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)

This report describes a third mucopolysaccharidosis in animals: canine mucopolysaccharidosis VII. The affected dog was the offspring of a father-daughter mating. Weakness in the rear legs was evident at 8 weeks of age and became progressively worse. He had a large head, a shortened maxilla, and corneal granularities. Most joints were extremely lax, easily subluxated, with joint capsules that were swollen and fluctuant. The dog was alert and had apparently normal pain perception. At 13 months of age, there was radiographic evidence of extensive skeletal disease including bilateral femoral head luxation, abnormalities in the shape and density of the carpal and tarsal bones, radiolucent lesions of the epiphyseal regions of most long bones, and cervical vertebral dysplasia and platyspondylia. The electrophoretic pattern of precipitated glycosaminoglycans indicated a predominance of chondroitin sulfate. The animal died suddenly from gastric dilatation. There was generalized hepatomegaly, thickening of the atrioventricular heart valves, and generalized polyarthropathy. Vacuolated cytoplasm was observed in hepatocytes, keratocytes, fibroblasts, chondrocytes and cells of the synovial membrane, retinal pigment epithelium, and cardiac valves. Neurons had cytoplasmic vacuoles. Electron microscopy demonstrated membrane-bound cytoplasmic inclusions in polymorphonuclear leukocytes, hepatocytes, synovium, heart valves and spleen. The activities of 12 lysosomal hydrolases were determined in liver from the affected and control dogs: beta-glucuronidase (EC 3.2.1.31), beta-hexosaminidases A and B (EC 3.2.1.30), alpha-hexosaminidase (EC 3.2.1.-), alpha-L-iduronidase (EC 3.2.1.76), alpha-galactosidase A (EC 3.2.1.22), beta-galactosidase (EC 3.2.1.23), arylsulfatases A and B (EC 3.1.6.1), acid alpha-mannosidase (EC 3.2.1.24), acid beta-mannosidase (EC 3.2.1.25), and N-acetyl-D-galactosamine-6-sulfate sulfatase (EC 3.1.6.-).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Beta-glucuronidase deficiency in a dog: a model of human mucopolysaccharidosis VII. 643 80

Microbial-derived beta-galactosidase (beta-gal) enzyme preparations improve in vivo lactose digestion and tolerance through enhanced gastrointestinal digestion of lactose. Three different beta-gal preparations, Lactogest (soft gel capsule), Lactaid (caplet), and DairyEase (chewable tablet) and placebo were fed to lactose maldigesters with either 20 g or 50 g of lactose to compare the efficacy of these products and to further establish a dose-response relationship for use. All enzyme preparations dramatically reduced both the peak and total breath hydrogen production when fed with milk containing 20 g of lactose. Four capsules of Lactogest, two caplets of Lactaid, or two tablets of DairyEase (each treatment containing approx 6000 IU) reduced total hydrogen production significantly (P < 0.05) below that observed with two capsules of Lactogest (containing approx 3000 IU) in a stoichiometric manner. Symptoms were significantly (P < 0.05) less severe with all the beta-gal products. In contrast, with 50 g of lactose in water, peak and total hydrogen production was modestly, but not significantly reduced by the enzyme treatment. Furthermore, symptom scores for bloating, cramping, nausea, pain, diarrhea, and flatus were not different between treatments and the control. The 50-g lactose dose appeared to overwhelm the ability of either 3000 or 6000 IU of beta-gal to assist significantly with lactose digestion. Results from these studies demonstrate the relative equivalency of chewable, caplet, and soft-gel beta-gal products, based on IUs of enzyme fed.
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PMID:Comparative effects of exogenous lactase (beta-galactosidase) preparations on in vivo lactose digestion. 822 76

Recombinant herpes simplex virus-1 encoding the rat preproenkephalin A (HSVLatEnk1) was generated for driving the expression of preproenkephalin A-derived peptides in dorsal root ganglia of rats in vivo. Three weeks after infection via the hind footpads, quantitative RT-PCR and in situ hybridization experiments showed a strong expression of preproenkephalin A mRNA in lumbar dorsal root ganglia. In addition, a 40-160% increase in radioimmunoassayable Met-enkephalin-like material concentrations was found in the dorsal spinal cord and dorsal root ganglia, respectively, at the lumbar level in HSVLatEnk1-infected rats as compared with animals infected with beta-galactosidase-encoding recombinant herpes simplex virus-1 or control rats. These data demonstrate the efficacy of the preproenkephalin A encoding vector and suggest that it should help in elucidating the role of Met-enkephalin-containing primary afferent fibers in pain transmission and/or control.
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PMID:Herpes simplex virus 1-mediated transfer of preproenkephalin A in rat dorsal root ganglia. 948 53

