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Biomedical subjects

B R Madewell

Publications and source records attributed to B R Madewell.

At least 19 recordsLinked to original sources
PubMed2005

Cyclin D3 expression in normal fetal, normal adult and neoplastic feline tissue.

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.

Animals↗
PubMed2002

Feline vaccine-associated fibrosarcoma: morphologic distinctions.

Forty-four primary feline vaccine-associated fibrosarcomas and 16 recurrences were examined histologically for detailed morphologic characterization with emphasis on tumor grade, presence of neoplastic multinucleated giant cells, presence and proportion of T and B lymphocytes within the tumor, and thin and intermediate filament contents of neoplastic and stromal cells. The microvascularity and proliferation rates of central and peripheral areas of the tumors were also quantified by computerized image analysis. For primary fibrosarcomas, 11 of 44 (25%) were grade I, 21 of 44 (47.7%) were grade II, and 12 of 44 (27.3%) were grade III. The recurrences followed a similar pattern: 4 of 16 (25%) were grade I, 8 of 16 (50%) were grade II, and 4 of 16 (25%) were grade III. A positive correlation was found between the presence of neoplastic multinucleated giant cells and tumor grade. These cells were present in 9 of 12 (75%) of grade III and none of the grade I tumors. Prominent peritumoral lymphoid aggregates or follicles were present in 59% of the tumors, and many contained high proportions of T lymphocytes, varying from 19 to 87%. All fibrosarcomas were immunoreactive for vimentin and 28 of 44 (64%) were reactive for alpha-smooth muscle actin. The actin-positive cells were either part of the tumor or formed a capsule around tumor nodules. The peripheral vascularity was significantly higher than the central vascular density but no difference was found in tumor cell proliferation rates between the two areas. Centrally located, fluid-filled micro- or macrocavitations were frequently observed in the large vaccine sarcomas and probably formed secondary to rapid tumor growth and central necrosis.

Animals↗
PubMed2001

Clinical outcome and diseases associated with extreme neutrophilic leukocytosis in cats: 104 cases (1991-1999).

OBJECTIVE: To describe diseases, prognosis, and clinical outcomes associated with extreme neutrophilic leukocytosis in cats. DESIGN: Retrospective study. ANIMALS: 104 cats with extreme neutrophilic leukocytosis. PROCEDURE: Medical records from 1991 to 1999 were examined to identify cats that had > or =50,000 WBC/microl with > or =50% neutrophils. Signalment, absolute and differential WBC counts, rectal temperature, clinical or pathologic diagnosis, duration and cost of hospitalization, and survival time were reviewed. RESULTS: Mean age of cats was 8.3 years, mean WBC count was 73,055 cells/microl, and mean absolute neutrophil count was 59,046 cells/microl. Mean duration of hospitalization was 5.9 days, and mean cost of hospitalization was $2,010. Twenty-nine (28%) cats were febrile, and 63 (61%) cats died. Overall median survival time was 30 days. Cats with neoplasia were nearly 14 times as likely to die unexpectedly as cats with other diseases. CONCLUSIONS AND CLINICAL RELEVANCE: Extreme neutrophilic leukocytosis was associated with a high mortality rate. The prognostic importance of extreme neutrophilic leukocytosis should not be overlooked. Cats and dogs have similar diseases, mortality rates, and treatment costs associated with extreme neutrophilic leukocytosis.

Animals↗
PubMed2001

Feline vaccine-associated fibrosarcoma: an ultrastructural study of 20 tumors (1996-1999).

Twenty feline vaccine-associated sarcomas were examined by transmission electron microscopy. Tumors contained pleomorphic spindle cells, histiocytoid cells, and giant cells. Most tumors contained myofibroblasts, which had morphologic features similar to those of fibroblasts. These cells were further distinguished by subplasmalemmal dense plaques and thin cytoplasmic actin myofilaments organized as elongated bundles concentrated at irregular intervals forming characteristic dense bodies. Intracellular crystalline particulate material was found in 5 of the 20 tumors. Energy dispersive X-ray spectroscopy was used to identify the crystalline material within one tumor as aluminum-based. One tumor from a feline leukemia virus-infected cat contained budding and immature retroviral particles.

Aluminum↗
PubMed2001

Expression of a transforming gene (E5) of bovine papillomavirus in sarcoids obtained from horses.

