Roscoe O. Brady

Skin-impedance in Fabry Disease: A prospective, controlled, non-randomized clinical study (2008)

Gupta, Surya N, Ries, Markus, Murray, Gary J, Quirk, Jane M, Brady, Roscoe O, Lidicker, Jeffrey R, ...

Abstract Background We previously demonstrated improved sweating after enzyme replacement therapy (ERT) in Fabry disease using the thermo-regularity sweat and quantitative sudomotor axon reflex...

Liposomal vaccines with conformation-specific amyloid peptide antigens define immune response and efficacy in APP transgenic mice (2007)

Hickman, David T, Pihlgren, Maria, Chuard, Nathalie, Giriens, Valérie, Meerschman, Carine, ...

We investigated the therapeutic effects of two different versions of Abeta(1-15 (16)) liposome-based vaccines. Inoculation of APP-V717IxPS-1 (APPxPS-1) double-transgenic mice with tetra-palmitoylated...

Long-term therapy with agalsidase alfa for Fabry disease: safety and effects on renal function in a home infusion setting (2006)

Schiffmann, Raphael, Ries, Markus, Timmons, Margaret, Flaherty, John T., Brady, Roscoe O.

Background. Fabry disease is an X-linked disorder of glycosphingolipid catabolism that is the result of an intracellular deficiency in the lysosomal enzyme α-galactosidase A (α-Gal A). This...

Long-term therapy with agalsidase alfa for Fabry disease: safety and effects on renal function in a home infusion setting (2005)

Schiffmann, Raphael, Ries, Markus, Timmons, Margaret, Flaherty, John T., Brady, Roscoe O.

Background. Fabry disease is an X-linked disorder of glycosphingolipid catabolism that is the result of an intracellular deficiency in the lysosomal enzyme α-galactosidase A (α-Gal A). This...

Long-term therapy with agalsidase alfa for Fabry disease: safety and effects on renal function in a home infusion setting (2005)

Schiffmann, Raphael, Ries, Markus, Timmons, Margaret, Flaherty, John T., Brady, Roscoe O.

Background. Fabry disease is an X-linked disorder of glycosphingolipid catabolism that is the result of an intracellular deficiency in the lysosomal enzyme α-galactosidase A (α-Gal A). This...

Lactosylceramide galactosidase: Comparison with other sphingolipid hydrolases in developing rat brain (1969)

Radin, Norman S., Hof, Liselotte, Bradley, Roy M., Brady, Roscoe O.

Four enzyme assays were carried out with brains from rats of age 4 days to about 320 days. The enzymes were acid hydrolases: lactosylceramide galactosidases, galactosylphenol galactosidase,...

Purification of serine racemase: Biosynthesis of the neuromodulator d-serine

Wolosker, Herman, Sheth, Kevin N., Takahashi, Masaaki, Mothet, Jean-Pierre, Brady, Roscoe O., Ferris, Christopher D., ...

High levels of d-serine occur in mammalian brain, where it appears to be an endogenous ligand of the glycine site of N-methyl-d-aspartate receptors. In glial cultures of rat cerebral cortex, d-serine...

Niemann-Pick C1 protein: Obligatory roles for N-terminal domains and lysosomal targeting in cholesterol mobilization

Watari, Hidemichi, Blanchette-Mackie, E. Joan, Dwyer, Nancy K., Glick, Jane M., Patel, Shutish, Neufeld, Edward B., ...

Niemann-Pick type C (NPC) disease is an inherited lipid storage disorder that affects the viscera and central nervous system. A characteristic feature of NPC cells is the lysosomal accumulation of...

Localization of Niemann–Pick C1 protein in astrocytes: Implications for neuronal degeneration in Niemann– Pick type C disease

Patel, Shutish C., Suresh, Sundar, Kumar, Ujendra, Hu, C. Y., Cooney, Adele, Blanchette-Mackie, E. Joan, ...

Niemann–Pick type C disease (NP-C) is an inherited neurovisceral lipid storage disorder characterized by progressive neurodegeneration. Most cases of NP-C result from inactivating mutations of...

Long-term enzyme correction and lipid reduction in multiple organs of primary and secondary transplanted Fabry mice receiving transduced bone marrow cells

Takenaka, Toshihiro, Murray, Gary J., Qin, Gangjian, Quirk, Jane M., Ohshima, Toshio, Qasba, Pankaj, ...

