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Papers by Daniel Medynski

FEBS Open Bio, Sep 17, 2018

Native 1-antitrypsin is a 52-kDa glycoprotein that acts as an antiprotease and is the physiologi... more Native 1-antitrypsin is a 52-kDa glycoprotein that acts as an antiprotease and is the physiological inhibitor of neutrophil serine proteases. The main function of 1-antitrypsin is to protect the lung from proteolytic damage induced by inflammation. 1-antitrypsin deficiency is a codominant autosomal disorder caused by pathogenic mutations in SERPINA1 gene, leading to reduced levels of serum 1-antitrypsin. The

Methods for production of recombinant alpha1-antitrypsin

Methods for Production of Recombinant Plasminogen and Plasmin Polypeptides

Clinical Cancer Research, 2005

We determined the antiangiogenic and anticancer activity of VEGI-192, a new isoform of TNFSF15 (V... more We determined the antiangiogenic and anticancer activity of VEGI-192, a new isoform of TNFSF15 (VEGI,TL1), with a Lewis lung cancer murine tumor model. Experimental Design: Recombinant human VEGI-192 was produced in Escherichia coli and purified to apparent homogeneity.The protein was given systemically via i.p., i.v., or s.c. injections to tumor-bearing C57BL/6 mice. Tumor growth rates, animal survival rates, and general toxicity were determined. Effect on endothelial cell/smooth muscle cell ratio of the tumor vasculature was analyzed. Results: Systemic administration ofVEGI-192 gave rise to a marked inhibition of tumor growth. As much as 50% inhibition of the tumor growth rate was achieved with treatment initiated when the tumor volumes reached nearly 5% of the body weight. Inhibition of tumor formation was also observed when VEGI-192 was given at the time of tumor inoculation. Consistently, we observed an increased survival time of the treated animals.TheVEGI-192-treated animals showed no liver or kidney toxicity. The treatment eliminated tumor endothelial cells but not vascular smooth muscle cells, which remained associated with a residual vascular structure consisting of the basement membrane. In addition, we carried out immunohistochemical analysis of rat kidneys and found that vascular endothelial cell growth inhibitor (VEGI) expression is largely limited to endothelial cells. Conclusions: Our findings indicate thatVEGI is an endogenous inhibitor of angiogenesis, and that systemic administration of the VEGI-192 isoform resulted in inhibition of tumor angiogenesis and growth.

Refolding, purification, and activation of miniplasminogen and microplasminogen isolated from E. coli inclusion bodies

Protein Expression and Purification, 2007

Two des-kringle derivatives of human plasminogen, microplasminogen and miniplasminogen, have been... more Two des-kringle derivatives of human plasminogen, microplasminogen and miniplasminogen, have been expressed at high levels as inclusion bodies in Escherichia coli using a T7 expression system. In each case, the isolated inclusion bodies were refolded and purified. A final yield of approximately 10% of total refolded protein was observed in each case. Both refolded molecules were successfully activated to their functional forms, microplasmin and miniplasmin, by the plasminogen activator urokinase. The kinetic properties of the refolded microplasmin and miniplasmin were comparable to full length, native plasmin.

Procédés pour la production de polypeptides de plasminogène et de plasmine de recombinaison

L'invention concerne des procedes destines a produire un polypeptide de plasminogene et de pl... more L'invention concerne des procedes destines a produire un polypeptide de plasminogene et de plasmine de recombinaison replie correctement. Le polypeptide de plasminogene de recombinaison denature est replie en solubilisant premierement le polypeptide avec un chaotrope, et en reduisant et oxydant des agents a un pH eleve, operations suivies par le repliage en presence d'une concentration reduite de chaotrope et la reduction et l'oxydation d'agent en presence d'arginine.

Nucleotide sequence for a cDNA encoding the α subunit of retinal transducin (GNAT1) isolated from the human eye

Nar, 1989

Interactions of Local Anesthetics with Torpedo Nicotinic Acetylcholine Receptors

Molecular and Cellular Mechanisms of Anesthetics, 1986

Genetic and Functional Studies of Pertussis Toxin Subsrates

Proceedings of The National Academy of Sciences, 1985

Transducin, a GTP-binding protein involved in phototransduction in the vertebrate retina, belongs... more Transducin, a GTP-binding protein involved in phototransduction in the vertebrate retina, belongs to a family of homologous coupling proteins that also includes G, and G1, the regulatory proteins of adenylate cyclase. Here we Abbreviations: Ta, a subunit of transducin; T /3y, -'y subunit complex of transducin; PDEase, phosphodiesterase, p[NH]ppG, guanosine 5'-[A3,y-imido]triphosphate; R*, photolyzed rhodopsin; G, and Gi, stimulatory and inhibitory coupling proteins of hormone-sensitive adenylate cyclase. cPresent address:

Genomic approaches to the development of prostate cancer diagnostics

Nature Genetics, 2001

Nucleotide sequence for a cDNA encoding the α subunit of retinal transducin (GNAT1) isolated from the human eye

