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Biomedical subjects

W J Penhale

Publications and source records attributed to W J Penhale.

At least 37 records · Page 2Linked to original sources

Measurement of protease thermostability, twitching motility and colony size of Bacteroides nodosus.

Total extracellular protease activity of Bacteroides nodosus in TAS liquid culture varied directly with cell mass and buffer concentration between 20 and 50 mM HEPES, MOPS and TES buffers, but not with Tris which gave anomalous high cell counts, nor with Na2Co3 which showed a decline of protease activity and cell mass. The stability of HEPES-buffered crude protease preparations were estimated on the basis of temperature or Ca2+ activity. Variation of the estimates for cellular twitching was greater than that for colony diameter in benign and virulent strains of B. nodosus. Surface translocation, quantified on the basis of colony diameter, reached a limit after 72 h incubation on modified TAS agar, ranging from 0.04 to 0.14 mm per h for six isolates tested.

Animals↗

Induction of diabetes in PVG/c strain rats by manipulation of the immune system.

A combination of thymectomy and sublethal irradiation (Tx-X) consistently induced diabetes in female rats of the PVG/c strain. The incidence of diabetes varied from 10.7% to 53.4% in seven successive Tx-X groups (mean 29.7%). Both clinical and subclinical disease was observed with the majority of affected animals developing the former condition. This was acute in onset, rapidly fatal (1-4 days) and characterized by ketosis and lipidemia. Overtly diabetic rats had markedly raised plasma glucose concentrations compared to normal rats of the same strain and plasma immunoreactive insulin concentrations were correspondingly depressed in this group. Histopathological change within the islets of Langerhans correlated with clinical status and ranged from diffuse atrophy in the majority of the acutely diabetic rats to mild and focal lymphocytic insulitis in a proportion of the non-diabetic rats. Islet cell autoantibodies were demonstrated by indirect immunofluorescence in approximately 25% of clinically diabetic animals. The majority of diabetic rats were found to be responsive to insulin and the clinical signs could be reversed by daily parenteral insulin administration. These observations implicate the immune system in diabetes generation and are consistent with an immune mediated pathogenesis as the underlying cause of the islet cell destruction. This syndrome may thus be a potentially useful animal model for type 1 (insulin dependent) diabetes in man.

Animals↗

The effect of lentinan on the resistance of mice to Mesocestoides corti.

CBA/H mice were given the immunomodulator lentinan in multiple, ascending doses before (prophylactic) or after (therapeutic) inoculation with tetrathyridia of Mesocestoides corti or as a single prophylactic dose. The latter was without effect, but increasing multiple prophylactic and therapeutic doses of lentinan resulted in a marked reduction in the numbers of parasites in the peritoneal cavity, particularly in those mice that received lentinan therapeutically. In mice that received multiple doses of lentinan, liver granulomas were larger than in controls and there was more collagen deposition and fibrosis. Encapsulated parasites were dead or dying, and such damage appeared to be mediated by increased numbers of macrophages and giant cells.

Animals↗

Humoral immunity in disseminated Aspergillus terreus infection in the dog.

Aspects of humoral immunity were studied in 17 dogs with disseminated aspergillosis (16 cases Aspergillus terreus, 1 case Aspergillus flavipes). All dogs had markedly raised serum IgG levels by single radial immunodiffusion (range 1500-6000 mg dl-1). Despite this, serum antibody to A. terreus was demonstrated in only 7/16 cases by agar gel diffusion, 9/16 cases by counter immunoelectrophoresis, 10/16 by ELISA and 11/16 by an indirect immunofluorescence assay. Serum antibody was also detected in 2/5 clinically normal relatives of 2 cases, indicating previous exposure or subclinical infection.

Animals↗

The influence of the normal microbial flora on the susceptibility of rats to experimental autoimmune thyroiditis.

Female PVG/c strain rats maintained under specific pathogen-free conditions until weaning were found to be significantly less susceptible to the induction of autoimmune thyroiditis by thymectomy and irradiation than conventionally reared rats of the same strain. Other SPF-derived strains had a similarly low susceptibility, thus pointing to an important external factor influencing the induction of autoimmunity by this procedure. It was found that the oral administration of antibiotics followed by fresh, homogenized, intestinal contents obtained from conventionally reared rats to newly weaned SPF PVG/c rats significantly augmented their autoimmune susceptibility. The offspring of female SPF rats which had been treated in late pregnancy with oral antibiotics and conventional intestinal contents were similarly more susceptible than the offspring of non-treated counterparts. It is proposed that the composition of the normal gastrointestinal flora of conventionally reared rats profoundly influences susceptibility to the induction of autoimmune thyroiditis in this particular experimental model, possibly by antigenic cross-reactivity with thyroid tissue.

Animals↗

Serum immunoglobulin A concentrations in normal and diseased dogs.