Fabry disease is a compelling target for gene therapy as a treatment strategy. A deficiency in the lysosomal hydrolase α-galactosidase A (α-gal A; EC 3.2.1.22) leads to impaired catabolism of...

Intercellular delivery of a herpes simplex virus VP22 fusion protein from cells infected with lentiviral vectors

Lai, Zhennan, Han, Ina, Zirzow, Gregory, Brady, Roscoe O., Reiser, Jakob

Effective gene therapy depends on the efficient transfer of therapeutic genes and their protein products to target cells. Lentiviral vectors appear promising for virus-mediated gene delivery and...

Mucolipidosis IV consists of one complementation group

Goldin, Ehud, Cooney, Adele, Kaneski, Christine R., Brady, Roscoe O., Schiffmann, Raphael

Mucolipidosis IV (MLIV) is an autosomal recessive disorder of unknown etiology characterized by severe visual impairment and psychomotor retardation. Recently, there has been considerable interest in...

d-Serine is an endogenous ligand for the glycine site of the N-methyl-d-aspartate receptor

Mothet, Jean-Pierre, Parent, Angèle T., Wolosker, Herman, Brady, Roscoe O., Linden, David J., Ferris, Christopher D., ...

Functional activity of N-methyl-d-aspartate (NMDA) receptors requires both glutamate binding and the binding of an endogenous coagonist that has been presumed to be glycine, although d-serine is a...

Constitutive achlorhydria in mucolipidosis type IV

Schiffmann, Raphael, Dwyer, Nancy K., Lubensky, Irina A., Tsokos, Maria, Sutliff, Vincent E., Latimer, John S., ...

Mucolipidosis type IV is an autosomal recessive lysosomal storage disease of unknown etiology that causes severe neurological and ophthalmological abnormalities. In an attempt to obtain insight into...

α-Galactosidase A deficient mice: A model of Fabry disease

Ohshima, Toshio, Murray, Gary J., Swaim, William D., Longenecker, Glenn, Quirk, Jane M., Cardarelli, Carol O., ...

Fabry disease is an X-linked inherited metabolic disorder that is caused by a deficiency of α-galactosidase A (α-Gal A). Progressive deposition of neutral glycosphingolipids that have terminal...

The neutral glycosphingolipid globotriaosylceramide promotes fusion mediated by a CD4-dependent CXCR4-utilizing HIV type 1 envelope glycoprotein

Puri, Anu, Hug, Peter, Jernigan, Kristine, Barchi, Joseph, Kim, Hee-Yong, Hamilton, Jillon, ...

Previously, we showed that the addition of human erythrocyte glycosphingolipids (GSLs) to nonhuman CD4+ or GSL-depleted human CD4+ cells rendered those cells susceptible to HIV-1 envelope...

Aging accentuates and bone marrow transplantation ameliorates metabolic defects in Fabry disease mice

Ohshima, Toshio, Schiffmann, Raphael, Murray, Gary J., Kopp, Jeffrey, Quirk, Jane M., Stahl, Stefanie, ...

Fabry disease is an X-linked metabolic disorder caused by a deficiency of α-galactosidase A (α-Gal A). The enzyme defect leads to the systemic accumulation of glycosphingolipids with α-galactosyl...

Adeno-associated viral vector-mediated gene transfer results in long-term enzymatic and functional correction in multiple organs of Fabry mice

Jung, Sung-Chul, Han, Ina P., Limaye, Advait, Xu, Ruian, Gelderman, Monique P., Zerfas, Patricia, ...

Fabry disease is a lysosomal storage disorder caused by a deficiency of the lysosomal enzyme α-galactosidase A (α-gal A). This enzyme deficiency leads to impaired catabolism of...

Synergistic contributions of cyclin-dependant kinase 5/p35 and Reelin/Dab1 to the positioning of cortical neurons in the developing mouse brain

Ohshima, Toshio, Ogawa, Masaharu, Hirasawa, Motoyuki, Longenecker, Glenn, Ishiguro, Koichi, ...

Cyclin-dependent kinase (Cdk) 5 is a unique member of the Cdk family, because Cdk5 kinase activity is detected only in the nervous tissue. Two neuron-specific activating subunits of Cdk5, p35 and...

Preselective gene therapy for Fabry disease

Qin, Gangjian, Takenaka, Toshihiro, Telsch, Kimberly, Kelley, Leslie, Howard, Tazuko, Levade, Thierry, ...

