Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Filariasis is a major public health problem throughout many regions of the tropics. The disease is caused by several species of filarial nematode including Wuchereria bancrofti and Brugia malayi, the agents of lymphatic filariasis, and Onchocerca volvulus, the cause of 'riverblindness'. Disease caused by these worms varies depending on the tissue location of the parasite, and is associated with episodes of acute and chronic inflammation. These pathologies, including elephantiasis and blindness, rank among the most disabling in the world. Studies aimed at characterizing the molecular nature of the inflammatory stimuli derived from filarial nematodes uncovered a long forgotten secret, their symbiont Wolbachia. LPS-like molecules from these intracellular bacteria are responsible for potent inflammatory responses from macrophages and in animal models of filarial disease. Wolbachia has also been associated with severe inflammatory reactions to filarial chemotherapy, being released into the blood following the death of the parasite. Recent studies in animal models even implicate Wolbachia in the onset of lymphodema and blindness. Taken together these studies suggest a major role for Wolbachia in the pathogenesis of filarial disease. It may be possible, through the use of antibiotic therapy, to clear worms of their bacteria, in the hope that this will prevent the onset and development of filarial pathology.
Curr Mol Med 2002 May
PMID:A new insight into the pathogenesis of filarial disease. 1204 32

Retinal degeneration, either acquired or inherited, is a major cause of visual impairment and blindness in humans. Inherited retinal degeneration comprises a large group of diseases that result in the loss of photoreceptor cells. To date, 131 retinal disease loci have been identified, and 76 of the genes at these loci have been isolated (RetNet Web site). Several of these genes were first considered candidates because of their chromosomal localization or homology to genes involved in retinal degeneration in other organisms. In this review, I will discuss recent advances in the identification of genes that cause retinal degeneration, and I will describe the mechanisms of photoreceptor death and potential treatments for retinal degenerative diseases.
Cell Mol Neurobiol 2001 Dec
PMID:Molecular aspects of retinal degenerative diseases. 1204 34

Glaucoma is a leading cause of blindness. Primary open-angle glaucoma, the most common form of glaucoma, is known to increase in prevalence with age. One of its major risk factors is an elevated intraocular pressure believed to be related to the trabecular meshwork (TM), a specialized tissue located at the chamber angle of the eye. Myocilin, a gene linked to open-angle glaucomas (OAG), has been found to be expressed in the TM and a broad range of other ocular and non-ocular tissues. The purpose of this study was to examine the distribution of myocilin protein and mRNA in the TM of normal human eyes to determine whether age-related changes exist. Studies with glaucomatous eyes were carried out concurrently. Immunoperoxidase staining experiments demonstrated positive immunoreactivity for myocilin protein in both the cells and beams in all regions of the TM. The staining intensity and the myocilin level as determined by dot blot assays were not correlated with the ages of donors ranging from 8 weeks to 93 years. Neither did myocilin mRNA, detected by in situ hybridization in cells throughout the TM and quantified by relative quantitative RT-PCR, vary with age. Myocilin mRNA and protein expression in diseased tissues was either comparable to that of normal tissues or reduced. This study represents the first in-depth investigation of myocilin expression in relation to age in the TM of human eyes. The results indicate an age independence, argue thus against a direct role of myocilin and reiterate the involvement of additional factors in the pathogenesis of glaucoma.
Int J Mol Med 2002 Jul
PMID:Age independent expression of myocilin in the human trabecular meshwork. 1206 Aug 48

Cone degeneration (cd ) is an autosomal recessive canine disease that occurs naturally in the Alaskan Malamute and German Shorthaired Pointer breeds. It is phenotypically similar to human achromatopsia, a heterogeneous autosomal recessive disorder associated with three distinct loci. Both the canine disease and its human counterparts are characterized by day-blindness and absence of retinal cone function in adults. We report linkage of the canine cd locus to marker C29.002 on canine chromosome 29 at recombination fraction theta = 0.0 with a maximum LOD score of 24.68 in a series of informative outbred pedigrees derived from cd-affected Alaskan Malamutes. Conserved gene order between CFA29 and the long arm of human chromosome 8 argued for homology between the cd locus and the human achromatopsia locus, ACHM3, at 8q21-22. The canine homolog of the cyclic nucleotide-gated channel beta-subunit gene (CNGB3), responsible for the human ACHM3 disease phenotype, was mapped within the zero-recombination interval for the cd locus. A deletion removing all exons of canine CNGB3 was identified in cd-affected Alaskan Malamute-derived dogs. A missense mutation in exon 6 (D262N, nucleotide 784) within a conserved region of the same gene was detected in German Shorthaired Pointers affected with an allelic disorder. Identification of these canine disorders as homologs of human ACHM3 underscores the power of recent developments in canine genomics, and provides a valuable system for exploring disease mechanisms and evaluating potential therapeutic measures in disorders of cone photoreceptors.
Hum Mol Genet 2002 Aug 01
PMID:Canine CNGB3 mutations establish cone degeneration as orthologous to the human achromatopsia locus ACHM3. 1214 Jan 85

