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Biomedical subjects

E J Ehrhart

Publications and source records attributed to E J Ehrhart.

At least 19 recordsLinked to original sources

Frequency of and risk factors associated with lingual lesions in dogs: 1,196 cases (1995-2004).

OBJECTIVE: To categorize histologic lesions affecting the tongue, determine the frequency with which they develop, and identify risk factors associated with their development in dogs. DESIGN: Retrospective case series. ANIMALS: 1,196 dogs. PROCEDURES: Diagnostic reports of lingual biopsy specimens from dogs evaluated from January 1995 to October 2004 were reviewed. RESULTS: Neoplasia comprised 54% of lingual lesions. Malignant tumors accounted for 64% of lingual neoplasms and included melanoma, squamous cell carcinoma, hemangiosarcoma, and fibrosarcoma. Large-breed dogs, especially Chow Chows and Chinese Shar-Peis, were at increased risk for melanoma. Females of all breeds and Poodles, Labrador Retrievers, and Samoyeds were more likely to have squamous cell carcinomas. Hemangiosarcomas and fibrosarcomas were commonly diagnosed in Border Collies and Golden Retrievers, respectively. Benign neoplasms included squamous papilloma, plasma cell tumor, and granular cell tumor. Small-breed dogs, especially Cocker Spaniels, were at increased risk for plasma cell tumors. Glossitis accounted for 33% of diagnoses; in most cases, the inciting cause was not apparent. Whereas large-breed dogs were more likely to have lingual neoplasia, small-breed dogs were more likely to have glossitis. Calcinosis circumscripta accounted for 4% of lingual lesions and predominately affected young large-breed dogs. The remaining submissions consisted mostly of various degenerative or wound-associated lesions. CONCLUSIONS AND CLINICAL RELEVANCE: The frequency of lingual lesions was not evenly distributed across breeds, sexes, or size classes of dogs. Veterinarians should be aware of the commonly reported lingual lesions in dogs so that prompt diagnosis and appropriate management can be initiated.

Age Factors↗

Anti-angiogenic effects of interleukin-12 delivered by a novel hyperthermia induced gene construct.

PURPOSE: Interleukin-12 (IL-12) is a pro-inflammatory cytokine possessing anti-cancer and anti-angiogenic properties. This study quantitatively assessed the anti-angiogenic effect of IL-12 delivered using an adenoviral vector with murine IL-12 placed under control of a heat shock promoter. This approach limits systemic toxicity by restricting IL-12 delivery locally to the tumour. The kinetics of the downstream cytokines interferon-gamma (IFN-gamma) and interferon inducible protein-10 (IP-10) and other molecules affecting angiogenesis, vascular endothelial growth factor (VEGF) and plasminogen activator inhibitor-1 (PAI-1) were also studied. MATERIALS AND METHODS: 4T1 tumours were grown in Balb/C mice and the AdhspmIL-12 construct was injected intra-tumourally. The tumours were heated after 24 h using a water bath. At various time points post-heating the tumours were collected and quantitatively assessed for cytokine production and vascularity. RESULTS: A significant reduction was seen in the tumour vasculature of the treated group vs. the control group mice. Systemic effects of IL-12 were limited to generalized immunostimulation. No hepatoxicity was noted. CONCLUSIONS: This study suggests that IL-12 can be effectively delivered using a gene-based approach with a heat shock promoter. This results in quantitatively measurable anti-angiogenesis and general immunostimulation. The complex inter-play of other pro- and anti-angiogenic factors (IFN-gamma, IP-10, VEGF and PAI-1) was also studied.

Adenoviridae↗

RT-PCR analysis of Candida albicans ALS gene expression in a hyposalivatory rat model of oral candidiasis and in HIV-positive human patients.

ALS gene expression was studied in the hyposalivatory rat model of oral candidiasis and in clinical specimens collected from HIV-positive patients to assess similarities in expression patterns between the model system and clinical isolates. Two Candida albicans strains, SC5314 and OY-2-76, were used in the rat model system and infection progressed for 3 or 5 days. The strains produced similar oral lesions at 3 days. At 5 days, strain OY-2-76 produced more superficial lesions containing relatively more yeast forms compared to invasive hyphal forms observed for strain SC5314. For all infections, the most severe lesions were observed on the tongue and gingiva overlying the mandible. ALS transcripts were easier to detect by RT-PCR later in infection and under other conditions where more fungal cells were present. Expression of ALS1, ALS2, ALS3 and ALS4 was observed in rats infected for 3 days with ALS5 and ALS9 transcripts detected after 5 days of infection. Expression of ALS6 was observed in a single specimen from a 5-day infection while ALS7 transcript was never found. Expression of all ALS genes was observed in oral clinical material collected from HIV-positive patients although ALS6 and ALS7 transcripts required an extra PCR amplification step to be detected. Overall, the patterns of ALS gene expression were similar between the rat model and human clinical specimens, suggesting that the model would be useful for studying the phenotype of al delta/al delta mutant strains.

