B R Madewell’s research while affiliated with University of California, Davis and other places

An 11-year-old Doberman Pinscher with clinical and histological skin features consistent with colour dilution alopecia had a long history of skin disease. The animal had hundreds of papules affecting the 'blue' haired areas of the hair coat. The predominant skin lesions included keratinizing infundibular cysts, keratin horns, perifollicular dermatitis, and sebaceous hyperplasia; these lesions were often accompanied by furunculosis and suppurative panniculitis. Over a 9-month period, 32 lesions were examined histologically, which included two lipomas, one infiltrative lipoma, one squamous papilloma, two mast cell tumours, four cavernous haemangiomas, one haemangiosarcoma, and three melanomas. It is unknown at present whether the colour dilution phenotype confers increased risk for tumours of the skin and or subcutaneous tissues.

Immunohistochemistry was used to examine feline lymphoid tumors for bcl-2 and MIB-1 expression. Tumor tissues from 29 cats were selected to represent 2 groups—cats that did not respond to chemotherapy and cats that responded to therapy. Median bcl-2 immunoreactivity was 60%, and median MIB-1 reactivity was 47%. There was no significant difference in median survival time between cats with tumors with high levels of bcl-2 expression and those with low levels of expression. There was no significant difference in median survival time between cats with tumors with high levels of MIB-1 expression and those with low levels of expression. Mean bcl-2 immunoreactivity was significantly (P= .0004) higher in low-grade (73.2%) than in high-grade (16.9%) lymphomas, whereas the mean MIB-1 immunoreactivity was significantly (P= .0201) higher in high-grade (61.2%) lymphomas than in low-grade (35.0%) lymphomas. The mean bcl-2 immunoreactivity was significantly (P= .0042) greater in T-cell lymphomas (66.8%) than in B-cell lymphomas (22.8%), whereas the mean MIB-1 immunoreactivity was significantly (P= .0052) lower in T-cell lymphomas (36.4%) than in B-cell lymphomas (65.2%). Although expression of bcl-2 and MIB-1 did not appear to be linked to responses to chemotherapy in cats with lymphoma, the data suggest a possible role for these regulatory proteins in the biology of feline lymphomas.

Twenty-four dogs with lymphosarcoma and hypercalcaemia were studied clinically, haematologically and biochemically. There was no age or breed predilection, although the St Bernard dog appeared to be over-represented. Male dogs were more frequently affected (62 per cent) than female dogs. Anorexia, weight loss, muscular weakness, depression, polydipsia, polyuria, and bilateral peripheral lymphadenopathy were the most frequently observed clinical signs and physical findings. Hypercalcaemia, creatinaemia, azotaemia, hypercalciuria, hyposthenuria, and decreased endogenous creatinine clearance were the most frequent laboratory abnormalities. Detailed gross and histopathologic examinations of 10 dogs revealed the multicentric anatomic form of lymphosarcoma, absence of skeletal metastases, and normal parathyroid glands. The dogs were clinically staged, and ten were histologically classified. Histologic staging revealed five diffuse histiocytic lymphomas, and five diffuse lymphocytic poorly differentiated lymphomas.

Abstract— An 8-year-old Chinese Shar pei dog was examined because of gross deformity of the hind limbs. The deforming soft tissue swellings were associated with mucinosis and mastocytosis. Résumé— Un Shar Peï de 8 ans a été examiné pour une déformation au niveau des membres postérieurs. Les épaissiessements des déformations des tissus mous étaient associés à une mucinose et une mastocytose. Zusammenfassung— Ein 8 Jahre alter Chinesischer Shar Pei wurde wegen makroskopischer Verformung der Hintergliedmaßen untersucht. Die deformierenden Weichteilschwellungen standen in Zusammenhang mit einer Muzinose und Mastozytose. Resumen Un perro Shar pei de 8 años de edad se examinó, debido a la presencia de vastas deformidades de los cuartos traseros. La deformidad de los tejidos blandos se asoció con mastocitosis y mucinosis.

Cyclin D3 is a tightly regulated cell cycle protein and member of the cyclin D family-a group of proteins that facilitates the progression of a cell through G(1) and into the S phase of the cell cycle. All cells use at least one of the cyclin D proteins for cell cycle regulation. In this study, feline tissues (normal fetal and adult, and neoplastic) were examined immunohistochemically for expression and topographical distribution of cyclin D3. Its distribution was similar to that in human tissues in health and neoplasia, and suggested a dual role of cyclin D3 in cell proliferation and differentiation. Immature lymphoid tissue and proliferating epithelial cells in health and neoplasia were immunoreactive for cyclin D3, whereas expression of the protein in other immunoreactive tissues reflected differentiated cell types. Immunoreactivity for cyclin D3 was particularly striking in germinal centre cells of normal lymph nodes and B-cell lymphomas, and in normal suprabasal epithelial cells of the skin and mucous membranes of the oropharynx and in squamous cell carcinomas at these sites.

