A5072655119- Porphyrin Metabolism and Disorders
- Heme Oxygenase-1 and Carbon Monoxide
- Liver physiology and pathology
- Neonatal Health and Biochemistry
- Liver Disease Diagnosis and Treatment
- Folate and B Vitamins Research
- Metabolism and Genetic Disorders
- Alcohol Consumption and Health Effects
- Cell Adhesion Molecules Research
- Pancreatic function and diabetes
- Methemoglobinemia and Tumor Lysis Syndrome
- Organ Transplantation Techniques and Outcomes
- Proteoglycans and glycosaminoglycans research
- Fibroblast Growth Factor Research
- TGF-β signaling in diseases
- Erythrocyte Function and Pathophysiology
- Eicosanoids and Hypertension Pharmacology
- Drug-Induced Hepatotoxicity and Protection
- Pancreatic and Hepatic Oncology Research
- Drug Transport and Resistance Mechanisms
- Hepatitis C virus research
- Hepatitis B Virus Studies
- Liver Disease and Transplantation
- Reproductive Health and Technologies
- Neurological and metabolic disorders
University of California, San Francisco
2013-2023
Union of Concerned Scientists
2020
San Francisco General Hospital
1986-2007
Chinese University of Hong Kong
2006
University of Buenos Aires
2004
Chang Gung Memorial Hospital
2004
Maine Medical Center
2004
Fundación Ciencias Exactas y Naturales
2004
Memorial
2003
La Roche College
2003
Hepatic lipocytes were isolated from normal rat liver and established in culture. A virtually pure isolate was obtained by fractionating enzymatically digested on a discontinuous gradient of arabinogalactan. Isolated cells displayed prominent rough endoplasmic reticulum typical cytoplasmic droplets containing vitamin A. Lipocytes primary culture shown immunofluorescence to secrete collagen types I, III, IV also laminin. Immunoassay media showed that during the first week type I (72.1-86.2%...
The subendothelial space of normal rat liver contains the constituent proteins a basal lamina, as judged by immunohistochemical study tissue sections. However, it is unknown whether these constitute complex with effects on hepatocellular function. We have examined this question, using hepatocytes cultured substrata matrix model interaction between cells and lamina in vivo. In cultures type I collagen substratum, albumin secretion decreased progressively after 2 d. By contrast, when were...
Up-regulation of hepatic delta-aminolevulinic acid synthase 1 (ALAS1), with resultant accumulation (ALA) and porphobilinogen, is central to the pathogenesis acute attacks chronic symptoms in porphyria. Givosiran, an RNA interference therapy, inhibits ALAS1 expression.In this double-blind, placebo-controlled, phase 3 trial, we randomly assigned symptomatic patients porphyria receive either subcutaneous givosiran (2.5 mg per kilogram body weight) or placebo monthly for 6 months. The primary...
We have examined the cell-specific expression of two fibronectin isoforms, EIIIA and EIIIB, during experimental hepatic fibrosis induced by ligation biliary duct. AT mRNA level, EIIIB were undetectable in normal liver but expressed early injury, preceding fibrosis. The cellular sources these changes determined fractionating at various time points after bile duct into its constituent cell populations extracting RNA from fresh isolates. EIIIA-containing was sinusoidal endothelial cells...
Parenchymal cells from adult rat liver have been established in primary monolayer culture. Donor animals are subjected to a partial hepatectomy and, 4 days later, prepared by collagenase perfusion of the regenerated liver. The hepatic parenchymal cells, separated nonparenchymal material and suspended serum-free medium, placed plastic tissue culture dishes, where they form within 24 h. exhibit minimal mitotic activity demonstrate several major metabolic functions characteristic vivo; these...
Expression of the group cytokines known as transforming growth factor-beta (TGF-beta 1, -beta 2 and 3) is increased during liver regeneration induced by a 70% partial hepatectomy. The origin these changes was examined in purified isolates hepatocytes, sinusoidal endothelial cells, Kupffer cells (liver macrophages), lipocytes (Ito or stellate cells) from normal regenerating liver. In liver, TGF-beta 1 levels were relatively high cells. After hepatectomy, an early peak 3 present all four cell...
Progenitor ("oval") cell expansion accompanies many forms of liver injury, including alcohol toxicity and submassive parenchymal necrosis as well experimental injury models featuring blocked hepatocyte replication. Oval cells can potentially become either hepatocytes or biliary epithelial may be critical to regeneration, particularly when replication is impaired. The regulation oval proliferation incompletely understood. Herein we present evidence that a TNF family member called TWEAK...
