Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

The effect of cyclosporine on hepatic ischemia was investigated. Hepatic ischemia was produced for 90 min in mongrel dogs. Experimental dogs were divided into three groups as follows: group A (control group), group B (CsA pretreatment group), group C (CsA posttreatment group). CsA was administered at a dose of 10 mg/kg body weight/day for 3 days in the pre- or postoperative period. Survival rates were 61.5% in group A, 84.6% in group B, and 30.8% in group C. Enzymatic activity such as aspartate aminotransferase and lactate dehydrogenase was highest in group C, lowest in group B, and intermediate in group A. Opposite results were obtained for serum albumin concentrations. The mechanisms of the effect was investigated using a 60-min hepatic ischemia model. Serum levels of beta-glucosidase and beta-galactosidase in group B were lower than those in group A and group C. Electronmicroscopic specimens taken at 16 h after 60-min hepatic ischemia demonstrated that the extent of ischemic injury was mildest in group B. The present study demonstrated a beneficial effect on hepatic ischemia of CsA administered for 3 days prior to the ischemia. One of the mechanisms for this beneficial effect could be the stabilization of lysosomal membranes. These results suggest that CsA should be administered to a donor before organ harvesting for liver transplantation because of this beneficial effect.
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PMID:Beneficial effect of cyclosporine pretreatment in canine liver ischemia. Enzymatic and electronmicroscopic studies. 190 40

The effect of glucocorticoids on the release of lysosomal enzymes was studied in liver ischemia created by dearterialization and in hemorrhagic shock in pigs. In shock the treatment with glucocoticoids suppressed the release of beta-glucosidase and beta-galactosidase into the circulation. The release of S-GOT was also suppressed in the treated group. However, a contrary effect was observed in liver ischemia indicating that glucocorticoids might even be harmful to the dearterialized hypoxic liver. Provided the plasma increase of acid hydrolases can be interpreted as quantitative signs of cell damage, the findings indicate that glucocorticoids may be of benefit in shock but not after hepatic dearterialization.
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PMID:Effect of glucocorticoids on release of lysosomal enzymes in liver ischemia and hemorrhagic shock in pigs. 445 84

An experimental model of canine normothermic renal ischemia was used to determine whether lysosomal urinary enzyme excretion reflects the extent of ischemic cellular injury, as assessed by subsequent renal function (serum creatinine level) and morphologic changes. The value of a lysosomal membrane-stabilizing agent (methylprednisolone) in protecting kidneys from ischemic damage by preventing lysosomal enzyme release was assessed. Results showed conclusively that urinary enzyme activities of beta-galactosidase and N-acetyl-beta-glucosaminidase are valuable indicators of renal cellular damage and functional outcome after ischemic injury, and that methylprednisolone at a dose of 30 mg/kg, given intravenously 1 hour before a 1-hour period of normothermic ischemia, protects the kidney both biologically and morphologically, by reducing the excretion of lysosomal enzymes after revascularization.
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PMID:Beneficial effects of methylprednisolone on urinary excretion of lysosomal enzymes in acute renal ischemia. 640 84

Vascular endothelial growth factor (VEGF) is a secreted endothelial cell-specific angiogenic growth factor. VEGF gene transfer strategies to stimulate focal angiogenesis could be used to ameliorate myocardial ischemia. To induce angiogenesis in vivo, we have constructed a replication-defective herpes simplex virus type 1 (HSV-1) amplicon vector that places the human VEGF-165 cDNA under the transcriptional control of the HSV immediate-early 4/5 promoter (HSVhvegf). Transduction of NIH 3T3 fibroblasts with HSVhvegf resulted in the secretion of high levels of biologically active VEGF, as assayed by microvascular endothelial mitogenesis. By use of an ex vivo protocol, BLK-CL4 fibroblasts were transduced with HSVhvegf or control HSVlac virus (expressing Escherichia coli beta-galactosidase), resuspended in basement membrane extract (matrigel), and coinjected subcutaneously into syngeneic C57BL/6 mice. One week later, the matrigel plugs with HSVhvegf showed a strong angiogenic response, in contrast to the plugs with HSVlac-transduced fibroblasts. These data indicate that transduction with HSVhvegf virus can induce an angiogenic response in vivo and suggest that this is a viable gene therapy approach for tissue ischemia.
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PMID:Expression of vascular endothelial growth factor from a defective herpes simplex virus type 1 amplicon vector induces angiogenesis in mice. 753 Jun 6