OBJECTIVE: To determine expression of a transforming gene (E5) of bovine papillomavirus in sarcoids, other tumors, and normal skin samples collected from horses with and without sarcoids. SAMPLE POPULATION: 23 sarcoids and 6 samples of normal skin obtained from 16 horses with sarcoids, 2 samples of normal skin and 2 papillomas obtained from horses without sarcoids, and 1 papilloma obtained from a cow. PROCEDURE: Protein was extracted from tissue samples collected from horses and incubated with agarose beads covalently coupled to Staphylococcus aureus protein A and an anti-E5 polyclonal antibody. Following incubation, proteins were eluted from the beads and electrophoresed on a 14% polyacrylamide gel and transferred to a polyvinylidene difluoride membrane. The E5 protein was detected by use of western blot analysis, using a chemiluminescence detection system. RESULTS: All 23 sarcoids had positive results for expression of E5 protein. Quantity of viral protein appeared to vary among sarcoids. All other tissues examined had negative results for E5 protein. Highest expression for E5 protein was observed in biologically aggressive fibroblastic variants of sarcoids, compared with expression in quiescent tumors. CONCLUSIONS AND CLINICAL RELEVANCE: This study documented that activation and expression of the E5 gene is evident in sarcoids obtained from horses. These data support the conclusion that infection with bovine papillomavirus is important in the initiation or progression of sarcoids in horses. Treatment strategies designed to increase immune recognition of virally infected cells are warranted.

Animals↗
PubMed2001

Bovine papillomavirus DNA in neoplastic and nonneoplastic tissues obtained from horses with and without sarcoids in the western United States.

OBJECTIVE: To determine the incidence of bovine papillomavirus (BPV) type 1 or 2 in sarcoids and other samples of cutaneous tissues collected from horses in the western United States. ANIMALS: 55 horses with sarcoids and 12 horses without sarcoids. PROCEDURE: Tissue samples (tumor and normal skin from horses with sarcoids and normal skin, papillomas, and nonsarcoid cutaneous neoplasms from horses without sarcoids) were collected. Tissue samples were analyzed for BPV-1 or -2 DNA, using a polymerase chain reaction (PCR) and restriction fragment length polymorphism. The PCR products from 7 sarcoid-affected horses were sequenced to evaluate percentage homology with expected sequences for BPV-1 or-2. RESULTS: Most (94/96, 98%) sarcoids contained BPV DNA. Sixty-two percent of the tumors examined had restriction enzyme patterns consistent with BPV-2. Thirty-one of 49 (63%) samples of normal skin obtained from horses with sarcoids contained BPV DNA. All samples subsequently sequenced had 100% homology with the expected sequences for the specific viral type. All tissues from healthy horses, nonsarcoid neoplasms, and papillomas were negative for BPV DNA. CONCLUSIONS AND CLINICAL RELEVANCE: Bovine papillomaviral DNA was detected in essentially all sarcoids examined. There appears to be regional variation in the prevalence of viral types in these tumors. The fact that we detected viral DNA in normal skin samples from horses with sarcoids suggests the possibility of a latent viral phase. Viral latency may be 1 explanation for the high rate of recurrence following surgical excision of sarcoids.

Animals↗
PubMed2000

Canine transmissible venereal tumour: a morphological and immunohistochemical study of 11 tumours in growth phase and during regression after chemotherapy.

Eleven dogs with canine transmissible venereal tumour (CTVT) were given vincristine sulphate chemotherapy to induce tumour regression. Biopsy specimens were collected from tumours during the growth phase, before chemotherapy, and again from the same dogs during the regression induced by chemotherapy. Laboratory assessment included cytology, histology, the number of tumour cells in relation to the number of intratumoral leucocytes, proliferative and apoptotic fractions of tumour cells, intratumoral vessel density, and fibrosis. The results revealed that during regression, tumour cell proliferation ceased, apoptosis increased, leucocytes increased (with increased proportion of T lymphocytes), tumour parenchyma collapsed around intratumoral vessels, and fibrosis increased. These results, which were similar to findings in dogs with spontaneous regression of CTVT, suggest that tumour immunity plays a role in tumour regression after modest chemotherapy.

Animals↗
PubMed2000

Apoptotic and proliferation indexes in canine lymphoma.

