PubMed Health⌕ Search

Biomedical subjects

W J Penhale

Publications and source records attributed to W J Penhale.

At least 55 records · Page 3Linked to original sources

Autoimmune haemolytic anaemia in dogs.

The clinical, haematological and immunological findings in 24 dogs with Coombs' positive haemolytic anaemia are described; 33% were Old English Sheepdogs. Dogs with intravascular haemolysis had a shorter history of illnesses, more severe clinical signs including vomiting, jaundice and fever, and had a poor survival rate compared to dogs with extravascular haemolysis. The anaemia was severe and regenerative in 18 dogs, and was characterised by spherocytosis and microscopic red cell agglutination, with leukocytosis. Serum IgG levels were elevated in 20 dogs, and changes in IgM, IgA, C3 and C4 were found. Antinuclear antibody was also demonstrated in 13 dogs, of which 7 were Old English Sheepdogs. It is suggested that a distinct multisystem autoimmune syndrome exists within the local Old English Sheepdog population.

Anemia, Hemolytic, Autoimmune↗

Sex hormones, immune responses, and autoimmune diseases. Mechanisms of sex hormone action.

Immune reactivity is greater in females than in males. In both experimental animals and in man there is a greater preponderance of autoimmune diseases in females, compared with males. Studies in many experimental models have established that the underlying basis for this sex-related susceptibility is the marked effects of sex hormones. Sex hormones influence the onset and severity of immune-mediated pathologic conditions by modulating lymphocytes at all stages of life, prenatal, prepubertal, and postpubertal. However, despite extensive studies, the mechanisms of sex hormone action are not precisely understood. Earlier evidence suggested that the sex hormones acted via the thymus gland. In recent years it has become apparent that sex hormones can also influence the immune system by acting on several nonclassic target sites such as the immune system itself (nonthymic lymphoid organs), the central nervous system, the macrophage-macrocyte system, and the skeletal system. Immunoregulatory T cells appear to be most sensitive to sex hormone action among lymphoid cells. Several mechanisms of action of sex hormones are discussed in this review. The possibility of using sex hormone modulation of immune responses for the treatment of autoimmune disorders is a promising area for future investigation.

Animals↗

The detection of canine autoantibodies to thyroid antigens by enzyme-linked immunosorbent assay, hemagglutination and indirect immunofluorescence.

Autoantibodies to thyroid antigens in serums from 34 clinically hypothyroid dogs were detected by various methods. Antibodies to thyroglobulin were detectable by enzyme-linked immunosorbent assay (ELISA) in 59%, by chromic chloride hemagglutination in 53% and by indirect immunofluorescence on formalin-fixed, paraffin-embedded, trypsin-digested thyroid tissue in 73% of samples. Antibody to thyroid microsomal antigen was detectable by ELISA in 29% of serums. Indirect immunofluorescence showed cytoplasmic fluorescence of thyroid follicular cells in several serums, however, this could not be confirmed as specific for microsomal antigen by absorption trials. Hemagglutination tests using commercially available tanned red cells coated with human antigens and indirect immunofluorescence assays on formalin-fixed tissue without trypsin digestion, on Bouin's fixed tissue, or on cryostat, methanol-fixed sections, were insensitive. Cryostat sections without methanol fixation were unsuitable due to tissue fragility. No method was recommended for routine diagnostic use. The ELISA test, because of its convenience, may be useful as a screening aid or adjunct to the diagnosis of thyroid disease.

Animals↗

Survey of thyroglobulin autoantibodies in dogs.

