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W F Robinson

Publications and source records attributed to W F Robinson.

At least 37 records · Page 2Linked to original sources

Leukemia inhibitory factor induces leukocyte infiltration and cartilage proteoglycan degradation in goat joints.

Recent studies have implicated leukemia inhibitory factor (LIF) in human joint disease. LIF is produced by cultured synovial cells and articular chondrocytes, stimulates cartilage and bone resorption, and has been detected in inflammatory exudates from arthritic joints. The aim of this study was to evaluate the effect of intraarticular injections of human recombinant LIF in the goat. Endotoxin-free, sterile normal saline containing 1 micrograms recombinant human LIF (rhLIF) was injected into the right radiocarpal joints (RCJs) of eight angora goats. The left RCJs were injected with an equivalent volume of vehicle alone (n = 6) or vehicle containing 1 micrograms human albumin (n = 2). Goat joints were examined for clinical features of inflammation, and synovial fluid (SF) was aspirated on days 0, 2, and 6 postinjection. Leukocyte counts and concentrations of keratan sulfate, IL-1 beta, and TNF-alpha were determined in the SF. Proteoglycan synthesis was determined ex vivo in cartilage explants obtained on day 6 postinjection. A statistically significant increase in joint swelling and effusion volume was observed in LIF-injected joints but not in control joints. In the LIF-injected RCJs, the leukocyte count increased from 82 +/- 9 cells/microliters before injection to 10,300 +/- 3357 cells/microliters at day 2 postinjection (p < 0.005) and declined to 678 +/- 113 cells/microliters at day 6 postinjection. Polymorphonuclear leukocytes and monocyte/macrophages predominated in the infiltrate. No appreciable change in leukocyte counts was observed in control joints.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Dental education.

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Education, Dental↗

The induction of in vivo superinfection and recombination using feline immunodeficiency virus as the model.

This study investigated the hypothesis that under certain conditions, superinfection of cats with feline immunodeficiency virus (FIV), may occur. One FIV isolate (T91) was used to inoculate three FIV and FeLV-free cats. Blood from an FIV-infected cat (N), which contained two variants and differed from T91 by at least 5% in nucleotide sequence in the env gene, was inoculated into a fourth cat. Both T91 and blood from N were inoculated simultaneously into a fifth cat. After 22 weeks, two of the three cats initially infected with T91 were challenged with blood from N. At 30 weeks following initial infection, peripheral blood mononuclear cells were obtained from all cats, DNA was extracted, and a segment of the env gene was PCR amplified, cloned and sequenced. Nucleotide sequence analysis of the cloned PCR product showed that virus strains used in initial infection were recovered from cats not challenged with a second variant. Challenge of cats with the blood of N following initial infection with T91 resulted in superinfection occurring in one cat and recombination occurring in the other. Furthermore, the use of blood as a source of challenge, in cats where superinfection and simultaneous infections were attempted, may have induced the appearance of variants which more closely resembled the most heterologous strain present in the infectious source.

Amino Acid Sequence↗

Autologous red cell agglutination test for antibodies to feline immunodeficiency virus.

The T-lymphotropic lentivirus, feline immunodeficiency virus (FIV) is now recognised as a major viral pathogen affecting domestic cat populations worldwide. A rapid, autologous red cell agglutination test for antibodies to FIV has been developed. A synthetic peptide analog corresponding to the immunodominant epitope within the FIV transmembrane glycoprotein gp40 residues (680-715) KVEAMEKFLYTAFAMQELGC (Acm)NQNQFFK(BrAc)KIPLELWTR was conjugated to an anti-feline erythrocyte antibody using a thio-ether linkage. Within 3 min of adding this reagent to 20 microliters of whole blood, circulating antibody to the peptide epitope caused agglutination of the red blood cells. The performance of this simple test is comparable with the two commercially available enzyme immunoassay (EIA) kits and an EIA based on this peptide. A variant of the gp40 (680-715) peptide corresponding to the FIV, PPR strain gp40 (678-716) sequence was also synthesised and no difference in reactivity was observed in an EIA on 211 seropositive samples, indicating that the peptide-based test may be applicable to other known strains of the virus.

Amino Acid Sequence↗

Nucleotide sequences of Australian isolates of the feline immunodeficiency virus: comparison with other feline lentiviruses.

Proviral DNA from four Australian isolates of feline immunodeficiency virus (FIV) was amplified by PCR and the nucleotide sequence determined for two conserved regions within gag (p15/p24) and pol (RT) genes. Comparison with the nucleotide and deduced amino acid sequence of two previously described U.S. isolates from California (Petaluma and PPR), and a third from Maryland (MD) as well as the Japanese isolate TM2, revealed a close similarity between the Australian and Californian isolates with 95-97% nucleotide and 96-99% amino acid homologies. By contrast, the Maryland and Japanese isolates were more distantly related with only 84-87% nucleotide and 90-94% amino acid homology with either the Australian or Californian isolates. The relationship of the Australian FIV isolates to other domestic isolates as well as eight lentiviral isolates from wild felidae (panthers) published previously, was investigated further by constructing a phylogenetic tree based on the pol sequence. This revealed two subgroups of FIV, an Australian/Californian group and a less tightly clustered Maryland/Japanese group. These results suggest that the genomic variability of FIV is reflected by more than simply geographic distance. Furthermore, the relative genetic homogeneity found between Australian isolates suggest a shorter period of evolution of the virus in Australia than in North America.

