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1. |
Trials and Tribulations: The Cost of Developing Gene Therapies |
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The FASEB Journal,
Volume 5,
Issue 15,
1991,
Page 3013-3014
Michael T. Lotze,
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ISSN:0892-6638
DOI:10.1096/fasebj.5.15.1743433
出版商:Wiley
年代:1991
数据来源: WILEY
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2. |
HARLAND G. WOOD |
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The FASEB Journal,
Volume 5,
Issue 15,
1991,
Page 3015-3017
Richard W. Hanson,
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PDF (616KB)
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ISSN:0892-6638
DOI:10.1096/fasebj.5.15.1743434
出版商:Wiley
年代:1991
数据来源: WILEY
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3. |
The value of accreditation of animal laboratory care |
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The FASEB Journal,
Volume 5,
Issue 15,
1991,
Page 3021-3022
Virginia M. Miller,
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PDF (323KB)
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ISSN:0892-6638
DOI:10.1096/fasebj.5.15.1743435
出版商:Wiley
年代:1991
数据来源: WILEY
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4. |
Anatomical distribution and function of dopamine receptors in the kidney |
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The FASEB Journal,
Volume 5,
Issue 15,
1991,
Page 3023-3030
Mustafa F. Lokhandwala,
Francesco Amenta,
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摘要:
Dopamine receptors of DA‐1 and DA‐2 subtypes are localized in various regions within the kidney including the renal vasculature (DA‐1) as well as sympathetic nerve terminals innervating the renal blood vessels (DA‐2). More recent studies using receptor‐ligand binding and receptor autoradiography have shown that DA‐1 receptors are localized at both the luminal and basolateral membranes at the level of the proximal tubules. Activation of these DA‐1 receptors by dopamine and by selective DA‐1 receptor agonists results in natriuresis and diuresis. The cellular signaling mechanisms responsible for this response appear to be DA‐1 receptor‐induced activation of adenylate cyclase and phospholipase C, which via the generation of various intracellular messenger systems cause inhibition of Na+‐H+antiport (luminal) and Na+, K+‐ATPase (basolateral), respectively. Both of these events consequently inhibit sodium reabsorption leading to natriuresis and diuresis. It is also known that dopamine can be synthesized within proximal tubular cells from L‐dopa, which is taken up from the tubular lumen, and this locally produced dopamine plays an important role in the regulation of sodium excretion particularly during increases in sodium intake. Furthermore, a defect in the renal dopaminergic mechanism may be one of the pathogenic factors in certain forms of hypertension. Finally, whereas DA‐1 receptor agonists are shown to be of therapeutic benefit in the treatment of hypertension, heart failure, and acute renal failure, some selective DA‐2 receptor agonists are effective antihypertensive agents.—Lokhandwala, M. F.; Amenta, F. Anatomical distribution and function of dopamine receptors in the kidney.FASEB J.5: 3023‐3030; 1991.
ISSN:0892-6638
DOI:10.1096/fasebj.5.15.1683844
出版商:Wiley
年代:1991
数据来源: WILEY
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5. |
New insights into the metabolic regulation of insulin action and insulin resistance: role of glucose and amino acids |
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The FASEB Journal,
Volume 5,
Issue 15,
1991,
Page 3031-3036
Stephen Marshall,
W. Timothy Garvey,
Roger R. Traxinger,
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摘要:
In primary cultured adipocytes, metabolic substrates such as glucose and amino acids have profound effects on modulating insulin's stimulatory actions on glucose uptake and protein synthesis. Insights into how substrates modulate insulin action were recently obtained when we discovered that the routing of incoming glucose through the hexosamine biosynthesis pathway leads to a refractory state over a period of several hours in which the ability of insulin to stimulate glucose uptake is severely impaired—a state known as insulin resistance. Gluta‐mine:fructose‐6‐phosphate amidotransferase was found to play a central role in the development of insulin resistance as this enzyme catalyzes the first and rate‐limiting step in the formation of hexosamine products. Collectively, these results are consistent with the idea that the hexosamine biosynthesis pathway serves as a glucose sensor coupled to a negative feedback system that can limit the extent of glucose uptake in response to hyperglycemic and hyperinsulinemic conditions.—Marshall, S.; Garvey, W. T.; Traxinger, R. R. New insights into the metabolic regulation of insulin action and insulin resistance: role of glucose and amino acids.FASEB J.5: 3031‐3036; 1991.
