Big Chemical Encyclopedia

Chemical substances, components, reactions, process design ...

Articles Figures Tables About

A -antitrypsin genes

T. Ferkol, F. Mularo, J. Hilliard, S. Lodish, J. C. Perales, A. Ziady, and M. Konstan, Transfer of the human a-antitrypsin gene into pulmonary macrophages in vivo, Am. J. Respir. Cell. Mol. Biol., 18 (1998) 591-601. [Pg.386]

The S variant has a mutation at amino acid position 264, where valine is substituted for glutamic acid. The S-aj-antitrypsin appears to have normal protease-inhibitory activity but is degraded intracellularly prior to secretion. The null alleles (PIQ) produce no immunologically or functionally active protein there are several such allelic variants described, generally involving deletion of large portions of the a,-antitrypsin gene. [Pg.50]

The a,-antitrypsin gene has been cloned. In experiments with sheep it was shown that the protein remains stable when administered as an aerosol. It is still functional after it has passed through the pulmonary epithelium. This research offers hope of an effective treatment for this frightful disease. [Pg.606]

Rosenfeld, M.A., Siegfried, W., Yoshimura, K., et al. (1991). Adenovirus-mediated transfer of a recombinant alpha 1-antitrypsin gene to the lung epithelium in vivo. Science, 252(5004), 431 134. [Pg.367]

Figure 21.4 DNA dose dependent expression of human a 1-antitrypsin gene in mice. Each mouse was transfected with various amounts of plasmid DNA (pCMV-hAAT). The serum concentration of human a 1-antitrypsin in mice was determined 24 hours post injection using ELISA. Error bar represents S.E.M. from five mice. Figure 21.4 DNA dose dependent expression of human a 1-antitrypsin gene in mice. Each mouse was transfected with various amounts of plasmid DNA (pCMV-hAAT). The serum concentration of human a 1-antitrypsin in mice was determined 24 hours post injection using ELISA. Error bar represents S.E.M. from five mice.
Figure 21.5 Persistence of transgene expression. Animals were injected with 1,6ml saline containing 1 Opg ( ) or 50[ig (o) of either pCMV-Luc (A) or pCMVhAAT (B) plasmid DNA. For luciferase gene expression, animals were sacrificed at various time intervals and luciferase activity in the liver was determined by standard luciferase assay. For human a 1-antitrypsin gene expression, blood was collected at appropriate times and serum concentration of human q 1-antitrypsin was determined by a standard ELISA. Error bars represent s.e.m. from three mice in A and five mice in B. Figure 21.5 Persistence of transgene expression. Animals were injected with 1,6ml saline containing 1 Opg ( ) or 50[ig (o) of either pCMV-Luc (A) or pCMVhAAT (B) plasmid DNA. For luciferase gene expression, animals were sacrificed at various time intervals and luciferase activity in the liver was determined by standard luciferase assay. For human a 1-antitrypsin gene expression, blood was collected at appropriate times and serum concentration of human q 1-antitrypsin was determined by a standard ELISA. Error bars represent s.e.m. from three mice in A and five mice in B.
DNA dose dependent expression of human a 1-antitrypsin gene in mice 426... [Pg.497]

Sequencing of the human dj-antitrypsin gene in 1984 initiated an explosion in the study of this disease. Transgenic mice were created to study the effects of dj-anti trypsin deficiency, and cell culture studies of the regulation of the gene became possible. In 1992, D. A. Lomas and colleagues (Lomas et al., 1992) showed that the accumulation of abnormal dj-antitrypsin in the ER of the liver was the result of polymerization of dj-antitrypsin.This discovery set the stage for the study of the effects of this polymerized material on the liver, which it is hoped will allow the mechanism of liver disease associated with dj-antitrypsin deficiency to be determined. [Pg.47]

It has been shown in cell culture models of cXj-antitrypsin that Z-oq-antitrypsin in the ER causes expression of a novel set of stress genes with products that have the role of restoring ER function to normal. Z-a,-Antitrypsin induces two signal transduction pathways the ER overload response and unfolded protein response pathways. Via these transduction pathways, the presence of Z-oq-antitrypsin, as opposed to M-(Xj-antitrypsin, induces an hepatic inflammatory response. It is thought that this ER-specific stress response results in hepatic injury. [Pg.50]

