold increase cells. These...
Dexamethasone exerts a stimulatory effect of rapid-onset on the polymerization actin. This has been documented in human endometrial adenocarcinoma Ishikawa cells, resulting an acute, dose-dependent decrease G/total-actin ratio. In present study we completely characterized this fast and apparently nongenomic dexamethasone actin assembly. We followed morphological alterations cytoskeleton measured time-dependent dynamics both by ruling out any changes total cells measuring its transcript....
The flavin-containing monooxygenases (FMOs) are important for the disposition of a variety toxicants, therapeutics, and dietary components. Although FMO1 is dominant isoform in fetal liver adult kidney intestine despite up to 10-fold intersubject variation expression, paucity information available on <i>FMO1</i> genetic variability. To address this issue, 24 samples from Coriell DNA Polymorphism Discovery Resource Panel were sequenced revealing 10 common single nucleotide polymorphisms...
This report identifies a novel variant form of the inherited bleeding disorder Glanzmann thrombasthenia, exhibiting only mild in physically active individual. The platelets cannot aggregate ex vivo with physiologic agonists activation, although microfluidic analysis whole blood displays moderate platelet adhesion and aggregation consistent bleeding. Immunocytometry shows reduced expression αIIbβ3 on quiescent that spontaneously bind/store fibrinogen, activation-dependent antibodies...