Adverse reaction to diazepam in cats.
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Animals↗
Biomedical subjects
J M Cullen
Publications and source records attributed to J M Cullen.
Phagocytosis by pig alveolar macrophages of Actinobacillus pleuropneumoniae serotype 2 mutant strains defective in haemolysin II (ApxII) and pleurotoxin (ApxIII).
The ability of pig alveolar macrophages to phagocytose Actinobacillus pleuropneumoniae HK 361, which produces both haemolysin II (ApxII) and pleurotoxin (ApxIII), has been studied. Macrophages incubated with HK 361 in the presence of normal pig serum were rapidly killed. Incubation of the macrophages with a haemolysin-deficient mutant (HK 361 e), which possesses only cytotoxic activity (ApxIII), also caused gross damage to the macrophages. A mutant (HK 361 h) which produces neither ApxII nor ApxIII in its culture supernatant allowed longer survival of the macrophages than did either the parent strain or mutant e when incubated with normal pig serum. Prolonged incubation with mutant h resulted in an increase in the number of damaged macrophages, but not to the same extent as with either HK 361 or mutant e. The number of mutant h cells phagocytosed in the presence of normal pig serum was low. The addition of either hyperimmune rabbit serum, raised against whole formalin-treated HK 361 cells, or convalescent pig serum from a pig recovering from a serotype 3 infection, which contained antibody against both ApxII and ApxIII, did not increase the survival of macrophages incubated with either HK 361 or mutant e. However, incubation of mutant h with convalescent pig serum did not result in damage-free macrophages. This serum, which possessed neutralizing capabilities against the toxic activities of ApxII and ApxIII, enhanced the number of mutant h cells phagocytosed compared to the numbers phagocytosed in normal pig serum. Killed bacteria were rapidly phagocytosed and did not damage macrophages.(ABSTRACT TRUNCATED AT 250 WORDS)
Actinobacillus pleuropneumoniae↗
Evidence that hepatocyte turnover is required for rapid clearance of duck hepatitis B virus during antiviral therapy of chronically infected ducks.
Duck hepatitis B virus (DHBV) DNA synthesis in congenitally infected ducks is inhibited by 2'-deoxycarbocyclic guanosine (2'-CDG). Three months of therapy reduces the number of infected hepatocytes at least 10-fold (W.S. Mason, J. Cullen, J. Saputelli, T.-T. Wu, C. Liu, W.T. London, E. Lustbader, P. Schaffer, A.P. O'Connell, I. Fourel, C.E. Aldrich, and A.R. Jilbert, Hepatology 19:393-411, 1994). The present study was performed to determine the kinetics of disappearance of infected hepatocytes and to evaluate the role of hepatocyte turnover in this process. Essentially all hepatocytes were infected before drug therapy. Oral treatment with 2'-CDG resulted in a prompt reduction in the number of infected hepatocytes. After 2 weeks, only 30 to 50% appeared to still be infected, and less than 10% were detectably infected after 5 weeks of therapy. To assess the possible role of hepatocyte turnover in these changes, 5-bromo-2'-deoxyuridine (BUdR) was administered 8 h before liver biopsy to label host DNA in hepatocytes passing through S phase, and stained nuclei were detected in tissue sections by using an antibody reactive to BUdR. The extent of nuclear labeling after 5 weeks was the same as that before therapy (ca. 1%). However, biopsies taken after 2 weeks of therapy showed a ca. 10-fold elevation in the number of nuclei labeled with BUdR. This result suggested that a rapid clearance of infected hepatocytes by 2'-CDG was caused not just by the inhibition of viral replication but also by an acceleration of the rate of hepatocyte turnover. To test this possibility further, antiviral therapy was carried out with another strong inhibitor of DHBV DNA synthesis, 5-fluoro-2',3'-dideoxy-3'-thiacytidine (524W), which did not accelerate hepatocyte turnover in ducks. 524W administration led to a strong inhibition of virus production but to a slower rate of decline in the number of infected hepatocytes, so that ca. 50% (and perhaps more) were still infected after 3 months of therapy. In addition, histopathologic evaluation of 2'-CDG-treated ducks revealed liver injury, especially at the start of therapy. No liver damage was observed during 524W therapy. These results imply that clearance of infected hepatocytes from the liver is correlated with hepatocyte turnover. Thus, in the absence of immune clearance or other sources for the accelerated elimination of infected hepatocytes, inhibitors of virus replication would have to be administered for a long period to substantially reduce the burden of infected hepatocytes in the liver.
