A5064650178- Glycosylation and Glycoproteins Research
- Lysosomal Storage Disorders Research
- Carbohydrate Chemistry and Synthesis
- Functional Brain Connectivity Studies
- Metabolism and Genetic Disorders
- Cellular transport and secretion
- Neurogenesis and neuroplasticity mechanisms
- Mental Health Research Topics
- Advanced Neuroimaging Techniques and Applications
- Virus-based gene therapy research
- Lipid Membrane Structure and Behavior
- Glycogen Storage Diseases and Myoclonus
- Sphingolipid Metabolism and Signaling
- Bipolar Disorder and Treatment
- Erythrocyte Function and Pathophysiology
- Schizophrenia research and treatment
- Cancer, Hypoxia, and Metabolism
- RNA Interference and Gene Delivery
- Diet, Metabolism, and Disease
- Trypanosoma species research and implications
- Lipid metabolism and biosynthesis
- Proteoglycans and glycosaminoglycans research
- Caveolin-1 and cellular processes
- Enzyme Catalysis and Immobilization
- HIV Research and Treatment
Harvard University
2015-2024
Beth Israel Deaconess Medical Center
2015-2024
Hadassah Medical Center
2017-2024
McLean Hospital
2013-2024
Berenson Allen Center for Noninvasive Brain Stimulation
2022
Hindustan Aeronautics Limited (India)
2021
Brady (Norway)
2021
Lemuel Shattuck Hospital
2021
Massachusetts Mental Health Center
2013-2020
Massachusetts General Hospital
1949-2019
ContextFabry disease is a metabolic disorder without specific treatment, caused by deficiency of the lysosomal enzyme α-galactosidase A (α-gal A). Most patients experience debilitating neuropathic pain and premature mortality because renal failure, cardiovascular disease, or cerebrovascular disease.ObjectiveTo evaluate safety efficacy intravenous α-gal for Fabry disease.Design SettingDouble-blind placebo-controlled trial conducted from December 1998 to August 1999 at Clinical Research Center...
Functional activity of N -methyl- d -aspartate (NMDA) receptors requires both glutamate binding and the an endogenous coagonist that has been presumed to be glycine, although -serine is a more potent agonist. Localizations it biosynthetic enzyme serine racemase approximate distribution NMDA closely than glycine. We now show selective degradation with -amino acid oxidase greatly attenuates receptor-mediated neurotransmission as assessed by using whole-cell patch–clamp recordings or indirectly...
Although cyclin-dependent kinase 5 (Cdk5) is closely related to other kinases, its activity detected only in the postmitotic neurons. Cdk5 expression and are correlated with extent of differentiation neuronal cells developing brain. purified from nervous tissue phosphorylates cytoskeletal proteins including neurofilament microtubule-associated protein tau vitro. These findings indicate that may have unique functions cells, especially regulation phosphorylation molecules. We report here...
Fabry disease is an X-linked lysosomal storage caused by deficiency of alpha-galactosidase A that affects males and shows expression in heterozygotes. The characteristic progressive renal insufficiency, cardiac involvement, neuropathology usually are ascribed to globotriaosylceramide accumulation the endothelium. However, no direct correlation exists between lipid clinical manifestations, treatment patients with recombinant enzymes does not reverse several key signs despite clearance from We...
High levels of D-serine occur in mammalian brain, where it appears to be an endogenous ligand the glycine site N-methyl-D-aspartate receptors. In glial cultures rat cerebral cortex, is enriched type II astrocytes and released upon stimulation with agonists non-N-methyl-D-aspartate glutamate The high discrete areas brain imply existence a biosynthetic pathway. We have purified from soluble enzyme that catalyzes direct racemization L-serine D-serine. Purified serine racemase has molecular mass...
d -Serine is localized in mammalian brain to a discrete population of glial cells near NMDA receptors, suggesting that -serine an endogenous agonist the receptor-associated glycine site. To explore this possibility, we have compared immunohistochemical localizations -serine, glycine, and receptors rat brain. In telencephalon, concentrated protoplasmic astrocytes, which are abundant neuropil close vicinity receptor 2A/B subunits. Ultrastructural examination CA1 region hippocampus reveals...
The use of Moloney murine leukemia virus (Mo-MLV)-based vectors to deliver therapeutic genes into target cells is limited by their inability transduce nondividing cells. To test the capacity HIV-based cells, we have generated replication-defective HIV type 1 (HIV-1) reporter carrying neomycin phosphotransferase or mouse heat stable antigen, replacing HIV-1 sequences encoding gp160. These also harbor inactive vpr , vpu and nef coding regions. Pseudotyped particles either ecotropic amphotropic...
The interpretability of results in psychiatric neuroimaging is significantly limited by an overreliance on correlational relationships. Purely studies cannot alone determine whether behavior-imaging relationships are causal to illness, functionally compensatory processes, or purely epiphenomena. Negative symptoms (e.g., anhedonia, amotivation, and expressive deficits) refractory current medications among the foremost causes disability schizophrenia. authors used a two-step approach...
