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R W Dunstan

Publications and source records attributed to R W Dunstan.

At least 19 recordsLinked to original sources
PubMed1996

Malignant transformation of human fibroblasts by ionizing radiation.

As one step in developing an assay for quantifying the induction of malignant transformation of human cells by ionizing radiation, we exposed cells from a non-tumorigenic, infinite life span, near-diploid fibroblast strain MSU-1.1 to 4.35 Gy 60Co radiation and assayed them for focus formation. The mean frequency of foci in the irradiated population was 6 x 10(-7) cells assayed. No foci were found in the control cells. Of four focus-derived cell strains studied in detail, two produced malignant tumours within 3-7 weeks. The other two did not produce tumours during the 12-month period of study. The tumours from one strain were classified as sarcomas composed exclusively of spindle-shaped cells. Tumours from the other strain were sarcomas consisting of a mixed population of round and spindle cells. Immunoprecipitation analysis of the status of the p53 gene in the focus-derived strains, using a mutant-specific anti-body (Pab240) and an antibody that recognizes both mutant and wild-type p53 protein (Pab421), showed that the tumorigenic strains were completely devoid of p53 protein. One non-tumorigenic strain expressed wild-type p53 protein, and the other expressed a lower molecular weight form of the protein. Karyotypic analysis showed that the tumour-derived cells from one tumorigenic strain had lost one copy of chromosome 6, 14, 16 and 17. The tumour-derived cells from the second strain had lost one copy of chromosome 7, 13, 14 and 17 and part of chromosome 6, as well as part of the other copy of chromosome 7 and 17. These results suggest that the common loss of one copy of chromosome 14, 17 and part of 6 plays a causal role in the malignant transformation of these cells. Furthermore, the results indicate that it will be possible to develop a system that uses near-diploid human fibroblasts to quantify radiation-induced malignant transformation.

Cell Transformation, Neoplastic↗
PubMed1994

T-cell receptor gene rearrangement in canine mycosis fungoides: further support for a canine model of cutaneous T-cell lymphoma.

Canine cutaneous T-cell lymphoma (CTCL) is a morphologic and immunophenotypic simulant of human mycosis fungoides (MF) characterized by an infiltrate of atypical, hyperconvoluted, epidermotropic T cells. To further support our hypothesis that canine MF is a useful model for the study of human CTCL, we have used Southern blotting to search for clonal T-cell proliferations in canine MF. Cellular DNA was extracted from normal dog buffy coat cells (n = 8), lesional canine MF skin (n = 8), canine MF buffy coat cells (n = 7), normal dog skin (n = 3), and normal human buffy coat cells (n = 5), digested with a panel of restriction enzymes and Southern blotted onto nylon membranes. All cases of canine MF were also immunophenotyped with anti-canine monoclonal antibodies to CD4, CD8, CD18, CD45RA, canine class II, T-cell activation antigens, and pan-B-cell antigens. Normal dogs gave reproducible digestion patterns in blood and skin, which differed from the human germline patterns when probed with a human T-cell receptor (TCR), beta chain constant region (C beta) cDNA. Common germline bands between the species included the 3.5-kb Eco RI, 3.4-kb Bam HI, 5.4-kb Sac I. These results confirmed that the TCR-beta gene is evolutionarily conserved between dog and man. Immunostaining revealed that 3/7 cases were CD4+ canine CTCL and 4/7 were CD8+ canine CTCL. Rearranged bands, deletion of germline bands, as well as minor alterations in electrophoretic mobility were observed in lesional DNA from seven of eight cases of canine MF, with at least two restriction digests in each case. Dog rearrangements were best detected with Bgl II, Eco RI, Eco RV, and Sac I, whereas deletions were detected with Bgl II, Sac I, Eco RV, and Bam HI. These studies demonstrate the presence of clonal TCR rearrangement in canine MF, further supporting the similarity of this tumor to human MF and its role as an animal model of CTCL.

Animals↗
PubMed1994

Full-thickness skin grafts from flaky skin mice to nude mice: maintenance of the psoriasiform phenotype.

Flaky skin (fsn) is an autosomal recessive mouse mutation with papulosquamous disease features similar to human psoriasis. In fsn/fsn skin, one sees marked acanthosis and hyperkeratosis with focal parakeratosis, subcorneal pustules, dermal capillary dilation, and a marked diffuse dermal infiltration of mixed inflammatory cells, predominantly lymphocytes. To determine if these pathologic features are a characteristic of the skin or a chronic autoimmune attack, we placed full-thickness skin grafts from affected homozygous (fsn/fsn) and normal littermate control (+/?) mice on the dorsal skin of genetically athymic nude (nu/nu) mice. After 10 weeks of observation, the grafts maintained the histologic phenotype of the donor animal. In the fsn/fsn grafts, there was persistence of both epidermal proliferation and dermal inflammation, characteristics of the mutation. The fsn/fsn phenotype was also confirmed by immunohistochemical evaluation for specific mouse keratinocyte marker expression. Based on tritiated thymidine uptake, we found DNA synthesis rates elevated threefold or more in fsn/fsn epidermis compared to littermate control mouse skin. Elevated rates of DNA synthesis remained a feature of the fsn/fsn grafts but not that of littermate control skin grafts. This study demonstrates that the psoriasiform phenotype of this mouse mutation can persist independent of the host thymic-derived immune system.