The retinitis pigmentosa GTPase regulator (RPGR) is encoded by the X-linked RP3 locus, which upon genetic lesions leads to neurodegeneration of photoreceptors and blindness. The findings that RPGR specifically and directly interacts in vivo and in vitro with retina-specific RPGR-interacting protein 1 (RPGRIP) and that human mutations in RPGR uncouple its interaction with RPGRIP provided the first clue for the retina-specific pathogenesis of X-linked RP3. Recently, mutations in RPGRIP were found to lead to the retinal dystrophy, Leber congenital amaurosis. However, mouse models null for RPGR had, surprisingly, a very mild phenotype compared with those observed in XlRP3-affected humans and dogs. Moreover, recent reports are seemingly in disagreement on the localization of RPGR and RPGRIP in photoreceptors. These discrepancies were compounded with the finding of RPGR mutations leading exclusively to X-linked cone dystrophy. To resolve these discrepancies and to gain further insight into the pathology associated with RPGR- and RPGRIP-allied retinopathies, we now show, using several isoform-specific antibodies, that RPGR and RPGRIP isoforms are distributed and co-localized at restricted foci throughout the outer segments of human and bovine, but not mice rod photoreceptors. In humans, they also localize in cone outer segments. RPGRIP is also expressed in other neurons such as amacrine cells. Thus, the data lend support to the existence of species-specific subcellular processes governing the function and/or organization of the photoreceptor outer segment as reflected by the species-specific localization of RPGR and RPGRIP protein isoforms in this compartment, and provide a rationale for the disparity of phenotypes among species and in the human.
Hum Mol Genet 2002 Aug 01
PMID:Species-specific subcellular localization of RPGR and RPGRIP isoforms: implications for the phenotypic variability of congenital retinopathies among species. 1214 Jan 92

The beneficial effect of plant foods on human health is unmistakable. Time and time again, studies have found foods of plant origin to reduce the risk of most major chronic illnesses suffered by the human population. Possible mechanisms for the preventative effects of these foods are discussed. Each of the plant groups reviewed was found to reduce the risk of one or more of the following: cardiovascular disease, cancer (lung, breast, colon, rectal, prostate, epithelial, stomach, esophageal, oral, pharynx, larynx, urinary tract, endometrium, pancreas, thyroid, liver, ovary, gallbladder, bladder, and kidney), diabetes, hypertension, bone degeneration, diverticulitis, constipation, gallstones, age-related blindness. Almost no evidence was found to suggest a negative effect on health due to consumption of these plant foods. Based on this material and a review of conserved animal signaling molecules we surmise that animals require these chemicals to enhance specific mammalian cellular processes, demonstrating phyto-zooidal signaling. Further, this diet dependency coupling between plants and animals probably evolved because of the abundance of a particular plant material in a local environment, which is now broken because of technological advances. In conclusion, the overwhelming majority of evidence shows that people may significantly decrease their risks of the aforementioned diseases by increasing their intake of these foods since they represent a natural method to enhance animal processes and signaling.
Int J Mol Med 2002 Oct
PMID:Communication between animal cells and the plant foods they ingest: phyto-zooidal dependencies and signaling (Review). 1223 87

Although glaucomatous optic nerve degeneration is a leading cause of worldwide blindness, neither the precise cellular mechanisms underlying neurodegeneration in glaucoma, nor effective strategies for neuroprotection are yet clear. This review focuses on diverse cellular events associated with glaucomatous neurodegeneration whose balance is critical for determination of ultimate cell fate. An improved understanding of the site of primary injury to optic nerve, the mediator pathways of apoptotic cell death and intrinsic protection mechanisms in retinal ganglion cells, the role of glial activation on the survival and death of retinal ganglion cell bodies and their axons, and the protective and destructive consequences of immune system involvement can facilitate development of effective neuroprotective strategies in glaucoma.
Mol Neurobiol 2002 Aug
PMID:Neurobiology of glaucomatous optic neuropathy: diverse cellular events in neurodegeneration and neuroprotection. 1239 55

