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Biomedical subjects

M J Day

Publications and source records attributed to M J Day.

At least 109 records · Page 6Linked to original sources

Prostatic carcinoma in two cats.

Clinical, radiological and pathological features of two cats with prostatic carcinoma are reported. In both cats the presenting history included signs of lower urinary tract disease with haematuria and dysuria. Prostatomegaly was visible radiographically in one cat; an irregular intraprostatic urethra was seen on retrograde contrast urethrography in both cats. In one of the cats, neoplasia was suspected on the basis of a transurethral catheter biopsy. Following a poor response to palliative treatment in both cases, euthanasia was performed with histological confirmation of the diagnosis.

Animals↗

Generalised amyloidosis in two Siamese cats: spontaneous liver haemorrhage and chronic renal failure.

Two cases are reported, illustrating the antemortem diagnosis of systemic amyloidosis in Siamese cats. A cat presenting with inappetence and depression was diagnosed as having systemic amyloidosis with spontaneous haemorrhage from the liver. In another cat from the same breeding cattery, chronic renal failure due to systemic amyloidosis was an incidental finding. Little treatment was possible in either case and both were later euthanased. The two cats had similar renal and hepatic pathology but different signs of disease.

Amyloidosis↗

Lymphocytic choriomeningitis virus-induced alterations of T helper-mediated responses in mice developing autoimmune hemolytic anemia during the course of infection.

The effect of LCMV on CD4+ T lymphocytes was analyzed in C3HeB/FeJ mice after infection with the Docile strain of this virus. Our results indicated that LCMV triggers: i) an inhibition of Th2 lymphocyte differentiation induced by concomitant immunization with a nonviral protein antigen; ii) a depression of T helper-dependent antibody responses elicited by such an immunization; and iii) a CD4+ cell-mediated proliferation of spleen cells leading to increased interleukin-4 and interferon-gamma message expression and IgG2a-restricted total immunoglobulin secretion. Taken together, these results indicate that LCMV profoundly affects CD4+ cell-mediated immune responses in infected animals. Such modulations of T-helper functions may explain the preponderance of IgG2a in the antierythrocyte autoimmune response induced by the virus in C3HeB/FeJ mice.

Anemia, Hemolytic↗

An investigation of phagocytosis and intracellular killing of Staphylococcus intermedius by canine neutrophils in vitro.

Bacterial infection (pyoderma) of the canine skin is largely caused by Staphylococcus intermedius and may be a primary, idiopathic disease or secondary to a range of other dermatological disorders. The immune response to this organism involves phagocytosis and killing by neutrophils. In this study, the effect of opsonisation of S. intermedius by clinical sera (n = 60) and sera from normal dogs (n = 20) was investigated by in vitro phagocytosis and killing assays. All sera from dogs with pyoderma were significantly more efficient at opsonisation for phagocytosis than normal dog sera (p < 0.001). Further, fresh serum was more effective at opsonisation of S. intermedius than heat-inactivated serum in this assay (p < 0.001). The results indicate that opsonisation is enhanced by serum from dogs with pyoderma; therefore the humoral response in clinical cases of canine pyoderma is, in terms of phagocytosis, protective. The small but significant reduction in phagocytosis of S. intermedius opsonised by heat-inactivated serum compared to fresh frozen serum suggests that complement plays a role, although minor, in opsonisation. An in vitro killing assay showed that normal canine neutrophils were able to effectively kill phagocytosed S. intermedius over a 90-min time course, but there was no significant enhancement of killing by prior incubation of the bacteria with any clinical serum as opposed to normal sera. This suggests that the humoral response to S. intermedius does not affect intracellular killing per se.

Animals↗

Prevention of autoimmune disease due to lymphocyte modulation by the B-subunit of Escherichia coli heat-labile enterotoxin.

We demonstrate that the receptor binding moiety of Escherichia coli heat-labile enterotoxin (EtxB) can completely prevent autoimmune disease in a murine model of arthritis. Injection of male DBA/1 mice at the base of the tail with type II collagen in the presence of complete Freund's adjuvant normally leads to arthritis, as evidenced by inflammatory infiltration and swelling of the joints. A separate injection of EtxB at the same time as collagen challenge prevented leukocyte infiltration, synovial hyperplasia, and degeneration of the articular cartilage and reduced clinical symptoms of disease by 82%. The principle biological property of EtxB is its ability to bind to the ubiquitous cell surface receptor GM1 ganglioside, and to other galactose-containing glycolipids and galactoproteins. The importance of receptor interaction in mediating protection from arthritis was demonstrated by the failure of a non-receptor-binding mutant of EtxB to elicit any protective effect. Analysis of T cell responses to collagen, in cultures of draining lymph node cells, revealed that protection was associated with a marked increase in interleukin 4 production concomitant with a reduction in interferon gamma levels. Furthermore, in protected mice there was a significant reduction in anti-collagen antibody levels as well as an increase in the IgG1/IgG2a ratio. These observations show that protection is associated with a shift in the Th1/Th2 balance as well as a general reduction in the extent of the anti-type II collagen immune response. This suggests that EtxB-receptor-mediated modulation of lymphocyte responses provides a means of preventing autoimmune disease.