To test the utility of gene therapeutic approaches for the treatment of pain, a recombinant herpes simplex virus, type 1, has been engineered to contain the cDNA for an opioid peptide precursor, human preproenkephalin, under control of the human cytomegalovirus promoter. This virus and a similar recombinant containing the Escherichia coli lacZ gene were applied to the abraded skin of the dorsal hindpaw of mice. After infection, the presence of beta-galactosidase in neuronal cell bodies of the relevant spinal ganglia (lacZ-containing virus) and of human proenkephalin (preproenkephalin-encoding virus) in the central terminals of these neurons indicated appropriate gene delivery and expression. Baseline foot withdrawal responses to noxious radiant heat mediated by Adelta and C fibers were similar in animals infected with proenkephalin-encoding and beta-galactosidase-encoding viruses. Sensitization of the foot withdrawal response after application of capsaicin (C fibers) or dimethyl sulfoxide (Adelta fibers) observed in control animals was reduced or eliminated in animals infected with the proenkephalin-encoding virus for at least 7 weeks postinfection. Hence, preproenkephalin cDNA delivery selectively blocked hyperalgesia without disrupting baseline sensory neurotransmission. This blockade of sensitization was reversed by administration of the opioid antagonist naloxone, apparently acting in the spinal cord. The results demonstrate that the function of sensory neurons can be selectively altered by viral delivery of a transgene. Because hyperalgesic mechanisms may be important in establishing and maintaining neuropathic and other chronic pain states, this approach may be useful for treatment of chronic pain and hyperalgesia in humans.
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PMID:Antihyperalgesic effects of infection with a preproenkephalin-encoding herpes virus. 1007 63

Despite many decades of drug development, effective therapies for neuropathic pain remain elusive. The recent recognition of spinal cord glia and glial pro-inflammatory cytokines as important contributors to neuropathic pain suggests an alternative therapeutic strategy; that is, targeting glial activation or its downstream consequences. While several glial-selective drugs have been successful in controlling neuropathic pain in animal models, none are optimal for human use. Thus the aim of the present studies was to explore a novel approach for controlling neuropathic pain. Here, an adeno-associated viral (serotype II; AAV2) vector was created that encodes the anti-inflammatory cytokine, interleukin-10 (IL-10). This anti-inflammatory cytokine is known to suppress the production of pro-inflammatory cytokines. Upon intrathecal administration, this novel AAV2-IL-10 vector was successful in transiently preventing and reversing neuropathic pain. Intrathecal administration of an AAV2 vector encoding beta-galactosidase revealed that AAV2 preferentially infects meningeal cells surrounding the CSF space. Taken together, these data provide initial support that intrathecal gene therapy to drive the production of IL-10 may prove to be an efficacious treatment for neuropathic pain.
Mol Pain 2005 Feb 25
PMID:Controlling neuropathic pain by adeno-associated virus driven production of the anti-inflammatory cytokine, interleukin-10. 1581 97

Galectin-1 (Gal1) was the first identified member of the galectin family of beta-galactosidase-binding proteins. Gal1 has important roles in processes fundamental to growth and survival of an organism, including cell adhesion, cell proliferation and apoptosis, and is expressed in many tissues, including the nervous system. In the 1980s, research focused on the developmental regulation of Gal1 expression during neurogenesis. Gal1 was found to be expressed mainly in peripherally-projecting neurons beginning early in neurogenesis, and its expression is maintained at high levels in subpopulations of these neurons in the adult rodent. Although the expression pattern of Gal1 implied that it may be involved in axonal guidance or targeting of subsets of sensory and motoneurons, possible roles of Gal1 in the nervous system had not been confirmed until recently. Gal1 has since been shown to be required for the proper guidance of subsets of primary olfactory axons (to targets in the olfactory bulb) and of primary somatosensory axons (to targets in the superficial dorsal horn). In addition, Gal1 has been implicated in the regenerative response of axons following peripheral nerve injury. Gal1 has been shown to promote axonal regeneration through the activation of macrophages. Also, Gal1 may act within the injured neuron to enhance regrowth: the injury-induced regulation of Gal1 in numerous types of peripherally- and centrally-projecting neurons correlates positively with the regenerative potential of their axons. In this review, we discuss the expression pattern of Gal1 in sensory and motoneurons, and the potential roles of Gal1 in development, axonal regeneration and neuropathic pain.
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PMID:Expression and functions of galectin-1 in sensory and motoneurons. 1602 60

