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A Kipar

Publications and source records attributed to A Kipar.

At least 19 recordsLinked to original sources

Regulation and role of REST and REST4 variants in modulation of gene expression in in vivo and in vitro in epilepsy models.

Repressor element-1 silencing transcription factor (REST) is a candidate modulator of gene expression during status epilepticus in the rodent. In such models, full-length REST and the truncated REST4 variant are induced and can potentially direct differential gene expression patterns. We have addressed the regulation of these REST variants in rodent hippocampal seizure models and correlated this with expression of the proconvulsant, substance P encoding, PPT-A gene. REST and REST4 were differentially regulated following kainic acid stimulus both in in vitro and in vivo models. REST4 was more tightly regulated than REST in both models and its transient expression correlated with that of the differential regulation of PPT-A. Consistent with this, overexpression of a truncated REST protein (HZ4, lacking the C-terminal repression domain) increased expression of the endogenous PPT-A gene. Similarly the proximal PPT-A promoter reporter gene construct was differentially regulated by the distinct REST isoforms in hippocampal cells with HZ4 being the major inducer of increased reporter expression. Furthermore, REST and REST4 proteins were differentially expressed and compartmentalized within rat hippocampal cells in vitro following noxious stimuli. This differential localization of the REST isoforms was confirmed in the CA1 region following perforant path and kainic acid induction of status epilepticus in vivo. We propose that the interplay between REST and REST4 alter the expression of proconvulsant genes, as exemplified by the PPT-A gene, and may therefore regulate the progression of epileptogenesis.

Animals↗

Lethal outbreak of disease associated with feline calicivirus infection in cats.

Recently, in the USA, virulent mutants of feline calicivirus (FCV) have been identified as the cause of a severe and acute virulent systemic disease, characterised by jaundice, oedema and high mortality in groups of cats. This severe manifestation of FCV disease has so far only been reported in the USA. However, in 2003, an outbreak of disease affected a household of four adult cats and an adult cat from a neighbouring household in the UK. Three of the adult cats in the household and the neighbouring cat developed clinical signs including pyrexia (39.5 to 40.5 degrees C), lameness, voice loss, inappetence and jaundice. One cat was euthanased in extremis, two died and one recovered. A postmortem examination of one of the cats revealed focal cellulitis around the right hock and right elbow joints. The principal finding of histopathological examinations of selected organs from two of the cats was disseminated hepatocellular necrosis with mild inflammatory infiltration. Immunohistology identified FCV antigen in parenchymal and Kupffer cells in the liver of both animals and in alveolar macrophages of one of them. In addition, calicivirus-like particles were observed by electron microscopy within the hepatocytes of one cat. FCV was isolated from two of the dead cats and from the two surviving cats. Sequence analysis showed that they were all infected with the same strain of virus, but that it was different from strains of FCV associated with the virulent systemic disease in cats in the USA. The outbreak was successfully controlled by quarantine in the owner's house.

Animals↗

Up-regulated expression of the alpha7 nicotinic acetylcholine receptor subunit on inflammatory infiltrates during Dictyocaulus viviparus infection.

Cholinergic signalling is known to affect immune cell function, but few studies have addressed its relevance during nematode infection. We therefore analysed the anatomical distribution and expression pattern of the nicotinic acetylcholine receptor (nAChR) alpha7 subunit in lungs obtained from Dictyocaulus viviparus-infected and uninfected control cattle. The analysis was performed on trachea and lung parenchyma from uninfected animals and animals necropsied at 15, 22 and 43 days post-infection (DPI). Localization of the alpha7 nAChR was evaluated by immunohistology and mRNA expression analysed by gene-specific reverse transcription-polymerase chain reaction (RT-PCR). In uninfected animals, tracheal, bronchial and bronchiolar epithelium and smooth muscle cells constitutively expressed the alpha7 nAChR, as did type I and II alveolar epithelial cells and alveolar macrophages and a few infiltrating leucocytes. By 15 DPI, immunohistology revealed a massive influx of alpha7 nAChR+ inflammatory cells into the lung parenchyma and tracheal wall. This was reflected in the RT-PCR results. At later time points, both parenchyma and tracheal wall contained large numbers of alpha7 nAChR+ leucocytes, but detection of transcript was restricted to the trachea. Recruitment of nAChR-containing leucocytes to the lungs of D. viviparus-infected cattle suggests that these cells may represent possible downstream targets for parasite-secreted acetylcholinesterases.