Animals↗
PubMed1993

Seasonal flank alopecia in boxers and Airedale terriers: 24 cases (1985-1992).

Clinical and histologic features of seasonal flank alopecia in 12 Airedale Terriers and 12 Boxers were reviewed. Most of the affected dogs were spayed females; however, sexually intact females as well as sexually intact and neutered male dogs with the disease were identified. Mean (+/- SD) age of onset was 3.6 +/- 2.4 years.

Alopecia↗
PubMed1992

Aneurysmal bone cyst in a six-month-old dog.

A 6-month-old female Yorkshire Terrier was examined because of acute left forelimb lameness secondary to a Salter-Harris type IV fracture of the lateral condyle of the humerus. Radiography revealed an eccentric, osteolytic lesion in the distal humeral metaphysis associated with a pathologic fracture. The limb was amputated, and the dog recovered. Microscopic examination revealed an extensive zone of hemorrhage and dilated coalescent spaces, which were filled with blood. Hemosiderin-laden macrophages and multinucleated giant cells were observed throughout the stroma. On the basis of clinical, radiographic, and histologic examinations, a diagnosis of aneurysmal bone cyst was made. Aneurysmal bone cysts generally have been detected in 11- to 13-year-old, medium- to large-sized dogs. They can develop secondary to malignant processes.

Animals↗
PubMed1992

Dermal dendrocytes and T-cells in canine mycosis fungoides. Support for an animal model of human cutaneous T-cell lymphoma.

BACKGROUND: An extensive upper dermal network of human Thy-1+/Factor XIIa+ dermal dendrocytes (DD) exists in human mycosis fungoides (MF). METHODS: Immunophenotyping and morphologic studies on serial frozen and paraffin sections from 15 cases of canine MF were performed to see if a similar network exists in this disease, as has been proposed as an animal model of human MF. Primary antibodies were anti-human Factor XIIIa, Factor XIIIs, anti-canine Thy-1, CD4, CD8, CD18, CD45RA, Class II, MAC387, KP-1, EBM-11, and several other pan-T, pan-B, and pan monocyte markers. RESULTS: Thy-1+/Factor XIIIa+DD were seen in all cases and confirmed on identical cells by double immunofluorescence. These were seen throughout the upper dermis, similar to DD in human MF. Canine DD expressed the macrophage marker 2A2+, and were Class II+, CD4+, CD8-, CD18+, EBM11-, Factor XIII-, MAC387-, and KP-1. Epidermal and dermal lymphocytes in canine MF were Thy-1-, CD4+, CD8-, CD18+, CD45RA-, EBM11-, MAC387-, Factor XIIIa-, Factor XIIIs- in some cases, whereas others had a predominance of CD8+ lymphocytes. CONCLUSIONS: Thus, canine MF is immunophenotypically similar to human MF. Additional support for this disease as a model of human MF is demonstrated by the rich network of Thy-1+/Factor XIIIa+ DD in the upper dermis of canine MF similar to human MF.

Animals↗
PubMed1990

Congenital ichthyosis in a llama.

A 1-month-old male cria was examined because of diffuse hyperkeratosis and conjunctivitis that had existed since birth. The mucocutaneous junction of the nostrils as well as the neck, coronary bands, and axillary and inguinal regions were the most severely affected areas. Orthokeratosis involving the epidermis and follicular infundibula was observed on skin biopsy specimens. Electron microscopy revealed 4 to 6 granular layers and inter- and intracellular vacuolation in the stratum corneum; diagnosis of ichthyosis was established.

Animals↗
PubMed1990

A user's guide to veterinary surgical pathology laboratories. Or, why do I still get a diagnosis of chronic dermatitis even when I take a perfect biopsy?

During the past decade, clinicians have come to rely more heavily on veterinary surgical pathology services to provide assistance in the diagnosis of inflammatory and neoplastic skin disease. To obtain maximum results from each skin biopsy, it is important that clinicians have a good understanding of the factors that can affect histologic evaluation after the biopsy specimen has been removed from the patient. This article discusses the role proper tissue fixation, trimming, and grooming can play in obtaining an accurate histologic evaluation. The importance of understanding the limits of dermatopathology in establishing a definitive diagnosis of many inflammatory and neoplastic skin diseases is emphasized.

Animals↗
PubMed1989

Extraskeletal osteosarcoma in two dogs.