The normal level of serum IgA in Western Australian dogs was defined by single radial immunodiffusion using sera from 100 healthy randomly selected adult crossbred animals. Serum IgA values of 185 animals from six breeds were also determined. The mean and variance of serum IgA of these groups were similar to the crossbred dogs with the exception of German shepherd dogs where these values were statistically greater. In addition, 210 dogs with a range of chronic diseases (autoimmune, hypersensitivity, pyoderma, neoplasia, demodecosis, disseminated aspergillosis) were assayed and low values recorded in five cases. In all disease groups the mean serum IgA value was significantly greater than in the crossbred group and the variance significantly greater in most of these groups. The German shepherd group were the only normal dogs with a mean and variance similar to those of the clinical series suggesting that this breed may have a primary defect in IgA metabolism.

Animals↗

Factors affecting the composition of mare uterine fluid.

The influx of protein and polymorphonuclear leucocytes (PMN) into the uterine lumen was examined at different intervals after intrauterine infusion of fluids. The intrauterine infusion of both phosphate buffered saline (PBS) and a solution of lipopolysaccharide (LPS) derived from Escherichia coli resulted in a biphasic influx of protein in the uterine flushings peaking three and six hours after infusion. LPS infusion caused an additional influx of protein at 24 hours. The initial influx of protein preceded a biphasic influx of PMN which peaked six and 24 hours after both infusions. Uterine flushings obtained following PBS and LPS infusion contained both serum-derived and uterine-specific proteins. To investigate whether the influxes were a general response to reproductive mucosal stimulation, several regions of the reproductive tract were subjected to physical manipulation. Results suggested that these influxes were initiated chiefly by stimulation of the cervical and, or, uterine region.

Animals↗

A review of major histocompatibility complex-disease associations in man and dog.

The organization and biology of the Major Histocompatibility Complexes (MHC) of man (HLA) and dog (DLA) are reviewed, and a summary is presented of laboratory techniques used to define allotypes. The nomenclature of this field and the mechanisms of disease association with the MHC are discussed. Currently recognized HLA-disease associations are enumerated, with emphasis on the value of the complement C4 marker. DLA-disease association studies into autoimmune disease, allergy and neoplasia are reviewed.

Animals↗

Dynamics of the acute uterine response to infection, endotoxin infusion and physical manipulation of the reproductive tract in the mare.

The uterine responses after the infusion of saline (PBS), a bacterial suspension, or lipopolysaccharide derived from Escherichia coli, and after stimulation of the reproductive tract were compared. All infusions provoked a response involving both serum proteins and leucocytes. Protein levels peaked within a few hours of infusion, whereas leucocyte concentration peaked later at around 6 h. Bacterial recovery from the uterus followed a similar pattern, with recovery falling dramatically by 12 h. In mares known to be susceptible to infection large numbers of bacteria were again recovered after 24 h. No differences were apparent between resistant and susceptible mares in protein or leucocyte concentrations. Stimulation of the cervix and uterus resulted in a protein and neutrophil response. In contrast, vaginal stimulation failed to provoke the uterine defences.

Animals↗

Disseminated aspergillosis in dogs.

Clinical and pathological findings are reported from a series of 12 cases of disseminated aspergillosis (A. terreus) in 11 German Shepherd dogs and one Dalmatian referred to Murdoch University Veterinary Hospital (MUVH) over the period 1980 to 1984. A preliminary study of humoral and cell mediated immune components and complement levels revealed no consistent abnormality in 9 dogs tested apart from raised IgG levels. Serum IgA levels were depressed in 30% of cases. Serial data from one extensively monitored case is presented. The unusual epidemiological and pathogenetic features of the disease are discussed.

Animals↗

Immunodiagnosis of autoimmune skin disease in the dog, cat and horse.

Skin biopsies from 47 dogs, 6 cats and 5 horses with suspected autoimmune skin disease were submitted for immunofluorescence from 1978 to 1985. These cases were predominantly Western Australian in origin, although a number were also referred from Queensland and Victoria. In 5 dogs, 2 cats and 2 horses immunoglobulin binding to intercellular cement substance and/or basement membrane was demonstrated by direct immunofluorescence. Antinuclear antibody was also demonstrated in several of these cases. Immunofluorescence was used in combination with histopathological examination to confirm the clinical diagnosis of autoimmune disease in 19/47 dogs, 4/6 cats and 2/5 horses. There was no age, breed or sex predisposition amongst the 19 positive dogs, however there was a higher incidence of antinuclear antibody (54%) than the normal canine population (10%) and other autoantibodies (rheumatoid factor) were sometimes present. Abnormalities in serum protein electrophoresis and serum complement C4 levels were also recorded in this group.

Animals↗

Beneficial effect of testosterone in the treatment of chronic autoimmune thyroiditis in rats.

