A5030215961- Biomedical Research and Pathophysiology
- Amino Acid Enzymes and Metabolism
- Neonatal Health and Biochemistry
- Metabolism and Genetic Disorders
- Methemoglobinemia and Tumor Lysis Syndrome
- Analytical Chemistry and Chromatography
- Diet and metabolism studies
- Biotechnology and Related Fields
- Biotin and Related Studies
- Advanced Chemical Sensor Technologies
- Mitochondrial Function and Pathology
- Erythrocyte Function and Pathophysiology
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Biochemical and Molecular Research
- Porphyrin Metabolism and Disorders
- Folate and B Vitamins Research
- Genomics and Rare Diseases
- Pharmaceutical Economics and Policy
- Mass Spectrometry Techniques and Applications
- Biochemical Acid Research Studies
- Metabolomics and Mass Spectrometry Studies
- Pharmacological Effects and Toxicity Studies
- Clinical Nutrition and Gastroenterology
- Intellectual Property and Patents
- Cellular transport and secretion
University of Michigan
2010-2023
Pediatrics and Genetics
1984-2022
Michigan United
1999-2022
Michigan Medicine
2022
Tulane University
2000-2005
Louisiana State Department of Health and Hospitals
2005
National Cancer Institute
2003
Mashhad University of Medical Sciences
2003
Tulane Medical Center
2002
University of New Orleans
2000
Mutations in SCN2A, a gene encoding the voltage-gated sodium channel Nav1.2, have been associated with spectrum of epilepsies and neurodevelopmental disorders. Here, we report phenotypes 71 patients review 130 previously reported patients. We found that (i) encephalopathies infantile/childhood onset (≥3 months age) occur almost as often those an early infantile (<3 months), are thus more frequent than reported; (ii) distinct can be seen within late group, including myoclonic-atonic epilepsy...
Certain aminothiols rapidly deplete cultured cystinotic skin fibroblasts of their abnormally high free (nonprotein) cystine pool. The content these cells if reduced by over 90% in 1 h with 0.1 mM cysteamine. This is more rapid than previously known methods removing from fibroblasts. disulfide, cystamine, also able to cystine. A patient nephropathic cystinosis and end-stage renal disease was treated cysteamine, both intravenously orally. Both administration lowered the patient's peripheral...
We treated 93 children with nephropathic cystinosis oral cysteamine (mean dose, 51.3 mg per kilogram of body weight day) for up to 73 months. This agent is known be effective in depleting cells cystine. In our study, the mean cystine depletion from leukocytes was 82 percent. A historical control group 55 received either ascorbic acid (27 children) or placebo (28). At age six, 2 17 controls had a serum creatinine level less than 1.0 deciliter, as compared 27 patients at least one year (odds...
The discovery of a trans-stimulation property associated with lysine exodus from lysosomes human fibroblasts has enabled us to characterize system mediating the transport cationic amino acids across lysosomal membrane fibroblasts. arginine, lysine, ornithine, diaminobutyrate, histidine, 2-aminoethylcysteine, and mixed disulfide cysteine cysteamine all caused radiolabeled fraction at pH 6.5. In contrast, neutral acidic did not affect rate exodus. trans-Stimulation was observed over range 5.5...
Human phagocytes can be triggered to generate large quantities of long-lived nitrogen-chlorine derivatives. This class oxidants detected as early 5 min after the addition phorbol myristate acetate or opsonized zymosan particles. Unlike all other oxygen metabolites known generated by phagocytes, compounds readily in cell supernatants 90 stimulation. The generation these is linear with neutrophil concentration, favored at alkaline pH, and inhibited supraphysiologic concentrations iodide...
Nephropathic cystinosis is a lethal disorder of lysosomal cystine storage due to defective transport. How causes this multisystemic culminating in end-stage renal disease not known, because the isolated from cellular metabolism by membrane. It here reported that both normal and nephropathic cystinotic fibroblasts cultured proximal tubule epithelial cells, increased an rate apoptosis. In fibroblasts, apoptosis 14.8% after exposure TNF-alpha versus 7.8% control fibroblasts. Anti-Fas antibodies...
