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Biomedical subjects

J E Dillberger

Publications and source records attributed to J E Dillberger.

At least 19 recordsLinked to original sources

Hemobartonella-like parasites in cynomolgus monkeys (Macaca fascicularis).

Red blood cell parasites were identified electron microscopically in five anemic adult female cynomolgus monkeys (Macaca fascicularis), two of which died during anemic episodes. Organisms typically were 0.3-0.5-micron round, oval, or reniform bodies on the surface or within vacuoles of erythrocytes. Based on their size, location in the erythrocyte, and internal ultrastructural features, organisms were classified as Hemobartonella-like. The relationship between the organisms and the anemias in these monkeys was unclear. This report adds rickettsial erythrocyte infections to the list of latent infections that can complicate research studies with cynomolgus monkeys.

Anaplasmataceae Infections

Antioxidant MDL 29,311 prevents diabetes in nonobese diabetic and multiple low-dose STZ-injected mice.

Recent investigations suggest a role for antioxidants in preventing IDDM. MDL 29,311 (4,4'-[methylenebis(thio)]bis](1,1- dimethylethyl)]-phenol) is an analogue of the antioxidant probucol. Administered as a 1% dietary admixture to female nonobese diabetic mice from 4 to 24 wk of age, MDL reduced the prevalence of diabetes from 49 to 4% at 24 wk of age (n = 50-61/group). Discontinuation of treatment at 24 wk of age did not result in a rapid onset of diabetes. Probucol (1%) did not prevent diabetes. Initiating MDL treatment at 4 or 8 wk of age was more effective (19 and 17%, respectively, compared with 60% in control mice) than initiating treatment at 12 wk of age (30% diabetic; n = 28-35/group). A lower dose of MDL (0.1%), started at 4 wk of age, decreased the prevalence of diabetes to 36%. Histopathology indicated that MDL did not prevent insulitis. MDL (0.1%) also was evaluated in combination with immunosuppressants. Compared with control mice (65% diabetic), the combination of MDL and deflazacort was more effective (21% diabetic) than either agent alone (39% diabetic for MDL and 59% diabetic for deflazacort), whereas the effectiveness of MDL, cyclosporin, and MDL plus cyclosporin was similar (39, 38, and 34% diabetic, respectively). In another model of IDDM, the multiple-low-dose streptozocin-injected mouse, MDL (1%) also reduced the prevalence of diabetes when administered beginning 8 wk before streptozocin (55% diabetic vs. 100% of control mice; n = 20-25/group). Probucol (1%) was ineffective. MDL appears effective in preventing the onset of disease in two mouse models of IDDM.

Aging

Prednisone is not a mouse carcinogen.

The carcinogenic potential of prednisone, a synthetic corticosteroid used as an anti-inflammatory and immunosuppressive agent, was investigated by feeding it to Crl:CD-1(ICR) mice (50/sex/dose) at doses of 0.25, 0.50, 1.0, and 5.0 mg/kg/day for 18 months. Prednisone did not significantly increase the incidence of neoplasms (p less than or equal to 0.05); on the contrary, it significantly decreased the incidence of hepatocellular tumors (p = 0.002 in males, p = 0.027 in females), male lacrimal/Harderian gland tumors (p = 0.05), female pulmonary adenomas (p = 0.047), female endothelial cell tumors (p = 0.035), and female lymphosarcomas (p = 0.02). This study suggests that long-term (lifetime) prednisone use does not increase cancer risk and may actually reduce it.

Animals

Malignant transformation of human fibroblasts by a transfected N-ras oncogene.

The only ras oncogene as yet identified in cells from human fibrosarcomas is N-ras, but the relationship between N-ras oncogene expression and the malignant state of these cell lines is not known. To determine if expression of an N-ras oncogene causes human cells to become malignant, we transfected the N-ras oncogene from human leukemia cell line 8402, cloned into a high expression vector pSV N-ras, into MSU-1.1 cells, a nontumorigenic, infinite life span fibroblast cell strain with a normal morphology and a stable near-diploid karyotype. The transformants formed distinct foci composed of morphologically transformed cells. Cells from such foci expressed higher than normal levels of N-ras protein, exhibited growth factor independence, and formed large colonies in soft agar at a high frequency. Injection of progeny of these focus-derived cells s.c. into athymic mice resulted in progressively growing, invasive malignant tumors (round cell, spindle cell, or giant cell sarcomas) which reached a diameter of 6 mm in 3 to 4 weeks. Injection of focus-derived or tumor-derived cells i.v. resulted in tumors in various organs of the mice. The focus-derived cell strain tested, as well as the majority of the cells derived from the tumor it produced, exhibited the same near-diploid karyotype as the parental MSU-1.1 cells. Cells transfected with an N-ras oncogene that was expressed at a normal level formed only a single, indistinct focus, and cells from that focus were not malignant.

