A5038621634- HIV/AIDS Research and Interventions
- T-cell and B-cell Immunology
- Cytokine Signaling Pathways and Interactions
- HIV, Drug Use, Sexual Risk
- Immune Response and Inflammation
- SARS-CoV-2 and COVID-19 Research
- Immune Cell Function and Interaction
- HIV Research and Treatment
- CRISPR and Genetic Engineering
- COVID-19 Clinical Research Studies
- Animal Genetics and Reproduction
- Viral Infectious Diseases and Gene Expression in Insects
- Dermatology and Skin Diseases
- Immunotherapy and Immune Responses
- Muscle Physiology and Disorders
- Long-Term Effects of COVID-19
- Monoclonal and Polyclonal Antibodies Research
- Connective Tissue Growth Factor Research
- Reproductive tract infections research
- Connective tissue disorders research
- Contact Dermatitis and Allergies
- Nuclear Receptors and Signaling
- SARS-CoV-2 detection and testing
- Psoriasis: Treatment and Pathogenesis
- Syphilis Diagnosis and Treatment
University of Washington
1995-2023
National Clinical Research
2023
Kenya Medical Research Institute
2022
Bristol-Myers Squibb (United States)
1995-1999
Bristol-Myers Squibb (Germany)
1996-1997
Antiretroviral preexposure prophylaxis is a promising approach for preventing human immunodeficiency virus type 1 (HIV-1) infection in heterosexual populations.We conducted randomized trial of oral antiretroviral therapy use as among HIV-1-serodiscordant couples from Kenya and Uganda. The HIV-1-seronegative partner each couple was randomly assigned to one three study regimens--once-daily tenofovir (TDF), combination tenofovir-emtricitabine (TDF-FTC), or matching placebo--and followed monthly...
Abstract Type III IFNs (IFN-λ/IL-28/29) are cytokines with type I IFN-like antiviral activities, which remain poorly characterized. We herein show that most cell types expressed both and after TLR stimulation or virus infection, whereas the ability of cells to respond IFN-λ was restricted a narrow subset cells, including plasmacytoid dendritic epithelial cells. To examine role IFN in defense, we generated IL-28Rα-deficient mice. These mice were indistinguishable from wild-type respect...
Background Antiretroviral-based interventions for HIV-1 prevention, including antiretroviral therapy (ART) to reduce the infectiousness of infected persons and pre-exposure prophylaxis (PrEP) susceptibility uninfected persons, showed high efficacy protection in randomized clinical trials. We conducted a prospective implementation study understand feasibility effectiveness these delivery settings. Methods Findings Between November 5, 2012, January 2015, we enrolled followed 1,013 heterosexual...
Members of the platelet-derived growth factor (PDGF) ligand family are known to play important roles in wound healing and fibrotic disease. We show that both transient stable expression PDGF-C results development liver fibrosis consisting deposition collagen a pericellular perivenular pattern resembles human alcoholic nonalcoholic fatty Fibrosis transgenic mice, as demonstrated by staining hydroxyproline content, is preceded activation proliferation hepatic stellate cells, shown collagen,...
Translational control is a major form of regulating gene expression during gametogenesis and early development in many organisms. We sought to determine whether the translational repression protamine 1 (Prm1) mRNA necessary for normal spermatid differentiation mice. To accomplish this we generated transgenic animals that carry Prm1 transgene lacking its 3' untranslated region. Premature translation caused precocious condensation nuclear DNA, abnormal head morphogenesis, incomplete processing...
Transgenic mice were generated using a purified 248-kb yeast artificial chromosome (YAC) bearing an intact 82-kb human beta-globin locus and 148 kb of flanking sequence. Seventeen F0 pups transgenic. RNase protection analysis RNA isolated from the blood 13 gamma- beta-globin-positive founders showed that only gene was expressed in adult founders. Studies F1 F2 fetuses demonstrated genes beta-locus YAC displayed proper developmental switches beta-like globin expression. Expression epsilon-...
Effective prevention against coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome 2 (SARS-CoV-2), is currently limited to nonpharmaceutical strategies. Laboratory and observational data suggested that hydroxychloroquine had biological activity SARS-CoV-2, potentially permitting its use for prevention.