Acetylcholinesterase↗

Age-related dynamics of constitutive cytokine transcription levels of feline monocytes.

Monocytes/macrophages are central mediators of inflammation and immunity and therefore of major interest in the study of immunosenescence. In healthy adult cats, monocytes have been shown to constitutively transcribe pro- and anti-inflammatory cytokines. However, in order to characterize the effect of age, feline monocyte functions were examined for changes in cytokine transcription levels in early stages of immunosenescence. For this purpose, isolated, short-term cultured monocytes from barrier-maintained adult cats of different ages (15 mo to 10 yr) were examined for transcription of IL-1 beta, IL-6, IL-10, IL-12 p40 and TNF-alpha by real-time PCR. Transcription levels of cytokines varied and were generally highest for IL-1 beta. For IL-1 beta, IL-6 and IL-12 p40, both young and old cats exhibited highest levels. The age association was significant. TNF-alpha appeared to be transcribed at similar levels over the examination period, whereas IL-10 tended to decline with age but without any statistical significant differences. The observed age association of the constitutive transcription of some cytokines indicates a drop in monocyte activities from youth to middle age, which is then followed by a (progressive) increase with increasing age. This provides evidence that monocytes are in part responsible for the pro-inflammatory status observed with ageing.

Aging↗

Two cases of FeLV-associated dermatoses.

Two cases of feline leukaemia virus (FeLV)-associated dermatosis are described. The first cat was affected by an ulcerative dermatitis identified as a giant-cell dermatosis. The second case was a cutaneous lymphoma. In both cases, FeLV antigens and FeLV genome were demonstrated in the affected skin immunologically and with polymerase chain reaction, respectively. The first case suggests that, like other retroviruses, at least some strains of FeLV can induce syncytium formation. As FeLV antigens and genome were demonstrated in a serologically negative cat, the second case suggests that focal skin FeLV replication may occur. FeLV-associated dermatoses are rare skin conditions that may be under-diagnosed.

Animals↗

Thrombo-ischaemic pinnal necrosis associated with fenbendazole treatment in a dog.

An 11-week-old, female West Highland white terrier was presented with necrosis of the distal third of both pinnae. Haematology, biochemistry and urinalysis, Coombs test, antinuclear antibody and cold autoagglutinin antibody tests were normal. A drug reaction to fenbendazole was diagnosed. The necrotic ear tips were surgically removed. Histopathology revealed extensive coagulative necrosis of the epidermis and superficial to mid-dermis, a moderate interstitial neutrophilic infiltrate and complete thrombotic occlusion and necrosis of blood vessels. There was also endothelial cell activation and proliferation with endothelial cell cushions protruding into the vascular lumen. Immunohistochemistry for factor VIII-related antigen confirmed endothelial cell involvement. This case represents an unusual, drug-induced, thrombo-ischaemic necrosis of the pinnae. It is also, to the authors' knowledge, the first report of fenbendazole sensitivity in a dog. The histopathology is similar to previous cases of proliferative thrombovascular pinnal necrosis, suggesting that drug reactions should be considered in this condition.

Animals↗

Morphologic features and development of granulomatous vasculitis in feline infectious peritonitis.

