Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ion-selective electrodes have recently been designed for determining the ionized concentration of magnesium (Mg2+) in serum. This development may allow new insights into some metabolic diseases of cattle. For this report, the concentrations of Mg2+, total magnesium (Mgtot), ionized calcium (Ca2+), total calcium (Catot), and inorganic phosphate (P(i)) were determined in sera from seventeen 3- to 16-year-old Brown Swiss and crossed Simmental/Red Holstein cows during the periparturient period. In each animal, a transient increase of Mg2+ and Mgtot serum concentrations was observed in association with the transient decrease in serum concentrations of Ca2+, Catot and P(i) after parturition. On average, throughout the study, the serum Mg2+ concentrations were 68.5% of those of Mgtot, whereas the serum Ca2+ concentrations were 52% of those of Catot. The possible mechanisms involved in the transient increase of Mg2+ and Mgtot serum concentrations are discussed.
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PMID:The concentration of ionized magnesium in serum during the periparturient period of non-paretic dairy cows. 757 93

To evaluate the eosinophil infiltration in lung tissues in asthmatic responses of Brown-Norway rats and guinea pigs, both of which were sensitized with ovalbumin (OA), the time course of changes in respiratory impedance (Zrs) and eosinophil influx after aerosol challenge with OA were measured. The effect of treatment with monoclonal antibody (MoAb) 1A29 against rat intercellular adhesion molecule-1 (ICAM-1) alone and a mixture of MoAb 1A29 and MoAb WT-3 against rat CD18 on asthmatic responses of the rats was studied. Finally, these expressions in lung tissues of the rats were recognized. The number of eosinophils in the subepithelial area was counted in sections of lung tissue stained with Giemsa's solution, using an Interaktive Build-Analyse System (IBAS). All of the rats and 80% of the guinea pigs developed an increase in Zrs 6-7 hours after challenge, indicating that these animals showed a late asthmatic response (LAR). The rats and the guinea pigs with a LAR had higher eosinophil counts than those with an immediate asthmatic response and sensitized, non-challenged animals (p < 0.01). The rats treated with MoAb 1A29 alone (n = 5) and a mixture of MoAb 1A29 and MoAb WT-3 (n = 8) developed significantly smaller increases in Zrs and a smaller eosinophil influx than the control animals treated with phosphate buffered saline (n = 15): 147.3 +/- 3.5, 134.8 +/- 11.6 versus 158.8 +/- 6.3% of baseline; 734 +/- 21, 545 +/- 108 versus 1006 +/- 147 cells/mm2 (p < 0.01). Immunoperoxidase staining of rat lung tissues using MoAb 1A29 or MoAb WT-3 was performed ICAM-1 immunoreactivity was positive in the basilar portion of the epithelium, in the vascular endothelium of the trachea and in the pulmonary vascular endothelium. ICAM-1 immunoreactivity was revealed to be upregulated after challenge. The number of CD18-positive cells in the trachea and in the subepithelial area increased after challenge. These results show that eosinophil infiltration corresponds closely to bronchoconstriction in LAR and that treatment with MoAbs to ICAM-1 and CD18 may be effective in reducing asthmatic symptoms.
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PMID:[Role of eosinophils and cell adhesion molecules in the asthmatic response to allergen]. 780 50

The type II restriction endonuclease EcoRV was crystallized as a complex with the substrate DNA undecamer AAAGATATCTT (recognition sequence underlined). These crystals diffract to much better resolution (2 A) than was the case for the previously reported complex with the decamer GGGATATCCC [Winkler, F. K., Banner, D. W., Oefner, C., Tsernoglou, D., Brown, R. S., Heathman, S. P., Bryan, R. K., Martin, P. D., Petratos, K., & Wilson, K. S. (1993) EMBO J. 12, 1781-1795]. The crystal structure contains one dimer complex in the asymmetric unit and was solved by molecular replacement. The same kinked DNA conformation characteristic for enzyme-bound cognate DNA is observed. Crystals, soaked with Mg2+, show the essential cofactor bound at only one active site of the dimer, and the DNA is not cleaved. The Mg2+ has one oxygen from the scissile phosphodiester group and two carboxylate oxygens, one form Asp74 and one from Asp90, in its octahedral ligand sphere. The scissile phosphodiester group is pulled by 1 A toward the Mg2+. After substrate cleavage in solution, isomorphous crystals containing the enzyme--product--Mg2+ complex were obtained. In this structure, each of the 5'-phosphate groups is bound to two Mg2+. The kinked DNA conformation is essentially maintained, but the two central adenines, 3' to the cleavage sites, form an unusual cross-strand base stacking. The structures have been refined to R factors of 0.16 at 2.1-2.0 A resolution maintaining very good stereochemistry. On the basis of these structures and inspired by recent kinetic data [Vipond, I. B., & Halford, S. E. (1994) Biochemistry (second paper of three in this issue)], we have constructed a transition state model with two metals bound to the scissile phosphorane group.
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PMID:Mg2+ binding to the active site of EcoRV endonuclease: a crystallographic study of complexes with substrate and product DNA at 2 A resolution. 781 64