Fabry disease is a lipid storage disorder resulting from mutations in the gene encoding the enzyme α-galactosidase A (α-gal A; EC 3.2.1.22). We previously have demonstrated long-term α-gal A...

Regulation of NMDA receptors by cyclin-dependent kinase-5

Li, Bing-Sheng, Sun, Miao-Kun, Zhang, Lei, Takahashi, Satoru, Ma, Wu, Vinade, Lucia, ...

Members of the N-methyl-d-aspartate (NMDA) class of glutamate receptors (NMDARs) are critical for development, synaptic transmission, learning and memory; they are targets of pathological disorders...

High-Titer Human Immunodeficiency Virus Type 1-Based Vector Systems for Gene Delivery into Nondividing Cells

Mochizuki, Hideki, Schwartz, Joan P., Tanaka, Koichi, Brady, Roscoe O., Reiser, Jakob

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....

Development of Multigene and Regulated Lentivirus Vectors

Reiser, Jakob, Lai, Zhennan, Zhang, Xian-Yang, Brady, Roscoe O.

Previously we described safe and efficient three-component human immunodeficiency virus type 1 (HIV-1)-based gene transfer systems for delivery of genes into nondividing cells (H. Mochizuki, J. P....

Design of an HIV-1 lentiviral-based gene-trap vector to detect developmentally regulated genes in mammalian cells

Lai, Zhennan, Han, Ina, Park, Misun, Brady, Roscoe O.

The recent development of HIV-1 lentiviral vectors is especially useful for gene transfer because they achieve efficient integration into nondividing cell genomes and successful long-term expression...

Long-term correction of globotriaosylceramide storage in Fabry mice by recombinant adeno-associated virus-mediated gene transfer

Park, Jinhee, Murray, Gary J., Limaye, Advait, Quirk, Jane M., Gelderman, Monique P., Brady, Roscoe O., ...

Fabry disease is an X-linked recessive inborn metabolic disorder characterized by systemic and vascular accumulation of globotriaosylceramide (Gb3) caused by a deficiency of the lysosomal enzyme...

GANGLIOSIDES IN DNA VIRUS-TRANSFORMED AND SPONTANEOUSLY TRANSFORMED TUMORIGENIC MOUSE CELL LINES

Mora, Peter T., Brady, Roscoe O., Bradley, Roy M., McFarland, Vivian W.

In mouse cell lines transformed by SV40 virus, a decrease was observed in the higher ganglioside homologues disialo-ceramidetetrahexoside and monosialo-ceramidetetrahexoside. Such change was observed...

Enzymatic Block in the Synthesis of Gangliosides in DNA Virus-Transformed Tumorigenic Mouse Cell Lines

Cumar, Federico A., Brady, Roscoe O., Kolodny, Edwin H., McFarland, Vivian W., Mora, Peter T.

The ganglioside pattern of both SV40- and polyoma virus-transformed mouse cell lines differs from that of the parent cell lines or of cell lines that have transformed spontaneously in tissue culture....

The metabolism of Tay-Sachs ganglioside: catabolic studies with lysosomal enzymes from normal and Tay-Sachs brain tissue

Tallman, John F., Johnson, William G., Brady, Roscoe O.

The catabolism of Tay-Sachs ganglioside, N-acetylgalactosaminyl- (N-acetylneuraminosyl) -galactosylglucosylceramide, has been studied in lysosomal preparations from normal human brain and brain...

Reduction of globotriaosylceramide in Fabry disease mice by substrate deprivation

Abe, Akira, Gregory, Susan, Lee, Lihsueh, Killen, Paul D., Brady, Roscoe O., Kulkarni, Ashok, ...

We used a potent inhibitor of glucosylceramide synthase to test whether substrate deprivation could lower globotriaosylceramide levels in α-galactosidase A (α-gal A) knockout mice, a model of Fabry...

Chemical chaperone therapy for brain pathology in GM1-gangliosidosis

Matsuda, Junichiro, Suzuki, Osamu, Oshima, Akihiro, Yamamoto, Yoshie, Noguchi, Akira, Takimoto, Kazuhiro, ...

We synthesized a galactose derivative, N-octyl-4-epi-β-valienamine (NOEV), for a molecular therapy (chemical chaperone therapy) of a human neurogenetic disease, β-galactosidosis (GM1-gangliosidosis...