Animals↗

An immunohistochemical study of the lesions of demodicosis in the dog.

Histopathological and immunohistochemical examination of skin biopsies from 32 dogs with demodicosis is reported. There was no association between the different clinical presentations of the disease and the histopathological character of the biopsies, which included absence of inflammation (n = 2), dominant perifolliculitis (n = 11), interface mural folliculitis (n = 7), mural folliculitis (n = 1), furunculosis (n = 10) and nodular dermatitis (n = 1). In eight of 32 biopsies colonies of coccoid bacteria or Malassezia pachydermatis-like yeasts were observed. IgG-bearing plasma cells were found in similar numbers in the inflammatory infiltrates of all types of histological lesion, and were invariably more numerous than IgM or IgA plasma cells. The IgG plasma cells were largely IgG4 in lesions of perifolliculitis, but consisted of a mixture of IgG2 and IgG4 where folliculitis or furunculosis was present. CD3+T lymphocytes were prominent within the interface infiltrates of follicular epithelium and also within the lesions of furunculosis. Dermal inflammatory cells and epidermal Langerhans cells expressing MHC Class II were observed in similar number in all types of lesion. The study demonstrated an active local cutaneous immune response in canine demodicosis, which increased as the dermal pathology progressed from perifolliculitis to furunculosis.

Animals↗

Aspects of the humoral immune response to Staphylococcus intermedius in dogs with superficial pyoderma, deep pyoderma and anal furunculosis.

Bacterial infection (pyoderma) of the canine skin is largely caused by Staphylococcus intermedius and may be a superficial or deep infection. Pyoderma may be a primary, idiopathic disease or secondary to a range of other dermatological disorders. In this study, the serum concentrations of IgG, IgA, antistaphylococcal IgG and antistaphylococcal IgA were measured by ELISA in normal dogs (n = 22), dogs with idiopathic deep pyoderma (n = 22), atopic dermatitis and superficial pyoderma (n = 24), atopic dermatitis without pyoderma (n = 25), flea bite dermatitis with superficial pyoderma (n = 8), pustular demodicosis (n = 8) and German shepherd dogs with anal furunculosis (n = 28). The serum IgG was significantly increased in dogs with atopy and superficial pyoderma (p < 0.001), and lower than normal in dogs with idiopathic deep pyoderma (p < 0.015). The concentration of serum IgA was significantly lower than normal in dogs with atopy uncomplicated by pyoderma (p < 0.015). The concentration of antistaphylococcal IgG in all clinical sera was significantly elevated (p < 0.001) when compared to normal dogs but concentrations of antistaphylococcal IgA were no greater than in normal dogs. Western blotting analysis for determination of the specificity of serum IgG antistaphylococcal antibody revealed that there were nine major epitopes. Discriminant analysis demonstrated that particular combinations of these epitopes were recognised more frequently by sera from dogs in different clinical groups.

Animals↗

Proliferative responses of peripheral blood mononuclear cells from normal dogs and dogs with autoimmune haemolytic anaemia to red blood cell antigens.

Autoimmune haemolytic anaemia (AIHA), one of the most common autoimmune diseases of the dog, is characterised by binding of autoantibody to erythrocyte membrane antigens leading to a decreased red blood cell (RBC) life-span. Failure of self-tolerance with activation of autoreactive T-lymphocytes is thought to play a key role in the initiation of such autoimmune events. Peripheral blood mononuclear cells (PBMC) were obtained from 11 clinically normal dogs, six clinically normal relatives of two littermate dogs which died from AIHA, and four dogs which had recovered from primary AIHA. Cells were stimulated in vitro with a panel of canine RBC-derived antigens (RBC membranes, glycophorin, spectrin, five 15-mer glycophorin peptides), the non-recall antigen keyhole limpet haemocyanin (KLH), and the mitogen concanavalin A (Con A). The kinetics of the proliferative responses to specific antigens were assessed by serially sampling the cultures from days 4 to 10. PBMC from all dogs responded strongly to Con A (day 2) and to KLH (maximal response on days 7 to 10) under appropriate culture conditions. Two of 11 normal dogs responded weakly to RBC membranes (mean stimulation index = 4.25). In contrast, PBMC from all dogs recovered from AIHA responded to RBC membranes (mean SI = 9.2 +/- 2.5) and occasionally to other erythrocyte antigens. Similar responses were recorded with PBMC from dogs related to AIHA cases. It is considered that although normal individuals harbour erythrocyte-reactive lymphocytes, such cells are primed in dogs with AIHA or a genetic susceptibility to this disease.