AIDS-Related Opportunistic Infections↗

Gastric adenocarcinoma and chronic gastritis in two related Persian cats.

Two 12.5-year-old castrated male Persian cats from the same household, whose dams were littermates, presented simultaneously with gastric adenocarcinoma associated with proliferative and fibrosing gastritis. Intralesional adult Ollulanus tricuspis nematodes and rare surface-associated spiral-shaped bacteria were identified in one cat. No etiologic agents were identified in tissues from the second cat; however, gastric mucosa was examined following anthelmintic treatment. Clinical signs in each cat had commenced 2 months apart and included vomiting, hematemesis, intermittent melena, and weight loss. This is the first report of gastric adenocarcinoma occurring in housemate cats or cats of common descent. Carcinogenesis may have been influenced by shared undetermined genetic and environmental factors, possibly including Ollulanus tricuspis, spiral-shaped bacteria, or other etiologies for chronic gastritis that remain unidentified.

Adenocarcinoma↗

Lipid-rich carcinoma of the mammary gland in a cat.

A 1.5-year-old female, intact, clinically healthy cat presented for a subcutaneous mass of the ventral abdomen. Surgical excision and microscopic examination of the mass were performed. Histologically, this was a discrete, unencapsulated, multilobular, expansile mass, which compressed the surrounding normal mammary tissue. Lobules were composed of tubuloacinar structures formed by atypical round to polygonal cells, which contained foamy to microvacuolated cytoplasm and variably sized, intracytoplasmic, distinct vacuoles causing nuclear peripheralization. Neoplastic cells demonstrated intense and diffuse immunoreactivity for cytokeratin and lacked immunoreactivity for vimentin. The vacuolar contents stained positively with Oil RedO and negatively with periodic acid-Schiff and Alcian blue stains. Histomorphologic, histochemical, and immunohistochemial analysis support a diagnosis of lipid-rich mammary carcinoma. This is the first report of a cat with a lipid-rich variant of mammary carcinoma.

Animals↗

Bacterial meningoencephalitis and ventriculitis due to migrating plant foreign bodies in three dogs.

Regional suppurative meningoencephalitis and ventriculitis of variable chronicity was diagnosed in three young dogs residing in Colorado. Grass awns were grossly identified in the right occipital cortex of one dog and in the right lateral ventricle of another. Intralesional plant material was microscopically evident in the dura mater overlying the right occipital cortex of the third dog. One grass awn was identified as a floret of Hordeum jabatum. In each case, aerobic culture of brain tissue identified multiple isolates of bacteria. The dogs presented with clinically variable, rapidly progressive neurologic dysfunction, including tetraplegia, depressed mentation, and episodic extensor rigidity, ataxia, circling, stupor, vocalization, and head-pressing. Encephalitis due to bacteria introduced from migrating plant foreign material is a potential sequela of intranasal, periocular, or pharyngeal foreign bodies.

Animals↗

Reversibility of the reproductive toxicity of gossypol in peripubertal bulls.

Gossypol has been shown to impair sperm production in male ruminants. The purpose of this study was to determine if the adverse effects of gossypol on spermatogenesis in peripubertal bulls were reversible. Twenty-eight crossbred Angus bulls were allocated into treated and control groups at 11 months of age. For 8 weeks, treated bulls were fed a ration containing 8 mg of free gossypol per kilogram of body weight per day while control bulls were fed a soybean meal ration free of gossypol. At 28-days intervals, scrotal circumference was measured and semen collected to assess sperm motility and morphology. Seven control and seven treated animals were castrated 56 days after the start of the experiment and the testes were examined histologically. The remaining bulls were fed a gossypol-free diet for 210 days prior to castration. There were significant increases in primary and secondary sperm abnormalities in treated bulls 28 and 56 days after gossypol feeding. The number of sperm with proximal droplets was significantly higher in gossypol-treated bulls, suggesting testicular degeneration. There was no significant effect on the sperm motility, scrotal circumference, or histopathological characteristics of the testes. Four weeks after the end of gossypol feeding, primary and secondary abnormalities were still increased in gossypol-treated bulls, however in subsequent collection periods the percentage of abnormalities were similar between groups. At 210 days, there was no treatment effect on scrotal circumference, and histological characteristics of the testes were not different between groups. The deleterious effects of gossypol on the morphological characteristics of spermatozoa were reversible. Gossypol (8 mg/kg per day for 56 days) increased sperm abnormalities but the effects were reversible.