Feline infectious peritonitis (FIP) is a fatal, coronavirus (CoV)-induced systemic disease in cats, characterized by granulomas in organs and granulomatous vasculitis. This study describes the morphologic features of granulomatous vasculitis in FIP as well as its development in the course of monocyte-associated feline CoV (FCoV) viremia in five naturally infected Domestic Shorthair cats with FIP. Monocyte-associated FCoV viremia was demonstrated by immunohistology, RNA in situ hybridization, and electron micropscopy. Granulomatous phlebitis at different stages of development was observed. Vasculitic processes ranged from attachment and emigration of FCoV-infected monocytes to vascular/perivascular granulomatous infiltrates with destruction of the vascular basal lamina. Monocytes as well as perivascular macrophages were activated because they were strongly positive for CD18 and expressed cytokines (tumor necrosis factor-alpha and interleukin-1beta) and matrix metalloproteinase-9. In addition, general activation of endothelial cells, represented by major histocompatibility complex II upregulation, was observed in all cases. These results confirm FIP as a monocyte-triggered systemic disease and demonstrate the central role of activated monocytes in FIP vasculitis.

Animals↗

Somatic mutations of the thyroid-stimulating hormone receptor gene in feline hyperthyroidism: parallels with human hyperthyroidism.

Hyperthyroidism is the most common endocrinopathy in cats, and is both clinically and histopathologically very similar to human toxic nodular goitre (TNG). Molecular studies on human TNG have revealed the presence of mis-sense mutations in the thyroid-stimulating hormone receptor (TSHR) gene, most frequently in exon 10. Our hypothesis was that similar mutations exist in hyperthyroid cats. Genomic DNA was extracted from 134 hyperplastic/adenomatous nodules (from 50 hyperthyroid cats), and analysed for the presence of mutations in exon 10 of the TSHR gene. 11 different mutations were detected, one silent and 10 mis-sense, of which nine were somatic mutations. 28 of the 50 cats (67/134 nodules) had at least one mis-sense mutation. The mis-sense mutations were Met-452-->Thr in 17 cats (35 nodules), Ser-504-->Arg (two different mutational forms) in two cats (two nodules), Val-508-->Arg in one cat (three nodules), Arg-530-->Gln in one cat (two nodules), Val-557-->Leu in 13 cats (36 nodules), Thr-631-->Ala or Thr-631-->Phe (each mutation seen in one nodule of one cat), Asp-632-->Tyr in six cats (10 nodules) and Asp-632-->His in one cat (one nodule). Five of these mutations have been associated previously with human hyperthyroidism. Of the 41 cats for which more than one nodule was available, 14 had nodules with different mutations. The identification of a potential genetic basis for feline hyperthyroidism is novel, increases our understanding of the pathogenesis of this significant feline disease, and confirms its similarity to TNG.

Animals↗

High viral loads despite absence of clinical and pathological findings in cats experimentally infected with feline coronavirus (FCoV) type I and in naturally FCoV-infected cats.

Specified pathogen-free cats were naturally infected with FCoV or experimentally infected with FCoV type I. Seroconversion was determined and the course of infection was monitored by measuring the FCoV loads in faeces, whole blood, plasma and/or monocytes. Tissue samples collected at necropsy were examined for viral load and histopathological changes. Experimentally infected animals started shedding virus as soon as 2 days after infection. They generally displayed the highest viral loads in colon, ileum and mesenteric lymph nodes. Seroconversion occurred 3-4 weeks post infection. Naturally infected cats were positive for FCoV antibodies and monocyte-associated FCoV viraemia prior to death. At necropsy, most animals tested positive for viral shedding and FCoV RNA was found in spleen, mesenteric lymph nodes and bone marrow. Both experimentally and naturally infected cats remained clinically healthy. Pathological findings were restricted to generalized lymphatic hyperplasia. These findings demonstrate the presence of systemic FCoV infection with high viral loads in the absence of clinical and pathological signs.

Animals↗

Reduced constitutive cytokine transcription in isolated monocytes of clinically healthy cats, infected with an FIV strain of low pathogenicity.