Nucleic Acids Research, 1989

FEBS Open Bio, Sep 17, 2018

Native 1-antitrypsin is a 52-kDa glycoprotein that acts as an antiprotease and is the physiologi... more Native 1-antitrypsin is a 52-kDa glycoprotein that acts as an antiprotease and is the physiological inhibitor of neutrophil serine proteases. The main function of 1-antitrypsin is to protect the lung from proteolytic damage induced by inflammation. 1-antitrypsin deficiency is a codominant autosomal disorder caused by pathogenic mutations in SERPINA1 gene, leading to reduced levels of serum 1-antitrypsin. The

Methods for production of recombinant alpha1-antitrypsin

Methods for Production of Recombinant Plasminogen and Plasmin Polypeptides

Clinical Cancer Research, 2005

We determined the antiangiogenic and anticancer activity of VEGI-192, a new isoform of TNFSF15 (V... more We determined the antiangiogenic and anticancer activity of VEGI-192, a new isoform of TNFSF15 (VEGI,TL1), with a Lewis lung cancer murine tumor model. Experimental Design: Recombinant human VEGI-192 was produced in Escherichia coli and purified to apparent homogeneity.The protein was given systemically via i.p., i.v., or s.c. injections to tumor-bearing C57BL/6 mice. Tumor growth rates, animal survival rates, and general toxicity were determined. Effect on endothelial cell/smooth muscle cell ratio of the tumor vasculature was analyzed. Results: Systemic administration ofVEGI-192 gave rise to a marked inhibition of tumor growth. As much as 50% inhibition of the tumor growth rate was achieved with treatment initiated when the tumor volumes reached nearly 5% of the body weight. Inhibition of tumor formation was also observed when VEGI-192 was given at the time of tumor inoculation. Consistently, we observed an increased survival time of the treated animals.TheVEGI-192-treated animals showed no liver or kidney toxicity. The treatment eliminated tumor endothelial cells but not vascular smooth muscle cells, which remained associated with a residual vascular structure consisting of the basement membrane. In addition, we carried out immunohistochemical analysis of rat kidneys and found that vascular endothelial cell growth inhibitor (VEGI) expression is largely limited to endothelial cells. Conclusions: Our findings indicate thatVEGI is an endogenous inhibitor of angiogenesis, and that systemic administration of the VEGI-192 isoform resulted in inhibition of tumor angiogenesis and growth.

Refolding, purification, and activation of miniplasminogen and microplasminogen isolated from E. coli inclusion bodies

Protein Expression and Purification, 2007

Two des-kringle derivatives of human plasminogen, microplasminogen and miniplasminogen, have been... more Two des-kringle derivatives of human plasminogen, microplasminogen and miniplasminogen, have been expressed at high levels as inclusion bodies in Escherichia coli using a T7 expression system. In each case, the isolated inclusion bodies were refolded and purified. A final yield of approximately 10% of total refolded protein was observed in each case. Both refolded molecules were successfully activated to their functional forms, microplasmin and miniplasmin, by the plasminogen activator urokinase. The kinetic properties of the refolded microplasmin and miniplasmin were comparable to full length, native plasmin.

Procédés pour la production de polypeptides de plasminogène et de plasmine de recombinaison

L'invention concerne des procedes destines a produire un polypeptide de plasminogene et de pl... more L'invention concerne des procedes destines a produire un polypeptide de plasminogene et de plasmine de recombinaison replie correctement. Le polypeptide de plasminogene de recombinaison denature est replie en solubilisant premierement le polypeptide avec un chaotrope, et en reduisant et oxydant des agents a un pH eleve, operations suivies par le repliage en presence d'une concentration reduite de chaotrope et la reduction et l'oxydation d'agent en presence d'arginine.

Nucleotide sequence for a cDNA encoding the α subunit of retinal transducin (GNAT1) isolated from the human eye

Nar, 1989

Interactions of Local Anesthetics with Torpedo Nicotinic Acetylcholine Receptors

Molecular and Cellular Mechanisms of Anesthetics, 1986

Genetic and Functional Studies of Pertussis Toxin Subsrates

Proceedings of The National Academy of Sciences, 1985

Transducin, a GTP-binding protein involved in phototransduction in the vertebrate retina, belongs... more Transducin, a GTP-binding protein involved in phototransduction in the vertebrate retina, belongs to a family of homologous coupling proteins that also includes G, and G1, the regulatory proteins of adenylate cyclase. Here we Abbreviations: Ta, a subunit of transducin; T /3y, -'y subunit complex of transducin; PDEase, phosphodiesterase, p[NH]ppG, guanosine 5'-[A3,y-imido]triphosphate; R*, photolyzed rhodopsin; G, and Gi, stimulatory and inhibitory coupling proteins of hormone-sensitive adenylate cyclase. cPresent address:

Genomic approaches to the development of prostate cancer diagnostics

Nature Genetics, 2001

Nucleotide sequence for a cDNA encoding the α subunit of retinal transducin (GNAT1) isolated from the human eye

Nucleic Acids Research, 1989