Animals↗
Antipyrine and caffeine dispositions in clinically normal dogs and dogs with progressive liver disease.
Dispositions of caffeine and antipyrine were compared as indicators of decreasing hepatic function in dogs with experimentally induced progressive liver disease. Dimethylnitrosamine, a hepatospecific toxin, was administered orally to 16 dogs; 6 dogs served as controls (group 1). Three classes of liver disease were defined by histologic features: mild (group 2; n = 5), moderate (group 3; n = 6), and severe (group 4; n = 5). Disposition of antipyrine, and 24 hours later, caffeine was studied 3 weeks after the last dose of toxin in each dog. For both drugs, rapid IV administration of 20 mg/kg of body weight was administered and serum samples were obtained at intervals for determination of at least 5 terminal-phase drug half-lives. For both drugs, clearance and mean residence time differed among groups (P < or = 0.01). Clearance of antipyrine and caffeine was decreased in groups 3 and 4, compared with groups 1 and 2. Antipyrine and caffeine mean residence times were longer in group-3 dogs, compared with dogs of groups 1 and 2. Correction of caffeine and antipyrine clearances for hepatic weight increased discrimination between groups 3 and 4. The clearance and mean residence time ratios of antipyrine to caffeine were calculated for each group and, when compared with values for group-1 dogs, were used to test for differences between the 2 drugs in response to disease. Ratios did not differ among groups. These results indicate that the disposition of antipyrine and caffeine may change similarly with progression of dimethylnitrosamine-induced liver disease.
Analysis of Variance↗
Nuclear ploidy of normal and neoplastic hepatocytes from woodchuck hepatitis virus-infected and uninfected woodchucks.
Flow cytometric analysis of the ploidy of normal and neoplastic hepatocyte nuclei obtained from adult woodchucks, a model of human hepadnavirus-induced hepatocellular carcinoma, was performed. All 36 samples of nuclei from non-neoplastic liver from woodchuck hepatitis virus-infected or uninfected liver were diploid, indicating that age-related nuclear polyploidization does not occur in this species, unlike other rodents. Individual or multiple hepatic neoplasms were obtained from each of 14 woodchuck hepatitis virus-infected woodchucks. Nineteen samples of hepatocellular carcinoma and eight adenomas were examined. Aneuploid nuclei were detected in 10 of the hepatocellular carcinomas and three of the adenoma samples. Similar DNA indexes, ranging from 1.11 to 1.22, were found in 7 of the 10 aneuploid HCCs and all 3 aneuploid adenomas. Nine of the 19 hepatocellular carcinoma samples and 5 of the 8 adenomas were diploid. Four of the diploid hepatocellular carcinomas had increased proportions of tetraploid nuclei. The presence of aneuploid nuclei was not related to histological appearance of the neoplasms or serum gamma-glutamyltranspeptidase levels. Because none of the hepatocellular carcinomas metastasized, the presence of aneuploidy could not be related to biological behavior. We determined the proportion of uninucleate and binucleate hepatocytes in hepatocellular carcinoma and nonneoplastic liver. Approximately 7% of hepatocytes were binucleate in nonneoplastic liver from woodchuck hepatitis virus-infected and uninfected liver. Only 2% of malignant hepatocytes were binucleate. The results of this study indicate that aneuploidy is a common change in hepatic neoplasms from woodchuck hepatitis virus-infected woodchucks.
Adenoma, Liver Cell↗
Production and characterization of a monoclonal antibody recognizing a cytoplasmic antigen of equine mononuclear phagocytes.