Animals

Malignant transformation of an infinite life span human fibroblast cell strain by transfection with v-Ki-ras.

To determine if human fibroblasts can be transformed into malignant cells by transfection of a K-ras oncogene, we transfected the provirus of Kirsten murine sarcoma virus (v-Ki-ras) into an infinite life span human cell strain, MSU-1.1, which has a normal morphology, is not anchorage independent, and has a stable, near-diploid karyotype. The transfected populations gave rise to distinct foci composed of morphologically-altered cells. The cells from several independent foci were isolated, propagated, and assayed for anchorage independence and/or tumorigenicity. They formed large-sized colonies in soft agar at a high frequency. Cell strains derived from colonies isolated from agar as well as focus-derived cell strains were injected subcutaneously into athymic mice to test for tumorigenicity. One cell strain yielded myxoid fibromas, the rest produced well-differentiated, progressively-growing, invasive, myxoid or spindle cell sarcomas. The karyotype of each of the cell strains tested, including cell strains derived from tumors, was identical to that of non-transfected MSU-1.1 cells. Two focus-derived strains, and two cell strains derived from sarcomas produced from them, were tested and shown by DNA and RNA hybridization to contain and express the v-Ki-ras oncogene. Radioimmunoprecipitation analysis showed that these strains expressed ras-specific p21 products not found in non-transfected MSU.1.1 cells. When injected intraperitoneally, a cell strain derived from a myxoid tumor gave rise to invasive myxoid tumors at various sites in the body. The same cell strain gave rise to invasive spindle cell sarcomas when injected into the tail vein of the animals.

Blotting, Northern

Neoplasia in ferrets: eleven cases with a review.

Records from a veterinary diagnostic laboratory in south Florida, U.S.A. were reviewed for cases of neoplasia in pet ferrets. Twelve ferret tumours were received over a four-year period; one case, a ferret with lymphocytic leukaemia and multi-organ involvement, had been reported previously. The other eleven tumours were: two chordomas of the tail, two sebaceous adenomas of the skin, a sebaceous epithelioma of the skin, a cutaneous mastocytoma, a malignant fibrous histiocytoma from the eyelid, a malignant mesenchymoma and an undifferentiated sarcoma from the dorsal abdominal cavity, a leiomyosarcoma found unattached in the abdominal cavity and an interstitial cell tumour of the testicle. A review of the literature yielded reports of 83 other tumours in domestic ferrets, black-footed ferrets and European polecats. Of the 95 ferret tumours, 46 were considered malignant. Tumours occurred in all organ systems except the respiratory tract and central nervous system. Affected ferrets ranged in age from 209 days to 12 years. The most frequently occurring tumours were ovarian stromal tumours (24 of 95), haemangiomas/haemangio-sarcomas (15 of 95). This information indicates that, contrary to previous opinion, ferrets appear to be subject to a similar incidence and variety of tumours as other animals.

Animals

Protothecosis in two cats.

Protothecosis was diagnosed in 2 cats from Florida with nodular skin lesions. Microscopically, lesions were composed of macrophages and multinucleated giant cells arranged in solid sheets in the dermis and subcutis. In both cats, characteristic algal endospores identified as Prototheca wickerhamii were observed within the cytoplasm of infiltrating cells.

Animals

A malignant nephroblastoma in an aged fox (Fennecus zerda).

A malignant nephroblastoma with pulmonary metastasis which was found at necropsy in an old fox is described. This is the first report of such a tumour in a fox. Nephroblastoma is rare in the family Canidae and usually occurs in young individuals. The presence of a tumour arising from embryonal tissue in an aged animal raises questions about the genesis and behaviour of this tumour. The tumour may have contributed to the animal's congestive heart failure as a result of the generalized pulmonary involvement, an erythropoietin-induced polycythaemia, or increased peripheral resistance via the renin-angiotensin system.

Animals

Topical fluorouracil. II. Postoperative administration in an animal model of glaucoma filtering surgery.

Unilateral posterior lip sclerectomies were performed in ten owl monkeys. Five milligrams of fluorouracil was injected subconjunctivally in each operated eye immediately after surgery. Three drops (approximately 2.4 mg/drop) of fluorouracil were instilled ten minutes apart in each operated eye twice daily on postoperative days 1 through 7 and once daily on postoperative days 8 through 15, 17, 19, and 21. One monkey died on the seventh postoperative day; its death could not be attributed to systemic fluorouracil toxicity. All of the operated eyes had filtering blebs after the full course of fluorouracil, but seven also had corneal epithelial defects. By the seventh postoperative week, two of the operated eyes manifested moderately severe corneal opacification. Ten weeks postoperatively, the electroretinographic a- and b-wave amplitudes averaged 17% and 12% less, respectively, in the seven operated eyes without clinically significant corneal opacification than in the unoperated fellow eyes. Only two eyes had blebs after the 12th postoperative week. Histopathologic examination was performed on five eyes, of which only two revealed patent sclerostomies. Although topical fluorouracil appears to delay bleb scarring, the corneal findings suggest that it may be more toxic than subconjunctival fluorouracil.

