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

Dermal and pulmonary tuberculous lesions were produced in rabbits with BCG, biopsied, incubated in vitro with tritiated thymidine ((3)HT) under hyperbaric oxygen, quickly frozen, sectioned in a cryostat, stained for the lysosomal enzyme beta-galactosidase, autoradiographed, stained for acid-fast bacilli and counterstained with hematoxylin. As macrophages developed into epithelioid cells, they could still divide-ie, incorporate (3)HT. However, once they became fully mature epithelioid cells that were 4-plus in beta-galactosidase, they could not do so. Tuberclebacilli did not stimulate macrophage division. On the contrary, macrophages containing bacilli did not divide, except when the lesions began. During the development of tuberculous lesions, macrophages (including those rich in enzymes and those containing bacilli) died, forming caseous centers. Therefore, local cell division did not seem to be the main mechanism by which macrophages reduced their bacillary load. Such division seemed mainly to occur in young macrophages that had recently immigrated into the lesions from the bloodstream and had not yet ingested bacilli.
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PMID:Macrophage accumulation, division, maturation, and digestive and microbicidal capacities in tuberculous lesions. I. Studies involving their incorporation of tritiated thymidine and their content of lysosomal enzymes and bacilli. 455 20

Keratinocyte growth factor (KGF) stimulates epithelial cell differentiation and proliferation, which are of major importance for wound healing. Local protein administration, however, has been shown to be ineffective due to enzymes and proteases in the wound fluid. We hypothesized that delivering KGF as a non-viral liposomal cDNA gene complex is a new approach that would effectively enhance dermal and epidermal regeneration. Twenty-two rats were given an acute wound and divided into two groups to receive weekly subcutaneous injections of liposomes plus the LacZ gene (0.2 microg, vehicle), or liposomes plus the KGF cDNA (2.2 microg) and LacZ cDNA (0.2 microg). Transfection was confirmed by histochemical assays for beta-galactosidase. Planimetry, histological and immunohistochemical techniques were used to determine protein expression, dermal and epidermal regeneration. Transfection and subsequent KGF expression was found in diving cells in the granulation tissue. Epidermal regeneration was improved by 170% in rats receiving the KGF cDNA constructs by exhibiting the most rapid area and linear wound re-epithelialization, P < 0.0001. KGF improved epidermal cell net balance by increasing skin cell proliferation and decreasing skin cell apoptosis, P < 0.0001. Dermal regeneration was further improved in KGF cDNA treated animals by an increased collagen deposition and morphology, P < 0.0001. KGF cDNA increased neo-vascularization and concomitant VEGF concentrations when compared with vehicle, P < 0.01. KGF cDNA did not only stimulate epithelial cells, but also mesenchymal cells through increases in IGF-I concentration, P < 0.005. Liposomes containing the KGF cDNA gene constructs were effective in improving epidermal and dermal regeneration. KGF gene transfer to acute wounds may represent a new therapeutic strategy to enhance wound healing.
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PMID:Non-viral liposomal keratinocyte growth factor (KGF) cDNA gene transfer improves dermal and epidermal regeneration through stimulation of epithelial and mesenchymal factors. 1214 Jul 34

Beta-catenin is a critical regulator of cell behavior during embryogenesis and neoplastic processes. It also plays a crucial role in repair by modulating dermal fibroblast activity during the proliferative phase of cutaneous wound healing. We hypothesize that growth factors liberated during the initial phase of wound healing convey signals to induce activation of beta-catenin-mediated TCF-dependent signaling during the proliferative phase. Dermal fibroblasts were isolated and cultured from mice containing a beta-galactosidase reporter responsive to beta-catenin-TCF transactivation (TCF-beta-gal). Cells were stimulated with growth factors present at the initial phase of wound healing. EGF and TGF-beta1 significantly increased beta-catenin protein levels and transcriptional activity, whereas beta-catenin mRNA expression was unaffected. This increase was attributed to inactivation of GSK-3beta, a kinase important for beta-catenin destabilization. Subcutaneous injection of EGF or TGF-beta1 before wounding of TCF-beta-gal mice resulted in larger scars and fibroblasts within these wounds that strongly stained for beta-galactosidase, indicating significant beta-catenin transcriptional activity in vivo. Thus, beta-catenin-mediated signaling is activated downstream of growth factors released during the initial phase of wound repair, and may act during the proliferative phase of wound healing to integrate signals from initial phase factors into the expression of genes important during the later, remodeling phase.
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PMID:Growth factors regulate beta-catenin-mediated TCF-dependent transcriptional activation in fibroblasts during the proliferative phase of wound healing. 1472 64