ISSN:0892-6638
DOI:10.1096/fasebj.5.15.1743436
出版商:Wiley
年代:1991
数据来源: WILEY
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6. |
Regulation of cardiac gene expression during myocardial growth and hypertrophy: molecular studies of an adaptive physiologic response |
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The FASEB Journal,
Volume 5,
Issue 15,
1991,
Page 3037-3064
Kenneth R. Chien,
Kirk U. Knowlton,
g Zhu,
Shu Chien,
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摘要:
Studies from both in vivo and in vitro model systems have provided an initial skeleton of the potential signaling pathways that might regulate cardiac genes during growth and hypertrophy. One of the first detectable changes in cardiac gene expression is the activation of a program of immediate early gene expression, which is distinct for the hypertrophic response, and is conserved in multiple models of both in vivo and in vitro hypertrophy. Diverse and distinct hormonal stimuli have been documented to activate several features of the hypertrophic response, including several autocrine and paracrine factors. Although the signaling mechanisms that link these factors with the activation of cardiac gene expression are unclear, recent studies suggest that the activation of protein kinase C may represent one of the most proximal common events in this signaling cascade. The activation of cardiac target genes induces a program of embryonic gene expression, including the atrial natriuretic factor (ANF) gene. Thecissequences that mediate cardiac‐specific and inducible expression of an embryonic marker gene (ANF) can be segregated by studies in both cultured cell models and in vivo models of hypertrophy in transgenic mice, suggesting that specific sets of regulatory elements may exist for inducible expression of this class of cardiac gene responses. However, the induction of a constitutively expressed contractile protein gene (MLC‐2) is mediated by a set of conserved elements that regulate both cardiac‐specific and inducible expression. Finally, a subset of cardiac muscle genes appears to be noninducible during in vivo or in vitro hypertrophy in myocardial cells, demonstrating specificity of transcriptional activation during the hypertrophic process. The development of a bona fide in vivo pressure overload model of hypertrophy in a small animal model that can be genetically manipulated, such as the in vivo murine model recently described, should allow a rigorous analysis of the role of these specific signaling mechanisms in the activation of the responses of cardiac genes during the hypertrophic process in vivo.—Chien, K. R.; Knowlton, K. U.; Zhu, H.; Chien, S. Regulation of cardiac gene expression during myocardial growth and hypertrophy: molecular studies of an adaptive physiologic response.FASEB J.5: 3037‐3046; 1991.
ISSN:0892-6638
DOI:10.1096/fasebj.5.15.1835945
出版商:Wiley
年代:1991
数据来源: WILEY
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7. |
Corticosteroids, receptors, and the organ‐specific functions of 11β‐hydroxysteroid dehydrogenase |
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The FASEB Journal,
Volume 5,
Issue 15,
1991,
Page 3047-3054
Carl Monder,
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摘要:
Reversible oxidation of the biologically active corticosteroids to the inactive 11‐dehydrocorticosteroids is catalyzed by 11β‐hydroxysteroid dehydrogenase (11βHSD). The properties of the enzyme based on clinical observations of individuals with defective 11βHSD expression, and laboratory studies of the properties and behavior of the enzyme, are consistent with separate 11β‐dehydrogenase and 11‐oxoreductase species. However, recombinant enzyme expressed in mammalian cells retain both activities, leading to the conclusion that 11βHSD is a unique, reversible enzyme. 11βHSD is present in most tissues, but its specific functions in most tissues are unknown. How the enzyme may mediate corticosteroid‐receptor interaction is illustrated by studies using kidney, testis, and brain. In kidney, 11βHSD prevents glucocorticoids from competing inappropriately with aldosterone for mineralocorticoid receptor (MR). Lack of enzyme in humans due to natural causes or inhibition by pharmacological agents results in maximum activation of MR by glucocorticoids, leading to the clinical symptoms of apparent mineralocorticoid excess. Leydig cells of the testes synthesize testosterone, a process that is suppressed by events initiated by the binding of corticosteroid to glucocorticoid receptors (GR). Depletion of active steroid mediated by 11βSHSD may initiate testosterone production at puberty and affect testosterone production during adult life, as for example during periods of stress. The heterogeneous distribution of MR and GR in the brain reflects the specific regional effects of glucocorticoids and mineralocorticoids on neural function. Colocalization of 11βHSD and corticosteroid receptors in brain may be important in controlling the specificity of corticosteroid interaction with GR and MR. The patterns of 11βHSD‐steroid‐receptor interaction illustrated with these three tissues may provide models applicable to other tissues in which corticosteroid receptors and 11βHSD coexist.— Monder, C. Corticosteroids, receptors, and the organ‐specific functions of 11β‐hydroxysteroid dehydrogenase.FASEB J.5: 3047‐3054; 1991.