In order to assess their capacity to produce and process recombinant proteins we introduced the Ui-antitrypsin gene driven by a mouse CMV/EFl-a hybrid promoter together with selection markers into one of the cell clones derived from neuronal precursors. Twelve individual clones were isolated and specific cellular productivity was determined. Several of the clones secreted more than 75 pg celT day , at least 6-fold more than the best CHO or G-line based producers isolated for this protein so far. Titers of 0.5 g L accumulated over 17 days of stationary culture in T-flasks. [Pg.775]

Brigham K L, et al. (2000). Transfection of nasal mucosa with a normal alphal-antitrypsin gene in alphal-antitrypsin-deficient subjects comparison with protein therapy. Hum. Gene Ther. 11 1023-1032. [Pg.1050]

Emphysema associated with a deficiency in the a-1 antitrypsin gene highest risk seen in smokers at genetic risk smokers and nonsmokers at genetic risk exhibit increased risk of emphysema. [Pg.269]

Carver RI, Chytil A Courtney M, Crystal RG. Clonal gene therapy transplanted mouse fibroblast clones express human alpha 1 -antitrypsin gene in vivo. Science 1987 237 762 64. [Pg.415]

Ferkol T, Mularo F, Hilliard J, Eodish S, Perales JC, Ziady A, et al. Transfer of the human alpha 1-antitrypsin gene into pulmonary macrophages in vivo. Am J Respir Cell Mol Biol 1998 18 591-601. [Pg.454]

These proteins are called acute phase proteins (or reactants) and include C-reactive protein (CRP, so-named because it reacts with the C polysaccharide of pneumococci), ai-antitrypsin, haptoglobin, aj-acid glycoprotein, and fibrinogen. The elevations of the levels of these proteins vary from as little as 50% to as much as 1000-fold in the case of CRP. Their levels are also usually elevated during chronic inflammatory states and in patients with cancer. These proteins are believed to play a role in the body s response to inflammation. For example, C-reactive protein can stimulate the classic complement pathway, and ai-antitrypsin can neutralize certain proteases released during the acute inflammatory state. CRP is used as a marker of tissue injury, infection, and inflammation, and there is considerable interest in its use as a predictor of certain types of cardiovascular conditions secondary to atherosclerosis. Interleukin-1 (IL-1), a polypeptide released from mononuclear phagocytic cells, is the principal—but not the sole—stimulator of the synthesis of the majority of acute phase reactants by hepatocytes. Additional molecules such as IL-6 are involved, and they as well as IL-1 appear to work at the level of gene transcription. [Pg.583]

At present, severe ai-antitrypsin deficiency liver disease can be successfully treated by liver transplantation. In the future, introduction of the gene for normal ttj-antitrypsin into hepatocytes may become possible, but this would not stop production of the PiZ protein. Figure 50-7 is a scheme of the causation of this disease. [Pg.590]

Yeast expression vectors have been among those most commonly used since the beginning of gene technology. Vectors based on baker s yeast, Saccharomyces cerevisiae, have been especially popular for robust expression of many types of recombinant proteins [90]. For instance, the first commercially available recombinant vaccine, the hepatitis B surface antigen vaccine, was produced from an S. cerevisiae vector [91]. Many other recombinant proteins have also been efficiently expressed in yeast including al-Antitrypsin [92], insulin [93], Epstein-Barr virus envelope protein [94], superoxide dismutase [95] and interferon-a [90]. [Pg.22]


See other pages where A -antitrypsin genes is mentioned: [Pg.119]    [Pg.631]    [Pg.48]    [Pg.51]    [Pg.119]    [Pg.631]    [Pg.48]    [Pg.51]    [Pg.589]    [Pg.100]    [Pg.354]    [Pg.388]    [Pg.341]    [Pg.168]    [Pg.423]    [Pg.351]    [Pg.48]    [Pg.67]    [Pg.521]    [Pg.229]    [Pg.292]    [Pg.558]    [Pg.746]    [Pg.746]    [Pg.82]    [Pg.783]    [Pg.783]    [Pg.629]    [Pg.194]    [Pg.255]    [Pg.99]    [Pg.73]    [Pg.73]   
See also in sourсe #XX -- [ Pg.390 ]




SEARCH



Antitrypsin

Antitrypsins

© 2024 chempedia.info