Proliferative and apoptotic fractions of tumors were evaluated in 41 dogs with lymphoma for prediction of response to chemotherapy. All dogs had advanced clinical stage tumors, were untreated prior to study, and received identical induction-remission chemotherapy. Tumor cell proliferation was determined in all pretreatment biopsy specimens and in 18 specimens collected at the time of clinical relapse from remission. Quantitative measures included mitotic index and immunoreactivities for proliferating cell nuclear antigen (PCNA) and Ki-67. Apoptotic index was evaluated from 40 dogs pretreatment and from 16 dogs at the time of first relapse. Pretreatment tumor values for Ki-67, PCNA, and apoptosis were compared with posttreatment values. The median first relapse-free interval (RFI) and overall survival (OS) time were 174 days and 445 days, respectively. Of the proliferation markers, only the results of the Ki-67 analysis were predictive for duration of the first RFI but not OS. Pretreatment apoptotic index was also predictive of the duration of first RFI but not OS. No significant predictive value for comparison of the pretreatment and postrelapse values was demonstrated. Ki-67 labeling index and apoptotic indexes were combined to form both a proliferation/apoptotic ratio (PAR) and a sum, or turnover index. Only the PAR was predictive for duration of first RFI on multivariate analysis. Other variables that were evaluated for their influence on treatment outcome included patient age, weight, gender, clinical stage, clinical substage, and tumor immunophenotype. Of these variables, only immunophenotype was found to be of value for predicting duration of first RFI and OS.

Animals↗
PubMed1999

Clinical outcome and associated diseases in dogs with leukocytosis and neutrophilia: 118 cases (1996-1998)

OBJECTIVE: To describe diseases, prognosis, and clinical outcomes associated with leukocytosis and neutrophilia in dogs. DESIGN: Retrospective study. ANIMALS: 118 dogs with leukocytosis and neutrophilia. PROCEDURE: Medical records from 1996 to 1998 were examined for dogs with WBC > or = 50,000 cells/microliter and neutrophilia > or = 50%. Signalment, absolute and differential WBC counts, body temperature, clinical or pathologic diagnosis, duration and cost of hospitalization, and survival time were reviewed. RESULTS: Mean age was 7.7 years, WBC count was 65,795 cells/microliter, and absolute neutrophil count was 53,798 cells/microliter. Mean duration of hospitalization was 7.4 days and cost of hospitalization was $2,028.00. Forty (34%) dogs were febrile, and 73 (62%) dogs died. Overall median survival time was 17 days. Dogs with neoplasia or fever were more likely to die than dogs that were hospitalized or had systemic or local infections. CLINICAL IMPLICATIONS: Leukocytosis and neutrophilia were associated with high mortality rate and have prognostic value. Given the mean duration and cost of hospitalization, frank discussion with an owner at first recognition of leukocytosis and neutrophilia may be warranted.

Animals↗
PubMed1999

Proliferation indices in spontaneous canine lung cancer: proliferating cell nuclear antigen (PCNA), Ki-67 (MIB1) and mitotic counts.

Proliferation indices were measured for specimens from 55 spontaneous canine lung tumours, collected by surgical biopsy from clinical patients and archived in paraffin wax blocks. These indices were then related to the mitotic index and histological type of the tumour. Proliferating cell nuclear antigen (PCNA) and Ki-67 (MIB1) proteins were detected immunohistochemically with a biotin-streptavidin amplified detection system on a representative tissue section from each tumour. Five adjacent, non-overlapping fields were selected at random, and 200 cells per field were examined in each section. For PCNA, cells were classified subjectively into negative, weak or strong reactivity groups, based on nuclear staining. MIB1 cells were classified as negative or positive, based on nuclear staining. Mitotic figures were counted in anti-PCNA-labelled and anti-MIB1-labelled sections, in the same tumour areas as those in which indices were established. Mitotic counts were also done on haematoxylin and eosin-stained tissue sections. Linear regression analysis showed that all PCNA, MIB1 and mitotic indices had highly significant positive correlations (P<0.0001) with each other. Adenosquamous and squamous cell carcinomas differed from other histological tumour types in having significantly higher proliferation indices. These data suggest that growth rates for lung tumours in the dog vary according to histological type. On the basis of differences in proliferation indices and the distribution of immunoreactivity between histological subtypes in this study, it would seem that immunohistochemical detection of PCNA and MIB/1 reactivity and analysis of mitotic figures in routinely processed tissues may be useful in the diagnosis of lung tumours. 1999 W.B. Saunders and Company Ltd.

Adenocarcinoma↗
PubMed1999

Clostridium difficile: a survey of fecal carriage in cats in a veterinary medical teaching hospital.

