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1.
Atopic dermatitis (AD) is thought to be caused by immunologic abnormalities expressed as a Th1/Th2 cytokine imbalance in both humans and dogs. Several studies have focused on the therapeutic effects of IFNγ in human AD with successful results; however, the mechanism of action of IFNγ is not fully understood. We investigated the effect of recombinant canine interferon gamma (rCaIFNγ) on 10 dogs with AD and evaluated the ratio of IL‐4 mRNA to IFNγ mRNA in peripheral blood mononuclear cells, serum total IgE levels, and histological changes in skin. After six injections of rCaIFNγ over a span of 2 weeks, seven of the 10 dogs showed improvement, and six of these seven dogs exhibited decreased IL‐4:IFNγ mRNA ratios. Two of the three cases that did not improve had increased IL‐4:IFNγ mRNA ratios. Total serum IgE levels were significantly decreased in nine of 10 cases. The number of IgE‐positive cells detected by immunostaining and the number of mast cells in skin biopsy samples were decreased. A reduction of epidermal cell layers was demonstrated by histopathology after treatment. These results demonstrated that rCaIFNγ may be a novel safe and effective therapeutic option for the treatment of canine AD, and the mechanism of action of rCaIFNγ may be related to the modulation of Th2 cytokines to Th1 cytokines with the reduction of serum IgE production. Funding: Self‐funded.  相似文献   

2.
Since William Coley utilized bacterial immunotherapy to treat sarcomas in the late 19th century, an association between infection and improved survival has been reported for human and canine osteosarcoma patients. One of the reasons for this improved survival is likely a reactivation of the host immune system towards an inflammatory anti‐tumour response, and one of the key players is the macrophage. Yet, despite their importance, the response of macrophages to infectious agents in the context of osteosarcoma has not been thoroughly evaluated. The aim of this study was to evaluate how in vitro exposure to a bacterial agent (Staphylococcus aureus) influenced canine and human macrophage differentiation in the presence of osteosarcoma. Our hypothesis was that S. aureus would, in the presence of osteosarcoma, induce a macrophage phenotype with significantly increased inflammatory signatures. Consistent with our hypothesis, human macrophages co‐cultured with osteosarcoma and S. aureus exhibited increased IFN‐γ, TNF‐α and IL‐12p70 cytokine secretion, decreased TGF‐β cytokine secretion and increased mRNA expression of TNF‐α when compared with macrophages co‐cultured with osteosarcoma and to macrophages cultured alone. Canine macrophages similarly exhibited increased IFN‐γ and TNF‐α cytokine secretion, decreased TGF‐β cytokine secretion, increased mRNA expression of TNF‐α and increased surface receptor expression of CD80 when co‐cultured with osteosarcoma and S. aureus. Collectively, the findings of this study suggest that infection upregulates the inflammatory immune response to counteract osteosarcoma‐induced immune suppression. This work informs a potential therapeutic strategy to optimize inflammatory stimuli for triggering an anti‐osteosarcoma macrophage response.  相似文献   

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Duffy A., Dow S., Ogilvie G., Rao S., Hackett T. Hematologic improvement in dogs with parvovirus infection treated with recombinant canine granulocyte‐colony stimulating factor. J. vet. Pharmacol. Therap. doi: 10.1111/j.1365‐2885.2009.01153.x. Previously, dogs with canine parvovirus‐induced neutropenia have not responded to treatment with recombinant human granulocyte‐colony stimulating factor (rhG‐CSF). However, recombinant canine G‐CSF (rcG‐CSF) has not been previously evaluated for treatment of parvovirus‐induced neutropenia in dogs. We assessed the effectiveness of rcG‐CSF in dogs with parvovirus‐induced neutropenia with a prospective, open‐label, nonrandomized clinical trial. Endpoints of our study were time to recovery of WBC and neutrophil counts, and duration of hospitalization. 28 dogs with parvovirus and neutropenia were treated with rcG‐CSF and outcomes were compared to those of 34 dogs with parvovirus and neutropenia not treated with rcG‐CSF. We found that mean WBC and neutrophil counts were significantly higher (P < 0.05) in the 28 dogs treated with rcG‐CSF compared to disease‐matched dogs not treated with rcG‐CSF. In addition, the mean duration of hospitalization was reduced (P = 0.01) in rcG‐CSF treated dogs compared to untreated dogs. However, survival times were decreased in dogs treated with rcG‐CSF compared to untreated dogs. These results suggest that treatment with rcG‐CSF was effective in stimulating neutrophil recovery and shortening the duration of hospitalization in dogs with parvovirus infection, but indicate the need for additional studies to evaluate overall safety of the treatment.  相似文献   