<ns4:p><ns4:bold>Background</ns4:bold>: Pre-exposure prophylaxis (PrEP) can provide high protection against HIV infection and is a recommended intervention for HIV-negative persons with substantial risk. Demonstration projects conducted in diverse settings worldwide illustrate practical examples of how PrEP be delivered. This manuscript presents estimates effectiveness patterns use within two-year demonstration project members heterosexual serodiscordant couples East Africa.</ns4:p><ns4:p>...
Treatment options for outpatients with COVID-19 could reduce morbidity and prevent SARS-CoV-2 transmission.In this randomized, double-blind, three-arm (1:1:1) placebo-equivalent controlled trial conducted remotely throughout the United States, adult laboratory-confirmed infection were recruited. Participants randomly assigned to receive hydroxychloroquine (HCQ) (400 mg BID x1day, followed by 200 x9days) or without azithromycin (AZ) (500 mg, then 250 daily x4days) (ascorbic acid folic (AZ)),...
Introduction: Pre-exposure prophylaxis (PrEP) can provide high protection against HIV infection and is a recommended intervention for HIV-negative persons with substantial risk, such as individuals partner living HIV. Demonstration projects of PrEP have been conducted in diverse settings worldwide to illustrate practical examples how be delivered. Methods: We evaluated delivery partners within heterosexual serodiscordant couples an open-label demonstration project East Africa. The model...
Oncostatin M belongs to the subfamily of hematopoietin cytokines that binds a receptor complex containing gp130. To date, only human form oncostatin has been identified, and its evolutionary conservation is unresolved. We have isolated bovine gene whose open reading frame encodes precursor protein 58% identical M. A comparison amino acid sequences predicts significant similarity, including four-alpha-helical-bundle structure placement disulfide bridges. As with protein, specific receptors on...
Previous analysis of the muscle creatine kinase (MCK) gene indicated that control elements required for transcription in adult mouse differed from those cell culture, suggesting distinct modes regulation occur vivo. To examine this further, we measured activity MCK transgenes containing E-box and promoter deletions a variety striated muscles. Simultaneous mutation three E boxes 1,256-bp 5' region, which abolished cultures, had strikingly different effects mice. The mutations transgene...
Regulatory regions of the mouse muscle creatine kinase (MCK) gene, previously discovered by analysis in cultured cells, were analyzed transgenic mice. The 206-bp MCK enhancer at nt-1256 was required for high-level expression MCK-chloramphenicol acetyltransferase fusion genes skeletal and cardiac muscle; however, unlike its behavior cell culture, inclusion 1-kb region DNA between basal promoter produced a 100-fold increase activity. Analysis control elements also indicated major differences...
Corticotroph-derived glycoprotein hormone (CGH), also referred to as thyrostimulin, is a noncovalent heterodimer of alpha 2 (GPHA2) and beta 5 (GPHB5). Here, we demonstrate that both subunits CGH are expressed in the corticotroph cells human anterior pituitary, well skin, retina, testis. activates TSH receptor (TSHR); (125)I-CGH binding expressing TSHR saturable, specific, high affinity. In competition studies, unlabeled potent competitor for (125)I-TSH binding, whereas does not compete...
Certain human papillomaviruses (HPV) have been implicated in the etiology of cervical malignancies, and E7 E6 gene products HPV type 16 are frequently expressed these lesions. However, cytolytic T-lymphocyte (CTL)-mediated responses to rarely detectable patients with cancer. To examine whether T-cell response is deficient during HPV-induced transformation, we produced lines transgenic (Tg) mice that oncogenes keratinized epithelia. The developed severe hypertrophy all epithelia, but no...
Safer conception strategies minimize HIV risk during condomless sex to become pregnant. Gaps remain in understanding the acceptability, feasibility and choices HIV-serodiscordant couples make when multiple safer options are available.We conducted a pilot study of comprehensive package for with immediate fertility desires Kenya from March 2016 April 2018. The intervention included antiretroviral therapy (ART) HIV-positive partners, oral pre-exposure prophylaxis (PrEP) HIV-negative daily...
We characterized the distribution of CD40 and ligand (CD40-L) in adult developing murine thymus. Before birth, was almost exclusively localized to scattered foci medullary cells. By birth there a dramatic upregulation expression by cortical epithelial cells, which accompanied consolidation foci. CD40-L + thymocytes displayed location. Analysis mice deficient indicated that CD40-L/CD40 interactions were not required for development compartment. Overexpression targeted altered thymic...