Fecal samples collected from 245 cats over a 6-month period were analyzed for the presence of Clostridium difficile. After culture on selective media, isolates were identified by a latex agglutination test, and the presence of toxin A and toxin B gene sequences was determined by polymerase chain reaction. Clostridium difficile was isolated from 23 (9.4%) of the cats, and 34.8% of that group were colonized with toxigenic strains. All of the cats colonized with toxigenic C. difficile had > or = 1 of the risk factors (antibiotic use, antineoplastic therapy, immunosuppressive virus infection) associated with C. difficile infection in humans. Clostridium difficile was not found in any of the cats from a clinically healthy outpatient group of cats examined from the same hospital nor in cats from a specific-pathogen-free research colony on the same campus tested during the same time period. The data obtained in this study confirm the presence of C. difficile in cats at a veterinary teaching hospital. DNA fingerprinting analysis of these isolates allowed separation of the strains into 5 groups. Type 4 strain found in 7 cats was also recovered from the floor drain in the same hospital, suggesting a possible source of infection. Whether the organism is of clinical significance in diarrheal diseases of cats remains to be determined.

Animals↗
PubMed1999

Topographic distribution of bcl-2 protein in feline tissues in health and neoplasia.

The bcl-2 family of genes encodes proteins that influence apoptosis. In the present immunohistochemical study, the topographic distribution of bcl-2 protein was examined in healthy feline fetal, neonatal, and adult tissues, a feline renal cell line, and feline tumors obtained from a veterinary hospital. The topographic distribution of bcl-2 in healthy tissues was similar to that described in human tissues. In lymphoid tissues, follicular mantle cells strongly expressed bcl-2. In complex and differentiating epithelium, bcl-2 expression was detected in stem cell and proliferation zones. Bcl-2 expression was also detected in lower crypts of the intestine and in skin basal layers. The feline Crandell kidney cells expressed bcl-2 diffusely throughout the cytoplasm. Of 180 tumors examined, bcl-2 was expressed almost uniformly in cutaneous basal cell tumors, thyroid adenomas, and mammary carcinomas and in 50% of the lymphomas examined. Bcl-2 may play a role in blocking apoptotic cell death in a broad range of normal feline tissues, whereas dysregulated bcl-2 may extend the life of certain tumors or render certain tumors resistant to therapy because most chemotherapeutic and radiotherapeutic agents eliminate tumor cells by triggering apoptosis.

Animals↗
PubMed1999

Preclinical study in cats of the pro-photosensitizer 5-aminolevulinic acid.

OBJECTIVE: To determine whether feline cells were able to convert 5-aminolevulinic acid (ALA) to protoporphyrin IX (PpIX) in vivo and in vitro, whether i.v. administration of ALA to healthy cats resulted in adverse effects, and whether PpIX accumulated in a squamous cell carcinoma (SCC) of a cat. ANIMALS: 4 healthy adult cats and 1 adult cat with a cutaneous SCC. PROCEDURE: In vitro production of PpIX was determined by incubating Crandell feline kidney cells with ALA. Effects of ALA administration and in vivo production of PpIX were determined by administering ALA (100, 200, or 400 mg/kg of body weight) to healthy cats and collecting skin biopsy specimens for up to 24 hours after drug administration. Blood samples were collected for CBC and serum biochemical analyses, and necropsies were performed. Accumulation of PpIX in a SCC was determined by treating a cat with a facial SCC with ALA and collecting specimens of the tumor and adjacent grossly normal skin. RESULTS: Incubation of ALA with feline cells resulted in time- and dose-dependent cytoplasmic accumulation of PpIX in vitro. After i.v. ALA administration, PpIX was detected in all tissues examined, with the highest fluorescence intensity in epithelia and in squamous cell carcinoma. The tumor-to-skin fluorescence intensity ratio was 5. All cats developed hepatotoxicoses. CONCLUSIONS AND CLINICAL RELEVANCE: Results from this limited number of cats suggest that ALA may be a useful photosensitizer in cats, but that doses > 100 mg/kg, i.v., may not be safe.

Aminolevulinic Acid↗
PubMed1999

Adjuvant therapy for melanoma in dogs: results of randomized clinical trials using surgery, liposome-encapsulated muramyl tripeptide, and granulocyte macrophage colony-stimulating factor.