Selective Effects of Glucocerebroside (Gaucher's Storage Material) on Macrophage Cultures

Gery, Igal, Zigler, J. Samuel, Brady, Roscoe O., Barranger, John A.

Although the enzymatic lesion in Gaucher's disease is well established, little is known concerning the pathogenic mechanisms involved in the clinical manifestations of the disease. In order to obtain...

Selective hepatic uptake of human β-hexosaminidase A by a specific glycoprotein recognition system on sinusoidal cells

Steer, Clifford J., Kusiak, John W., Brady, Roscoe O., Jones, E. Anthony

Intravenously administered 125I-labeled human β-hexosaminidase A (β-N-acetylglucosaminidase; 2-acetamido-2-deoxy-β-D-glucoside acetamidodeoxyglucohydrolase, EC 3.2.1.30) was rapidly cleared from...

Absence of a Specific Ganglioside Galactosyltransferase in Mouse Cells Transformed by Murine Sarcoma Virus

Fishman, Peter H., Brady, Roscoe O., Bradley, Roy M., Aaronson, Stuart A., Todaro, George J.

The ganglioside composition of a nonproducer subclone (derived from BALB/c 3T3 mouseembryo cells) transformed by Kirsten murine sarcoma virus was drastically altered compared to the nontransformed...

Perinatal abrogation of Cdk5 expression in brain results in neuronal migration defects

Hirasawa, Motoyuki, Ohshima, Toshio, Takahashi, Satoru, Longenecker, Glenn, Honjo, Yasuyuki, ...

Cyclin-dependent kinase 5 (Cdk5) is essential for the proper development of the CNS, as is evident from the perinatal lethality of conventional Cdk5 knockout (Cdk5-/-) mice. Cdk5 is also implicated...

Interaction of human chorionic gonadotropin with membrane components of rat testes

Pacuszka, Tadeusz, Osborne, James C., Brady, Roscoe O., Fishman, Peter H.

Previous studies demonstrating that gangliosides interacted with thyrotropin and human chorionic gonadotropin (hCG) suggested that gangliosides participate in the transduction of the hormonal message...

Bioluminescent imaging of a marking transgene and correction of Fabry mice by neonatal injection of recombinant lentiviral vectors

Yoshimitsu, Makoto, Sato, Takeya, Tao, Kesheng, Walia, Jagdeep S., Rasaiah, Vanessa I., Sleep, Gillian T., ...

Successful therapy for many inherited disorders could be improved if the intervention were initiated early. This is especially true for lysosomal storage disorders. Earlier intervention may allow...

Increased activity of cyclin-dependent kinase 5 leads to attenuation of cocaine-mediated dopamine signaling

Takahashi, Satoru, Ohshima, Toshio, Cho, Andrew, Sreenath, Taduru, Iadarola, Michael J., Pant, Harish C., ...

Cocaine, a drug of abuse, increases synaptic dopamine levels in the striatum by blocking dopamine reuptake at axon terminals. Cyclin-dependent kinase 5 (Cdk5) and its activator p35, proteins involved...

Cyclin-dependent kinase 5 activity regulates pain signaling

Pareek, Tej K., Keller, Jason, Kesavapany, Sashi, Pant, Harish C., Iadarola, Michael J., Brady, Roscoe O., ...

Several molecules and cellular pathways have been implicated in nociceptive signaling, but their precise molecular mechanisms have not been clearly defined. Cyclin-dependent kinase 5 (Cdk5) is a...

A multifunctional cytoprotective agent that reduces neurodegeneration after ischemia

Jiang, Zhi-Gang, Lu, X.-C. May, Nelson, Valery, Yang, Xiaofang, Pan, Weiying, Chen, Ren-wu, ...

Cellular and molecular pathways underlying ischemic neurotoxicity are multifaceted and complex. Although many potentially neuroprotective agents have been investigated, the simplicity of their...

Purification of serine racemase: Biosynthesis of the neuromodulator d-serine

Wolosker, Herman, Sheth, Kevin N., Takahashi, Masaaki, Mothet, Jean-Pierre, Brady, Roscoe O., Ferris, Christopher D., ...

High levels of d-serine occur in mammalian brain, where it appears to be an endogenous ligand of the glycine site of N-methyl-d-aspartate receptors. In glial cultures of rat cerebral cortex, d-serine...