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6.
Interferons have attracted considerable attention due to their vital roles in the host immune response and low induction of antibiotic resistance. In this study, total RNA was extracted from spleen cells of chicken embryos inoculated with Newcastle disease vaccine, and the full‐length chicken interferon‐γ (ChIFN‐γ ) gene was amplified by RT‐PCR. The full complementary DNA sequence of the ChIFN‐γ gene was 495 bp long and was cloned into the prokaryotic expression vector pProEX?HTb. The plasmid was transformed into Escherichia coli DH5α and the expression of ChIFN‐γ was induced by isopropyl β‐D‐1‐thiogalactopyranoside. Sodium dodecyl sulfate – polyacrylamide gel electrophoresis and Western blot results showed the expressed fusion protein had a molecular weight of approximately 18 kDa and was recognized by an anti‐His mAb. Moreover, ChIFN‐γ was found to demonstrate anti‐viral activity in vitro . To test the in vivo function of ChIFN‐γ in broilers under heat stress, a total of 100 broilers were randomly assigned to either a control group or a treated group, in which they were hypodermically injected with recombinant ChIFN‐γ. Results demonstrated ChIFN‐γ affects the messenger RNA expression levels of heat shock protein 70 (HSP70) in the heart and lung tissues, and decreases the concentration of HSP70 in serum. Therefore, we conclude recombinant ChIFN‐γ can reduce heat stress to some extent in vivo .  相似文献   

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9.
Background: Increased serum tumor necrosis factor‐α (TNFα) activity has been associated with onset of serious inflammatory diseases in dogs. Development of treatment with TNFα‐antagonists has been limited by the unavailability of suitable reagents and potency assays for TNFα. Objectives: The objectives of this study were to optimize a cell‐based assay to measure anti‐TNFα activity in serum and plasma from hyperimmune (vaccinated with an Escherichia coli J5 bacterin) and unvaccinated canine donors; to use the assay to determine whether hyperimmune serum inhibits TNFα activity in vivo; and to determine whether soluble TNF receptor‐1 (sTNFR1, a naturally occurring TNFα antagonist) contributes to anti‐TNFα activity. Methods: Commercial plasma and serum from hyperimmune‐frozen plasma (HFP) donors and unvaccinated fresh‐frozen plasma (FFP) donors were used in the study. An L929‐cell TNFα‐inhibition assay (LTIA) was optimized to measure anti‐TNFα activity. Using a rat subcutaneous pouch model of inflammation, the effects of HFP, FFP, a synthetic TNFα antagonist (Etanercept), and carprofen on TNFα activity were compared in vivo. Immunofluorescence was used to measure soluble sTNFR1 concentration. Results: Using the optimized LTIA, HFP serum but not FFP serum decreased canine TNFα activity (P<.01). HFP plasma and Etanercept (but not FFP plasma or carprofen) significantly decreased TNFα activity in pouch exudates (P<.05). A significantly higher concentration of sTNFR1 was found in HFP than FFP serum. Conclusions: Using the LTIA, anti‐TNFα activity is readily measured in canine serum and inflammatory exudates. sTNFR1 appears to contribute to anti‐TNFα activity in HFP serum. These results suggest HFP should be investigated further as a potential immunotherapeutic agent for controlling canine diseases in which TNFα is implicated.  相似文献   

10.

Background

GM2‐gangliosidosis is a fatal neurodegenerative lysosomal storage disease (LSD) caused by deficiency of either β‐hexosaminidase A (Hex‐A) and β‐hexosaminidase B (Hex‐B) together, or the GM2 activator protein. Clinical signs can be variable and are not pathognomonic for the specific, causal deficiency.