An enzyme-linked immunosorbent assay was used to detect autoantibodies to thyroglobulin in dogs with and without clinical evidence of thyroid disease. Autoantibodies were found in 59% of 34 clinically hypothyroid dogs, 43% of 65 dogs with nonthyroidal endocrine diseases, 47% of 64 healthy dogs closely related to antibody-positive canine hospital patients, and 13% of 1,057 canine hospital patients without endocrine disorders. Dogs with bacterial skin disease and alopecia of unknown causes had an increased prevalence of autoantibodies compared with the prevalence of autoantibodies in healthy dogs and dogs with other diseases. Three breeds of dogs, Great Danes, Irish Setters, and Old English Sheepdogs, had an increased occurrence of autoantibodies compared with that in other breeds and dogs of mixed breeding. A familial tendency to thyroid autoimmunity was demonstrated in a group of Great Dane dogs. The occurrence of autoantibodies was not influenced by age or sex. Thyroid function, as assessed by total thyroxine estimation, was depressed in hospitalized dogs compared with the thyroid function in healthy dogs, irrespective of thyroglobulin-antibody status. Two of 11 autoantibody-positive dogs monitored for an 18-month period developed low thyroxine concentration and depressed thyroid responsiveness to exogeneous thyrotropin stimulation.

Adrenal Insufficiency↗

The effects of selective immunosuppression on resistance to Mesocestoides corti in strains of mice showing high and low initial susceptibility.

Previous work has shown that C57BL/6 mice had the lowest initial susceptibility to Mesocestoides corti of six strains of mice examined. Parasite burdens in this strain and in CBA/H mice, a strain showing a higher initial susceptibility to M. corti, were compared following selective immunosuppressive treatments. Irradiation, splenectomy and the administration of cyclophosphamide and methyl prednisolone all resulted in higher parasite burdens in C57BL/6 mice. In contrast these treatments had a minimal effect on parasite burdens in CBA/H mice. In the light of these results the role of antibody in controlling parasite proliferation is discussed.

Adrenal Cortex Hormones↗

Factors influencing the establishment of Mesocestoides corti in mice following oral inoculation of tetrathyridia.

Factors which influence the establishment of tetrathyridia of Mesocestoides corti in mice following inoculation per os were examined. Only a proportion of the tetrathyridia penetrate the gut wall and gain access to the peritoneal cavity and liver, and most of these penetrate through the wall of the small intestine. It appears that tetrathyridia must attach to the intestinal mucosa and commence penetration immediately or they pass into the large intestine and are voided. Establishment was not influenced by strain, sex or age of host. However, the temperature at which tetrathyridia were maintained before inoculation influence their ability to penetrate the intestinal wall. Additionally it appears that tetrathyridia have to undergo a morphological change before or during, this penetration phase.

Animals↗

The effects of female sex steroids on the development of autoimmune thyroiditis in thymectomized and irradiated rats.

Female PVG/c strain rats are more susceptible to the induction of autoimmune thyroiditis initiated by thymectomy and irradiation (Tx-X) than similarly treated males. Pre-pubertal ovariectomy was found to further augment this susceptibility. The administration of oestrogen or progesterone to groups of 4 week old ovariectomized Tx-X animals over a period of 15 weeks significantly altered the course of the events leading to the induction of this condition. Thus oestrogen administered repeatedly at dose levels of 1 microgram and 10 micrograms/100 g body weight resulted in partial suppression of thyroiditis with a corresponding change in the incidence of antibodies to thyroglobulin. Similarly, oestrogen administered by a single implantation had a suppressive effect on the development of autoimmunity in ovariectomized Tx-X females. Oestrogen given by either of these procedures also reduced the incidence of both thyroiditis and autoantibody induction in orchidectomized male Tx-X rats. In contrast to the inhibitory effects of oestrogen, the repeated administration of progesterone at a dose of 250 ng and 1,500 micrograms/100 g body weight appeared to augment the levels of autoimmunity. It is concluded that the differential susceptibility to the induction of autoimmunity by thymectomy and irradiation is the direct consequence of sex hormonal influences. Furthermore, the higher incidence of the disease in the female would appear to be determined by the balance between the activity of oestrogen and progesterone which would further appear to have antagonistic influences in this particular situation.

Animals↗

Pathophysiology of Mesocestoides corti infection in the mouse.