Measles virus (MV) causes the regression of human lymphoma xenografts. The purpose of this study was to determine if canine lymphoid cells could be infected in vitro with MV or canine distemper virus (CDV, the canine Morbillivirus equivalent of MV) and determine if in vitro viral infection leads to apoptotic cell death. Reverse transcriptase-PCR was used to examine the expression of both signal lymphocyte activation molecule (CD150) and membrane cofactor molecule (CD46) mRNA. An attenuated CDV expressing enhanced green fluorescent protein was used to infect canine cells in vitro. Both flow cytometry and reverse transcriptase-PCR was used to document CDV infection. Cell death was examined using a propidium iodide staining assay and Annexin V binding. Canine lymphoid cell lines and neoplastic B and T lymphocytes collected from dogs with spontaneous lymphoma expressed the Morbillivirus receptor CD150 mRNA. In contrast, only neoplastic lymphocytes expressed detectable levels of CD46 mRNA. Although MV did not infect canine cells, CDV efficiently infected between 40% and 70% of all three canine lymphoid lines tested. More importantly, CDV infected 50% to 90% of neoplastic lymphocytes isolated from dogs with both B and T cell lymphoma. Apoptosis of CDV-infected cell lines was documented. Attenuated CDV may be a useful treatment for canine lymphoma. As such, dogs with lymphoma may represent a biologically relevant large animal model to investigate the feasibility, safety, and efficacy of Morbillivirus therapy in a clinical setting with findings that may have direct applicability in the treatment of human non-Hodgkin's lymphoma.

The boxer breed of dog is at high risk for a variety of neoplasms including lymphoma. In this observational study, tissue sections from boxer dogs with lymphoma were immunostained for T and B lymphocyte distinction, and the results compared with similar studies carried out on lymphoma tissues from temporally selected cohorts of golden retriever and rottweiler dogs. The frequency of T-cell lymphomas was significantly (P < 0.001 for all comparisons) higher in the boxers than in the rottweilers or golden retrievers. We are unaware of other reports linking immunotype of canine lymphoma with breed; whether other brachycephalic breeds of dogs have a similar preponderance of T-cell lymphoma awaits further study.

Thymidine kinase (TK) is a cellular enzyme which is involved in a 'salvage pathway' of DNA synthesis. It is activated in the G1/S phase of the cell cycle, and its activity has been shown to correlate with the proliferative activity of tumor cells.... Clinical studies have reported high serum TK concentrations in a variety of neoplasias. The majority of these studies concerned hematological malignancies. TK seems to be a useful marker in non-Hodgkin's lymphoma, where it correlates with clinical staging and provides marked prognostic information on (progression-free) survival.

In this pilot study, 13 dogs of various breeds and ages with a variety of advanced tumors were treated with the antiangiogenic copper complexing drug tetrathiomolybdate. Dose escalations were performed to determine the safe and effective dose in dogs. The study was designed to last for a 6-month period for each dog entered. Dogs were examined weekly for the first 3 months and then every other week for the next 3 months. Complete blood count, serum biochemistry panel, and measurement of serum ceruloplasmin (Cp) content were conducted at each visit to monitor response to drug administration. Serum Cp was used as a surrogate marker of copper status. The owner reported toxicity at each visit. The dog was examined for physical abnormalities. Tumor measurements were completed every 2 weeks using direct measurements of the tumor with calipers in three planes or by direct measurements of the tumor using radiographic or ultrasonographic images in two planes. Tumor response was evaluated only after dogs achieved a 4-week reduction in their serum Cp content. Tumor responses were defined as either disease stabilization or reduction in tumor volume. Nine dogs achieved Cp reduction. Of those dogs, five had no response to treatment, whereas four dogs had tumor responses after Cp reduction, characterized as either disease stabilization or reduction in tumor volume, for the remainder of the study period. There was only mild self-limiting toxicity with use of the drug. J. Trace Elem. Exp. Med. 17:9–20, 2004. © 2004 Wiley-Liss, Inc.

To determine whether there was a decline in the percentage of dogs undergoing necropsies and whether there was substantial agreement or disagreement between clinical and pathologic diagnoses. Retrospective study. 623 dogs. Medical records of hospitalized dogs that died or were euthanatized and necropsied at a veterinary teaching hospital in 1989 and 1999 were reviewed. Clinical and pathologic diagnoses were recorded and compared. There was a significant decline in the necropsy rate of hospitalized dogs that died or were euthanatized in 1999, compared with 1989. In both 1989 and 1999, there was disagreement between the clinical and pathologic diagnoses in approximately a third of the cases. Despite improved diagnostic methods, the accuracy of diagnosis did not improve significantly in 1999, compared with 1989. Necropsy is the best method to assess overall diagnostic accuracy. Increased availability of teaching funds may promote efforts to have necropsies performed in veterinary teaching hospitals.