This study examined the role of extracellular matrix in regulating phenotype hepatic lipocytes, major source liver. Lipocytes (Ito, stellate, or fat-storing cells) were purified from normal rat liver and established primary culture on either uncoated plastic, plastic coated with individual proteins, a complete gel matrix, basement membrane-like derived Engelbreth-Holm-Swarm (EHS) murine tumor. The ultrastructure lipocytes cultured resembled that cells liver, whereas had dispersed nuclear...
Erythropoietic protoporphyria is a severe photodermatosis that associated with acute phototoxicity. Patients this condition have excruciating pain and markedly reduced quality of life. We evaluated the safety efficacy an α-melanocyte-stimulating hormone analogue, afamelanotide, to decrease improve life.We conducted two multicenter, randomized, double-blind, placebo-controlled trials subcutaneous implants containing 16 mg afamelanotide. in European Union (74 patients) United States (94 were...
Induction of delta aminolevulinic acid synthase 1 (ALAS1) gene expression and accumulation neurotoxic intermediates result in neurovisceral attacks disease manifestations patients with acute intermittent porphyria, a rare inherited heme biosynthesis. Givosiran is an investigational RNA interference therapeutic agent that inhibits hepatic ALAS1 synthesis.
Background and Aims Acute hepatic porphyria comprises a group of rare genetic diseases caused by mutations in genes involved heme biosynthesis. Patients can experience acute neurovisceral attacks, debilitating chronic symptoms, long‐term complications. There is lack multinational, prospective data characterizing the disease current treatment practices severely affected patients. Approach Results EXPLORE prospective, natural history study activity clinical management patients with who...
Transforming growth factor β (TGF-β) is a well characterized cytokine that appears to play major role in directing the cellular response injury, driving fibrogenesis, and, thus, potentially underlying progression of chronic injury fibrosis. In this study, we report use novel TGF-β receptor antagonist block fibrogenesis induced by ligation common bile duct rats. The consisted chimeric IgG containing extracellular portion type II receptor. This “soluble receptor” was infused at time injury;...
The endothelins (ETs) form a group of three vasoactive peptides (ET-1, ET-2, and ET-3) for which two types cellular receptors have been identified, A B ET (ETA ETB receptors, respectively). To address possible targets ETs within the liver, we isolated four principal liver cell populations placed them in short-term primary culture. By ligand-binding assay mRNA levels, expression was greatest on hepatic lipocytes (Ito cells or fat-storing cells), are perisinusoidal exhibiting features smooth...
Acetoacetylated (AcAc) and acetylated (Ac) low density lipoproteins (LDL) are rapidly cleared from the plasma (t1/2 approximately equal to 1 min). Because macrophages, Kupffer cells, a lesser extent, endothelial cells metabolize these modified in vitro, it was of interest determine whether or macrophages could be responsible for vivo uptake lipoproteins. As previously reported, liver is predominant site AcAc LDL; however, we have found that spleen, bone marrow, adrenal, ovary also...
Hepatic parenchymal cells from adult rats, established in vitro as a monolayer, have been evaluated by electron microscopy. Within 24 h after the initial seeding, incubated were polygonal and close apposition with three to six neighboring cells. The ultrastructure of monolayer was examined at this time 3 10 days incubation. With exception few enlarged mitochondria, organelles both 1- 3-day indistinguishable quantitatively morphologically those found intact liver. After incubation, however,...
We report a proteinase that degrades basement-membrane (type IV) collagen and is produced by the liver. Its cellular source lipocytes (fat-storing or Ito cells). Lipocytes were isolated from normal rat liver established in primary culture. The cells synthesize secrete neutral proteinase, which gelatin-substrate gel electrophoresis filtration chromatography, has molecular mass of 65,000 D. enzyme secreted latent form activated p-aminophenylmercuric acetate but not trypsin. Enzyme activity...
<h3>Importance</h3> Autosomal recessive erythropoietic protoporphyria (EPP) and X-linked (XLP) are rare photodermatoses presenting with variable degrees of painful phototoxicity that markedly affects quality life. The clinical variability, determinants severity, genotype/phenotype correlations these diseases not well characterized. <h3>Objective</h3> To describe the baseline characteristics, genotypes, disease severity in a large patient cohort EPP or XLP. <h3>Design, Setting,...
Upregulation of hepatic delta-aminolevulinic acid synthase 1 with accumulation potentially toxic heme precursors and porphobilinogen is fundamental to the pathogenesis acute porphyria.evaluate long-term efficacy safety givosiran in porphyria.Interim analysis ongoing ENVISION study (NCT03338816), after all active patients completed their Month 24 visit. Patients porphyria (≥12 years) recurrent attacks received (2.5 mg/kg monthly) (n = 48) or placebo 46) for 6 months (double-blind period); 93...