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1.
Comp Immunol Microbiol Infect Dis ; 105: 102114, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38142559

RESUMO

Modified live canine distemper virus (CDV) vaccines are widely used and considered both safe and effective. Although there are occasional literature reports of suspected vaccine-induced disease, there are none where the vaccine strain has been identified in affected tissues. Here we describe two such cases in different litters. In litter A, five of ten puppies presented with fever, anorexia, vomiting, and diarrhea a few days post-vaccination. Four puppies died or were euthanized, and autopsy revealed atypical necrosis of the lymphoid tissue. In litter B, two of five puppies developed typical neurological signs some months post-vaccination and autopsy revealed encephalitis. In all cases, affected organs tested positive for CDV on immunohistochemistry, and CDV RNA extracted from the lesions confirmed the presence of vaccine strain. Since multiple puppies from each litter were affected, it cannot be excluded without further studies that some undiagnosed inherited immunodeficiency disorder may have been involved.


Assuntos
Vírus da Cinomose Canina , Cinomose , Doenças do Cão , Vacinas Virais , Cães , Animais , Vacinas Virais/efeitos adversos , Cinomose/diagnóstico , Cinomose/prevenção & controle , Vacinação/efeitos adversos , Vacinação/veterinária , Vacinas Atenuadas/efeitos adversos , Vírus da Cinomose Canina/genética , Doenças do Cão/diagnóstico
2.
PLoS One ; 13(9): e0204073, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30235266

RESUMO

Ciliopathies presenting as inherited hepatorenal fibrocystic disorders are rare in humans and in dogs. We describe here a novel lethal ciliopathy in Norwich Terrier puppies that was diagnosed at necropsy and characterized as diffuse cystic renal disease and hepatic fibrosis. The histopathological findings were typical for cystic renal dysplasia in which the cysts were located in the straight portion of the proximal tubule, and thin descending and ascending limbs of Henle's loop. The pedigree of the affected puppies was suggestive of an autosomal recessive inheritance and therefore, whole exome sequencing and homozygosity mapping were used for identification of the causative variant. The analyses revealed a case-specific homozygous splice donor site variant in a cilia related gene, INPP5E: c.1572+5G>A. Association of the variant with the defect was validated in a large cohort of Norwich Terriers with 3 cases and 480 controls, the carrier frequency being 6%. We observed that the identified variant introduces a novel splice site in INPP5E causing a frameshift and formation of a premature stop codon. In conclusion, our results suggest that the INPP5E: c.1572+5G>A variant is causal for the ciliopathy in Norwich Terriers. Therefore, genetic testing can be carried out in the future for the eradication of the disease from the breed.


Assuntos
Cirrose Hepática/enzimologia , Cirrose Hepática/genética , Mutação/genética , Monoéster Fosfórico Hidrolases/genética , Rim Policístico Autossômico Recessivo/enzimologia , Rim Policístico Autossômico Recessivo/genética , Sítios de Splice de RNA/genética , Animais , Cílios/metabolismo , Cães , Células Epiteliais/metabolismo , Feminino , Regulação da Expressão Gênica , Homozigoto , Rim/patologia , Cirrose Hepática/patologia , Masculino , Organogênese , Linhagem , Monoéster Fosfórico Hidrolases/metabolismo , Rim Policístico Autossômico Recessivo/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Sequenciamento do Exoma
3.
Acta Vet Scand ; 56: 84, 2014 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-25492266

RESUMO

BACKGROUND: Leishmania spp. are zoonotic protozoans that infect humans and other mammals such as dogs. The most significant causative species in dogs is L. infantum. In dogs, leishmaniosis is a potentially progressive, chronic disease with varying clinical outcomes. Autochthonous cases of canine leishmaniosis have not previously been reported in the Nordic countries. RESULTS: In this report we describe the first diagnosed autochthonous cases of canine leishmaniosis in Finland, in which transmission via a suitable arthropod vector was absent. Two Finnish boxers that had never been in endemic areas of Leishmania spp., had never received blood transfusions, nor were infested by ectoparasites were diagnosed with leishmaniosis. Another dog was found with elevated Leishmania antibodies. A fourth boxer dog that had been in Spain was considered to be the source of these infections. Transmission occurred through biting wounds and semen, however, transplacental infection in one of the dogs could not be ruled out. Two of the infected dogs developed a serious disease and were euthanized and sent for necropsy. The first one suffered from membranoproliferative glomerulonephritis and the second one had a chronic systemic disease. Leishmania sp. was detected from tissues by PCR and/or IHC in both dogs. The third infected dog was serologically positive for Leishmania sp. but remained free of clinical signs. CONCLUSIONS: This case report shows that imported Leishmania-infected dogs may pose a risk for domestic dogs, even without suitable local arthropod vectors.