Strategies for retargeting adenoviral (Ad) vectors have been developed, but their in vivo efficacy remains to be demonstrated. Gene delivery to specific ocular cell types represents an approach to treating many diseases that cause irreversible blindness. One of these cell types, the photoreceptor (PR), is not infected by standard Ad5-based vectors. We evaluated gene delivery after intraocular injection of Ads pseudotyped with three different fiber proteins and found three distinct patterns of infection. An intravitreally injected Ad5 vector readily infected the iris, corneal endothelium, and ciliary body, while few cells in the retina expressed transgene product. In contrast, an Ad3-pseudotyped virus selectively transduced ciliary body, of interest for treating diseases such as glaucoma. A vector pseudotyped with the fiber protein of Ad37 transduced PRs as well as ciliary body. This finding has potential application to the treatment of retinal degenerative or neovascular diseases. These studies demonstrate cell type-selective gene delivery in vivo with retargeted Ads, provide information about the cellular tropisms of several Ad serotypes, and should lead to improved strategies for preserving vision.
Mol Ther 2003 Jan
PMID:In vivo transduction of photoreceptors or ciliary body by intravitreal injection of pseudotyped adenoviral vectors. 1257 15

Usher syndrome type I (USH1) is the most frequent cause of hereditary deaf-blindness in humans. Seven genetic loci (USH1A-G) have been implicated in this disease to date, and four of the corresponding genes have been identified: USH1B, C, D and F. We carried out fine mapping of USH1G (chromosome 17q24-25), restricting the location of this gene to an interval of 2.6 Mb and then screened genes present within this interval for mutations. The genes screened included the orthologue of the Sans gene, which is defective in the Jackson shaker deaf mutant and maps to the syntenic region in mice. In two consanguineous USH1G-affected families, we detected two different frameshift mutations in the SANS gene. Two brothers from a German family affected with USH1G were found to be compound heterozygotes for a frameshift and a missense mutation. These results demonstrate that SANS underlies USH1G. The SANS protein contains three ankyrin domains and a sterile alpha motif, and its C-terminal tripeptide presents a class I PDZ-binding motif. We showed, by means of co-transfection experiments, that SANS associates with harmonin, a PDZ domain-containing protein responsible for USH1C. In Jackson shaker mice the hair bundles, the mechanoreceptive structures of inner ear sensory cells, are disorganized. Based on the known interaction between USH1B (myosin VIIa), USH1C (harmonin) and USH1D (cadherin 23) proteins and the results obtained in this study, we suggest that a functional network formed by the USH1B, C, D and G proteins is responsible for the correct cohesion of the hair bundle.
Hum Mol Genet 2003 Mar 01
PMID:Usher syndrome type I G (USH1G) is caused by mutations in the gene encoding SANS, a protein that associates with the USH1C protein, harmonin. 1258 94

Corneal disease is the most common cause of bilateral blindness in the world. Visual loss in this condition is often due to changes in morphology and function of the corneal epithelial surface. Corneal disease-1 (corn1) and corn1(2J) are spontaneous mouse mutants that develop irregular thickening of the corneal epithelium, similar to that observed in human corneal surface disease. These autosomal-recessive mutations cause an increase in the rate of proliferation of the corneal epithelial cells. Here, we report that the phenotypes in both mutants are caused by mutations within the destrin gene (also known as actin-depolymerizing factor). By positional cloning, we identified a deletion encompassing the entire coding sequence of the destrin gene in corn1 mice, and a point mutation (Pro106Ser) in the coding sequence of destrin in corn1(2J) mice. In situ analysis showed that destrin is highly expressed in the corneal epithelium. Consistent with the cellular roles for destrin, an essential regulator of actin filament turnover that acts by severing and enhancing depolymerization of actin filament, we observed that the corn1 mutations increased the content of filamentous actin in corneal epithelial cells. Our results suggest an in vivo connection between remodeling of the actin cytoskeleton and the control of cell proliferation, and a new pathway through which an aberrant actin cytoskeleton can cause epithelial hyperproliferation.
Hum Mol Genet 2003 May 01
PMID:Aberrant actin cytoskeleton leads to accelerated proliferation of corneal epithelial cells in mice deficient for destrin (actin depolymerizing factor). 1270 Jan 71


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