PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “HOMOLOGOUS WASTING DISEASE”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 55 records · Page 3Linked to original sources
PubMed2002

Genetic characterization of porcine circovirus-2 field isolates from PMWS pigs.

PMWS is a new emerging disease in swine herds worldwide. Field isolates of PCV-2, a putative major causative agent of PMWS, were isolated and genetically characterized. Viral genome of two field isolates (PC201DJ and PC201SS) from pigs showing typical PMWS was sequenced. The nucleotide sequence homology with other PCV-2 isolates was ranging from 95% to 99% in complete viral genomic sequence. The highly conserved nonanucleotide motif of replication origin was identical to that of other PCV-2 isolates. To determine the genetic heterogeneity of PCV-2 isolates, the phylogenetic tree based on the complete genome of PCV-2 isolates were constructed. Two PCV-2 field isolates were closely related to Canadian isolates of PCV-2. PCV-2 isolated from field may have an origin of North America and is possibly originated from importation of breeding stocks. The result indicates that although the genome of PCV-2 is relatively stable in general, minor genetic variations exist among PCV-2 isolates from the different geographic locations. These differences of viral genome might have an important implication for genetic characteristics of PCV-2 infection. Three major immunorelevant epitopes of capsid protein showed variations in amino acid sequences. Also, the variance of amino acid sequence in antigenic epitope existed between two Korean PCV-2 isolates.

Animals↗
PubMed1998

Characterization of novel circovirus DNAs associated with wasting syndromes in pigs.

Porcine circovirus (PCV) was initially recognized as a contaminant of continuous pig kidney cell lines and was not thought to be pathogenic. Antibodies reactive to the cell culture isolate of PCV (PCV PK-15) are prevalent in the swine population worldwide. Recently, PCV PK-15-like antigen and nucleic acid were demonstrated in lesions associated with wasting syndromes in pigs in North America and Europe. Monoclonal antibodies raised to circoviruses isolated from pigs with wasting syndromes highlighted differences between these circoviruses and the PCV PK-15 cell culture isolate. This has led to speculation that a new pathogenic PCV may have emerged in the swine populations of several countries. We report the cloning and characterization of novel circovirus DNAs purified from virus isolates made from tissues of North American and European pigs with wasting syndromes. These North American and European circoviruses form a closely related group at the nucleotide sequence level (> 96% intra-group nucleotide sequence identity) but exhibit < 80% nucleotide sequence identity with the PCV PK-15 cell culture isolate. This report provides evidence for a new type of possibly pathogenic PCV. We propose that these new circoviruses should be referred to as PCV2 as opposed to the original PK-15 cell culture isolate, which should be referred to as PCV1.

Amino Acid Sequence↗
PubMed1997

Interactions between subunits of the human epithelial sodium channel.

The human epithelial sodium channel (hENaC) mediates Na+ transport across the apical membrane of epithelia, and mutations in hENaC result in hypertensive and salt-wasting diseases. In heterologous expression systems, maximal hENaC function requires co-expression of three homologous proteins, the alpha, beta, and gammahENaC subunits, suggesting that hENaC subunits interact to form a multimeric channel complex. Using a co-immunoprecipitation assay, we found that hENaC subunits associated tightly to form homo- and heteromeric complexes and that the association between subunits occurred early in channel biosynthesis. Deletion analysis of gammahENaC revealed that the N terminus was sufficient but not necessary for co-precipitation of alphahENaC, and that both the N terminus and the second transmembrane segment (M2) were required for gamma subunit function. The biochemical studies were supported by functional studies. Co-expression of gamma subunits lacking M2 with full-length hENaC subunits revealed an inhibitory effect on hENaC channel function that appeared to be mediated by the cytoplasmic N terminus of gamma, and was consistent with the assembly of nonfunctional subunits into the channel complex. We conclude that the N terminus of gammahENaC is involved in channel assembly.

Animals↗
PubMed2002

Endogenously expressed epithelial sodium channel is present in lipid rafts in A6 cells.