Administration, Topical

Focal mucinosis in dogs: seven cases and review of cutaneous mucinoses of man and animals.

Seven dogs had one or more asymptomatic nodules, papules, or plaques on the skin or oral mucosa. The primary histologic feature was the accumulation of excess mucin within the dermis or submucosa. Based upon the clinical presentation and the histopathologic changes, it was proposed that these lesions represent the canine analogue of focal mucinosis in man, and that the same name be applied to the lesion in dogs. The criteria for the diagnosis of focal mucinosis were: (1) the presence of a single (rarely multiple) papule, nodule, or plaque which may be firm, rubbery, or soft, (2) the accumulation of mucin which disrupts and separates collagen fibers, (3) mild to extensive fibroblast proliferation, and (4) a mild mononuclear cell infiltration. The mucinoses of man and animals were reviewed.

Animals

Polycystic kidneys in a ferret.

Polycystic kidneys were found at necropsy in an adult ferret with a history of seizures and a palpable abdominal mass. Both kidneys contained numerous fluid-filled cysts of various sizes. The ferret may provide an animal model for the study of polycystic disease in man.

Animals

Sequential neuropathology of dogs treated with vigabatrin, a GABA-transaminase inhibitor.

Vigabatrin (Sabril) is a gamma-aminobutyric acid-transaminase (GABA-T) inhibitor that is effective in the treatment of certain types of drug-resistant or uncontrolled epilepsy but is known to cause microscopic vacuolation (intramyelinic edema) in the brains of treated rats, mice, and dogs. The effects of high oral doses (300 mg/kg/day) of vigabatrin administered orally to Beagle dogs were studied during treatment weeks 1-12 and recovery weeks 13, 14, 16, 20, 24, and 28. Emesis, loose stools, and anorexia and 3 drug-related deaths were observed during the first 4 wk of treatment but were virtually nonexistent thereafter because of adaptation to the drug aided by food supplementation. In more sensitive areas of the brain (columns of the fornix, thalamus, and hypothalamus), microscopic quantitative differences between background vacuolation in controls and drug-related vacuolation in treated dogs could be delineated after 4 wk, generally reached highest levels of severity between 8 and 12 wk, and were reversible upon cessation of dosing. Inhibition of brain GABA-T and elevation of brain GABA were noted after 1 wk of treatment. During the course of treatment vigabatrin ranged between 4-17 nmol/ml (plasma) and 42-1,570 nmol/ml [cerebrospinal fluid (CSF)] while CSF GABA concentrations were 4-32 nmol/ml (treated dogs) and 0.1-0.6 nmol/ml (control dogs). Although the cause of vigabatrin-induced microvacuolation is unknown, the results of the study demonstrated that GABA-T inhibition with subsequent GABA elevation occurred within the first week of treatment and was followed by the onset of detectable microvacuolation several weeks later.

4-Aminobutyrate Transaminase

Age-related pancreatic islet changes in Sprague-Dawley rats.

To characterize the clinical pathologic and morphologic features of spontaneous age-related changes in pancreatic islets observed in Crl:CD (SD)BR rats, I reviewed data from rats used as controls in 10 toxicity studies from 1987 to 1992. Rats were 3.5-26 mo old at necropsy. At necropsy, rats were weighed, and serum, urine, and pancreas samples were collected. Serum was analyzed for glucose, triglyceride, and cholesterol concentrations; urine was analyzed for glucose and ketones; and samples of pancreas were stained with hematoxylin and eosin, Masson's trichrome stain, or for insulin by an immunoperoxidase method with a Masson's trichrome counterstain and examined microscopically. Male rats gained weight more rapidly than females and were visibly obese by 5 mo. Weight gain was accompanied by increased fasting triglyceride and cholesterol concentrations. Triglyceride increased more than cholesterol: from 3.5 to 17 mo of age, triglyceride concentrations increased 3.4-fold in males and 3.1-fold in females. By 14 mo of age, rats generally had fasting triglyceride concentrations > 200 mg/dl (2.2 microM). Fasting glucose concentrations generally were slightly (< 30%) greater in males than females. More males than females had glucose > 200 mg/dl (11 mM); several males had glucose > 300 mg/dl (16.5 mM). Glucosuria was not detected in any rat. Ketonuria was much more common in males than in females, but its incidence did not parallel that of obesity and hypertriglyceridemia; instead, ketonuria was most common in young males and decreased with age. Morphologic islet changes were observed in rats as young as 3.5 mo old, and their incidence increased with age.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma, Islet Cell