Uridine diphosphate-N-acetylglucosamine (UDP-NAG) enolpyruvyl transferase from Enterobacter cloacae catalyzes the transfer of an enolpyruvyl moiety from phosphoenolpyruvate (PEP) to the 3-hydroxyl of UDP-NAG to form enolpyruvyl UDP-NAG and inorganic phosphate. Indirect evidence for the involvement of a covalent intermediate, in which the C-2 of O-phosphothioketal moiety is attached to Cys-115, in the reaction catalyzed by UDP-NAG enolpyruvyl transferase has been reported by Wanke and Amrhein [Wanke, C., & Amrhein, N. (1993) Eur. J. Biochem. 218, 861-870]. In the enzyme from Escherichia coli, a noncovalent tetrahedral intermediate in which the C-2 of PEP is attached to the 3-OH of UDP-NAG via an ether linkage has been isolated by Marquardt et al. [Marquardt, J.L., Brown, E.D., Walsh, C.T., & Anderson, K.S. (1993) J. Am. Chem. Soc. 115, 10398-10399]. In this study, we provide direct evidence for the formation of a covalent O-phosphothioketal enzyme intermediate from UDP-NAG enolpyruvyl transferase of E. cloacae overexpressed in E. coli. The intermediate was obtained by incubation of the enzyme with [2,3-13C2]PEP and UDP-NAG and was characterized by solution-state 1D 13C and 31P NMR, 13C DEPT NMR, and 1H[13C]2D HMQC NMR spectroscopy. The 13C NMR spectra showed two coupled resonances at 29.3 and 88.7 ppm which were assigned to the C-3 and C-2 of the covalent intermediate, and the 13C DEPT confirmed that C-3 was a methyl group and C-2 was quaternary.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Detection of the covalent intermediate of UDP-N-acetylglucosamine enolpyruvyl transferase by solution-state and time-resolved solid-state NMR spectroscopy. 799 65

The yeast TRP3 gene encodes a bifunctional protein with anthranilate synthase II and indoleglycerol-phosphate synthase activities. Replacing ten consecutive non-preferred codons in the indoleglycerol-phosphate synthase region of the TRP3 gene with synonymous preferred codons (to create the TRP3pr gene; translational pause replaced) causes a 1.5-fold reduction in relative indoleglycerol-phosphate synthase activity [Crombie, T., Swaffield, J.C. & Brown, A.J.P. (1992) J. Mol. Biol. 228, 7-12]. Here, we report that both the anthranilate synthase II and indoleglycerol-phosphate synthase domains are affected to similar extents when the translational pause is removed. Also, structural modelling of the yeast indoleglycerol-phosphate synthase domain against the X-ray crystal structure of indoleglycerol-phosphate synthase from Escherichia coli indicates that the translational pause lies in a region of structural divergence between similar structures. To probe the role of cytoplasmic heat-shock protein 70 (Hsp 70) chaperones in Trp3 protein folding, anthranilate synthase and indoleglycerol-phosphate synthase activities were measured in ssa and ssb mutants. Neither indoleglycerol-phosphate synthase nor anthranilate synthase were affected significantly in the ssb mutant. However, depletion of Hsp70 proteins encoded by the SSA genes led to decreased anthranilate synthase and indoleglycerol-phosphate synthase activities from the TRP3 gene, suggesting that both domains depend to some extent upon the SSA chaperone family. The data are consistent with roles for both the translational pause and Ssa chaperones in Trp3 protein folding in vivo.
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PMID:The folding of the bifunctional TRP3 protein in yeast is influenced by a translational pause which lies in a region of structural divergence with Escherichia coli indoleglycerol-phosphate synthase. 800 82