The epithelial sodium channel (ENaC) present in the kidney collecting duct, distal colon, and the lung is responsible for salt reabsorption and whole body volume regulation. It is composed of three homologous subunits, alpha, beta, and gamma, and mutations to these subunits can lead to the salt wasting disease pseudohypoaldosteronism type I, associated with decreased channel density at the plasma membrane or to the hypertensive disorder, Liddle's syndrome, in which channel residency time at the plasma membrane is enhanced. Regulation of ENaC trafficking and turnover is therefore critical to sodium homeostasis. In this study we examined whether ENaC is present in the cholesterol-enriched microdomains commonly called lipid rafts, in the endogenously expressing A6 cell line. We demonstrate that a fraction of alpha, beta, and gamma ENaC is present in detergent-insoluble membranes, that subunits exist in membranes that float on discontinuous sucrose density gradients, and that methyl-beta-cyclodextrin treatment causes a redistribution of ENaC subunits to higher density membranes. Furthermore, chronic aldosterone stimulation results in a shift in the membrane density of all three subunits. Biotinylation of apical membrane proteins revealed that ENaC is present in lipid rafts on the plasma membrane. In conclusion, these results show that ENaC is present in lipid rafts both intracellularly and on the cell surface. Raft association may be important for trafficking and/or function of the channel.

Cells, Cultured↗
PubMed1998

Nucleotide sequence of porcine circovirus associated with postweaning multisystemic wasting syndrome in pigs.

This article describes the nucleotide sequence of a porcine circovirus (PCV) which possesses a high degree of association with postweaning multisystemic wasting syndrome (PMWS), a newly described disease of young pigs. The DNA sequence of this PMWS-associated PCV (pmws PCV) has 68% homology with that of a previously published nonpathogenic strain of PCV. The strains appear to be closely related yet distinct from one another.

Amino Acid Sequence↗
PubMed1973

Prophylaxis and immunization in mice by use of virus-free defective T particles to protect against intracerebral infection by vesicular stomatitis virus.

Defective interfering T particles of vesicular stomatitis virus provide remarkable protection against viral disease and death when introduced intracerebrally in large numbers along with an otherwise rapidly fatal low dose of standard infectious virus. This profound prophylactic effect of defective T particles is due to homologous autointerference since it is serotype-specific and interferon is not induced. This protective effect can be demonstrated only with preparations of T particles that have been purified completely free of infectious virions. When pure T particles are injected intracerebrally along with large doses of infectious virus, they convert an otherwise rapidly fatal disease process to a slowly progressing virus infection that generally terminates in death after many days of wasting disease and paralysis. Intracerebral injection of virus-free T particles alone is apparently innocuous to mice and stimulates immunity to massive doses of homologous infectious virus. In vitro, virus-free T particles at extremely high multiplicities depress cellular RNA and protein synthesis and kill BHK21 cells in culture, but do not exhibit such effects at moderately high multiplicities.

Animals↗
PubMed1990

The pathogenesis of bovine virus diarrhoea virus infections.

Bovine virus diarrhoea virus (BVDV) disease in cattle ranges from the transient acute infections, which may be inapparent or mild, to mucosal disease which is inevitably fatal. On occasions the acute infections can lead to clinical episodes of diarrhoea and agalactia but as these syndromes cannot be reproduced experimentally, the pathogenesis remains unclear. The immunosuppressive effect of acute BVDV infections can enhance the clinical disease of other pathogens and this may be an important part of the calf respiratory disease complex. Although BVDV antigen has been demonstrated within the lymphoid tissues, for prolonged periods, the evidence for viral latency remains to be proven. Venereal infection is shown to be important in the transfer of virus to the foetus and congenital infections can cause abortions, malformations and the development of persistently viraemic calves. The two biotypes of the virus, non-cytopathogenic and cytopathogenic, are described. Their sequential role in the pathogenesis of mucosal disease arises from the initial foetal infection with the non-cytopathogenic virus and the subsequent production of persistently viraemic calves. These calves may later develop mucosal disease as a result of superinfection with a "homologous" cytopathogenic virus. The possible origin of this biotype by mutation is discussed. Chronic disease is defined as a progressive wasting and usually diarrhoeic condition; it is suggested that this may develop following superinfection of persistently viraemic cattle with a "heterologous" cytopathogenic biotype.

Acute Disease↗
PubMed1997

Expression and cloning of the human X-linked hypophosphatemia gene cDNA.

X-linked hypophosphatemia (XLH), which is a heritable metabolic bone disease characterized biochemically by selective renal phosphate (Pi) wasting, is associated with mutations in the PEX (Phosphate-regulating gene with homologies to Endopeptidases on the X-chromosome) gene. To further explore the physiologic role of PEX and define its effect in XLH we have determined the expression and tissue distribution. Northern analysis found abundant PEX mRNA in a restricted pattern, predominantly in adult ovary and fetal lung. In addition, PEX expression was also found in adult lung and fetal liver. A PEX cDNA of 2550 basepairs, which contains the full PEX coding region, was isolated from a human ovary cDNA library. The PEX cDNA shows high homology to other membrane-bound zinc metallopeptidases. The presence of PEX in nonosseous tissues strongly suggests features of a systemic role, rather than a unique function in bone development.