Lysosomes constitute only 4% of the intracellular volume a normal human fibroblast. When fibroblasts are incubated for 2-5 min with 20 microM [35S]cystine in Krebs-Ringer phosphate solution at pH 7.4, minimum 50-60% total radioactivity taken up by cells is found sequestered into lysosomal compartment form cysteine. A transport system, highly specific cysteine, appears to facilitate this rapid cysteine sequestration. Time courses [35S]cysteine uptake isolated, Percoll-purified fibroblast...
AN increasing number of patients have been diagnosed as having biotin-responsive multiple carboxylase deficiency.1 2 3 4 5 6 7 8 This genetic disorder involves defects in the metabolism biotin and produces deficiencies at least three biotin-containing carboxylases: propionyl-CoA (PCC), 3-methylcrotonyl-CoA (MCC), pyruvate (PC). All responded to oral administration 10 mg or more per day, with normalization clinical biochemical abnormalities.There appear be two forms disorder: a neonatal form...
The purpose of this report was to provide detailed information on the safety and feasibility surgical procedures associated with first ex vivo liver-directed gene therapy trial for treatment homozygous familial hypercholesterolemia (FH).Familial is an autosomal dominant disease in which encoding low density lipoprotein receptor defective. Patients mutation have extraordinarily high levels cholesterol accelerated atherosclerosis die prematurely myocardial infarction. concept based...
Familial hypercholesterolemia (FH) is an autosomal dominant disorder caused by a deficiency in the receptor that clears low density lipoprotein (LDL) from serum (reviewed Ref. 1 and 2). Patients with one abnormal LDL allele have moderate elevations plasma suffer premature coronary artery disease (CAD). Approximately 5% of all patients under 45 who had myocardial infarction carry this trait. two genes (homozygous deficient patients) severe life-threatening childhood. Strategies for treating...
Cystinosis is a rare genetic disease characterized by defective lysosomal cystine transport and increased cystine. How causes the lethal nephropathic phenotype unknown. It was shown recently that cultured fibroblasts renal proximal tubule epithelial cells whose lysosomes are cystine-loaded display two-fold or greater increase in apoptosis after both intrinsic extrinsic stimuli. The mechanism for Protein kinase Cdelta (PKCdelta) proapoptotic protein has been vitro to be activated via...
Cysteamine (2-aminoethanethiol) has been given orally to 19 patients with néphropathie cystinosis for periods of 8-24 months in doses ranging from 50 70 mg base/kg/day. Adverse reactions were noted 3 early the study when a rapidly increasing dosage schedule was followed. The included hyperthermia, lethargy and rash. These not seen started on very low which increased gradually at 3-week intervals level depleted leukocytes about 90% their free cystine. All three resolved within 24 h cessation...
Incubation of normal human skin fibroblasts or derived from patients with erythrocyte deficiency gamma-glutamylcysteine synthetase (gamma-glutamylcysteine synthetase-deficient) in culture medium containing L-[35S]cystine resulted incorporation radioactivity into protein, cysteine, and glutathione, gamma-Glutamylcysteine synthetase-deficient synthesized glutathione [35S]cystine at 30% the rate cells contained amount glutathione. Cystinotic incorporated large intracellular cystine pool not...
Analog inhibition studies of the uptake proline, serine, and threonine into human fibroblast lysosomes, purified on Percoll gradients, reveal presence three new transport systems. These systems fail to show Na+ requirement usual for plasma membrane. Proline lysosomes occurs mainly by two routes: a predominant route half-saturating at 0.01 mM, lower-affinity route, 0.07 mM. The latter so far appears specific L-proline its 3,4-dehydro derivative. high affinity has broad scope, recognizing...
Lysosomes contain enzymatic activities capable of degrading nucleic acids to their constituent nucleosides, but the manner by which these degradation products are released from lysosome is unknown. To investigate this process, human fibroblast lysosomes, purified on Percoll density gradients, were incubated with [3H]adenosine at pH 7.0, and amount adenosine taken up lysosomes was measured. Adenosine uptake attained a steady state 12 min 37 degrees C unaffected presence 2 mM MgATP or changes...