Amino Acid Sequence↗

Biochemical characterization of canine blood group antigens: immunoprecipitation of DEA 1.2, 4 and 7 and identification of a dog erythrocyte membrane antigen homologous to human Rhesus.

Despite the clinical significance of the canine blood group antigens, relatively little is known of the biochemistry of these molecules. In this study the canine blood group antigens DEA (dog erythrocyte antigen) 1.2, 4 and 7 were immunoprecipitated from red blood cells (RBC) bearing the corresponding blood group, and molecular weights of 85 kD (DEA 1.2), 32-40 kD (DEA 4) and 53-66 kD (DEA 7) assigned. DEA 1.2 and DEA 4 each appeared as a single band, whereas DEA 7 comprised three distinct bands (53, 58 and 66 kD). Polyclonal antisera specific for two peptides derived from the sequence of the human Rhesus blood group (Rh30A-C and Rh50A-C) were used in western blotting against canine and human erythrocyte membranes. The Rh30A-C antiserum identified a band of molecular weight 32 kD in both human and canine RBC, and the antiserum specific for Rh50A-C identified a band of 38-60 kD in human membranes and of 40-53 kD in canine RBC. This finding is consistent with conservation of areas of the Rhesus protein sequence between human and canine erythrocytes.

Amino Acid Sequence↗

Infection of C3HeB/FeJ mice with the docile strain of lymphocytic choriomeningitis virus induces autoantibodies specific for erythrocyte Band 3.

C3HeB/FeJ mice infected with the docile strain of lymphocytic choriomeningitis virus (LCMV-d) develop a persistent infection with a transient haemolytic anaemia. Immunoglobulin can be eluted from the red blood cells (RBC) of these mice but it cannot be detected on the RBC by a conventional antiglobulin test. The present study demonstrates that RBC from such mice bear erythrocyte autoantibodies which are predominantly of the IgG2a subclass, with lower levels of autoantibodies of the IgG1, IgG2b and IgG3 subclasses. To identify the target antigen the autoantibodies were eluted from the RBC of LCMV-infected mice. The eluted autoantibody bound to intact normal RBC and precipitated a 105000 MW component that corresponds to murine Band 3 protein. A monoclonal antibody derived from mice infected with LCMV-d also precipitated mouse Band 3, and reacted specifically by enzyme-linked immunosorbent assay against a purified preparation of Band 3. This study has shown that in C3H mice infected with LCMV-d which develop autoimmune haemolytic anaemia, the target autoantigen is erythrocyte membrane Band 3.

Anemia, Hemolytic, Autoimmune↗

Immunopathogenesis of canine aural haematoma.

Data are presented from 15 dogs with aural haematoma. The series included six Labrador retrievers and four golden retrievers and the mean age was 8.0 +/- 3.02 years. Five dogs had evidence of pruritic skin disease and five further cases had other concurrent disease. Haematology and serum biochemistry were normal in 12 and 13 of the 15 dogs, respectively. All dogs were Coombs' negative and serum antinuclear antibody had negative or low titres in all the 11 cases tested. Histopathological examination of biopsies from the affected ears revealed variable degrees of erosion of auricular cartilage with fibrovascular granulation tissue filling the cartilage defects. There was minimal perichondral inflammation. The biopsies were studied by immunohistochemistry for deposition of immunoglobulin G (IgG), immunoglobulin M (IgM) and complement C3. In one dog there was basement membrane zone deposition of IgG and in another there was focal interepithelial deposition of both IgG and IgM. The findings of this study do not support an autoimmune pathogenesis for canine aural haematoma, but suggest that an early immunological event may underlie the observed cartilage erosion.

Animals↗

Low serum immunoglobulin concentrations in related Weimaraner dogs.

Chronic, recurrent disease involving the alimentary tract, joints, skin and peripheral lymph nodes, central nervous system and conjunctivae was recorded over a 229 day period in a young Weimaraner dog, first presented at 15 weeks of age. The dog had a left shift neutrophilia during periods of active disease and persistently subnormal levels of serum immunoglobulin G (IgG; 2.8 to 9.2 mg/ml) and IgA (< 0.1 to 0.26 mg/ml) in the absence of circulating immune complexes. One littermate died suddenly at 27 weeks of age and a second littermate had an episode of pyoderma. Both of these dogs had low serum IgG (3.5 to 7.2 mg/ml) and the second littermate also had reduced serum IgA (< 0.1 to 0.15 mg/ml). The dam of the litter and three other related dogs had reduced serum IgA (0.22 to 0.31 mg/ml); circulating immune complexes were not recorded in any of the related dogs. This case is the first of putative immunodeficiency of Weimaraners in the UK. Inability to synthesise adequate concentrations of serum immunoglobulins should be considered a primary defect in this disorder.