An IgG1 mouse monoclonal antibody, designated 1.646, is described which recognizes a cytoplasmic antigen of equine mononuclear phagocytes. Indirect fluorescent antibody staining of peripheral blood leukocytes reveals a granular cytoplasmic staining, predominantly in adherent blood mononuclear cells. Indirect fluorescent antibody staining is positive for alveolar and peritoneal macrophages. In some horses, a few neutrophils are also stained. In equine tissue samples stained by immunohistochemistry, the distribution of positive cells is consistent with the distribution of tissue macrophages. The most intense and reliable staining occurs with splenic and lymph node macrophages. Hepatic Kupffer cells also stain with antibody 1.646, although the intensity of that staining is somewhat variable between horses. A granular pattern of staining typical of lipofuscin deposition is also seen in liver sections. There is also pale staining of some biliary and renal tubular epithelium. Equine erythrocytes, platelets and lymphocytes are not recognized by this antibody, and neither are monocyte/macrophages of human, canine or feline origin. Antibody 1.646 recognizes two proteins (150 and 30 kDa) of equine monocyte-derived macrophages when assayed by Western immunoblot. Because of the distribution of staining (tissue mononuclear phagocytes, lipofuscin-containing storage granules, biliary and renal tubular epithelium, and some neutrophils) we hypothesize that antibody 1.646 recognizes a cytoplasmic antigen that is closely associated with lysosomal membranes.
Animals↗
Actinobacillus pleuropneumoniae RTX-toxins: uniform designation of haemolysins, cytolysins, pleurotoxin and their genes.
The three different pore-forming RTX-toxins of Actinobacillus pleuropneumoniae are reviewed, and new and uniform designations for these toxins and their genes are proposed. The designation ApxI (for Actinobacillus pleuropneumoniae RTX-toxin I) is proposed for the RTX-toxin produced by the reference strains for serotypes 1, 5a, 5b, 9, 10 and 11, which was previously named haemolysin I (HlyI) or cytolysin I (ClyI). This protein is strongly haemolytic and shows strong cytotoxic activity towards pig alveolar macrophages and neutrophils; it has an apparent molecular mass in the range 105 to 110 kDa. The genes of the apxI operon will have the designations apxIC, apxIA, apxIB, and apxID for the activator, the structural gene and the two secretion genes respectively. The designation ApxII is proposed for the RTX-toxin which is produced by all serotype reference strains except serotype 10 and which was previously named App, HlyII, ClyII or Cyt. This protein is weakly haemolytic and moderately cytotoxic and has an apparent molecular mass between 103 and 105 kDa. The genes of the apxII operon will have the designations apxIIC for the activator gene and apxIIA for the structural toxin gene. In the apxII operon, no genes for secretion proteins have been found. Secretion of ApxII seems to occur via the products of the secretion genes apxIB and apxID of the apxI operon. The designation ApxIII is proposed for the nonhaemolytic RTX-toxin of the reference strains for serotypes 2, 3, 4, 6 and 8, which was previously named cytolysin III (ClyIII), pleurotoxin (Ptx), or macrophage toxin (Mat).(ABSTRACT TRUNCATED AT 250 WORDS)
Actinobacillus pleuropneumoniae↗
Lymphocytes protect against and are not required for reovirus-induced myocarditis.
Many studies suggest that host lymphocytes are damaging, rather than protective, in virally induced myocarditis. We have investigated the role of lymphocyte-based immunity in murine myocarditis by using a myocarditic reovirus (reovirus serotype 3 8B), nonmyocarditic reoviruses, adoptive transfer experiments, and mice with severe combined immunodeficiency (SCID mice). Prior to infection, passive transfer of monoclonal antibodies specific for 8B capsid proteins protected neonatal mice against 8B-induced myocarditis, indicating that humoral immunity can protect against myocarditis. Some monoclonal antibodies acted by blocking viral spread to and/or replication in the heart. Passive transfer of reovirus-immune, but not naive, spleen cells prior to infection protected neonatal mice from 8B-induced myocarditis. Depletion of either CD4 or CD8 T cells resulted in increased viral titer in the heart but did not abrogate immune cell-mediated protection against myocardial injury. This shows that both CD4 and CD8 T cells can act independently to protect myocardial tissue from reovirus infection. In addition, reovirus 8B caused extensive myocarditis in SCID mice. This confirms a prior report (B. Sherry, F. J. Schoen, E. Wenske, and B. N. Fields, J. Virol. 63:4840-4849, 1989) that T cells are not required for reovirus-induced myocarditis and demonstrates for the first time that B cells are not required for reovirus-induced myocarditis. We used SCID mice and a panel of reoviruses to assess (i) the relationship between growth in the heart and myocardial damage and (ii) the possibility that nonmyocarditic reoviruses exhibit a myocarditic phenotype in the absence of functional lymphocytes. Growth in the heart was not the sole determinant of myocarditic potential in SCID mice. Although 8B induced myocarditis in SCID mice, no or minimal myocarditis was found in SCID mice infected with four reovirus strains previously shown (B. Sherry and B. N. Fields, J. Virol. 63:4850-4856, 1989) to be nonmyocarditic or poorly myocarditic in normal neonatal mice. We conclude that (i) humoral immunity and cellular immunity are protective against, and not required for, reovirus-induced myocarditis and (ii) the potential to induce cardiac damage is a property of the virus independent of lymphocyte-based immunity.