Twenty-five barrier-maintained cats had been experimentally infected for 9.5 months with an FIV strain of low pathogenicity, FIV Zurich 2. Animals were clinically healthy and did not exhibit any haematological changes. FIV proviral DNA was demonstrated in peripheral blood lymphocytes of all cats and in monocytes of most animals, identifying FIV Zurich 2 as a both lympho- and monocytotropic strain. Monocytes were isolated from FIV-infected cats as well as from age-matched uninfected control cats, short-term cultured and examined for cytokine (IL-1beta, IL-6, IL-10, IL-12 p40 and TNF-alpha) transcription by real-time PCR. Constitutive transcription of cytokines in monocytes from FIV-infected cats was restricted to IL-1beta and, in the majority of samples, TNF-alpha. For all cytokines, transcription levels were significantly lower in FIV-infected cats than in control cats. Transcription was often least intense in those samples where FIV infection of the monocyte fraction was not demonstrated. Results show that infection of cats with an FIV strain of low pathogenicity was associated with depression of constitutive cytokine transcription in monocytes even if clinical and haematological changes were not observed.

Animals↗

Septicaemia in emerald monitors (Varanus prasinus Schlegel 1839) caused by Streptococcus agalactiae acquired from mice.

The present study was performed to investigate both the identity and the source of the bacteria responsible for a fatal septicaemia observed in a group of three subadult emerald monitors (Varanus prasinus Schlegel 1839). The emerald monitors were necropsied and examined by light microscopy, including immunohistology, and by electron microscopy. Tissue samples were additionally submitted for bacteriological, virological and parasitological examinations. The virological and parasitological results were noncontributory, whereas the bacteriological investigation resulted in the isolation of gram-positive cocci which were characterized biochemically and serologically and by molecular analysis. The death of the emerald monitors was caused by a partially leukocyte-associated septicaemic infection with streptococci of serological group B of serotype V. Phenotypically and genotypically identical group B streptococci were isolated from the intestine of subadult mice, obtained from the feed used for the monitors. The genotypical characterization included an identical DNA fingerprint of strains of both origins, indicating the epidemiological relation between the feeding mice and the infections of the monitors.

Animals↗

Immunopathological studies on feline cutaneous and (muco)cutaneous mycobacteriosis.

Eight cases of feline (muco)cutaneous mycobacteriosis were studied to identify the causative agent and examine for phenotype and functional characteristics (expression of interleukin (IL)-1beta, IL-6, IL-12, tumour necrosis factor-alpha and inducible nitric oxide synthase) of the inflammatory cells. Polymerase chain reaction and sequencing identified the causative agents as Mycobacterium tuberculosis or M. avium complex in each four cases. Lesions were characterised by pyogranulomatous infiltration, with variability in the presence and size of necrotic areas, the presence of multinucleated giant cells and the degree of lymphocyte infiltration. Macrophages were positive for myeloid/histiocyte antigen (calprotectin), suggesting they represented freshly recruited monocytes; further differentiation to epithelioid cells and multinucleated giant cells was associated with loss of the myeloid/histiocyte antigen. Lymphocytes were found disseminated in the infiltrate (predominantly T cells) and as B cell-dominated accumulations mainly in the periphery of the lesions. Acid-fast bacilli were numerous. In M. tuberculosis complex infection, extracellular bacilli were most prominent, whereas in M. avium complex infection, bacilli were mainly located intracellularly. All cytokines examined as well as inducible nitric oxide synthase (iNOS) were variably expressed by macrophages, epithelioid cells and multinucleated giant cells. Expression was most intense in degenerating macrophages loaded with intracellular bacilli, but was also seen cell-free within necrotic areas. The intense induction of cytokine and iNOS expression especially in infected macrophages suggests a relatively low virulence for these infectious agents in cats. Furthermore, the confinement of the bacilli to lesions indicates a successful response to infection.

Animals↗

Pemphigus foliaceus.