Liver histology and serum enzyme and protein changes were studies in two strains of mice showing different initial susceptibilities to infection with Mesocestoides corti. The results show an increase in ALT and AST levels during the period of invasion and proliferation in the liver and a decrease in the levels of these two enzymes following encapsulation of the parasite in the liver and liver regeneration. A progressive loss of albumin was accompanied by increases in the levels of the beta- and gamma-globulins. These changes are discussed in the light of our knowledge of the effects of this parasite upon its host.

Alanine Transaminase↗

BCG-induced inhibition and destruction of Taenia taeniaeformis in mice.

Pretreatment of mice with BCG induced a high level of protection against infection with Taenia taeniaeformis. Protection was manifested both during and after establishment by the parasite suggesting that two separate mechanisms were stimulated by BCG. The first inhibits initial establishment by the parasite and may be antibody mediated. The second is responsible for the destruction of developing strobilocerci in the liver and may require the involvement of cellular defence mechanisms.

Animals↗

The influence of testosterone on the development of autoimmune thyroiditis in thymectomized and irradiated rats.

Orchidectomy was found to potentiate the development of autoimmune thyroiditis induced by thymectomy and irradiation (Tx-X) in male PVG/c strain rats. Conversely, testosterone administration to orchidectomized Tx-X rats markedly reduced or inhibited the development of this condition. When given in varying quantities by injection in oil over a period of 15 weeks the inhibitory effect on the development of both thyroiditis and thyroglobulin autoantibodies was found to be directly related to dose. Levels between 150 ng and 150 micrograms/100 gm body weight reduced the incidence and severity of the disease whilst levels of 500 micrograms and 5000 micrograms abrogated these autoimmune effects. Testosterone in implant form had a similar effect. Low doses of testosterone administered by either procedure were also found to be beneficial to entire female Tx-X rats. These results indicate that sex steroid hormones have an important modulatory influence on the genesis of autoimmune thyroiditis. Furthermore, it is also apparent in this particular model that this influence can be demonstrated in the absence of the thymus gland

Animals↗

Pathological changes in inbred strains of mice following early thymectomy and irradiation.

Mice subjected to thymectomy and irradiation were found to develop a range of pathological change in various organs. These changes were accompanied by antibodies to a variety of self-components. The pattern of pathological and autoimmune change was found to vary with the strain. This strain-related expression did not appear to be associated with the major histocompatibility complex (H-2).

Animals↗

Thyroid transplantation developing autoimmune thyroiditis following thymectomy and irradiation.

Post-irradiation transplantation of normal thyroids under the renal capsule of syngenetic thymectomized and irradiated (Tx-X) rats leads to the development of thyroiditis in the ectopic grafted thyroids. A close correlation was observed between the extent of the lesions in the grafted and recipient's own thyroid. The histopathology of both grafted and recipient thyroid was similar and was characterized by infiltration with mononuclear cells together with some plasma cells. Conversely, grafting of affected thyroids from Tx-X rats to normal animals resulted in the regression of the lesion in the graft and no evidence thyroiditis was observed in either the graft or the recipient's thyroid when these were examined 60 days post-grafting. Thyroids derived from normal animals grafted to syngenetic normal rats were found to remain healthy and intact over a 60-day period. In contrast to normal animals, Tx-X rats were unable to reject totally in transplanted allogeneic thyroids by 28 days post-grafting, suggesting that some impairment of cell-mediated immunity follows this treatment. These findings indicate that the pathological change occurring in the thyroid gland of Tx-X rats is not attributable to the local effect of irradiation of the thyroids and adds further support to the concept that the process is immunologically mediated by thyroid-specific circulating components in the absence of normal immune regulatory function.

Animals↗

The enhancement of tetrathyridial proliferation of Mesocestoides corti in mice by B.C.G.

The effects of different doses of B.C.G. given at various periods before infection, on the development of tetrathyridia of Mesocestoides corti was studied. B.C.G. administration was found to exert a complex influence upon M. corti infection in mice. Either enhancement or inhibition of parasite proliferation may occur, depending upon dosage level and the time interval between B.C.G. administration and parasite challenge.

Animals↗