Niemann-Pick C1 protein: Obligatory roles for N-terminal domains and lysosomal targeting in cholesterol mobilization

Watari, Hidemichi, Blanchette-Mackie, E. Joan, Dwyer, Nancy K., Glick, Jane M., Patel, Shutish, Neufeld, Edward B., ...

Niemann-Pick type C (NPC) disease is an inherited lipid storage disorder that affects the viscera and central nervous system. A characteristic feature of NPC cells is the lysosomal accumulation of...

Localization of Niemann–Pick C1 protein in astrocytes: Implications for neuronal degeneration in Niemann– Pick type C disease

Patel, Shutish C., Suresh, Sundar, Kumar, Ujendra, Hu, C. Y., Cooney, Adele, Blanchette-Mackie, E. Joan, ...

Niemann–Pick type C disease (NP-C) is an inherited neurovisceral lipid storage disorder characterized by progressive neurodegeneration. Most cases of NP-C result from inactivating mutations of...

Long-term enzyme correction and lipid reduction in multiple organs of primary and secondary transplanted Fabry mice receiving transduced bone marrow cells

Takenaka, Toshihiro, Murray, Gary J., Qin, Gangjian, Quirk, Jane M., Ohshima, Toshio, Qasba, Pankaj, ...

Fabry disease is a compelling target for gene therapy as a treatment strategy. A deficiency in the lysosomal hydrolase α-galactosidase A (α-gal A; EC 3.2.1.22) leads to impaired catabolism of...

Intercellular delivery of a herpes simplex virus VP22 fusion protein from cells infected with lentiviral vectors

Lai, Zhennan, Han, Ina, Zirzow, Gregory, Brady, Roscoe O., Reiser, Jakob

Effective gene therapy depends on the efficient transfer of therapeutic genes and their protein products to target cells. Lentiviral vectors appear promising for virus-mediated gene delivery and...

Mucolipidosis IV consists of one complementation group

Goldin, Ehud, Cooney, Adele, Kaneski, Christine R., Brady, Roscoe O., Schiffmann, Raphael

Mucolipidosis IV (MLIV) is an autosomal recessive disorder of unknown etiology characterized by severe visual impairment and psychomotor retardation. Recently, there has been considerable interest in...

d-Serine is an endogenous ligand for the glycine site of the N-methyl-d-aspartate receptor

Mothet, Jean-Pierre, Parent, Angèle T., Wolosker, Herman, Brady, Roscoe O., Linden, David J., Ferris, Christopher D., ...

Functional activity of N-methyl-d-aspartate (NMDA) receptors requires both glutamate binding and the binding of an endogenous coagonist that has been presumed to be glycine, although d-serine is a...

Constitutive achlorhydria in mucolipidosis type IV

Schiffmann, Raphael, Dwyer, Nancy K., Lubensky, Irina A., Tsokos, Maria, Sutliff, Vincent E., Latimer, John S., ...

Mucolipidosis type IV is an autosomal recessive lysosomal storage disease of unknown etiology that causes severe neurological and ophthalmological abnormalities. In an attempt to obtain insight into...

α-Galactosidase A deficient mice: A model of Fabry disease

Ohshima, Toshio, Murray, Gary J., Swaim, William D., Longenecker, Glenn, Quirk, Jane M., Cardarelli, Carol O., ...

Fabry disease is an X-linked inherited metabolic disorder that is caused by a deficiency of α-galactosidase A (α-Gal A). Progressive deposition of neutral glycosphingolipids that have terminal...

The neutral glycosphingolipid globotriaosylceramide promotes fusion mediated by a CD4-dependent CXCR4-utilizing HIV type 1 envelope glycoprotein

Puri, Anu, Hug, Peter, Jernigan, Kristine, Barchi, Joseph, Kim, Hee-Yong, Hamilton, Jillon, ...

Previously, we showed that the addition of human erythrocyte glycosphingolipids (GSLs) to nonhuman CD4+ or GSL-depleted human CD4+ cells rendered those cells susceptible to HIV-1 envelope...

Aging accentuates and bone marrow transplantation ameliorates metabolic defects in Fabry disease mice

Ohshima, Toshio, Schiffmann, Raphael, Murray, Gary J., Kopp, Jeffrey, Quirk, Jane M., Stahl, Stefanie, ...

