Biomedical subjects

J E Sagartz

Publications and source records attributed to J E Sagartz.

11 recordsLinked to original sources

PubMed1997

Thyroid-stimulating hormone promotes growth of thyroid carcinomas in transgenic mice with targeted expression of the ret/PTC1 oncogene.

Thyroid carcinomas from mice bearing a thyroid-targeted ret/PTC1 oncogene were studied for responsiveness to endogenous thyroid-stimulating hormone (TSH) to evaluate the effect of TSH on tumor progression. Mice of both sexes were maintained for either 3 or 6 months on a low-iodine diet (LID; < 0.05 ppm) to decrease thyroid hormone production and increase endogenous pituitary TSH secretion. Nontransgenic littermates served as controls. Lesions in mice on LID were observed only in the thyroid and pituitary glands. LID induced marked hyperplasia of thyroid follicular cells of nontransgenic control mice at both time points despite a return of TSH levels to normal values after 6 months of treatment. All transgenic mice had bilateral thyroid carcinomas with histologic features resembling human papillary thyroid carcinoma. The LID resulted in a progressive increase in thyroid area weight and tumor cellularity with the development of a prominent spindle-cell component in the thyroid carcinomas after 6 months. There was no evidence, however, of local or distant metastasis of the thyroid carcinomas. Despite the lack of histologic differentiation, the spindle-cell population retained focal immunoreactivity for thyroglobulin. Our results show that ret/PTC1-induced thyroid follicular cell carcinomas retain TSH responsiveness and maintain a benign biologic behavior despite histologic evidence of anaplasia.

Animals↗

PubMed1997

Overexpression of p53 tumor suppressor protein in spontaneously arising neoplasms of dogs.

OBJECTIVE: To determine prevalence of p53 tumor suppressor protein overexpression in spontaneously arising tumors of dogs, using the CM-1 polyclonal antibody and immunohistochemical methods. DESIGN AND SAMPLE POPULATION: Retrospective analysis was performed on archived, paraffin-embedded tumor tissue from dogs. A total of 226 tumors were evaluated, including tumors of epithelial, mesenchymal, and round cell origins. PROCEDURES: Overexpression of p53 was detected by indirect immunohistochemical methods, using the CM-1 rabbit anti-human p53 polyclonal primary antibody. Protein overexpression was determined by use of a grading system based on percentage of stained tumor nuclei. RESULTS: Nuclear overexpression of p53 was detected in most squamous cell carcinomas, nasal adenocarcinomas, and perianal gland adenocarcinomas. Hemangiopericytomas, transitional cell carcinomas, mammary adenocarcinomas, apocrine gland adenocarcinomas, intestinal adenocarcinomas, mast cell tumors, and cutaneous histiocytomas had low numbers of nuclei overexpressing p53. Remaining tumor types had intermediate p53 nuclear overexpression. Cytoplasmic staining was observed in some carcinomas, particularly intestinal adenocarcinomas. CONCLUSIONS: Overexpression of p53 is common in spontaneously arising neoplasms of dogs. CLINICAL RELEVANCE: Prospective determination of p53 status in some tumor types may be as clinically useful in determining prognosis and predicting survival times for dogs with cancer as it is for human beings with cancer.

Animals↗

PubMed1996

p53 tumor suppressor protein overexpression in osteogenic tumors of dogs.

Alterations in the p53 tumor suppressor gene have been implicated in the genesis and/or progression of the majority of human cancers, including osteosarcoma. Stabilization of the protein by mutation or interaction with other proteins prolongs its half-life, rendering it detectable by immunohistochemistry. Osteosarcoma is the most common primary canine bone tumor and is characterized by frequent early metastases. Multilobular tumors of bone involve primarily flat bones of the head and are low-grade malignancies with lower metastatic potential. The objectives of this study were to determine the prevalence of p53 protein overexpression in 106 osteogenic tumors of dogs using an indirect immunohistochemical method and to compare p53 overexpression between tumors with different clinical behavior. A polyclonal p53 antibody (CM-1) served as the primary antibody. Tumors were scored based upon an estimate of the percentage of tumor cells stained. Significant differences in the prevalence of overexpression were observed between osteosarcomas (72%) and multilobular tumors of bone (20%, P = 0.0020). Osteosarcomas of the appendicular skeleton had a significantly higher prevalence of p53 overexpression (84%) than did osteosarcomas of the axial skeleton (56%, P = 0.0060). Our results show that p53 tumor suppressor protein is overexpressed in the majority of canine osteosarcomas. The higher prevalence of overexpression in osteosarcomas versus multilobular tumors of bone and in osteosarcomas of the appendicular skeleton versus those of the axial skeleton suggests that alterations in p53 expression correlate with highly aggressive tumor behavior.