Animals↗

Immunohistochemistry of atrial and brain natriuretic peptides in control cats and cats with hypertrophic cardiomyopathy.

Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are cardiac hormones involved in electrolyte and fluid homeostasis. Our laboratory has investigated the use of ANP and BNP as diagnostic markers of cardiac disease in cats. We hypothesize that the cardiac distribution of ANP and BNP increases in cats with hypertrophic cardiomyopathy (HCM). Accordingly, we evaluated the immunohistochemical distribution of ANP and BNP in hearts of four cats with naturally occurring HCM relative to five healthy controls. Indirect immunoperoxidase was performed with polyclonal immunoglobulin G against feline ANP (1-28) and proBNP (43-56). In control cats, ANP and BNP immunoreactivity was restricted to the atria. Staining for both peptides was most intense adjacent to the endocardial surface. Auricles stained more diffusely than atria for both peptides. The interstitial capillaries and nerve fibers within the heart were positive only for BNP. Atrial immunoreactivity for ANP and BNP was more diffuse and had a less distinctly layered pattern in HCM than in control cats. Ventricular cardiomyocytes of HCM cats were negative for ANP but stained lightly and diffusely for BNP. The capillaries and nerve fibers remained positive for BNP. We conclude that in cats with HCM, the cardiac distribution of ANP and BNP is more diffuse in the atria and that novel expression of BNP in the ventricular cardiomyocytes occurs.

Animals↗

Progression of an orbital T-cell rich B-cell lymphoma to a B-cell lymphoma in a dog.

An 11-year-old Shetland Sheepdog was presented for exophthalmos caused by a locally extensive, poorly defined mass located behind the right eye. The primary orbital mass was identified by light microscopy and immunohistochemistry as a T-cell rich B-cell lymphoma (TCRBCL) composed predominantly of BLA.36-positive large neoplastic lymphoid cells admixed with fewer CD3- and CD79a-positive small lymphocytes. The dog was treated for lymphoma, but 6 months after presentation it was euthanatized for suspected hepatic and gastrointestinal metastasis. Gross findings revealed an enlarged liver with multiple well-demarcated, randomly distributed 0.1-1.5-cm white nodules, five firm white submucosal jejunal nodules, and ileocecal, mediastinal, and hilar lymphadenopathy. Metastatic liver lesions consisted of sheets of monomorphic large neoplastic lymphoid cells that effaced and expanded portal and centrilobular zones. These cells were morphologically similar to the large neoplastic cells of the original orbital tumor and were CD3-negative and variably BLA.36-positive, consistent with B-cell lineage. Similar cells comprised the jejunal nodules and effaced the lymph nodes. The progression of TCRBCL to a diffuse B-cell lymphoma in this case is consistent with reported human cases and has not been previously reported in the dog.

Animals↗

Light and electron microscopic features of eperythrozoon-like parasites in a North American opossum (Didelphis virginiana).

Epierythrocytic parasites associated with a severe anemic episode have not been previously reported in the opossum. A Wright-Giemsa-stained peripheral blood smear from an anemic North American opossum (Didelphis virginiana) revealed numerous organisms attached to red blood cells either singularly or in chains. Ring forms of the organism were common and could be found free in the plasma. Electron microscopy revealed that these organisms were attached to the intact plasma membrane in depressions on the surface of red blood cells. Delicate fibrils between the organism and adjacent membrane were observed. The organisms were round to oval with a diameter of 300-750 nm and were enclosed by a single limiting membrane. The light and electron microscopic features of these epierythrocytic organisms are similar to those reported for Eperythrozoon and Haemobartonella species.

Anemia↗

Detection of Als proteins on the cell wall of Candida albicans in murine tissues.

A murine model of disseminated candidiasis was utilized to determine whether Candida albicans Als proteins are produced in vivo. The kidneys, spleen, heart, liver, and lungs were collected from mice inoculated with one of three C. albicans strains (SC5314, B311, or WO-1). Immunohistochemical analysis of murine tissues by using a rabbit polyclonal anti-Als serum indicated that Als proteins were produced by each C. albicans cell in the tissues examined. Patterns of staining with the anti-Als serum were similar among the C. albicans strains tested. These data indicated that Als protein production was widespread in disseminated candidiasis and that, despite strain differences in ALS gene expression previously noted in vitro, Als protein production in vivo was similar among C. albicans strains. The extensive production of Als proteins in vivo and their presence on the C. albicans cell wall position these proteins well for a role in host-pathogen interaction.