Minimal transformants of rat F111 fibroblasts were established after infection with the large T antigen (large T)-encoding retroviral expression vector pZIPTEX (M. Brown, M. McCormack, K. Zinn, M. Farrell, I. Bikel, and D. Livingston, J. Virol. 60:290-293, 1986). Coexpression of small t antigen (small t) in these cells efficiently led to their progression toward a significantly enhanced transformed phenotype. Small t forms a complex with phosphatase 2A and thereby might influence cellular phosphorylation processes, including the phosphorylation of large T. Since phosphorylation can modulate the transforming activity of large T, we asked whether the phosphorylation status of large T in minimally transformed cells might differ from that of large T in maximally transformed FR(wt648) cells and whether it might be altered by coexpression of small t. We found the phosphate turnover on large T in minimally transformed cells significantly different from that in fully transformed cells. This resulted in underphosphorylation of large T in minimally transformed cells at phosphorylation sites previously shown to be involved in the regulation of the transforming activity of large T. However, coexpression of small t in the minimally transformed cells did not alter the phosphate turnover on large T during progression; i.e., it did not induce a change in the steady-state phosphorylation of large T. This suggests that the helper function of small t during the progression of these cells was not mediated by modulating phosphatase 2A activity toward large T.
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PMID:Analysis of simian virus 40 small t antigen-induced progression of rat F111 cells minimally transformed by large T antigen. 838 10

Injection of a low dose of mercuric chloride into Brown Norway (BN) rats caused a marked decrease in the concanavalin A (ConA)-induced generation of interferon-gamma-producing cells (IFN-gamma pc) in spleen cell cultures prepared 1 h after mercury administration. A second injection 48 h later caused a further diminution of IFN-gamma pc down to 30% of the number generated in splenocyte cultures of phosphate-buffered saline (PBS)-injected controls. Injection of Lewis rats with either one or two doses of HgCl2 revealed no inhibitory effect on splenic IFN-gamma production. The presence of the reduced form of glutathione (GSH) in the culture medium was found to be essential in these experiments. In the absence of GSH there was an overall 20-fold reduction of the number of IFN-gamma pc in splenocyte cultures of normal or PBS-injected rats, which was further reduced to a 60- to 70-fold-lower level in cultures of rats exposed to HgCl2. This mercury-mediated extra reduction could be fully reversed with an excess (2 mM) of GSH in Lewis but not in BN splenocyte cultures. Since the bivalent Hg2+ ion is known to bind to and inactivate sulfhydryl groups of proteins and low molecular weight thiols, most notably GSH, we investigated a possible role for thiols in IFN-gamma production. It was found that the generation of IFN-gamma pc in normal BN and Lewis splenocyte cultures was strongly dependent on GSH or its precursor cysteine in the culture medium. Other thiol compounds were also effective but disulfides were completely inactive. Depletion of intracellular GSH in ConA-stimulated splenocytes by buthionine sulfoximide (BSO), an inhibitor of de novo GSH biosynthesis, strongly inhibited the generation of IFN-gamma pc. The inhibitory effect of BSO was not abolished by the addition of interleukin-2 (IL-2), but was mimicked with antibodies directed to the IL-2 receptor. The data stress the importance of GSH in the enhancement of IL-2-mediated IFN-gamma production and are most consistent with a model in which mercury interferes with T cell IFN-gamma production by affecting the intracellular availability of GSH. The strain-specific susceptibility to mercury-mediated inhibition of IFN-gamma production is discussed.
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PMID:Mercuric chloride down-regulates T cell interferon-gamma production in brown Norway but not in Lewis rats; role of glutathione. 844 15