Early thymectomy and sublethal irradiation of normal rats consistently induces a sex-dependent chronic autoimmune thyroiditis. Females are much more susceptible to this autoimmune disorder than are males. The possible therapeutic effects of testosterone (Te) on established autoimmune thyroiditis has been investigated in this model. The pathologic condition of the gland before treatment was monitored by a thyroid grafting and extirpation techniques. Te administration by either parenteral injection or implantation caused significant regression of established thyroiditis. Repeated doses of Te ester in oil were found to be more effective than powdered free-Te given by implantation, and frequently produced complete resolution of chronic lesions involving the entire gland. In these thyroids, there was reappearance of normal thyroid architecture and complete absence of mononuclear cellular infiltration. However, no inhibitory effect on serum autoantibody production to thyroglobulin was noted with any form of Te treatment. These observations strengthen the concept that cellular rather than humoral mechanisms are involved in the pathogenesis of thyroiditis.

Animals↗

Complement C4 allotype association with and serum C4 concentration in an autoimmune disease in the dog.

Serum C4 concentrations and C4 allotypes were determined wherever possible on eight dogs with an autoimmune disorder characterized by antinuclear antibody (ANA) positivity, pyrexia, and seronegative arthritis. Three of the six dogs tested serially showed hypocomplementemia at disease onset with return to normal concentrations with clinical remission following steroid therapy. All five dogs C4 allotyped were phenotypically identical. The phenotype (C4-4) was significantly increased in the diseased dogs. Thus C4 allotype may provide a marker for susceptibility to development of an autoimmune disorder in the dog. Serum C4 concentrations may help in disease diagnosis and monitoring the effectiveness of therapy.

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Immunologic study of systemic aspergillosis in German shepherd dogs.

Data are presented from a series of eight cases of disseminated canine aspergillosis (A. terreus) in German Shepherd dogs referred to Murdoch University Veterinary Hospital. Immunoglobulin determination revealed depression of serum IgA (cases 1 and 5) and IgM (case 2) levels and elevated levels of IgG in all cases. Total complement activity (CH50) and complement components tests, (C3, C4) were present in normal amounts in all cases. Using agar gel diffusion, serum antibody to A. terreus was found in only one case and aspergillus antigenaemia in two of the remainder. Lectin transformation of lymphocytes in two dogs was found to be depressed relative to normal controls in case 1 and initially in case 2. Two dogs failed to respond to the intradermal injection of A. terreus antigen.

Animals↗

Experimental thyroid autoimmunity in the dog.

Thyroid autoimmunity was induced in 6 crossbred dogs by a single injection of thyroid extract in complete Freund's adjuvant alone, or followed by reimmunization with thyroid extract and incomplete Freund's adjuvant or peanut oil. Total thyroxine levels, autoantibodies to thyroglobulin and thyroid microsomal antigen and thyroid histopathological changes were sequentially monitored for up to 150 days. All dogs developed fluxuating levels of thyroid autoantibodies detectable by enzyme-linked immunosorbent-assay (ELISA). Histopathological damage was observed in one or more thyroid gland biopsies in 4 of the dogs, in 3 cases the lesions were of lymphocytic thyroiditis, in the fourth dog the lesion was a granulomatous reaction. Histopathological thyroid damage was observed in biopsies taken during periods of maximal autoantibody titer. Fixed immunoglobulin was not demonstrable in thyroid gland biopsies by direct immunofluorescence. In 5 dogs total thyroxine levels fell to below the normal range at some period during the study. However in only one dog did this correlate with a time when biopsy findings revealed histopathological thyroid damage. High levels of thyroid autoantibody may indicate histopathological thyroid damage in dogs, however lower levels of thyroid antibody may be found without evidence of histological damage or alteration in thyroid function.

Adjuvants, Immunologic↗

Autoantibodies to pancreatic islet cells in canine diabetes mellitus.

Indirect immunofluorescence on normal canine pancreatic tissue fixed in Bouin's solution was used to detect islet cell antibodies in dogs with diabetes mellitus, other endocrine diseases, and pancreatitis. 18 of 25 dogs with diabetes mellitus alone, 2 of 8 dogs with diabetes mellitus and concurrent pancreatitis, and 2 of 2 dogs with diabetes mellitus and concurrent pancreatic exocrine insufficiency were positive for autoantibody. 2 of 12 dogs with hypoadrenocorticism, 3 of 6 dogs with hyperadrenocorticism, 6 of 28 dogs with hypothyroidism and one of 19 dogs with pancreatitis alone were also antibody positive. None of 20 healthy dogs or 20 dogs with disorders other than those of the pancreas or endocrine organs were antibody positive. Islet cell antibodies were demonstrated in dogs with diabetes mellitus and other endocrine disorders. The possibility of autoimmune involvement in the development of diabetes mellitus in the dog should be considered.

Animals↗