A sphingomyelin-cleaving enzyme has been found in rat liver tissue. The enzyme, originally present subcellular particulate fractions, could be released a soluble form by treatment with appropriate detergents and was partially purified conventional procedures. most highly preparations catalyzed the hydrolysis of sphingomyelin, whereas lecithin phosphatidylethanolamine were unaffected. products reaction identified as phosphorylcholine ceramide. Lecithin competitive inhibitor reaction.
Significance Historically, most research on the biological origins of psychiatric illness has focused individual diagnostic categories, studied in isolation. Mounting evidence indicates that nominally distinct diagnoses are not separated by clear neurobiological boundaries. Here, we derive functional connectomic signatures over 1,000 individuals, including patients presenting with different categories impairment (psychosis), clinical diagnoses, and severity as reflected treatment seeking....
ABSTRACT Previously we designed novel pseudotyped high-titer replication defective human immunodeficiency virus type 1 (HIV-1) vectors to deliver genes into nondividing cells (J. Reiser, G. Harmison, S. Kluepfel-Stahl, R. O. Brady, Karlsson, and M. Schubert, Proc. Natl. Acad. Sci. USA 93:15266–15271, 1996). Since then have made several improvements with respect the safety, flexibility, efficiency of vector system. A three-plasmid expression system is used generate HIV-1 particles by...
Background Fabry disease is an X-linked lysosomal deficiency of α-galactosidase A that results in cellular accumulation galacto-conjugates such as globotriosylceramide, particularly blood vessels. It associated with early-onset stroke and kidney heart failure. Methods Results Using [ 15 O] H 2 O PET, we found increased resting regional cerebral flow without evidence occlusive vasculopathy or hypoperfusion. Because nitric oxide known to play important role vascular tone reactivity, studied...
The IgM in three patients with paraproteinemia and peripheral neuropathy was shown to bind human myelin-associated glycoprotein (MAG) that had been purified homogeneity by gel filtration on Sepharose CL-6B. antigenic determinant reacting the from all carbohydrate part of MAG molecule. In addition, same bound a single ganglioside sciatic nerve. results indicate paraproteins these react is shared between nerve ganglioside.
Members of the N -methyl- d -aspartate (NMDA) class glutamate receptors (NMDARs) are critical for development, synaptic transmission, learning and memory; they targets pathological disorders in central nervous system. NMDARs phosphorylated by both serine/threonine tyrosine kinases. Here, we demonstrate that cyclin dependent kinase-5 (Cdk5) associates with phosphorylates NR2A subunits at Ser-1232 vitro intact cells. Moreover, show roscovitine, a selective Cdk5 inhibitor, blocks long-term...
NCTC 2071 cells are unable to synthesize the monosialoganglioside GM1. When grown in chemically defined medium these contained no detectable GM1 and did not accumulate 3': 5'-cyclic AMP response choleragen. Incubation of with [3H]GM1 permitted quantification ganglioside uptake which was dependent on time concentration medium. Responsiveness choleragen demonstrated binding as few 17,000 molecules per cell; a maximal observed 10(5) cell. With increasing cellular content GM1, rate rise...
The intracellular accumulation of unesterified cholesterol was examined during 24 h low density lipoprotein (LDL) uptake in normal and Niemann-Pick C fibroblasts by fluorescence microscopy with filipin staining immunocytochemistry. Perinuclear derived from filipin-sterol complexes observed both mutant cells 2 h. This perinuclear reached its peak at 6 Subsequent development the remaining 18 LDL incubation primarily limited to plasma membrane region cells. In contrast, developed a much more...
Fabry disease is an underdiagnosed, treatable, X-linked, multisystem disorder.To test the hypothesis that quality of life and sweating are decreased among pediatric patients with disease, compared control subjects, to provide quantitative natural history data novel clinical end points for therapeutic trials.Prospective, cross-sectional, observational study.Referral National Institutes Health.Twenty-five male children (mean age: 12.3 +/- 3.5 years) 21 age-matched subjects.Quality (measured...
Gangliosides inhibit 125I-labeled thyrotropin binding to the receptors on bovine thyroid plasma membranes, guinea pig retro-orbital tissue and human adipocyte membranes. This inhibition by gangliosides is critically altered number location of sialic acid residues within ganglioside structure, efficacy having following order: GD1b greater than GT1 GM1 GM2 = GM3 GD1a. The results from interaction gangliosides, rather membrane gangliosides. Fluorescence studies show that associated with a...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTHE SYNTHESIS OF MALONYL-C14 COENZYME AE. G. Trams and R. O. BradyCite this: J. Am. Chem. Soc. 1960, 82, 11, 2972–2973Publication Date (Print):June 1, 1960Publication History Published online1 May 2002Published inissue 1 June 1960https://pubs.acs.org/doi/10.1021/ja01496a080https://doi.org/10.1021/ja01496a080research-articleACS PublicationsRequest reuse permissionsArticle Views206Altmetric-Citations167LEARN ABOUT THESE METRICSArticle Views are the...