Fabry disease is an X-linked metabolic disorder caused by a deficiency of α-galactosidase A (α-Gal A). The enzyme defect leads to the systemic accumulation of glycosphingolipids with α-galactosyl...

Adeno-associated viral vector-mediated gene transfer results in long-term enzymatic and functional correction in multiple organs of Fabry mice

Jung, Sung-Chul, Han, Ina P., Limaye, Advait, Xu, Ruian, Gelderman, Monique P., Zerfas, Patricia, ...

Fabry disease is a lysosomal storage disorder caused by a deficiency of the lysosomal enzyme α-galactosidase A (α-gal A). This enzyme deficiency leads to impaired catabolism of...

Synergistic contributions of cyclin-dependant kinase 5/p35 and Reelin/Dab1 to the positioning of cortical neurons in the developing mouse brain

Ohshima, Toshio, Ogawa, Masaharu, Hirasawa, Motoyuki, Longenecker, Glenn, Ishiguro, Koichi, ...

Cyclin-dependent kinase (Cdk) 5 is a unique member of the Cdk family, because Cdk5 kinase activity is detected only in the nervous tissue. Two neuron-specific activating subunits of Cdk5, p35 and...

Preselective gene therapy for Fabry disease

Qin, Gangjian, Takenaka, Toshihiro, Telsch, Kimberly, Kelley, Leslie, Howard, Tazuko, Levade, Thierry, ...

Fabry disease is a lipid storage disorder resulting from mutations in the gene encoding the enzyme α-galactosidase A (α-gal A; EC 3.2.1.22). We previously have demonstrated long-term α-gal A...

Regulation of NMDA receptors by cyclin-dependent kinase-5

Li, Bing-Sheng, Sun, Miao-Kun, Zhang, Lei, Takahashi, Satoru, Ma, Wu, Vinade, Lucia, ...

Members of the N-methyl-d-aspartate (NMDA) class of glutamate receptors (NMDARs) are critical for development, synaptic transmission, learning and memory; they are targets of pathological disorders...

High-Titer Human Immunodeficiency Virus Type 1-Based Vector Systems for Gene Delivery into Nondividing Cells

Mochizuki, Hideki, Schwartz, Joan P., Tanaka, Koichi, Brady, Roscoe O., Reiser, Jakob

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....

Development of Multigene and Regulated Lentivirus Vectors

Reiser, Jakob, Lai, Zhennan, Zhang, Xian-Yang, Brady, Roscoe O.

Previously we described safe and efficient three-component human immunodeficiency virus type 1 (HIV-1)-based gene transfer systems for delivery of genes into nondividing cells (H. Mochizuki, J. P....

Design of an HIV-1 lentiviral-based gene-trap vector to detect developmentally regulated genes in mammalian cells

Lai, Zhennan, Han, Ina, Park, Misun, Brady, Roscoe O.

The recent development of HIV-1 lentiviral vectors is especially useful for gene transfer because they achieve efficient integration into nondividing cell genomes and successful long-term expression...

Long-term correction of globotriaosylceramide storage in Fabry mice by recombinant adeno-associated virus-mediated gene transfer

Park, Jinhee, Murray, Gary J., Limaye, Advait, Quirk, Jane M., Gelderman, Monique P., Brady, Roscoe O., ...

Fabry disease is an X-linked recessive inborn metabolic disorder characterized by systemic and vascular accumulation of globotriaosylceramide (Gb3) caused by a deficiency of the lysosomal enzyme...

GANGLIOSIDES IN DNA VIRUS-TRANSFORMED AND SPONTANEOUSLY TRANSFORMED TUMORIGENIC MOUSE CELL LINES

Mora, Peter T., Brady, Roscoe O., Bradley, Roy M., McFarland, Vivian W.

In mouse cell lines transformed by SV40 virus, a decrease was observed in the higher ganglioside homologues disialo-ceramidetetrahexoside and monosialo-ceramidetetrahexoside. Such change was observed...

Enzymatic Block in the Synthesis of Gangliosides in DNA Virus-Transformed Tumorigenic Mouse Cell Lines

Cumar, Federico A., Brady, Roscoe O., Kolodny, Edwin H., McFarland, Vivian W., Mora, Peter T.

The ganglioside pattern of both SV40- and polyoma virus-transformed mouse cell lines differs from that of the parent cell lines or of cell lines that have transformed spontaneously in tissue culture....