Our in vivo study used an ErbB3 receptor transfection strategy to determine if topical application of EGF-like ligands would enhance repair. Partial-thickness porcine wounds transfected with adenoviral particles containing an ErbB3 receptor gene or a vehicle beta-galactosidase gene were introduced and wounds were concomitantly supplied with a variety of EGF-like ligands--EGF, epiregulin (EPR), heparin binding EGF (HB-EGF), and heregulin/neuregulin (HRG). Comparisons of cutaneous repair (resurfacing, dermal depth, proliferation, macrophage infiltration, microvascular density, apoptosis) were assessed after a 5-day healing interval. Differential effects were noted. In wounds transfected with additional ErbB3, either EPR or HB-EGF promoted resurfacing greater than EGF, HRG, or controls. Dermal responses differed significantly after EPR or HB-EGF treatments compared to EGF, HRG, ErbB3 only, or empty vehicle. Hallmarks of enhanced wound maturity were noted in EPR- and HB-EGF-treated wounds transfected with ErbB3. Our data confirmed that an ErbB3-driven pathway mediates a net positive influence in an in vivo model closely resembling human repair. The sensitivity in this system was sufficient to reveal differential outcomes following stimulation with various EGF ligands. We conclude that selective stimulation through an ErbB3-driven pathway shows promise as a therapeutic strategy to hasten wound maturity.
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PMID:Modulation of porcine wound repair with a transfected ErbB3 gene and relevant EGF-like ligands. 1743 84

Necrosis in TRAM (transverse rectus abdominis myocutaneous) still occurs in flap breast reconstruction. Blood flow may be improved by vascular endothelial growth factor (VEGF), an endogenous protein that stimulates neovascularization. Experimental studies of gene therapy with plasmid vector expressing human VEGF (hVEGF) presented inadequate results. Low level of gene expression could be the cause. To prove that high level of VEGF gene expression can minimize necrosis of TRAM flap, electroporation of VEGF plasmid was tested.Forty-two adult, male, Wistar-EPM rats were randomly distributed in 6 groups of 7 animals and 50 microg of vectors were injected in the intradermal layer of TRAM flap donor region, by electroporation: LacZ (beta-galactosidase gene); CG (no substance injected and flap elevated); P2G (empty gT plasmid in area 2); PV2G (gT-VEGF165 in area 2); P4G (empty gT plasmid in area 4); PV4G (gT-VEGF165 in area 4). Five days after flap elevation, the animals were euthanized and the degree of necrosis was analyzed by histology and paper template method.Dermal X-gal staining after electroporation with pSV2lacZ proved high rate of gene transfer. Mean values of necrosis by the paper template method were: CG (74.5%), P2G (62.2%), PV2G (41.1%), P4G (76.6%), and PV4G (59%). Degree of necrosis, preservation of muscle layer, and degree of infiltrates seen by histology were in accordance with mean values of necrosis.Intradermal injection of gT-VEGF165 in area 2, by electroporation, was effective in reducing unipedicle TRAM flap necrosis, in rats.
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PMID:Electroporation of vascular endothelial growth factor gene in a unipedicle transverse rectus abdominis myocutaneous flap reduces necrosis. 2009 14