Adenoviruses have been proposed as potential vectors for gene therapy in the central nervous system, but there are no reports of their use in the treatment of a brain disease. Because central administration of interleukin-1 receptor antagonist protein (IL-1ra) reduces ischemic brain damage, we determined whether a recombinant adenovirus vector carrying the human IL-1ra cDNA (Ad.RSVIL-1ra) could be used to ameliorate brain injury in permanent focal ischemia. Groups of six rats received intraventricular injections of Ad.RSVIL-1ra or a control adenovirus containing the Escherichia coli beta-galactosidase gene (Ad.RSVlacZ). Histochemical staining for beta-galactosidase 5 days after virus injection indicated that transgene expression was confined primarily to the cells lining the ventricle. The concentrations of IL-1ra injected animals, achieving levels of 9.1 +/- 3.3 ng/g in brain and 23.7 +/- 22.5 ng/ml in CSF. In these animals, cerebral infarct volume resulting from 24 h of permanent middle cerebral artery occlusion was reduced 64%. These studies demonstrate that adenoviral vectors can be used to deliver genes that attenuate brain injury.
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PMID:Attenuation of stroke size in rats using an adenoviral vector to induce overexpression of interleukin-1 receptor antagonist in brain. 779 Apr 4

The functional significance of ammonia production in brain under physiological or pathological conditions is not clearly known. NH4+ stimulates Na+, K+ activated ATPase causing stabilization of neuronal membranes of which gangliosides are major structural components. Moreover ammonia is known to inhibit lysosomal enzymes which include enzymes degrading gangliosides. Gangliosides have been shown to stimulate neuritogenesis in neuronal cultures and prevent the damage of the neurons from glutamate toxicity particularly in areas of brain ischemia. Hyperammonemia without any behavioural changes was induced in experimental rats by intraperitoneal administration of either a single dose (0.8 mmol/100 g wt.) or by six 'hourly' doses (0.6 mmol/100 g wt.) of ammonium acetate. An increase in the content of gangliosides along with a rise in the content of GD1A and GD1B without any change in beta-galactosidase and N-acetylhexosaminidase was observed in cerebral cortex, cerebellum, and brain stem, following the administration of single dose of ammonium acetate. Gangliosides, after extraction from the different brain regions, were estimated by the thiobarbituric acid method and expressed in terms of sialic acid. Individual gangliosides were separated and estimated by thin layer chromatography using resorcinol as the staining agent. These results suggest that ammonia production in the neuronal pathways in brain either as a result of repeated stimulation under physiological conditions or as a result of focal ischemia or injury, may likewise cause an increase in the content of gangliosides which may help in neuritic growth (physiological conditions facilitating synaptic plasticity) and may exert a protective effect on the neurons in the ischemic area against glutamate toxicity.
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PMID:Functional relationship between ammonia and gangliosides in brain. 817 76

Advances in liver surgery and transplantation have lead to a steady increase in the number of these interventions. Prompt quantitative assessment of hepatic of hepatic function and a patient's subsequent morbidity and mortality following surgery remain difficult despite the currently utilized historic markers of hepatic parenchymal injury (e.g., aspartate transaminase [AST], lactate dehydrogenase [LDH] gamma-glutamyl transpeptidase [GGT]). Increases in serum glycohydrolase activities appear to provide sensitive and quantitative markers of hepatic ischemia/reperfusion injury. In 10 male swine (25 to 35 kg body weight) following 30, 45, and 90 minutes of acute hepatic ischemia, the systemic release of eight different glycohydrolases and lipid peroxides into serum were determined and compared with pre- and postischemic serum levels of LDH, GGT, and AST. The rapid release of glycohydrolases into serum was directly proportional to the length of the ischemic period from 30 to 90 minutes; e.g., beta-glucosidase, mean 1.9-fold increase at 30 minutes; 8.3-fold at 45 minutes; and 22.8-fold at 90 minutes; P < .002) and the activities peaked within the first 3 hours postischemia. In constrast, AST, LDH, and GGT were released slowly and peaked 20 to 30 hours after hepatic blood flow was restored. In swine with fatal outcomes (90 minutes of ischemia), all enzyme levels increased continuously during the final hours of life. However, in swine that survived hepatic ischemia/reperfusion injury (45 minutes of ischemia) the glycohydrolases, but not AST, LDH, and GGT, declined after 2 to 3 hours' postischemia and the serum lipid peroxide levels followed the same pattern. Serum beta-galactosidase and beta-glucosidase levels are sensitive markers that rise as quickly as traditional enzyme markers (AST, LDH, GGT) following hepatic ischemic injury; moreover, the glycohydrolases have the added value of serving as predictors of survival.
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PMID:Glycohydrolases as markers of hepatic ischemia-reperfusion injury and recovery. 870 56