Extraskeletal osteosarcoma (ESOS) of the spleen and jejunum was diagnosed in 2 dogs. As an extremely uncommon type of tumor that has proven difficult to treat, ESOS is associated with high rate of local recurrence and metastatic disease. Extraskeletal osteosarcoma principally affects older dogs, has no apparent breed predilection, and may develop more frequently in males. The cause of ESOS is unknown, but may involve malignant metaplasia of pluripotential mesenchymal cells into osteoblasts. Macroscopically, ESOS usually is observed as a hard mass and may appear similar to calcified hematoma or myositis ossificans. The classic radiographic appearance of ESOS is a soft tissue mass with focal mineralization and without adjacent bone involvement.

Animals↗
PubMed1989

Natural killer cell activity in untreated and treated dogs with lymphoma.

Natural killer (NK) cell activity and function were determined for 11 untreated and treated dogs with lymphoma. Concurrent chromium release and single cell binding assays, methods used to measure overall cytotoxic activity and that from individual cells, respectively, were performed at effector-to-target cell ratios of 50:1 and 100:1, with incubation periods of 12 and 16 hours. Significant reduction was achieved in overall activity for untreated dogs, using a 16-hour incubation period and an effector-to-target ratio of 100:1 (P less than 0.05). Decreased activity (P less than 0.025) was also achieved for those dogs that were administered combination chemotherapy, consisting of such drugs as cyclophosphamide, vincristine, prednisone, and doxorubicin. There was no significant difference in binding or cytotoxic activity by individual cells in the untreated or treated dogs, compared with the healthy controls. Short- or long-term treatment with glucocorticoids did not influence overall NK cll activity or individual cell cytotoxicity. The overall cytotoxic activity in untreated dogs was reduced, but these dogs had relatively normal numbers of NK cells compared with paracontrols. This suggests that a defect in recycling or the ability to kill targets repetitively, may be involved. A similar defect was found in NK cells of dogs treated aggressively with combination chemotherapy.

Animals↗
PubMed1988

Neuroendocrine carcinoma of the gallbladder in a dog.

A 9-year-old Bullmastiff with hematemesis was determined to have primary neuroendocrine carcinoma of the gallbladder. Despite the dismal prognosis when these unusual tumors are located in the liver, the hematemesis resolved, and there was no obvious tumor regrowth in this dog 10 months after cholecystectomy.

Animals↗
PubMed1988

Bacterial population and histologic changes in dogs with perianal fistula.

Ages of 44 dogs with perianal fistula, ranged from 6 months to 13 years (mean, 5.2 years). German Shepherd Dogs and Irish Setters were statistically (P less than 0.01) over-represented compared with those breeds in a canine hospital population (n = 22,047) for the same period. There was a 2:1 male-to-female ratio, with 38 (86.4%) of dogs sexually intact and 6 (13.6%) of dogs neutered. Eleven types of bacterial organisms were recovered from deep perianal tissues of which Escherichia coli, Staphylococcus aureus, beta-hemolytic streptococci, and Proteus mirabilus were most common. Organisms were not recovered from 7 dogs. Of 93 isolates, 88.3% were susceptible to gentamicin, 80.5% to cephalothin, 79.2% to chloramphenicol, and 74% to trimethoprim-sulfamethoxazole. Fifty-one biopsy specimens from 44 dogs were classified as having early, intermediate-, and late-stage lesions based on the amount of fibrosis, severity of the inflammatory response, and, if present, depth of sinus tracts. In most biopsy specimens, all 3 stages were represented in the same histologic section. In 45 specimens, most inflamed lesions were in the dermis of the zona cutanea. Hidradenitis was present in 22 biopsy specimens and was associated with the formation of epithelial-lined sinus tracts.

Anal Canal↗
PubMed1988

A disease resembling junctional epidermolysis bullosa in a toy poodle.

A disease resembling junctional epidermolysis bullosa in humans is described in a toy poodle. Shortly after birth, the affected animal developed vesicles and bullae on the pads of the feet and the mucous membranes of the oral cavity. The lesions rapidly increased in number and severity, eventually involving the glabrous skin of the ventral abdomen. Due to the severity of the lesions, the animal was euthanized when it was 48 h old. Histopathologic, ultrastructural and immunohistochemical evaluation defined a minimally inflamed subepidermal vesicular disease with separation occurring at the zona lucida of the basement membrane zone. Laminin and type IV collagen were present at the base of the vesicle.

Animals↗
PubMed1987

Synovial chondrometaplasia in five dogs.

Synovial chondrometaplasia was diagnosed in 5 dogs. Four dogs improved dramatically after surgical removal of subsynovial nodules, but the fifth improved only slightly. This potentially treatable condition is recognized in human beings, and has been described in dogs in the German scientific literature. Synovial chondrometaplasia should be suspected if numerous joint mice are visualized radiographically, without an obvious inciting cause. It also should be suspected when periarticular osteophytes are found radiographically in unusual locations.

Animals↗