Animals↗

Necrotizing mycotic vasculitis with cerebral infarction caused by Aspergillus niger in a horse with acute typholocolitis.

An 18-year-old Morgan mare was presented to the Veterinary Medical Teaching Hospital, University of Illinois, with a 10-day history of watery diarrhea, depression, and dysphagia. On admission, the animal was severely dehydrated, depressed, and unable to swallow and had no clinical signs of diarrhea. The respiratory and heart rate and body temperature were within normal limits. Following fluid therapy, the mare developed severe watery diarrhea and continued to be depressed, incoordinated, and dysphagic. The animal died on the fourth day after admission and was sent to the Laboratories of Veterinary Diagnostic Medicine for necropsy. Gross postmortem findings were consistent with an acute cerebral infarction in the right cerebral hemisphere, an acute necrotizing typhlocolitis, multifocal petechial and ecchymotic hemorrhages, enlarged and congested pars intermedia of the pituitary gland, and marked bilateral adrenocortical hyperplasia with multifocal areas of necrosis and hemorrhage. Histologic evaluation of the affected brain demonstrated an area of coagulative necrosis of the gray matter, with hemorrhage, vasculitis, and thrombosis. There were many fungal hyphae 3.5-6.0 microm, pale basophilic, septate, and occasionally branching at 45 degrees present in the arterial walls and throughout the necrotic tissue. Immunohistochemical analysis revealed Aspergillus niger as the etiologic agent responsible for the mycotic vasculitis and infarction in the brain. Bacteria culture and immunohistochemical staining of the colon and cecum failed to demonstrate specific pathogens.

Acute Disease↗

Effects of a controlled-release cisplatin delivery system used after resection of mammary carcinoma in mice.

OBJECTIVE: To evaluate efficacy of a controlled-release cisplatin delivery system, used after marginal resection of mammary carcinoma (ie, resection of grossly evident tumor) in mice, to prevent tumor regrowth and metastasis. ANIMALS: 42 female C3H-HeJ mice. PROCEDURE: Mice were inoculated with mammary carcinoma cells. Between 2 and 6 days later, tumors were marginally resected and mice were assigned to 1 of 3 groups: no treatment (control; n = 14), cisplatin administered intraperitoneally (i.p. cisplatin; 14), and cisplatin delivered by use of an open-cell polylactic acid system placed within the tumor bed (slow-release cisplatin; 14). Tumor regrowth was measured daily. Mice were euthanatized 14 days after surgery, and complete necropsies were performed. RESULTS: Tumor regrowth was not detected in the slow-release cisplatin group; however, tumor regrowth was detected in 7 of 14 mice in the i.p. cisplatin group and 14 of 14 mice in the control group. Median (+/-SD) number of days to tumor regrowth was 13.5+/-0.64 and 7.79+/-0.87 in the i.p. cisplatin and control groups, respectively. Mice in the i.p. cisplatin group had significantly delayed tumor regrowth, compared with control mice. Metastases to lungs were detected in 8 of 14 control mice but were not detected in mice in either cisplatin treatment group. CONCLUSIONS AND CLINICAL RELEVANCE: The open-cell polylactic acid with cisplatin delivery system was successful in delaying local tumor regrowth and metastasis in mice with marginally resected mammary carcinoma. Use of a controlled-release cisplatin delivery system may be an effective adjunct treatment following excision of mammary carcinoma in humans and other animals.

Animals↗

Latent transforming growth factor beta1 activation in situ: quantitative and functional evidence after low-dose gamma-irradiation.