Objectives

To characterize the phenotype and genotype of GM2‐gangliosidosis disease in an affected dog.

Animals

One affected Shiba Inu and a clinically healthy dog.

Methods

Clinical and neurologic evaluation, brain magnetic resonance imaging (MRI), assays of lysosomal enzyme activities, and sequencing of all coding regions of HEXA, HEXB, and GM2A genes.

Results

A 14‐month‐old, female Shiba Inu presented with clinical signs resembling GM2‐gangliosidosis in humans and GM1‐gangliosidosis in the Shiba Inu. Magnetic resonance imaging (MRI) of the dog's brain indicated neurodegenerative disease, and evaluation of cerebrospinal fluid (CSF) identified storage granules in leukocytes. Lysosomal enzyme assays of plasma and leukocytes showed deficiencies of Hex‐A and Hex‐B activities in both tissues. Genetic analysis identified a homozygous, 3‐base pair deletion in the HEXB gene (c.618‐620delCCT).

Conclusions and Clinical Importance

Clinical, biochemical, and molecular features are characterized in a Shiba Inu with GM2‐gangliosidosis. The deletion of 3 adjacent base pairs in HEXB predicts the loss of a leucine residue at amino acid position 207 (p.Leu207del) supporting the hypothesis that GM2‐gangliosidosis seen in this dog is the Sandhoff type. Because GM1‐gangliosidosis also exists in this breed with almost identical clinical signs, genetic testing for both GM1‐ and GM2‐gangliosidosis should be considered to make a definitive diagnosis.  相似文献   

11.
Although androgen therapy resistance and poor clinical outcomes are seen in most canine prostate cancer cases, there are only a few tools for analysing canine prostate cancer by using a cell biological approach. Therefore, to evaluate androgen‐independent neoplastic cell growth, a new canine prostate cancer cell line (CHP‐1) was established in this study. CHP‐1 over‐expressed the co‐chaperone small glutamine‐rich tetratricopeptide repeat‐containing protein α (SGTA), which is over‐expressed in human androgen‐independent prostate cancer. The CHP‐1 xenograft also showed SGTA over‐expression. Although CHP‐1 shows poor androgen receptor (AR) signalling upon dihydrotestosterone stimulation, forced expression of AR enabled evaluation of AR signalling. Taken together, these results suggest that CHP‐1 will be a useful model for investigating the pathogenesis of androgen‐dependent and androgen‐independent canine prostate cancer.  相似文献   

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13.
Atopic dermatitis (AD) is very common in dogs, but its pathogenesis is not yet fully understood. It has been suggested that a Th2‐dominant status may be associated with the occurrence of canine AD. IL‐12 is thought to be important for the differentiation of Th1 cells. The IL‐12 receptor β2 (IL‐12Rβ2) gene is considered to play a critical role in signal transduction and is attracting attention as one of the causative genes of AD in humans. The purpose of this study was to investigate the relationship between IL‐12Rβ2 gene expression and canine AD. The canine IL‐12Rβ2 gene was cloned by RT‐PCR and its nucleotide sequences were determined. Canine IL‐12Rβ2 showed 76.8% homology at the amino acid level with human IL‐12Rβ2, and its structural motifs were well conserved. cDNA with a 91 bp deletion including the transmembrane region was also cloned, which consequently produced a frame shift and an early stop codon. The deletion region corresponded to exon 14 of the human IL‐12Rβ2 gene on chromosome 1. The expression of deleted canine IL‐12Rβ2 mRNA in phytohemagglutinin‐stimulated peripheral blood mononuclear cells was examined in seven healthy dogs and 11 AD dogs. Both deleted and intact mRNAs were expressed at constant ratios in healthy and AD dogs. The results indicate that the deletion of the transmembrane region is not associated with the occurrence of AD, and that the expression of the deleted mRNA may be constitutive and produced by alternative splicing. Funding: Self‐funded.  相似文献   