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Administration, Oral↗

Hypereosinophilic paraneoplastic syndrome in a cat with intestinal T cell lymphosarcoma.

A 10-year-old, neutered female, domestic shorthair cat was presented with a recent history of weight loss, polydipsia, diarrhoea and vomiting. On physical examination, intestinal thickening and mesenteric lymph node enlargement were apparent. Clinical investigations revealed peripheral blood eosinophilia, eosinophilic abdominal effusion and eosinophilic mesenteric lymphadenitis. There was a temporary response to treatment with glucocorticoids but signs progressed and the cat was euthanased. On histology, there was eosinophilic infiltration and fibroplasia of intestine and mesenteric lymph nodes. Large aggregates of neoplastic round cells in the intestine and lymph nodes were identified as T lymphocytes using immunohistochemistry. A diagnosis of intestinal T cell lymphosarcoma was made. This case demonstrates that hypereosinophilic paraneoplastic syndrome may occur in cats with lymphosarcoma. Eosinophil chemotaxis may be a response to the production of interleukin-5 by neoplastic lymphocytes.

Animals↗

Cytokine mRNA levels in isolated feline monocytes.

Real-time PCR systems were developed to quantitate cytokine expression in short-time cultivated feline monocytes. Feline-specific interleukin-1beta (IL-1beta), IL-6, and tumor necrosis factor-alpha (TNF-alpha) primers as well as TaqMan probes were designed and were adapted to a quantitative PCR system which had been previously established for feline IL-10 and IL-12 p40. Quantitative analysis of cytokine messenger RNA (mRNA) transcription based on the comparison of the cytokine with the housekeeping gene feline glyceraldehyde-3-phosphate dehydrogenase (GAPDH), providing universally expressed mRNA. GAPDH mRNA was readily detectable in cDNA prepared from short-time cultivated peripheral blood monocytes. Cytokine mRNA was demonstrated in all samples at variable amounts. IL-1beta and TNF-alpha mRNA was constitutively expressed whereas IL-6, IL-10 and IL-12 p40 mRNA was generally expressed at a lower level and was occasionally not detected. There was a great variability of cytokine production between individual cats and at different time points in the same cat.

Animals↗

Fatal gastrointestinal infection with 'Flexispira rappini'-like organisms in a cat.

A 4-month-old male British Blue cat with catarrhal to haemorrhagic enteritis showed massive colonization of the stomach, small intestine and caecum with spiral-shaped bacilli. In the stomach, organisms were located in foveolae and gland lumina and within unaltered and degenerate epithelial cells. Inflammatory infiltration was moderate and T cell dominated. In the intestine, bacilli were found in the gut lumen, berween villi, in crypt lumina and within epithelial cells. Degeneration of crypt epithelial cells as well as crypt dilation and moderate to massive macrophage-dominated infiltration of the mucosa and submucosa were observed. Immunohistochemically, bacilli were positive with an antibody against Helicobacter. Ultrastructurally, the organisms strongly resembled 'Flexispira rappini', a spiral-shaped Helicobacter species known as a normal intestinal colonizer in dogs and mice.

Animals↗

Experimental infection of mice with Borna disease virus (BDV): replication and distribution of the virus after intracerebral infection.

To develop an animal model resembling natural asymptomatic Borna disease virus (BDV) infections, BDV He/80 rat brain homogenate was passaged four times in adult SJL/J mice. Within 12 months of observation, mice did not develop overt signs of disease. Nucleotide sequencing of the rat isolate and the mouse isolates at the fourth passage revealed no difference in the deduced amino acids. Viral RNA was found in brain, heart, kidney, lung, liver, and urinary bladder. Infectious virus was isolated from brain, but also from heart and lung tissue. Immunohistochemically, BDV was demonstrated in nerves in the abdominal cavity, ganglion coeliacum, and adrenal glands, but not in organ parenchyma. Occasionally, viral RNA was detected in mononuclear blood cells.

Animals↗