Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.2.1.23 (beta-galactosidase)
 14,648 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immunologic challenge with lipopolysaccharide (LPS) or interleukin-1beta (IL-1beta) produces a functional response within the paraventricular nucleus of the hypothalamus (PVN) and leads to changes in gene expression within PVN neurons. Regulated expression of neuropeptide genes within neurons of the PVN is a potential mechanism by which an organism can adapt to stressful challenges. Here, the authors used a transgenic mouse model in which expression of a readily measurable beta-galactosidase reporter was driven in PVN neurons by human proenkephalin regulatory sequences. This proenkephalin-beta-galactosidase transgene has been demonstrated previously to respond appropriately to a variety of stressors. It is demonstrated that expression of the proenkephalin transgene product was up-regulated significantly in a subset of PVN neurons 6 hours following intraperitoneal LPS (16-400 microg/kg) administration, remained elevated at 12 hours, and fell below basal levels by 24 hours. A more rapid and transient pattern of transgene up-regulation in the PVN followed administration of intraperitoneal IL-1beta (10 microg/kg) with significant induction by 2 hours, peak levels reached by 4 hours, and a return toward basal levels by 6 hours. IL-1beta (10-50 ng/mouse) administered intracerebroventricularly also led to up-regulation of the transgene 6 hours following infusion. Transgene expression was not up-regulated in hypothalamic slice cultures treated directly with IL-1beta (5-10 ng/ml media). Up-regulation of transgene expression does not appear to result from local action of IL-1beta at the level of the PVN but, rather, through as yet unidentified intermediates. The authors demonstrate phosphorylation of the cyclic amino-3-hydroxy-5-methyl-4-isoxazolepropionate response element binding protein, a transcription factor known to interact with proenkephalin regulatory sequences within the transgene, in the PVN following LPS administration. LPS induced up-regulation of the transgene was blocked by pretreatment with naltrexone, indicating an additional role for endogenous opioid systems in regulation of the PVN response to immune challenge.
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PMID:Proenkephalin transgene regulation in the paraventricular nucleus of the hypothalamus by lipopolysaccharide and interleukin-1beta. 1002 10

Using a panel of hybrid clones (common shrew--Chinese hamster and common shrew--mouse), the syntheny and localization of the following genes was determined: genes for alpha-galactosidase (GLA), acid phosphatase (ACP1), and phosphoglycerate kinase (PGK1) on chromosome de; adenosine kinase (ADK) and glucuronidase 2 (GUS2) on chromosome ik; glutamic-oxaloacetic transaminase 2 (GOT2) and peptidase D (PEPD) on chromosome hn; and glyoxalase 1 (GLO1) and phosphoglucomutase 2 (PGM2) on chromosome go. Gene for beta-galactosidase (GLB1) was assigned to arm p of chromosome mp. Thus, including previously mapped genes, the cytogenetic map of the common shrew contains 39 genes. They form seven syntheny groups and mark eight out of ten chromosomes.
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PMID:[Chromosomal localization of 10 genes on the cytogenetic map of the common shrew Sorex araneus L]. 1042 Feb 72

Experimental studies evaluated the responses of murine cardiac graft recipients to high and low levels of lipopolysaccharide (LPS) contaminating plasmid DNA preparations. Immediately prior to transplantation, graft recipients were transfected by injecting the quadriceps muscles with plasmids that encoded the murine interleukin (IL)-4 gene and beta-galactosidase (beta-gal) gene. Graft recipients transfected with plasmids encoding only the beta-gal gene served as negative plasmid controls. Three groups of mice were transfected with plasmids containing high levels of contaminating LPS: (a) nontransplanted C57B1/6 mice, (b) C57B1/6 cardiac isograft recipients, (c) DBA/2 (H-2d)-->C57BL/6 (H-2b) cardiac allograft recipients. Unexpectedly, graft failure within 24 h was observed in IL-4 transfected isograft and allograft recipients, but not in mice transfected with the beta-gal gene alone. However, histopathological findings, for example, vascular cell adhesion moelcule-1 (VCAM-1) expression in cardiac grafts and mononuclear lung infiltration, were remarkably similar for both treatment groups and consistent with LPS-induced pathology. LPS assays were used to evaluate four different methods of plasmid purification for degree of LPS contamination. A successful strategy for reducing levels of LPS contamination was identified and transfection experiments repeated in cardiac allograft recipients receiving LPS inoculum that were minimized and standardized (6.4 EU/mouse) for all treatment groups. Despite receiving substantially lower levels of LPS, in all treatment groups there was persistent cardiac graft endothelial cell activation manifested by VCAM-1 expression and persistent, albeit less severe, lung pathology. We found that plasmid contamination with LPS was unavoidable and that even very low levels can alter immune responses in transplant recipients confounding data interpretation. Thus, it is imperative to account for LPS contamination in experiments utilizing plasmid DNA for gene transfer, especially in experimental models of immunity and inflammation.
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PMID:Gene therapy in transplantation: pathological consequences of unavoidable plasmid contamination with lipopolysaccharide. 1054 38