14.
α‐1,3‐Galactosyltransferase (α‐GalT), an enzyme creating Galα1‐3Gal (α‐Gal) epitope on the cell surface in some mammalian species such as pigs, is known to be a key factor that causes hyperacute rejection upon transplantation from pigs to humans. To establish the RNA interference‐based suppression of endogenous α‐GalT messenger RNA (mRNA) synthesis in porcine preimplantation embryos, we determined the suitable embryonic stage at which stage such approach is possible by using the semi‐quantitative RT‐PCR (qRT‐PCR) and the cytochemical method using a fluorescence‐labeled Bandeiraea simplicifolia Isolectin B4 (BS‐I‐B4). Staining with BS‐I‐B4 demonstrated that α‐Gal epitope expression was first recognized at the 8‐cell stage, and increased up to the hatched blastocyst stage. Single embryo‐based qRT‐PCR also confirmed this pattern. These results indicate that creation of α‐Gal epitope is proceeded by de novo synthesis of α‐GalT mRNA in porcine preimplantation embryos with peaking at the blastocyst stage.  相似文献   

15.
We investigated whether the limited access to androgens during late prenatal period alters expression of steroidogenic enzymes involved in androgen production: 3β‐hydroxysteroid dehydrogenase/Δ5‐Δ4 isomerase (3β‐HSD), cytochrome P450 17α‐hydroxylase/17,20‐lyase (CYP17) and 17β‐hydroxysteroid dehydrogenase type 1 (17β‐HSD1) or type 3 (17β‐HSD3) in the foetal porcine gonads. Pregnant gilts were injected with anti‐androgen flutamide (for seven days, 50 mg/day/kg bw) or corn oil (control) starting at 83 (GD90) or 101 (GD108) gestational day. To assess 3β‐HSD, CYP17 and 17β‐HSD1 or 17β‐HSD3 expression, real‐time PCR and immunohistochemistry were performed. In testes from flutamide‐treated foetuses, increased 3β‐HSD and CYP17 mRNA expression was observed in the GD90 group, while decreased 3β‐HSD and 17β‐HSD3 mRNA expression and increased CYP17 mRNA expression were found in the GD108 group. CYP17 and 17β‐HSD3 were localized in Leydig cells. Following flutamide administration, the intensity of CYP17 immunostaining was higher in both treated groups, while 17β‐HSD3 intensity was lower in the GD108 group. In ovaries from flutamide‐treated foetuses in the GD90 group, mRNA level for 3β‐HSD was elevated, but it was diminished for CYP17 and 17β‐HSD1. In the GD108 group, flutamide treatment led to lower mRNA level for 3β‐HSD but higher for CYP17. 3β‐HSD was found in granulosa cells, while CYP17 was localized within egg nests and oocytes of forming follicles. Following flutamide treatment, the intensity of 3β‐HSD and CYP17 immunostaining was higher in the GD90 and GD108 groups, respectively. Immunohistochemical staining for 3β‐HSD was restricted to the ovary. Concluding, diminished androgen action in the porcine foetal gonads during late gestation induces changes in steroidogenic enzymes expression, which may led to changes in gonadal function. However, it seems that androgens exert diverse biological effects depending on the gestational period.  相似文献   

16.
Background: Myelin‐like material in canine cerebrospinal fluid (CSF) specimens has been attributed to demyelinating or myelomalacic conditions. In our experience, myelin‐like material is observed frequently, especially in lumbar samples, and in a variety of disease conditions. Objectives: The objective of this study was to determine if there are associations between the presence of myelin‐like material and CSF collection site, body weight, underlying disease, and patient outcome. Methods: Wright–Giemsa‐stained cytocentrifuged specimens of CSF from the cerebellomedullary cistern (n=51) and lumbar cistern (n=47) of 98 dogs with neurologic disease were evaluated retrospectively for the presence and amount of extracellular myelin‐like material. Results were compared based on collection site, body weight, type of neurologic disease, and outcome. Results: Myelin‐like material was observed in 20/98 (20%) samples and was more frequently observed in lumbar (17/47, 36%) than cerebellomedullary samples (3/51, 6%) (P=.0028). Samples from dogs <10 kg were more likely to contain myelin (14/36, 39%) compared with dogs ≥10 kg (5/60, 8%) (P=.0052). Larger amounts of myelin‐like material were observed in CSF from dogs with intervertebral disk disease compared with other diseases (P=.045). No association was found between myelin‐like material and outcome. Conclusion: The association of extracellular myelin‐like material in canine CSF samples with sampling site and body weight suggests it is more often an artifact of collection technique and anatomy rather than the result of neurologic disease. Myelin‐like material in CSF is not associated with a poorer prognosis.  相似文献   