Animals↗

PubMed1996

Lymphangiosarcoma in a young dog.

Lymphangiosarcoma was diagnosed from biopsy material obtained from an 8-week-old puppy with a progressively enlarging subcutaneous inguinal swelling. Histologically, the tumor was composed of endothelial cells immediately adjacent to large collagen bundles. Tumor cells formed irregular vascular channels which extended along the connective tissue investments of small vessels and nerves of the subcutis and deep dermis. Similar neoplastic tissue extensively infiltrated an inguinal lymph node. Neoplastic cells were immunohistochemically stained for factor 8-related antigen and were weakly positive when compared with several hemangiomas and hemangiosarcomas. Transmission electron microscopy revealed numerous micropinocytotic vesicles and a continuous basal lamina. The puppy was euthanatized at 8 months of age due to severe septic polyarthritis. Lymphangiosarcoma was documented at the site of the original tumor as well as in the axillary lymph node at necropsy.

Animals↗

PubMed1996

Targeted expression of the ret/PTC1 oncogene induces papillary thyroid carcinomas.

The ret/PTC oncogene, a rearranged form of the ret proto-oncogene, has been found to be restricted to human papillary thyroid carcinomas. This report shows that transgenic mice with thyroid-targeted expression of the ret/PTC1 oncogene developed thyroid carcinomas with considerable similarities to human papillary thyroid carcinomas, particularly in the nuclear cytologic features and the presence of local invasion. Our findings indicate that ret/PTC2 is not only a biomarker associated with papillary thyroid carcinomas, but is also the only proven specific genetic event leading to the development of papillary thyroid carcinoma.

Animals↗

PubMed1995

Phagocytic activity of FRTL-5 rat thyroid follicular cells as measured by ingestion of fluorescent latex beads.

A rat thyroid cell line (FRTL-5) was used to study the phagocytic activity of thyroid follicular cells using fluorescent latex beads and flow cytometric analysis. Morphologic studies demonstrated that latex beads were engulfed and located within cytoplasmic vacuoles of thyrocytes. Flow cytometric evaluation of cell suspensions revealed high levels of fluorescence in cells engulfing latex beads. Using thyrotropin (TSH) as a stimulator of thyroid function and human interleukin-1 beta as an inhibitor, protocols were established for measuring the effects of these substances on either basal or TSH-induced phagocytosis. Cells exposed to latex beads over time in basal (0H) or TSH-containing medium had an increase in time-dependent phagocytic activity which was maximal after 24 or 8 h, respectively. Treatment of FRTL-5 cells with either a stimulator or an inhibitor revealed maximal change in phagocytic activity after 72 h as measured by the percentage of phagocytic cells as well as the mean fluorescence intensity. Phagocytic activity and iodide trapping by FRTL-5 cells were qualitatively similar in both sensitivity and magnitude of change in the assays used in this study. Phagocytosis of fluorescent latex beads represents a sensitive nonradioactive assay of thyrocyte function whose regulation is similar to iodide trapping.

Animals↗

PubMed1995

Systemic mastocytosis in a goat.

Systemic mastocytosis was diagnosed in a 4-year-old, female Nubian goat. Clinically, the animal was depressed and had severe macrocytic hypochromic anemia and leukopenia. Postmortem examination revealed neoplastic mast cells invading the heart, lung, liver, spleen, lymph nodes, and bone marrow. Eosinophils were frequently admixed with infiltrating mast cells in all organs. Using routine light microscopy, histochemistry, and transmission electron microscopy, metachromatic and periodic acid-Schiff-positive granules were identified within the cytoplasm of neoplastic mast cells. Erythrophagocytosis was observed in some neoplastic cells, although its contribution to the anemia was not clear. This report represents the first description of mast cell neoplasia in the goat.