Amino Acid Sequence↗

Extensive sequence variation of feline immunodeficiency virus env genes in isolates from naturally infected cats.

In an investigation of the evolution of feline immunodeficiency virus (FIV) in vivo, sequential isolates from a persistently infected cat were examined by direct sequencing following amplification of selected subgenomic regions by polymerase chain reaction (PCR). Three isolates, T90, T91, and T92, obtained over a three-year period revealed no changes to regions known to be conserved within gag and pol genes. Additionally, no change occurred within gag and pol in an isolate recovered from a second cat which was experimentally infected with T90. Changes were detected within an N-terminal region of the envelope glycoprotein gp 120 (env). These consisted of point mutations, some of which would result in amino acid substitutions and the predicted amino acid changes tended to cluster within variable domains. Inoculation of T90 into a second cat resulted in a different pattern of mutations than that observed for the three isolates from the first cat. In all cases, virus isolates derived from the same cat were much more highly related to each other (extent of env variation was 0.5-1.5%) than to isolates from other cats (10-12% env variation). The rate of change of FIV was estimated to be 3.4 x 10(-3) nucleotide substitutions per site per year for the env gene and less than 10(-4) nucleotide substitutions per site per year for the gag and pol genes, values concordant with that found for human immunodeficiency virus 1. Both nucleotide and amino acid changes in the gp 120 region were found to be directional, suggesting that selective pressures influence FIV envelope gene sequences.

Amino Acid Sequence↗

Feline immunodeficiency virus infection: plasma, but not peripheral blood mononuclear cell virus titer is influenced by zidovudine and cyclosporine.

The plasma and peripheral blood mononuclear cell (PBMC) titer of feline immunodeficiency virus (FIV) in experimentally infected cats was assessed following administration of either zidovudine or cyclosporine. Treatments were begun 24 h post infection (p.i.) and continued for 4 weeks. Zidovudine treatment did not prevent establishment of infection with FIV, but plasma virus titers were significantly lower than controls at 2 weeks p.i. This reduction of plasma virus titer by zidovudine was not maintained at subsequent sampling times. Similarly, cyclosporine treatment initially lowered plasma virus titers at 2 weeks p.i., but at 4 weeks p.i. the plasma virus titers in cyclosporine-treated cats were significantly higher than in the untreated group. In the untreated group, plasma virus titers declined rapidly to an undetectable level by 14 weeks p.i. Neither zidovudine or cyclosporine treatment significantly influenced the titer of FIV in PBMCs. In all groups (untreated, zidovudine and cyclosporine) the titers in PBMC were high for the duration of the experiment. The decline in plasma virus titers in immunocompetent cats combined with the effect of cyclosporine on plasma titers strongly suggest that the immune system plays a major role in clearing FIV from plasma. In contrast, it appears that the immune response has little impact on PBMC virus titers. This shows that for complete assessment of antiviral agents, both cell-free and cell-associated virus titers must be examined. We also suggest that the limitation of viral titers in PBMC may be of critical importance in the control of lentiviral infection.

Amino Acid Sequence↗

Feline immunodeficiency virus: quantification in peripheral blood mononuclear cells and isolation from plasma of infected cats.

The titer of feline immunodeficiency virus in peripheral blood mononuclear cells (PBMC) and the presence of infectious virus in plasma was investigated over 20 week period in 8 experimentally infected cats, 3 uninfected cats and 2 naturally infected cats by end point dilution cultures using a feline T-lymphoblastoid cell line (MYA-1). FIV was isolated from PBMC of all infected cats, but not from the uninfected cats. FIV was also isolated consistently from 100 microliters plasma from most of the experimentally infected cats, but not from the 2 naturally infected cats. The virus titer in PBMCs in both experimentally and naturally infected cats was comparatively high, ranging from 10 TCID/10(6) PBMC to 14,286 TCID/10(6) PBMC. The titers in PBMC of individual cats remained unchanged or varied only slightly over the 20 week period. In contrast, the titers varied substantially between cats, with significantly higher titers in the youngest litter (4 cats) than in the oldest litter (3 cats). This suggests that there is an age-related factor influencing the level of PBMC virus titers in experimental infection with FIV. A similar age-related susceptibility has been shown with feline leukemia virus. More importantly, the sustained titers in the experimentally infected cats bear close resemblance to infection of children with human immunodeficiency virus. These data reinforce suggestions that age and immune maturity have a fundamental influence on PBMC and plasma titers in lentivirus infections.

Animals↗

Tests to combat lentiviruses in domestic animals. Biotechnology Research Group.