Disorders of calcium, phosphorus and magnesium homeostasis in ruminants provide natural models for the study of the physiology and pathophysiology of these minerals. The knowledge that can be acquired with a better understanding of the pathogenesis of these diseases could give useful clues in the puzzle of human osteoporosis. In the present study, the case of parturient paresis of dairy cows is reexamined with a newly developed technique for the measurements of serum ionized magnesium concentrations (Mg2+). The concentrations of total magnesium (Mgtot), ionized calcium (Ca2+), total calcium (Catot), and inorganic phosphate (Pi) were also determined in the sera of seventeen 3- to 16-year-old Brown Swiss and crossed Simmental/Red Holstein cows during the periparturient period. In each animal, a transient increase of Mg2+ and Mgtot serum concentrations was observed in association with the transient decrease after parturition of Ca2+, Catot and Pi serum concentrations. On average, throughout the study, serum Mg2+ concentrations were 68.5% of those of Mgtot whereas serum Ca2+ concentrations were 52% of those of Catot. The possible mechanisms involved in the transient increase of Mg2+ and Mgtot serum concentrations are discussed and the relevance of this data for osteoporosis is outlined.
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PMID:Postparturient hypocalcemia of dairy cows: a model for the study of the interdependence of Ca, Pi, and Mg homeostasis. 857 48

We evaluated the role of very late antigen-4 (VLA-4) in asthmatic responses. Brown-Norway rats were sensitized with ovalbumin and then challenged with ovalbumin. Respiratory impedance, and the influx of eosinophils and of VLA-4-positive cells were measured. Eosinophils were stained with Giemsa's solution and VLA-4-positive cells were detected by an immunocytochemical method with a monoclonal antibody against rat VLA-4 (MR alpha 4-1). The numbers of eosinophils and of VLA-4-positive cells in sections of lung tissue from the rats were counted. The effect of MR alpha 4-1 and of a new anti-allergic drug, TYB-2285, on late asthmatic responses was also studied. Respiratory impedance had increased in all the rats by 6-7 hours after the challenge, which indicated that these animals had a late asthmatic response. These rats had more eosinophils and more VLA-4-positive cells than did sensitized animals that were not challenged. The rats given MR alpha 4-1 had significantly smaller increases in respiratory impedance and less eosinophil influx than did those given only phosphate-buffered saline. The rats given TYB-2285 had significantly smaller increases in impedance and less influx of eosinophils and of VLA-4-positive cells. These results show that infiltration of eosinophils and of VLA-4-positive cells corresponds closely with the late asthmatic response, and they suggest that the VLA-4/VCAM-1 pathway plays an important role in this response. These data also suggest that the infiltration of VLA-4-positive cells can be used to evaluate the effect of anti-allergic drugs on the late asthmatic response.
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PMID:[Role of adhesion molecules (VLA-4) in the asthmatic response to allergens]. 858 16

We investigated the expression of mRNA of basic fibroblast growth factor (bFGF) and FGF receptor 1 in rat retina after laser photocoagulation using in situ hybridization method. Pigmented rats (Brown Norway strain) received weak photocoagulation by krypton laser (500 microns, 0.05 sec, 60 mW) in the posterior retina. On 1, 3, 5, 7, 14 days after laser photocoagulation, the rats were fixed by perfusion with phosphate-buffered 4% paraformaldehyde and the eyes were enucleated. The eyes were further fixed by immersion in the same fixative, then quickly frozen in liquid nitrogen and finally sectioned with a cryostat. In situ hybridization was performed on frozen sections with digoxigenin (DIG) labeled riboprobes synthesized from rat bFGF cDNA and FGF receptor 1 cDNA. In normal chorioretinal tissue, the signals of bFGF and FGF receptor 1 mRNA were seen in the ganglion cell layer and inner nuclear layer. On day 3 after photocoagulation, we observed expression of bFGF and FGF receptor 1 mRNA in the proliferating retinal pigment epithelial (RPE) cells and endothelial cells of choriocapillaris at the photocoagulated lesion. We also observed expression of bFGF mRNA in some macrophage-like cells. On day 14 after photocoagulation, these expressions had disappeared. Our results suggest that bFGF may be involved in the process of retinal wound healing after laser photocoagulation.
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PMID:[Expression of basic fibroblast growth factor and its receptor in the process of wound healing of rat retina after laser photocoagulation]. 864 38


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