The biological activity of transforming growth factor beta1 (TGF-beta) is controlled by its secretion as a latent complex in which it is noncovalently associated with latency-associated peptide (LAP). Activation is the extracellular process in which TGF-beta is released from LAP, and is considered to be a primary regulatory control. We recently reported rapid and persistent changes in TGF-beta immunoreactivity in conjunction with extracellular matrix remodeling in gamma-irradiated mouse mammary gland. Our hypothesis is that these specific changes in immunoreactivity are indicative of latent TGF-beta activation. In the present study, we determined the radiation dose response and tested whether a functional relationship exists between radiation-induced TGF-beta and collagen type III remodeling. After radiation exposures as low as 0.1 Gy, we detected increased TGF-beta immunoreactivity in the mammary epithelium concomitant with decreased LAP immunostaining, which are events consistent with activation. Quantitative image analysis demonstrated a significant (P=0.0005) response at 0.1 Gy without an apparent threshold and a linear dose response to 5 Gy. However, in the adipose stroma, loss of LAP demonstrated a qualitative threshold at 0.5 Gy. Loss of LAP paralleled induction of collagen III immunoreactivity in this tissue compartment. We tested whether TGF-beta mediates collagen III expression by treating animals with TGF-beta panspecific monoclonal antibody, 1D11.16, administered i.p. shortly before irradiation. Radiation-induced collagen III staining in the adipose stroma was blocked in an antibody dose-dependent manner, which persisted through 7 days postirradiation. RNase protection assay revealed that radiation-induced elevation of total gland collagen III mRNA was also blocked by neutralizing antibody treatment. These data provide functional confirmation of the hypothesis that radiation exposure leads to latent TGF-beta activation, support our interpretation of the reciprocal shift in immunoreactivity as evidence of activation, and implicate TGF-beta as a mediator of tissue response to ionizing radiation. The sensitivity of activation to low radiation doses points to a potential role for TGF-beta in orchestrating tissue response to oxidative stress. As such, radiation may be useful as a probe to delineate the consequences of latent TGF-beta activation in situ.

Animals↗

Pancreatic beta cell tumor in ferrets: 20 cases (1986-1994).

OBJECTIVE: To characterize survival times, disease-free intervals, and prognostic variables in ferrets with pancreatic beta cell neoplasia. DESIGN: Retrospective study. ANIMALS: 20 ferrets with histologically confirmed pancreatic beta cell tumors. PROCEDURE: Medical records of ferrets with pancreatic beta cell tumors were reviewed. Variables such as age, sex, duration of clinical signs, existence of other neoplasia, single versus multiple masses in the pancreas, benign or malignant histologic features, and the type of treatment used at redevelopment of clinical signs were examined to determine their relationship to survival times and disease-free intervals. RESULTS: Duration of clinical signs prior to diagnosis and initial surgery was inversely correlated with survival time and disease-free interval. Overall median survival time for all ferrets with pancreatic beta cell tumors was 483 days. Median disease-free interval for ferrets that had abdominal surgery for pancreatic beta cell tumor removal was 240 days. Distant tumor metastasis was not found in this group of ferrets, but local tumor recurrence was common. In 4 ferrets that had a second celiotomy, removal of recurrent pancreatic tumors did not prolong survival but did result in a second disease-free interval. CLINICAL IMPLICATIONS: Pancreatic beta cell tumors should be considered in ferrets over 2 years of age that have clinical signs of seizures, episodic lethargy, ptyalism, ataxia, and hind limb weakness. In the study reported here, complete surgical excision of the tumor resulted in temporary resolution of clinical signs in ferrets; however, redevelopment of clinical signs at a later time was common.

Animals↗

Immunohistochemical evidence of rapid extracellular matrix remodeling after iron-particle irradiation of mouse mammary gland.

High-LET radiation has unique physical and biological properties compared to sparsely ionizing radiation. Recent studies demonstrate that sparsely ionizing radiation rapidly alters the pattern of extracellular matrix expression in several tissues, but little is known about the effect of heavy-ion radiation. This study investigates densely ionizing radiation-induced changes in extracellular matrix localization in the mammary glands of adult female BALB/c mice after whole-body irradiation with 0.8 Gy 600 MeV iron particles. The basement membrane and interstitial extracellular matrix proteins of the mammary gland stroma were mapped with respect to time postirradiation using immunofluorescence. Collagen III was induced in the adipose stroma within 1 day, continued to increase through day 9 and was resolved by day 14. Immunoreactive tenascin was induced in the epithelium by day 1, was evident at the epithelial-stromal interface by day 5-9 and persisted as a condensed layer beneath the basement membrane through day 14. These findings parallel similar changes induced by gamma irradiation but demonstrate different onset and chronicity. In contrast, the integrity of epithelial basement membrane, which was unaffected by sparsely ionizing radiation, was disrupted by iron-particle irradiation. Laminin immunoreactivity was mildly irregular at 1 h postirradiation and showed discontinuities and thickening from days 1 to 9. Continuity was restored by day 14. Thus high-LET radiation, like sparsely ionizing radiation, induces rapid-remodeling of the stromal extracellular matrix but also appears to alter the integrity of the epithelial basement membrane, which is an important regulator of epithelial cell proliferation and differentiation.

Animals↗