Animals↗

Review of thymic pathology in 30 cats and 36 dogs.

Data are presented from 30 cats and 36 dogs in which thymic disease was recognised clinically or on postmortem examination. The diagnoses included thymic lymphoma (19 cats, 12 dogs), thymoma (five cats, 18 dogs), thymic branchial cyst formation or cystic change (one cat, four dogs), thymic hyperplasia (two cats), congenital hypoplasia (one cat, one dog), thymic haemorrhage (one cat, one dog) and thymic amyloidosis (one cat). Thymic lymphoma occurred in younger dogs and cats, and was recorded equally among domestic shorthaired and purebred (especially Siamese) cats. Eight cats with thymic lymphoma were tested for feline leukaemia virus and four were positive. Thymoma occurred more frequently in older cats and dogs, and in Labradors and German shepherd dogs. Thymic tumours were associated with paraneoplastic hypercalcaemia (six dogs), megaoesophagus (two dogs) or interface dermatitis with basement membrane immune complex deposition (one cat). Non-neoplastic thymic diseases were associated with myasthenia gravis (one cat), pemphigus foliaceus (one cat) and superficial necrolytic dermatitis (one cat).

Amyloidosis↗

Polyostotic lymphoma in a young dog: a case report and literature review.

An eight-month-old female German shepherd dog had pathological fractures affecting the distal radius and ulna and ribs. Radiographically, there were bilaterally symmetrical osteolytic lesions affecting the metaphyses of multiple long bones, ribs and skull and the dog had splenomegaly. Histologically, the spleen, thymus and bones were infiltrated with large lymphoblastic cells with a high mitotic rate; the diagnosis was lymphoma. Lymphoma primarily affecting bone is an uncommon diagnosis in the dog but it should be considered in young animals with osteolytic lesions affecting multiple bones.

Animals↗

Autoreactive T cell specificity in autoimmune hemolytic anemia of the NZB mouse.

Splenic T cells from Coombs'-positive New Zealand Black (NZB) mice proliferated consistently in vitro in response to the integral red blood cell (RBC) membrane protein Band 3, the antigen previously shown to be the target for the pathogenic RBC autoantibodies. The responding cells predominantly express CD4 and the proliferative response is blocked by antibodies to the NZB major histocompatibility complex class II but not by antibodies to an irrelevant H-2 haplotype. NZB splenic T cells also proliferated in response to the internal membrane skeleton protein spectrin. By contrast, T cells from BALB/c and DBA2 mice, which bear the same H-2 haplotype as NZB mice, but which do not develop autoimmune hemolytic anemia (AIHA), fail to respond to Band 3. It is considered that these results support the hypothesis that Band 3-reactive T cells provide help for the production of pathogenic anti-Band 3 autoantibodies in NZB mice. T cells from Coombs'-negative NZB mice as young as 3 weeks old proliferated in response to Band 3; moreover, the RBC from Coombs'-negative mice bore elevated levels of autoantibody as judged by a sensitive direct enzyme-linked anti-globulin test. Thus, the pathology of AIHA develops at a much earlier age than was thought previously.

Aging↗

Canine lymphomatoid granulomatosis: an immunophenotypic analysis of three cases.

Three dogs had a history of multiple progressive lesions affecting the skin, subcutis or skeletal muscles. The lesions developed over a period of several months, and each case demonstrated late cardiopulmonary complications. Post-mortem examination revealed multicentric, angio-destructive, lymphohistiocytic, proliferative lesions typical of the rare disorder lymphomatoid granulomatosis. Immunohistochemical examination demonstrated variable CD3 antigen expression by the atypical cell population in two of the three cases. This provides the first evidence that canine lymphomatoid granulomatosis may be a form of atypical T-cell lymphoma similar to the comparable disorder that occurs in man.

Animals↗

Disseminated aspergillosis in a dog: an immunohistochemical study.

An immunohistopathological study of a case of disseminated aspergillosis in a 4-year-old female German shepherd dog was carried out to characterize the cellular infiltrate within the granulomatous lesions of various organs. Polyclonal antibodies specific for canine immunoglobulins IgG, IgM, IgA, complement C3c, human CD3 antigen (pan T-lymphocyte marker), human lysozyme and alpha-1-antitrypsin and a monoclonal antibody for myeloid/ histocyte antigen (MAC 387) (macrophage marker) were used. In the mycotic granulomata of the heart, liver, spleen and kidneys a correlation was found between the numbers of CD3+ T lymphocytes and lysozyme+ macrophages (r = 0.9944, P = 0.0056), and between the numbers of CD3+ T lymphocytes and MAC 387+ macrophages (r = 0.9943, P = 0.0057).

Animals↗