The metabolism of Tay-Sachs ganglioside: catabolic studies with lysosomal enzymes from normal and Tay-Sachs brain tissue

Tallman, John F., Johnson, William G., Brady, Roscoe O.

The catabolism of Tay-Sachs ganglioside, N-acetylgalactosaminyl- (N-acetylneuraminosyl) -galactosylglucosylceramide, has been studied in lysosomal preparations from normal human brain and brain...

Reduction of globotriaosylceramide in Fabry disease mice by substrate deprivation

Abe, Akira, Gregory, Susan, Lee, Lihsueh, Killen, Paul D., Brady, Roscoe O., Kulkarni, Ashok, ...

We used a potent inhibitor of glucosylceramide synthase to test whether substrate deprivation could lower globotriaosylceramide levels in α-galactosidase A (α-gal A) knockout mice, a model of Fabry...

Chemical chaperone therapy for brain pathology in GM1-gangliosidosis

Matsuda, Junichiro, Suzuki, Osamu, Oshima, Akihiro, Yamamoto, Yoshie, Noguchi, Akira, Takimoto, Kazuhiro, ...

We synthesized a galactose derivative, N-octyl-4-epi-β-valienamine (NOEV), for a molecular therapy (chemical chaperone therapy) of a human neurogenetic disease, β-galactosidosis (GM1-gangliosidosis...

Selective Effects of Glucocerebroside (Gaucher's Storage Material) on Macrophage Cultures

Gery, Igal, Zigler, J. Samuel, Brady, Roscoe O., Barranger, John A.

Although the enzymatic lesion in Gaucher's disease is well established, little is known concerning the pathogenic mechanisms involved in the clinical manifestations of the disease. In order to obtain...

Selective hepatic uptake of human β-hexosaminidase A by a specific glycoprotein recognition system on sinusoidal cells

Steer, Clifford J., Kusiak, John W., Brady, Roscoe O., Jones, E. Anthony

Intravenously administered 125I-labeled human β-hexosaminidase A (β-N-acetylglucosaminidase; 2-acetamido-2-deoxy-β-D-glucoside acetamidodeoxyglucohydrolase, EC 3.2.1.30) was rapidly cleared from...

Absence of a Specific Ganglioside Galactosyltransferase in Mouse Cells Transformed by Murine Sarcoma Virus

Fishman, Peter H., Brady, Roscoe O., Bradley, Roy M., Aaronson, Stuart A., Todaro, George J.

The ganglioside composition of a nonproducer subclone (derived from BALB/c 3T3 mouseembryo cells) transformed by Kirsten murine sarcoma virus was drastically altered compared to the nontransformed...

Perinatal abrogation of Cdk5 expression in brain results in neuronal migration defects

Hirasawa, Motoyuki, Ohshima, Toshio, Takahashi, Satoru, Longenecker, Glenn, Honjo, Yasuyuki, ...

Cyclin-dependent kinase 5 (Cdk5) is essential for the proper development of the CNS, as is evident from the perinatal lethality of conventional Cdk5 knockout (Cdk5-/-) mice. Cdk5 is also implicated...

Interaction of human chorionic gonadotropin with membrane components of rat testes

Pacuszka, Tadeusz, Osborne, James C., Brady, Roscoe O., Fishman, Peter H.

Previous studies demonstrating that gangliosides interacted with thyrotropin and human chorionic gonadotropin (hCG) suggested that gangliosides participate in the transduction of the hormonal message...

Bioluminescent imaging of a marking transgene and correction of Fabry mice by neonatal injection of recombinant lentiviral vectors

Yoshimitsu, Makoto, Sato, Takeya, Tao, Kesheng, Walia, Jagdeep S., Rasaiah, Vanessa I., Sleep, Gillian T., ...

Successful therapy for many inherited disorders could be improved if the intervention were initiated early. This is especially true for lysosomal storage disorders. Earlier intervention may allow...

Increased activity of cyclin-dependent kinase 5 leads to attenuation of cocaine-mediated dopamine signaling

Takahashi, Satoru, Ohshima, Toshio, Cho, Andrew, Sreenath, Taduru, Iadarola, Michael J., Pant, Harish C., ...

Cocaine, a drug of abuse, increases synaptic dopamine levels in the striatum by blocking dopamine reuptake at axon terminals. Cyclin-dependent kinase 5 (Cdk5) and its activator p35, proteins involved...