Micro-needle arrays increase skin permeability by forming channels through the outer physical barrier, without stimulating pain receptors populating the underlying dermis. It was postulated that micro-needle arrays could facilitate transfer of DNA to human skin epidermis for cutaneous gene therapy applications. Platinum-coated "wet-etch" silicon micro-needles were shown to be of appropriate dimensions to create micro-conduits, approximately 50 microm in diameter, extending through the stratum corneum (SC) and viable epidermis. Following optimisation of skin explant culturing techniques and confirmation of tissue viability, the ability of the micro-needles to mediate gene expression was demonstrated using the beta-galactosidase reporter gene. Preliminary studies confirmed localised delivery, cellular internalisation and subsequent gene expression of pDNA following micro-needle disruption of skin. A combination of this innovative gene delivery platform and the ex vivo skin culture model will be further exploited to optimise cutaneous DNA delivery and address fundamental questions regarding gene expression in skin.
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PMID:Cutaneous DNA delivery and gene expression in ex vivo human skin explants via wet-etch micro-fabricated micro-needles. 1630 10

In this study, we evaluated the possible use of lentiviral vectors in the treatment of neuropathic pain. We chose to administer GDNF-expressing vectors because of the known beneficial effect of this trophic factor in alleviation of neuropathic pain in adult rodents. Lentiviral vectors expressing either GDNF or control, green fluorescent protein or beta-galactosidase, were injected unilaterally into the spinal dorsal horn 5 weeks before a spinal nerve ligation was induced (or sham surgery for the controls). We observed that intraspinally administered lentiviral vectors resulted in a large and sustained expression of transgenes in both neurons and glial cells. Injection of GDNF-expressing viral vectors induced a significant reduction of ATF-3 up-regulation and IB4 down-regulation in damaged DRG neurons. In addition, it produced a partial but significant reversal of thermal and mechanical hyperalgesia observed following the spinal nerve ligation. In conclusion, our study suggests that lentiviral vectors are efficient tools to induce a marked and sustained expression of trophic factors in specific areas of the CNS and can, even if with some limitations, be efficient in the treatment of neuropathic pain.
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PMID:Reversal of neurochemical changes and pain-related behavior in a model of neuropathic pain using modified lentiviral vectors expressing GDNF. 1650 88

Herpes Simplex Virus type 1 (HSV-1) vectors are known to inhibit nociceptive transmission at the spinal cord after peripheral applications. Similar approaches may also be useful when applied at the supraspinal pain control system as the system includes pronociceptive (facilitatory) components. We performed a study aimed to analyse the migration of HSV-1 along with the inhibition of pronociception from the medullary dorsal reticular nucleus (DRt), a major facilitatory component of the supraspinal pain control system. To study the migration, a HSV-1 vector expressing lacZ under control of the human cytomegalovirus (hCMV) promoter was injected in the DRt and the expression of beta-galactosidase (beta-gal) was detected at 2, 4, 7, 10 and 14 days. Numerous beta-gal-immunoreactive neurons were observed at the injection site until day 4, and at some of the brain areas projecting to the DRt until day 7. To block the pronociceptive effects of the DRt, a HSV-1 vector expressing the preproenkephalin transgene, under the control of hCMV promoter, was injected into the DRt. Behavioural evaluation was performed at the time-points referred above, using the paw withdrawal latency test to evaluate thermal nociceptive responses. Anti-hyperalgesic effects persisted during 4 days, decreasing after that time-point. The present study demonstrates that selective migration of HSV-1 should be considered in gene therapy strategies based on HSV-1 injections into the brain. The study also shows that it is possible to decrease pain facilitation from the brain using opioidergic inhibition of pronociceptive supraspinal areas.
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PMID:Dynamic of migration of HSV-1 from a medullary pronociceptive centre: antinociception by overexpression of the preproenkephalin transgene. 1904 88

Neuropathic pain is a very complex disease, involving several molecular pathways. Current available drugs are usually not acting on the several mechanisms underlying the generation and propagation of pain. We used spared nerve injury model of neuropathic pain to assess the possible use of human mesenchymal stem cells (hMSCs) as anti-neuropathic tool. Human MSCs were transplanted in the mouse lateral cerebral ventricle. Stem cells injection was performed 4 days after sciatic nerve surgery. Neuropathic mice were monitored 7, 10, 14, 17, and 21 days after surgery. hMSCs were able to reduce pain-like behaviors, such as mechanical allodynia and thermal hyperalgesia, once transplanted in cerebral ventricle. Anti-nociceptive effect was detectable from day 10 after surgery (6 days post cell injection). Human MSCs reduced the mRNA levels of the pro-inflammatory interleukin IL-1beta mouse gene, as well as the neural beta-galactosidase over-activation in prefrontal cortex of SNI mice. Transplanted hMSCs were able to reduce astrocytic and microglial cell activation.
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PMID:Intra-brain microinjection of human mesenchymal stem cells decreases allodynia in neuropathic mice. 1993 63


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