Amino Acid Sequence↗
PubMed1991

The pathways for bovine virus diarrhoea virus biotypes in the pathogenesis of disease.

BVDV infections of cattle ranges from the transient acute infections, which may be inapparent or mild, to mucosal disease which is inevitably fatal. On occasions the acute infections can lead to clinical episodes of diarrhoea an agalactia but as these syndromes cannot be reproduced experimentally, the pathogenesis remains unclear. The immunosuppressive effect of acute BVDV infections can enhance the clinical disease of other pathogens and this may be an important part of the calf respiratory disease complex. Although BVDV antigen has been demonstrated within the lymphoid tissues, for prolonged periods, the evidence for viral latency remains to be proven. Venereal infection is shown to be important in the transfer of virus to the foetus and congenital infections can cause abortions, malformations and the development of persistently viraemic calves. The two biotypes of BVDV, non-cytopathogenic and cytopathogenic, are described. Their sequential role in the pathogenesis of mucosal disease arises from the initial foetal infection with the non-cytopathogenic virus and the subsequent production of persistently viraemic calves. These calves may later develop mucosal disease as a result of superinfection with a "homologous" cytopathogenic virus and the possible origin of this biotype by mutation is discussed. Chronic disease is defined as a progressive wasting and usually diarrhoeic condition; it is suggested that this may develop following superinfection of persistently viraemic cattle with a "heterologous" cytopathogenic biotype.

Animals↗
PubMed2006

Two novel PHEX mutations in Taiwanese patients with X-linked hypophosphatemic rickets.

BACKGROUND: X-linked hypophosphatemic rickets (XLH) is an X-linked dominant disease characterized by renal phosphate wasting, hypophosphatemia, aberrant vitamin D metabolism, and defective bone mineralization. The disease is caused by mutations in the PHEX gene (phosphate-regulating gene with homologies to endopeptidases on the X-chromosome) located at Xp22.1. To date, a variety of PHEX mutations have been identified in these patients. METHODS: PCR and direct sequencing was performed for all exons and intron-exon boundaries of the PHEX gene in two XLH families. RESULTS: Two novel mutations, including a missense mutation (L206W) in exon 5 and a frameshift mutation (nucleotide 1826_1830delAAAAG, stop after codon 610) in exon 18 were discovered and the laboratory and radiographic findings for these patients analyzed. CONCLUSIONS: We found that PHEX gene mutations were responsible for XLH in these Taiwanese patients. Additional studies are needed to enhance understanding of the role of PHEX in XLH pathogenesis.

Adult↗
PubMed2000

Evidence of a molecular barrier limiting susceptibility of humans, cattle and sheep to chronic wasting disease.

Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE) of deer and elk, and little is known about its transmissibility to other species. An important factor controlling interspecies TSE susceptibility is prion protein (PrP) homology between the source and recipient species/genotypes. Furthermore, the efficiency with which the protease-resistant PrP (PrP-res) of one species induces the in vitro conversion of the normal PrP (PrP-sen) of another species to the protease-resistant state correlates with the cross-species transmissibility of TSE agents. Here we show that the CWD-associated PrP-res (PrP(CWD)) of cervids readily induces the conversion of recombinant cervid PrP-sen molecules to the protease-resistant state in accordance with the known transmissibility of CWD between cervids. In contrast, PrP(CWD)-induced conversions of human and bovine PrP-sen were much less efficient, and conversion of ovine PrP-sen was intermediate. These results demonstrate a barrier at the molecular level that should limit the susceptibility of these non-cervid species to CWD.