We established a mouse melanoma model expressing beta-galactosidase for the study of tumor immunotherapy. The recombinant vector p3gal was constructed by inserting a beta-galactosidase gene into the MCS of plasmid pcDNA3. The vector then transfected the B16 cells. Through selection with 500 microg/ml G418 and in situ X-Gal staining, the melanoma cell line galB16, stably expressing beta-galactosidase was obtained. The melanoma model was successfully established after inoculation in mouse with galB16 cells. In situ X-Gal staining showed that the tumor cells expressed beta-galactosidase in vivo. With the model, we designed animal experiments for mouse tumor immunotherapy. Twenty mice were randomly assigned to four parallel groups. They received i.m. injection with saline, DNA vaccine p3gal (100 microg/mouse), adjuvant CpG 1826 (20 microg/mouse), or p3gal+CpG 1826 respectively. Our result suggested that the DNA vaccine containing beta-galactosidase gene could protect mice against the galB16 tumor challenge. In addition, when combining with the adjuvant CpG 1826, the effect was increased prominently.
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PMID:[Establishment of mouse melanoma model expressing beta-galactosidase and its application in the research of DNA vaccines against tumor]. 1563 60

Atherosclerosis results from accumulation of macrophages and extracellular matrix in the arterial wall. Decorin, a small matrix proteoglycan, is able to regulate cell proliferation, migration and growth factors' activity. We investigated the effect of decorin overexpression on atherosclerosis progression in apolipoprotein E-deficient (ApoE(-/-)) mice. Female ApoE(-/-) mice, 10 weeks old (early treatment, n = 20) and 20 weeks old (delayed treatment, n = 20) were administered intravenously with either an adenovirus (2.5 x 10(9) plaque-forming units/mouse) containing human decorin gene (Ad-Dcn) or beta-galactosidase (LacZ), or PBS. Transgenic decorin was mainly expressed in the liver, and was secreted in the plasma up to 4 weeks. Six weeks after treatment, no significant difference in aortic root lesion size was observed between LacZ- and PBS-control groups. In contrast, Ad-Dcn-treated mice showed significantly reduced atherosclerotic lesions as compared to controls in both early and delayed treatment groups (2.9 +/- 1.1% versus 5.5 +/- 0.4%; p = 0.004 and 13.4 +/- 1.3% versus 19.9 +/- 1.41%; p = 0.009, respectively). In parallel, macrophage, gelatinase activity and collagen plaque content were also reduced. Interestingly, plasma triglycerides were reduced and decorin formed complexes with transforming growth factor-beta1 (TGF-beta1) that resulted in reduced circulating free-TGF-beta1. In conclusion, systemic overexpression of decorin reduces inflammation, triglycerides and fibrosis in atherosclerotic plaques of ApoE(-/-) mice resulting in slowing down of disease progression.
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PMID:Decorin overexpression reduces atherosclerosis development in apolipoprotein E-deficient mice. 1618 63

Previously, we reported that a recombinant vaccinia virus (VACV) carrying a light-emitting fusion gene enters, replicates in, and reveals the locations of tumors in mice. A new recombinant VACV, GLV-1h68, as a simultaneous diagnostic and therapeutic agent, was constructed by inserting three expression cassettes (encoding Renilla luciferase-Aequorea green fluorescent protein fusion, beta-galactosidase, and beta-glucuronidase) into the F14.5L, J2R (encoding thymidine kinase) and A56R (encoding hemagglutinin) loci of the viral genome, respectively. I.v. injections of GLV-1h68 (1x10(7) plaque-forming unit per mouse) into nude mice with established (approximately 300-500 mm3) s.c. GI-101A human breast tumors were used to evaluate its toxicity, tumor targeting specificity, and oncolytic efficacy. GLV-1h68 showed an enhanced tumor targeting specificity and much reduced toxicity compared with its parental LIVP strains. The tumors colonized by GLV-1h68 exhibited growth, inhibition, and regression phases followed by tumor eradication within 130 days in 95% of the mice tested. Tumor regression in live animals was monitored in real time based on decreasing light emission, hence demonstrating the concept of a combined oncolytic virus-mediated tumor diagnosis and therapy system. Transcriptional profiling of regressing tumors based on a mouse-specific platform revealed gene expression signatures consistent with immune defense activation, inclusive of IFN-stimulated genes (STAT-1 and IRF-7), cytokines, chemokines, and innate immune effector function. These findings suggest that immune activation may combine with viral oncolysis to induce tumor eradication in this model, providing a novel perspective for the design of oncolytic viral therapies for human cancers.
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PMID:Eradication of solid human breast tumors in nude mice with an intravenously injected light-emitting oncolytic vaccinia virus. 1794 38


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