Cyclin-dependent kinase 5 activity regulates pain signaling

Pareek, Tej K., Keller, Jason, Kesavapany, Sashi, Pant, Harish C., Iadarola, Michael J., Brady, Roscoe O., ...

Several molecules and cellular pathways have been implicated in nociceptive signaling, but their precise molecular mechanisms have not been clearly defined. Cyclin-dependent kinase 5 (Cdk5) is a...

A multifunctional cytoprotective agent that reduces neurodegeneration after ischemia

Jiang, Zhi-Gang, Lu, X.-C. May, Nelson, Valery, Yang, Xiaofang, Pan, Weiying, Chen, Ren-wu, ...

Cellular and molecular pathways underlying ischemic neurotoxicity are multifaceted and complex. Although many potentially neuroprotective agents have been investigated, the simplicity of their...

Enzyme replacement therapy: conception, chaos and culmination.

Brady, Roscoe O

Soon after the enzymatic defects in Gaucher disease and in Niemann-Pick disease were discovered, enzyme replacement or enzyme supplementation was proposed as specific treatment for patients with...

Effective cell and gene therapy in a murine model of Gaucher disease

Enquist, Ida Berglin, Nilsson, Eva, Ooka, Andreas, Månsson, Jan-Eric, Olsson, Karin, Ehinger, Mats, ...

Gaucher disease (GD) is a lysosomal storage disorder due to an inherited deficiency in the enzyme glucosylceramidase (GCase) that causes hepatosplenomegaly, cytopenias, and bone disease as key...

Cyclin-dependent kinase 5 modulates nociceptive signaling through direct phosphorylation of transient receptor potential vanilloid 1

Pareek, Tej K., Keller, Jason, Kesavapany, Sashi, Agarwal, Nitin, Kuner, Rohini, Pant, Harish C., ...

Transient receptor potential vanilloid 1 (TRPV1), a ligand-gated cation channel highly expressed in small-diameter sensory neurons, is activated by heat, protons, and capsaicin. The phosphorylation...

Proteomics of specific treatment-related alterations in Fabry disease: A strategy to identify biological abnormalities

Moore, David F., Krokhin, Oleg V., Beavis, Ronald C., Ries, Markus, Robinson, Chevalia, Goldin, Ehud, ...

Fabry disease is inherited as an X-linked disorder secondary to deficiency of α-galactosidase A, resulting in abnormal metabolism of substances containing α-d-galactosyl moieties. As a consequence,...

Genomic abnormalities of the murine model of Fabry disease after disease-related perturbation, a systems biology approach

Moore, David F., Gelderman, Monique P., Ferreira, Paulo A., Fuhrmann, Steven R., Yi, Haiqing, Elkahloun, Abdel, ...

Fabry disease is a disorder of α-d-galactosyl-containing glycolipids resulting from a deficiency of α-galactosidase A. Patients have a poorly understood vascular dysregulation. We hypothesized that...

Liposomal vaccines with conformation-specific amyloid peptide antigens define immune response and efficacy in APP transgenic mice

Muhs, Andreas, Hickman, David T., Pihlgren, Maria, Chuard, Nathalie, Giriens, Valérie, Meerschman, Carine, ...

We investigated the therapeutic effects of two different versions of Aβ1–15 (16) liposome-based vaccines. Inoculation of APP-V717IxPS-1 (APPxPS-1) double-transgenic mice with tetra-palmitoylated...

Murine models of acute neuronopathic Gaucher disease

Enquist, Ida Berglin, Bianco, Christophe Lo, Ooka, Andreas, Nilsson, Eva, Månsson, Jan-Eric, Ehinger, Mats, ...

Gaucher disease (GD) is an autosomal recessive lysosomal storage disorder caused by mutations in the glucosidase, beta, acid (GBA) gene that encodes the lysosomal enzyme glucosylceramidase (GCase)....

Elevated globotriaosylsphingosine is a hallmark of Fabry disease

Aerts, Johannes M., Groener, Johanna E., Kuiper, Sijmen, Donker-Koopman, Wilma E., Strijland, Anneke, Ottenhoff, Roelof, ...

Fabry disease is an X-linked lysosomal storage disease caused by deficiency of α-galactosidase A that affects males and shows disease expression in heterozygotes. The characteristic progressive...