Pretreatment by a sublethal insult is associated with induction of stress proteins and with protection from subsequent injury. Heat pretreatment protects the brain from subsequent ischemia, and is shown here to protect primary astrocyte cultures from subsequent oxygen-glucose deprivation. To determine whether the expression of a single stress protein, HSP-70, could account for much of this protection, we expressed HSP-70 or beta-galactosidase in astrocytes using retroviral vectors. Only 12% of astrocytes expressing HSP-70 died after 7 hours of oxygen-glucose deprivation compared to 65% of astrocytes expressing beta-galactosidase and 82% of normal astrocytes. Our data provide direct evidence that selective expression of HSP-70 enhances the survival of astrocytes challenged with heat or oxygen-glucose deprivation.
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PMID:Over-expression of HSP-70 protects astrocytes from combined oxygen-glucose deprivation. 873 Jul 98

A non-contracting scar following myocardial infarction can adversely affect ventricular topography and hemodynamic function. Gene transfer has the potential to prevent or alter such pathophysiological processes. Normal myocardium is a proven target for delivery of DNA or viral vectors but the potential for gene therapy in ischemic myocardium has not been evaluated. In an initial series of experiments, we determined whether the direct injection of reporter genes into hearts subjected to coronary artery occlusion followed by reperfusion could result in gene expression comparable to the levels observed in non-occluded normal hearts. Anesthetized rats were subjected to 15 min or 60 min of proximal coronary occlusion or sham operation. Luciferase gene under the control of the Rous sarcoma virus promoter was injected directly into the anterior left wall. At 1 week, high expression of luciferase was observed in both the ischemic/reperfused and non-ischemic tissue. Thus DNA transfer by direct injection is possible after ischemic injury and uptake and expression are not impaired. In a second series of experiments, myocardial infarcts in dogs were injected with a beta-galactosidase expressing retroviral vector. LNPOZ. Six to 11 days later frozen sections revealed macroscopically visible expression of beta-galactosidase activity. Not only can foreign genes be taken up by direct injection of DNA or retroviruses into ischemic/reperfused myocardium but they can be transcribed and the protein synthetic machinery of the injured cells can produce recombinant polypeptides that retain enzymatic activity. These results open the way for the investigation of gene therapy in models of ischemia.
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PMID:Ischemic/reperfused myocardium can express recombinant protein following direct DNA or retroviral injection. 874 21

A replication-deficient adenovirus was used for ex vivo gene transfer into rat heart grafts under conditions simulating clinical transplantation. The adenoviral vector, AdHCMVsp1LacZ, containing an expression cassette of Escherichiae coli lacZ, was used to perfuse heart grafts during cold ischemia before transplantation. Heart grafts were perfused with University of Wisconsin (UW) solution containing either 0 pfu, 5 x 10(10) pfu, or 1 x 10(11) pfu of viral vector, and were preserved for either 2 or 4 h and then transplanted into syngeneic recipients. The animals were killed at 1, 7, and 14 days after transplantation. The infection rate was assessed by histochemical staining for beta-galactosidase. Using polymerase chain reaction (PCR), viral DNA presence was confirmed in every graft perfused with viral vectors. The protein production from the transfected gene was confirmed by a functional protein assay. An efficient gene transfer was achieved with an infection rate of 1%-1.5% for all cardiac myocytes, as assessed by 5-bromo-4-chloro-indolyl-beta-D-galactopyranoside (X-gal) staining. All studies were negative in the control grafts. Gene expression persisted for at least 10 days after transplantation. We thus conclude that an efficient adenovirus-mediated gene transfection and expression of gene products can be achieved in ex vivo perfusion of the heart graft during cold preservation.
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PMID:Adenovirus-mediated gene transfer using ex vivo perfusion of the heart graft. 885 96


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