Spontaneous canine oral melanoma (COM) is a highly metastatic cancer, resistant to chemotherapy, and can serve as a model for cancer immunotherapy. Liposome-encapsulated muramyl tripeptide-phosphatidylethanolamine (L-MTP-PE) can activate the tumoricidal activity of the monocyte-macrophage system following i.v. injection. The objective of these studies was to evaluate the therapeutic effectiveness of L-MTP-PE administered alone and combined with recombinant canine granulocyte macrophage colony-stimulating factor (rcGM-CSF) in dogs undergoing surgery for oral melanoma. Ninety-eight dogs with histologically confirmed, clinically staged, oral melanoma were entered into two randomized, double-blind, surgical adjuvant trials. In trial 1, 50 dogs were stratified based on clinical stage and randomized to once a week L-MTP-PE or lipid equivalent (control). When all of the clinical stages were combined, no difference in disease-free survival or in survival time (ST) were detected. However, within stage I, dogs receiving L-MTP-PE had a significant increase in ST compared with control, with 80% of the dogs treated with L-MTP-PE still alive at >2 years. Within each stage II and stage III, there was no difference detected between the treatment groups. In trial 2, 48 dogs were stratified on the basis of clinical stage and extent of surgery (simple resection or radical excision), treated with L-MTP-PE two times a week, and randomized to rcGM-CSF or saline (placebo) given s.c. daily for 9 weeks. Within each stage and when all of the stages were combined, there was no difference between the treatment groups. In both studies, stage I COM is associated with a better prognosis. No effect on survival was observed with regard to tumor location in the oral cavity, sex, type/extent of surgery, or age. In a subset of dogs tested, pulmonary alveolar macrophage cytotoxicity was enhanced with combined rcGM-CSF and L-MTP-PE but not in dogs treated with L-MTP-PE alone. The present study indicates that after surgery, L-MTP-PE administered alone or combined with rcGM-CSF showed no significant antitumor activity in treating advanced stage COM. In early stage COM, L-MTP-PE was shown to result in a prolongation of ST. Furthermore, this study provides additional rationale for the use of the dog model for human malignant melanoma.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1998

K-ras mutations in 239PuO2 canine lung neoplasms.

Single-strand conformational polymorphism (SSCP) analysis and direct sequencing methods were used to examine lung tumors derived from a cohort of beagle dogs with inhalational exposures to 239PuO2. These exposures were done at Pacific Northwest Laboratories where 18-month-old beagle dogs were given 239PuO2 by single-dose inhalation and allowed to live out their life-spans. Formalin-fixed paraffin-embedded blocks of tissues from 25 dogs exposed to 239PuO2 by aerosol inhalation which later developed lung tumors were available for this study. Two of 25 tumors had mutations within exon 1 of K-ras detected by SSCP analysis. Both mutations were GGT to GAT transitions at codon 12 confirmed by direct sequencing experiments. One was an adenocarcinoma from the medium-high exposure group and the other was a broncheolo-alveolar carcinoma from the medium-low exposure group. The rate of K-ras mutations in plutonium-induced lung tumors described herein (8%) was greater than previously described in canine plutonium-induced lung tumors (0%), but was less than that which we have described in spontaneous canine lung cancer (16%), less than that reported for human spontaneous non-small cell lung cancer (13-36%) and less than that described in rats with spontaneous lung cancer (40%) or lung tumors following 239Pu inhalation exposure (46%).

Administration, Inhalation↗
PubMed1998

Results of chemotherapy for cats with alimentary malignant lymphoma: 21 cases (1993-1997)

OBJECTIVE: To determine clinical and pathologic findings in cats with alimentary malignant lymphoma and results of treatment with a combination of prednisone, L-asparaginase, vincristine, cyclophosphamide, doxorubicin, and methotrexate. DESIGN: Retrospective study. ANIMALS: 21 cats with alimentary malignant lymphoma. PROCEDURE: Medical records were reviewed, and information on signalment, clinical history and signs, previous treatments, and results of laboratory tests, thoracic radiography, and abdominal ultrasonography were obtained. RESULTS: Test results in all cats were negative for FeLV; 3 of 19 were positive for feline immunodeficiency virus. Thirteen tumors were stage III, 7 were stage IV, and 1 was stage V. Diagnosis was confirmed on the basis of microscopic examination of histologic (n = 13) or cytologic (8) specimens. Immunophenotyping was performed on 13 tumors; 10 were T-cell and 3 were B-cell lymphomas. Overall median duration of first remission was 20 weeks. Overall median survival time was 40 weeks. The only factor significantly associated with duration of first remission was whether cats had a complete response following induction chemotherapy; duration of first remission was significantly associated with survival time. Cats tolerated treatment well; only 1 cat had a delay in the treatment schedule because of neutropenia. CLINICAL IMPLICATIONS: Use of a multidrug chemotherapeutic protocol that includes L-asparaginase and doxorubicin results in minimal adverse effects and prolonged survival times in cats with alimentary malignant lymphoma.

Animals↗