ISSN:0892-6638
DOI:10.1096/fasebj.5.15.1743437
出版商:Wiley
年代:1991
数据来源: WILEY
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8. |
Glycosidase inhibitors: inhibitors of N‐linked oligosaccharide processing |
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The FASEB Journal,
Volume 5,
Issue 15,
1991,
Page 3055-3063
Alan D. Elbein,
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摘要:
The biosynthesis of the various types of N‐linked oligosaccharide structures involves two series of reactions:1) the formation of the lipid‐linked saccharide precursor, Glc3Man9(GlcNAc)2‐pyrophosphoryl‐dolichol, by the stepwise addition of GlcNAc, mannose and glucose to dolichyl‐P, and2) the removal of glucose and mannose by membrane‐bound glycosidases and the addition of GlcNAc, galactose, sialic acid, and fucose by Golgilocalized glycosyltransferases to produce different complex oligosaccharide structures. For most glycoproteins, the precise role of the carbohydrate is still not known, but specific N‐linked oligosaccharide structures are key players in targeting of lysosomal hydrolases to the lysosomes, in the clearance of asialoglycoproteins from the serum, and in some cases of cell:cell adhesion. Furthermore, many glycoproteins have more than one N‐linked oligosaccharide, and these oligosaccharides on the same protein frequently have different structures. Thus, one oligosaccharide may be of the high‐mannose type whereas another may be a complex chain. One approach to determining the role of specific structures in glycoprotein function is to use inhibitors that block the modification reactions at different steps, causing the cell to produce glycoproteins with altered carbohydrate structures. The function of these glycoproteins can then be assessed. A number of alkaloid‐like compounds have been identified that are specific inhibitors of the glucosidases and mannosidases involved in glycoprotein processing. These compounds cause the formation of glycoproteins with glucose‐containing high mannose structures, or various high‐mannose or hybrid chains, depending on the site of inhibition. These inhibitors have also been useful for studying the processing pathway and for comparing processing enzymes from different organisms.—Elbein, A. D. Glycosidase inhibitors: inhibitors of N‐linked oligosaccharide processing.FASEB J.5: 3055‐3063; 1991.
ISSN:0892-6638
DOI:10.1096/fasebj.5.15.1743438
出版商:Wiley
年代:1991
数据来源: WILEY
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9. |
Multiple mechanisms regulate muscle fiber diversity |
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The FASEB Journal,
Volume 5,
Issue 15,
1991,
Page 3064-3070
Peter Gunning,
Edna Hardeman,
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摘要:
Adult skeletal muscles are composed of clusters of multinucleated muscle cells called myofibers. At least three different types of myofibers can be detected within mammals based on their physiological properties and their expression of different contractile protein isoforms. Different skeletal muscles display a wide range of combinations of myofibers. Recent work has demonstrated that multiple mechanisms are responsible for the generation of these myofiber types during development. Muscle progenitor cells have been dissected into two categories on the basis of which isoforms of myosin heavy chain (MHC) they express when they differentiate. Neural and other environmental influences act to modify decisions concerning the type of contractile protein a myofiber may express, and this is most apparent for MHC. The other contractile protein gene families are initially regulated independent of the MHC gene family. One or more events late in development are responsible for coordinating isoform expression between the gene families to generate the adult phenotype. Studies of muscle gene expression have revealed that regulation can occur at the levels of transcription, alternative splicing of primary transcripts, mRNA stability, and translation. The current challenge is to decipher how environmental and functional information is intrepreted in terms of the activity of the regulators of muscle gene expression.—Gunning, P.; Hardeman, E. Multiple mechanisms regulate muscle fiber diversity.FASEB J.5: 3064‐3070; 1991.
ISSN:0892-6638
DOI:10.1096/fasebj.5.15.1835946
出版商:Wiley
年代:1991
数据来源: WILEY
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10. |
Transglutaminases: multifunctional cross‐linking enzymes that stabilize tissues |
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The FASEB Journal,
Volume 5,
Issue 15,
1991,
Page 3071-3077
Charles S. Greenberg,
Paul J. Birckbichler,
Robert H. Rice,
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摘要:
Transglutaminases catalyze the posttranslational modification of proteins by transamidation of available glutamine residues. This action results primarily in the formation of∊‐(γ‐glutamyl)lysine cross‐links but includes the incorporation of polyamines into suitable protein substrates as well. The covalent isopeptide crosslink is stable and resistant to proteolysis, thereby increasing the resistance of tissue to chemical, enzymatic, and mechanical disruption. The plasma transglutaminase, factor XIIIa, is formed at sites of blood coagulation and impedes blood loss by stabilizing the fibrin clot. The squamous epithelium constituting the protective callus layer of skin is formed by the action of keratinocyte transglutaminase (TGK) and epidermal transglutaminase (TGE). The tissue transglutaminase (TGC) is a cytoplasmic enzyme present in many cells including those in the blood vessel wall. TGCfunction is unknown, although it could function to stabilize intra‐ and extra‐cellular molecules in a wide variety of physiologic or pathologic processes. The amino acid sequences of factor XIII, TGC, and TGKestablish them as a homologous gene family and also reveal a striking homology to the erythrocyte membrane protein, band 4.2. This review summarizes the current information on structures, functions, and evolution of the most prominent members of this gene family.—Greenberg, C. S.; Birckbichler, P. J.; Rice, R. H. Transglutaminases: multifunctional cross‐linking enzymes that stabilize tissues.FASEB J.5: 3071‐3077; 1991.
ISSN:0892-6638
DOI:10.1096/fasebj.5.15.1683845
出版商:Wiley
年代:1991
数据来源: WILEY
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