Anemia, Hypochromic↗

PubMedDate not supplied

Phagocytosis of fluorescent beads by rat thyroid follicular cells (FRTL-5): comparison with iodide trapping as an index of functional activity of thyrocytes in vitro.

The ability of FRTL-5 rat thyroid follicular cells to engulf latex beads by phagocytosis was evaluated using flow cytometry and compared to iodide trapping in response to selected growth factors, second messengers, and chemicals. Cell suspensions were analyzed to determine the percentage of fluorescence-positive cells as well as the fluorescence intensity of positive cells. Phagocytosis was stimulated by forskolin, cholera toxin, 8-Br-cAMP, calcitriol, and transforming growth factor-beta. In contrast, phagocytosis was inhibited by insulin, calcium, and aminotriazole, but not by sodium iodide. The results of this study showed that phagocytosis of latex beads was regulated in a manner similar to iodide trapping and could be altered by the addition of numerous compounds. Phagocytic activity was stimulated by both cAMP-dependent and cAMP-independent pathways. Flow cytometric evaluation of phagocytosis of fluorescent latex beads represents a simple, rapid, nonradioactive index of thyroid function in vitro.

Amitrole↗

PubMedDate not supplied

Phenobarbital does not promote hepatic tumorigenesis in a twenty-six-week bioassay in p53 heterozygous mice.

The tumorigenic potential of phenobarbital was examined in a 26-wk carcinogenesis bioassay using p53 heterozygous mice and wild-type controls. Fifteen mice/sex/genotype were exposed to either 500 or 1,000 ppm phenobarbital in the diet. Dietary administration of 3,750 ppm p-cresidine, a transspecies mutagenic carcinogen, to both heterozygous and wild-type mice served as a positive control. Phenobarbital treatment caused increases in liver:body weight ratios and histologic evidence of centrilobular hepatocellular hypertrophy. No tumors were observed in any phenobarbital-treated mice. Mice given p-cresidine exhibited a moderate reduction in body weight gain over the course of the study. Heterozygous mice treated with p-cresidine exhibited a high incidence of urinary bladder tumors. Similar tumors were also present in a small number of p-cresidine-treated wild-type mice. Our results demonstrate the lack of a hepatic tumor response to phenobarbital, a compound that is a potent and potent and prototypic hepatic microsomal enzyme inducer, a nongenotoxic rodent carcinogen, and a human noncarcinogen. This finding supports the continued utility of this model as an alternative to the mouse bioassay for human carcinogenic safety assessment of potentially genotoxic carcinogenes because it did not produce a false-positive response to this potent nongenotoxic agent.

Aniline Compounds↗

PubMedDate not supplied

Association of cecal spirochetes with pasty vents and dirty eggshells in layers.

Feces-stained eggshells, diarrhea, and typhlitis were identified in two commercial laying flocks in Ohio. Hens with diarrhea had spirochetes in cecal lumina and crypts. On culture, the spirochetes were motile and non-hemolytic, did not produce indole, had 12 to 15 axial filaments, were 9.2 to 11.7 microns in length and 240 to 370 nm in diameter, and had a wavelength of 5.1 to 6.5 microns on transmission electron microscopy.

Animals↗

PubMedDate not supplied

Necrotizing typhlocolitis associated with a spirochete in rheas (Rhea americana).

Necrotizing typhlocolitis was diagnosed in 13 juvenile common rheas (Rhea americana) from three separate of geographically isolated Ohio flocks, with mortality ranging from 25% to 80%. At postmortem examination, a diphtheritic membrane covered ulcerated cecal mucosa. Histologically, cecal sections showed necrosis and granulomatous-to-suppurative inflammation that extended into the submucosa and often surrounded large eosinophilic colonies of bacteria. Warthin-Starry staining showed these colonies to be composed of entangled spirochetes that invaded the submucosa and frequently were present transmurally. Similar organisms were identified by Warthin-Starry staining in the cecum of a juvenile rhea from a fourth flock that histologically had mild lymphocytic typhlitis. Scanning and transmission electron microscopy demonstrated the presence of a spirochete in the ceca. Anaerobic culture yielded a gram-negative, beta-hemolytic spirochete. Coccidia, histomonads, and Salmonella spp. were consistently absent.

Animals↗