Amino Acid Sequence↗
PubMed2023

Assessment of systemic AAV-microdystrophin gene therapy in the GRMD model of Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a progressive muscle wasting disease caused by the absence of dystrophin, a membrane-stabilizing protein encoded by the DMD gene. Although mouse models of DMD provide insight into the potential of a corrective therapy, data from genetically homologous large animals, such as the dystrophin-deficient golden retriever muscular dystrophy (GRMD) model, may more readily translate to humans. To evaluate the clinical translatability of an adeno-associated virus serotype 9 vector (AAV9)-microdystrophin (&#x3bc;Dys5) construct, we performed a blinded, placebo-controlled study in which 12 GRMD dogs were divided among four dose groups [control, 1 &#xd7; 1013 vector genomes per kilogram (vg/kg), 1 &#xd7; 1014 vg/kg, and 2 &#xd7; 1014 vg/kg; n = 3 each], treated intravenously at 3 months of age with a canine codon-optimized microdystrophin construct, rAAV9-CK8e-c-&#x3bc;Dys5, and followed for 90 days after dosing. All dogs received prednisone (1 milligram/kilogram) for a total of 5 weeks from day -7 through day 28. We observed dose-dependent increases in tissue vector genome copy numbers; &#x3bc;Dys5 protein in multiple appendicular muscles, the diaphragm, and heart; limb and respiratory muscle functional improvement; and reduction of histopathologic lesions. As expected, given that a truncated dystrophin protein was generated, phenotypic test results and histopathologic lesions did not fully normalize. All administrations were well tolerated, and adverse events were not seen. These data suggest that systemically administered AAV-microdystrophin may be dosed safely and could provide therapeutic benefit for patients with DMD.

Animals↗
PubMed1992

Targeted disruption of the mouse transforming growth factor-beta 1 gene results in multifocal inflammatory disease.

Transforming growth factor-beta 1 (TGF-beta 1) is a multifunctional growth factor that has profound regulatory effects on many developmental and physiological processes. Disruption of the TGF-beta 1 gene by homologous recombination in murine embryonic stem cells enables mice to be generated that carry the disrupted allele. Animals homozygous for the mutated TGF-beta 1 allele show no gross developmental abnormalities, but about 20 days after birth they succumb to a wasting syndrome accompanied by a multifocal, mixed inflammatory cell response and tissue necrosis, leading to organ failure and death. TGF-beta 1-deficient mice may be valuable models for human immune and inflammatory disorders, including autoimmune diseases, transplant rejection and graft versus host reactions.

Animals↗
PubMed2006

Analysis of gene expression differences between utrophin/dystrophin-deficient vs mdx skeletal muscles reveals a specific upregulation of slow muscle genes in limb muscles.

Dystrophin deficiency leads to the progressive muscle wasting disease Duchenne muscular dystrophy (DMD). Dystrophin-deficient mdx mice are characterized by skeletal muscle weakness and degeneration but they appear outwardly normal in contrast to DMD patients. Mice lacking both dystrophin and the dystrophin homolog utrophin [double knockout (dko)] have muscle degeneration similar to mdx mice, but they display clinical features similar to DMD patients. Dko limb muscles also lack postsynaptic membrane folding and display fiber-type abnormalities including an abundance of phenotypically oxidative muscle fibers. Extraocular muscles, which are spared in mdx mice, show a significant pathology in dko mice. In this study, microarray analysis was used to characterize gene expression differences between mdx and dko tibialis anterior and extraocular skeletal muscles in an effort to understand the phenotypic differences between these two dystrophic mouse models. Analysis of gene expression differences showed that upregulation of slow muscle genes specifically characterizes dko limb muscle and suggests that upregulation of these genes may directly account for the more severe phenotype of dko mice. To investigate whether any upregulation of slow genes is retained in vitro, independent of postsynaptic membrane abnormalities, we derived mdx and dko primary myogenic cultures and analyzed the expression of Myh7 and Myl2. Real-time reverse transcriptase-polymerase chain reaction analysis demonstrates that transcription of these slow genes is also upregulated in dko vs mdx myotubes. This data suggests that at least part of the fiber-type abnormality is due directly to the combined absence of utrophin and dystrophin and is not an indirect effect of the postsynaptic membrane abnormalities.

Animals↗
PubMed1993

mnd2: a new mouse model of inherited motor neuron disease.

The autosomal recessive mutation mnd2 results in early onset motor neuron disease with rapidly progressive paralysis, severe muscle wasting, regression of thymus and spleen, and death before 40 days of age. mnd2 has been mapped to mouse chromosome 6 with the gene order: centromere-Tcrb-Ly-2-Sftp-3-D6Mit4-mnd2-D6Mit 6, D6Mit9-D6Rck132-Raf-1, D6Mit11-D6Mit12-D6Mit14, mnd2 is located within a conserved linkage group with homologs on human chromosome 2p12-p13. Spinal motor neurons of homozygous affected animals are swollen and stain weakly, and electromyography revealed spontaneous activity characteristic of muscle denervation. Myelin staining was normal throughout the neuraxis. The clinical observations are consistent with a primary abnormality of lower motor neuron function. This new animal model will be of value for identification of a genetic defect responsible for motor neuron disease and for evaluation of new therapies.

Animals↗