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1.
Sci Rep ; 6: 35395, 2016 10 13.
Article in English | MEDLINE | ID: mdl-27734949

ABSTRACT

Cystinosis is a rare autosomal recessive disorder characterized by lysosomal cystine accumulation due to loss of function of the lysosomal cystine transporter (CTNS). The most common mutation in cystinosis patients of Northern Europe consists of a 57-kb deletion. This deletion not only inactivates the CTNS gene but also extends into the non-coding region upstream of the start codon of the TRPV1 gene, encoding the capsaicin- and heat-sensitive ion channel TRPV1. To evaluate the consequences of the 57-kb deletion on functional TRPV1 expression, we compared thermal, mechanical and chemical sensitivity of cystinosis patients with matched healthy controls. Whereas patients heterozygous for the 57-kb deletion showed normal sensory responses, homozygous subjects exhibited a 60% reduction in vasodilation and pain evoked by capsaicin, as well as an increase in heat detection threshold. Responses to cold, mechanical stimuli or cinnamaldehyde, an agonist of the related nociceptor channel TRPA1, were unaltered. We conclude that cystinosis patients homozygous for the 57-kb deletion exhibit a strong reduction of TRPV1 function, leading to sensory deficiencies akin to the phenotype of TRPV1-deficient mice. These deficits may account for the reported sensory alterations and thermoregulatory deficits in these patients, and provide a paradigm for life-long TRPV1 deficiency in humans.


Subject(s)
Cystinosis/metabolism , Gene Deletion , Homozygote , TRPV Cation Channels/metabolism , Acrolein/analogs & derivatives , Acrolein/chemistry , Adolescent , Adult , Alleles , Capsaicin/chemistry , Codon , Cystinosis/genetics , Europe , Female , Hot Temperature , Humans , Lysosomes/metabolism , Male , Mutation , Sequence Deletion , TRPA1 Cation Channel/metabolism , TRPV Cation Channels/genetics , Young Adult
2.
Vet Parasitol ; 183(3-4): 224-30, 2012 Feb 10.
Article in English | MEDLINE | ID: mdl-21852041

ABSTRACT

Bovine eosinophilic myositis (BEM) is a subclinical myopathy characterized by multifocal white to grey-green discolorations in skeletal muscles, heart, tongue and oesophagus. These lesions are found at slaughter or during meat cutting and result in considerable economic losses. The etiology and pathogenesis are unclear, although it has been suggested, that Sarcocystis species are involved. To elucidate their role, two calves were repeatedly injected intramuscularly with adjuvanted Sarcocystis antigen. The morphological changes at the injection sites in these calves were histologically and immunohistochemically compared to spontaneous lesions from 44 BEM condemned carcasses sampled in slaughterhouses. Experimental intramuscular injection of Sarcocystis antigen resulted in lesions at the injection sites that were similar to the lesions of natural cases of BEM. They were characterized by massive infiltration of eosinophilic granulocytes, reactive macrophages (MAC387(+) cells), T-cells (CD3(+)) and B-cells (CD20(+)). Both in the experimental and in the natural cases, COX-2 expression was present in endothelial cells adjacent to lesional areas. MHC class II(+) staining was found amongst others in muscle cells surrounding the lesion. These results show that Sarcocystis antigens can induce an inflammatory response in bovine muscle having the characteristics of natural BEM.


Subject(s)
Antigens, Protozoan/immunology , Cattle Diseases/parasitology , Eosinophilia/veterinary , Muscle, Skeletal/pathology , Myositis/veterinary , Sarcocystis/immunology , Sarcocystosis/veterinary , Animals , Antibodies, Protozoan/analysis , Antigens, Protozoan/administration & dosage , Antigens, Protozoan/adverse effects , Cattle , Cattle Diseases/pathology , Cyclooxygenase 2/metabolism , Eosinophilia/parasitology , Eosinophilia/pathology , Eosinophils/cytology , Eosinophils/immunology , Granulocytes/cytology , Granulocytes/immunology , Injections, Intramuscular/veterinary , Lymphocytes/cytology , Lymphocytes/immunology , Macrophages/cytology , Macrophages/immunology , Major Histocompatibility Complex , Male , Muscle, Skeletal/cytology , Muscle, Skeletal/parasitology , Myositis/parasitology , Myositis/pathology , Sarcocystosis/parasitology , Sarcocystosis/pathology
3.
J Food Prot ; 70(6): 1523-6, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17612088

ABSTRACT

Sarcocystis hominis, one of the three species of Sarcocystis that cause muscular cysts in cattle, is a protozoan parasite that can infect the human intestinal tract. The objective of the present study was to develop a new molecular identification method capable of discriminating among the bovine Sarcocystis species and to apply this tool in combination with stereomicroscopy to determine the presence of Sarcocystis spp. in minced beef in Belgium, with special attention to Sarcocystis hominis. A PCR technique based on the 18S rRNA sequence and by sequencing of the amplicon was highly specific. Sequence analysis of PCR products from thick-walled cysts collected from minced beef in Belgium revealed that S. hominis was present in 97.4% of the samples. Because the consumption of raw minced beef is common in Belgium and certain other European countries, these findings may point to an underestimated risk to public health.


Subject(s)
DNA, Protozoan/analysis , Food Contamination/analysis , Food Parasitology , Meat Products/parasitology , Sarcocystis/isolation & purification , Animals , Base Sequence , Consumer Product Safety , Humans , Polymerase Chain Reaction/methods , Public Health , Risk Assessment , Sarcocystis/genetics , Species Specificity
4.
J Comp Pathol ; 132(2-3): 237-41, 2005.
Article in English | MEDLINE | ID: mdl-15737352

ABSTRACT

This report describes a case of a carcinosarcoma or true malignant mixed tumour (salivary gland type) of the trachea in a Belgian Blue heifer. At post-mortem examination a nodular, well-circumscribed, firmly attached mass was found in the tracheal wall, severely compressing the tracheal lumen. Histologically the tumour was biphasic, with varying proportions of epithelial elements dispersed throughout a matrix showing varying degrees of myxo-chondroid and cartilaginous differentiation. The histological features of the tumour were consistent with a combination of an adenoid cystic carcinoma and a chondrosarcoma. Immunolabelling demonstrated smooth muscle actin in the cytoplasm of both the epithelial and mesenchymal components, thus fulfilling the diagnostic criteria for a mixed tumour. To our knowledge this is the first report of a mixed tumour of the trachea in a domestic animal.


Subject(s)
Carcinoma, Adenoid Cystic/veterinary , Carcinosarcoma/veterinary , Cattle Diseases/pathology , Chondrosarcoma/veterinary , Tracheal Neoplasms/veterinary , Actins/analysis , Animals , Biomarkers, Tumor/analysis , Carcinoma, Adenoid Cystic/chemistry , Carcinoma, Adenoid Cystic/pathology , Carcinosarcoma/chemistry , Carcinosarcoma/pathology , Cattle , Chondrosarcoma/chemistry , Chondrosarcoma/pathology , Fatal Outcome , Female , Immunohistochemistry/methods , Immunohistochemistry/veterinary , Tracheal Neoplasms/chemistry , Tracheal Neoplasms/pathology
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