17.
Radiotherapy represents the standard of care for intranasal carcinomas. Responses to tyrosine kinase inhibitors (TKIs) have been reported but data on expression of target receptor tyrosine kinases (rTKs) is limited. This study characterizes the expression of vascular endothelial growth factor receptor (VEGFR), platelet‐derived growth factor receptor (PDGFR)‐α and PDGFR‐β in canine intranasal carcinomas. Histological samples from 187 dogs were retrieved. Immunohistochemistry was performed using commercially available antibodies. Expression of rTKs was classified into weak, moderate or intense and additionally recorded as cytoplasmic, membranous, cytoplasmic‐membranous, nuclear or stromal. VEGFR was expressed in 158 dogs with predominantly moderate expression (36.9%) and a cytoplasmic‐membranous expression pattern (70.9%). PDGFR‐α was detected in 133 with predominantly weak expression (57.9%) and cytoplasmic pattern (87.9%). PDGFR‐β was identified in 74 patients with a predominantly moderate expression (17.6%) and cytoplasmic expression pattern (63.5%). Co‐expression of rTKs was common. These results confirm expression of VEGFR, PDGFR‐α and PDGFR‐β in canine intranasal carcinomas and support the utility of TKIs.  相似文献   

18.
Japanese Black (JB) calves are more susceptible to infectious diseases compared to Holstein (Hol) calves. To clarify the immunological differences between JB and Hol calves, expression of cytokine messenger RNA (mRNA) was examined using peripheral CD4+, CD8+ and γδ T cells. Healthy calves, 24 from each species, were examined. Blood samples were obtained from calves at 1 week, 1 month and 3 months old, eight calves for each age of each species. Peripheral blood mononuclear cells were stimulated with phytohemagglutin (PHA), and T cell subsets were isolated by positive selection using magnetic cell sorting (MACS). Levels of interlekin (IL)‐2, IL‐4, IL‐10 and interferon (IFN)‐γ mRNA in three T cell subsets were analyzed. WC1‐N1+ γδ T cell percentages were significantly lower in JB calves at 1 week and 1 month of age compared to Hol calves. In addition JB calves had significantly lower IL‐2, IL‐10 and IFN‐γ mRNA in WC1‐N1+ γδ T cells at 1 and 3 months of age, whereas there were no significant differences in cytokine mRNA of CD4+ and CD8+ cells between the two groups. Decreased cytokine mRNA and cell number of peripheral γδ T cells may affect negatively on the immune system of JB calves.  相似文献   

19.
Cutaneous mast cell tumours (MCTs) are the most frequent malignant skin tumours in dogs. Mutations in the c‐KIT proto‐oncogene are correlated with the pathogenesis and aggressiveness of MCTs. To date, studies have focused on c‐KIT mutations and KIT protein localization, with a general lack of mRNA‐level analyses. In this study, c‐KIT mRNA expression was investigated in canine MCTs by RNA in situ hybridization (RNA‐ISH). Furthermore, we evaluated associations between c‐KIT mRNA expression and the histological grade, KIT immunohistochemical staining pattern and other clinicopathological parameters. c‐KIT mRNA expression was observed in all MCT samples, appearing as clusters of dots in the cytoplasm of neoplastic cells. A significant correlation was detected between c‐KIT mRNA expression (quantified according to the H‐score and the percentage of positive cells) and the histological grade (determined using two‐and three‐tier grading systems; P < .05). We also found a significant positive correlation (all P < .05) between c‐KIT mRNA expression and the proliferation indices (mitotic index, Ki‐67, and Ag67). However, no significant associations with c‐KIT expression from RNA‐ISH were found with respect to different KIT staining patterns. Overall, these results demonstrate that c‐KIT mRNA expression might be an additional tool for measuring the c‐KIT status in canine cutaneous MCTs and could serve as a potential prognostic factor. Further studies should evaluate the prognostic significance of c‐KIT mRNA expression in a large and uniform cohort of canine MCTs.  相似文献   

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