Since the discovery of human immunodeficiency virus (HIV) as the cause of AIDS the study of other members of the virus group lentivirinal has intensified. A major outcome of this research have been the development of "state of the art" diagnostic tests. While it has long been realised that these viruses were important causes of slowly developing diseases in sheep and horses other lentiviruses have recently been implicated in similar disease situations in goats, cats and cattle. Membership of the lentivirus group of viruses has increased dramatically over the past fifteen years and it is likely that most if not all mammalian species will be found to be infected with their own lentivirus. This paper will describe the problems caused by these viruses in domestic animals and the steps being taken to prevent their spread. Biotechnology companies have a major role in devising simple and economical tests to detect the viruses and antibodies to these viruses. In addition if a vaccine can be produced against any of the animal viruses this will perhaps enable a similar vaccine to be prepared against HIV.

Animals↗

A cytotoxic haemolysin from Treponema hyodysenteriae--a probable virulence determinant in swine dysentery.

The haemolysin from a virulent strain of Treponema hyodysenteriae was extracted and injected into ligated loops of the ileum and colon of germ-free pigs. It caused severe epithelial damage, especially to the differentiated cells at the tips of the villi in the ileum and the cells in the intercrypt zones of the colon; goblet cells were less affected. The changes in the colon were similar to those seen in natural cases of swine dysentery. The ligated loop offers a means of investigating pathogenic mechanisms and the mode of action of the toxin. This study demonstrated that the haemolysin was a potent cytotoxin for pig enterocytes, and a probable virulence determinant in swine dysentery.

Animals↗

Hereditary nephritis in the bull terrier: evidence for inheritance by an autosomal dominant gene.

A high prevalence of renal failure has been reported in bull terriers in Australia. The pattern of inheritance was analysed in a family of 33 bull terriers in which 10 dogs had renal disease manifested by proteinuria, ultrastructural abnormalities in the glomerular basement membrane, renal failure, or 'end stage' kidneys. The presence of at least one affected parent for each affected offspring, the approximately equal male/female ratio and the apparent absence of 'generation-skipping', strongly supported an autosomal dominant mode of inheritance, assuming a fully penetrant single major gene locus. Further evidence was not compatible with either an autosomal recessive or X-linked inheritance pattern. This contrasts with the X-linked inheritance shown in Alport's-type human hereditary nephritis and hereditary glomerulopathy in the samoyeds. Hereditary nephritis in the bull terrier should be a useful model for non-Alport's-type human hereditary nephritis, which is also reported to have an autosomal dominant inheritance pattern.

Animals↗

Chronic renal disease in bull terriers.

Chronic renal failure was diagnosed in 15 Bull terrier dogs. The dogs ranged in age from one to 8 years. History and clinical findings typically included lethargy, anorexia, polyuria, polydipsia and weight loss. Affected dogs were azotaemic, had elevated serum phosphate and cholesterol, and proteinuria was apparent in all dogs tested (13/13). The concentration of urine was consistently in the nil to minimally concentrated range (specific gravities 1.011-1.017). In those dogs necropsied, both kidneys were approximately two-thirds normal size, tough in consistency, with a pale cortex and a finely nodular capsular surface. Histologically, there was marked nephron loss, diffuse interstitial fibrosis and focal dense radial fibrosis which was especially evident in the renal medulla. Tubular dilation was widespread with focal mineralisation of tubular epithelium and adjacent basement membranes. Glomeruli were often shrunken and segmentally fibrotic. Some Bowman's spaces were extremely dilated. Many less severely affected glomeruli had thickened basement membranes.

Animals↗

The pathology and aetiology of lung lesions in goats infected with caprine arthritis-encephalitis virus.

Fifty dairy goats, of various ages, sexes and breeds were selected for examination on the basis of positive serological reactions to caprine arthritis-encephalitis virus (CAEV). Thirty-one had lung lesions including chronic interstitial pneumonia of caudal or cranioventral lobes, bronchopneumonia, verminous pneumonia, pulmonary cryptococcosis or combinations of these. The only infective agent recovered from all the chronic interstitial pneumonia cases examined was CAEV, which was also recovered from lung tissue of 3 goats with arthritis but no lung lesions. The presence of CAEV in lavaged alveolar macrophages from normal lung tissue and from lungs affected with chronic interstitial pneumonia and verminous pneumonia, and the demonstration of a marked increase in nonspecific esterase staining macrophages in areas of chronic interstitial pneumonia, are discussed in relation to the aetiology of the pneumonia.

Animals↗

Congenital hypothyroidism in Scottish Deerhound puppies.

Two Scottish Deerhound puppies had clinical and pathological features consistent with the diagnosis of congenital non-goitrous hypothyroidism. They were from separate litters, but were the progeny of the same sire and dam. The puppies were smaller, had shorter limbs and shorter, broader heads than their littermates. They also had histories of weakness, difficulty in walking and somnolence. A characteristic radiographic feature was the absence of epiphyseal growth centres. Both had depressed serum thyroxine (T4) levels and one did not respond to exogenous thyroid stimulating hormone. On necropsy, the thyroid glands were small, the follicles varied in size and contained little or no colloid. The adenohypophysis contained many cells with markedly vacuolated cytoplasm. It is suggested that the clinicopathological pattern is the result of a primary thyroid abnormality. Possible mechanisms include either primary thyroid hypoplasia or an unresponsiveness to thyroid stimulating hormone.

Animals↗