Assuntos
Doenças do Cão/transmissão , Leishmania/isolamento & purificação , Leishmaniose/veterinária , Animais , Doenças do Cão/parasitologia , Cães , Feminino , Finlândia , Leishmaniose/parasitologia , Leishmaniose/transmissão , Masculino , Reação em Cadeia da Polimerase/veterinária , Espanha
4.
Genes Chromosomes Cancer ; 42(2): 193-9, 2005 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15543620

RESUMO

Several chromosomal regions are recurrently amplified or deleted in lung tumors, but little is known about the underlying genes, which could be important mediators in tumor formation or progression. In lung cancer, the RB1-CCND1-CDKN2A pathway, involved in the G1-S transition, is damaged in nearly all tumors. In the present study, we localized a novel amplicon in lung tumors to a fragment of less than 0.5 Mb at 12q13.3-q14.1 by using comparative genomic hybridization (CGH) on cDNA microarrays. This approach enabled us to identify 10-15 genes with the most consistent amplifications. Semiquantitative RT-PCR analyses of 13 genes in this region showed that four of them (CDK4, CYP27B1, METTL1, and TSFM) were also highly up-regulated. Immunohistochemical (IHC) analysis of 141 tumor samples on a tissue microarray showed that CDK4 was expressed at a high level in 23% of lung tumors. Six (21.4%) of the tumors with high CDK4 expression (n = 28) were shown by fluorescence in situ hybridization (FISH) to contain the 12q13.3-q14.1 amplification. For CDK4, a positive correlation was found between gene copy number (FISH and CGH array), mRNA expression (RT-PCR), and level of protein expression (IHC). CDK4 expression did not correlate with CDKN2A methylation status. Amplification of CDK4 has been described in other tumor types, but its role in lung cancer remains to be elucidated. Although CDK4 amplification seems to be a relatively rare event (4.3%) in lung tumors, it indicates the significance of the RB1-CCND1 pathway in lung tumorigenesis.


Assuntos
Cromossomos Humanos Par 12/genética , Quinases Ciclina-Dependentes/genética , Amplificação de Genes/genética , Neoplasias Pulmonares/genética , Proteínas Proto-Oncogênicas/genética , Mapeamento Cromossômico/métodos , Quinase 4 Dependente de Ciclina , DNA de Neoplasias/genética , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/patologia , Análise em Microsséries/métodos , Hibridização de Ácido Nucleico/métodos
5.
J Pathol ; 203(1): 584-93, 2004 May.
Artigo em Inglês | MEDLINE | ID: mdl-15095482

RESUMO

To identify new potential diagnostic markers for lung cancer, the expression profiles of 37 lung tumours were analysed using cDNA arrays. Seven samples were from small-cell lung cancer (SCLC), two from large-cell neuroendocrine tumours (LCNEC), and 28 from other non-small-cell lung cancers (mainly squamous cell cancer and adenocarcinoma). Principal component analysis and the permutation test were used to detect differences in the gene expression profiles and a set of genes was found that distinguished high-grade neuroendocrine carcinomas (SCLC and LCNEC) from other lung cancers. In addition, several genes, such as caveolin-1 (CAV1) and caveolin-2 (CAV2), were constantly deregulated in all types of tumour sample, compared with normal tissue. The expression of these two genes was investigated further at the protein level on a tissue microarray containing tumours from 161 patients and normal tissues. Immunostaining for CAV1 was negative in 48% of tumours, whereas 28% of the tumours did not express CAV2. Lack of CAV1 protein expression was not caused by methylation or mutation. In stage I adenocarcinomas, CAV2 protein expression correlated with shorter survival. In conclusion, the present study was able to identify genes that have not previously been implicated in lung cancer by the combined use of two different array techniques. Some of these genes may provide novel diagnostic markers for lung cancer.


Assuntos
Biomarcadores Tumorais/análise , Caveolinas/análise , DNA Circular/análise , DNA de Neoplasias/análise , Neoplasias Pulmonares/diagnóstico , Adenocarcinoma/diagnóstico , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Carcinoma Neuroendócrino/diagnóstico , Carcinoma Neuroendócrino/genética , Carcinoma Neuroendócrino/metabolismo , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma de Células Pequenas/diagnóstico , Carcinoma de Células Pequenas/genética , Carcinoma de Células Pequenas/metabolismo , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Caveolina 1 , Caveolina 2 , Caveolinas/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Imuno-Histoquímica/métodos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Masculino , Pessoa de Meia-Idade , Mutação/genética , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Análise de Componente Principal/métodos , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos
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