Animals↗
Histologic characterization of hepatic carcinogenesis in transgenic mice expressing SV40 T-antigens.
The development of hepatic neoplasms was histologically characterized in transgenic mice that expressed an albumin enhancer-promoter/SV40 T-antigen fusion gene. At least five transgenic and three control mice were examined at monthly intervals over a 3-month period. At 1 month of age, five transgenic mice (two male, three female) and three controls (one male, two female) were examined. Five transgenic mice (two male, three female) and three controls (one male, two female) were examined at 2 months of age. Fourteen transgenic mice (12 male, two female) and three controls (two male, one female) were examined at 3 months of age. At 1 month of age, liver-to-body weight ratios of transgenic mice were increased nearly twofold as compared with controls. Histologically, livers from transgenic mice were characterized by dysplastic hepatocytes with marked variation in nucleus and cell size. At 2 months of age, livers from transgenic mice were 2.5 times larger than control livers and contained numerous 1-5-mm cystic spaces. Transgenic livers also contained multiple eosinophilic, basophilic, and clear foci, as well as cystic, hyperplastic bile ducts and biliary adenomas. At 3 months of age, transgenic livers were enlarged over eightfold as compared with controls and contained numerous cysts and solid masses up to 2 cm in diameter. Trabecular, glandular, and anaplastic hepatocellular carcinomas, as well as benign and malignant biliary neoplasms, were diagnosed. No metastasis was observed. Subcutaneous trabecular hepatocellular carcinomas developed in two of three syngeneic mice that had received transplants of a solid hepatic neoplasm, confirming the neoplastic behavior of these tumors.(ABSTRACT TRUNCATED AT 250 WORDS)
Adenoma, Bile Duct↗
Morphologic characterization of castor oil-induced colitis in ponies.
Ten ponies (160-250 kg, ages 17 months to 20 years) developed severe diarrhea within 24 hours of castor oil administration (2.5 ml/kg orally). The diarrhea was most severe between 24 and 48 hours post-dosing and subsided by 72 hours. Ponies were euthanatized at 24, 48, and 72 hours post-dosing and intestine was evaluated histologically and ultrastructurally. Twenty-four hours after dosing, the mucosa of the cecum and ventral colon had extensive superficial epithelial erosion and neutrophil infiltration. In the ileum, the epithelium of villous tips was separated from the lamina propria. Scanning electron microscopic examination of the cecal mucosa revealed that basement membranes were exposed in most areas except within necks of crypts. Ultrastructurally, changes in superficial enterocytes of the cecum and ventral colon were characterized by loss of microvilli, distortion of the cytoplasmic terminal web, expansion of the cytoplasmic matrix with formation of precipitates, and widening of intercellular spaces between junctional complexes. Enterocytes located within necks of crypts were flattened along the basement membrane and extended to margins of erosions. Venules within the superficial lamina propria were occluded by fibrin thrombi. Erosions in the cecum and ventral colon of ponies examined 48 hours after treatment were less extensive than those of ponies examined at 24 hours. At 48 hours post-dosing, basement membranes adjacent to crypts were covered by cuboidal enterocytes characterized ultrastructurally by sparse, irregularly shaped microvilli located on broad cytoplasmic protrusions and by numerous free ribosomes. These features indicated that immature enterocytes had migrated from crypts to resurface the eroded mucosa.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Indocyanine green disposition in healthy dogs and dogs with mild, moderate, or severe dimethylnitrosamine-induced hepatic disease.
Disposition kinetics of indocyanine green (ICG) were used to evaluate hepatic function in healthy Beagles (group 1; n = 6) and Beagles with progressive hepatic disease induced by oral administration of dimethylnitrosamine, a hepatospecific toxin. Three classes of hepatic disease were defined by histologic features: mild (group 2; n = 5), moderate (group 3; n = 6), and severe (group 4; n = 5). Disposition of ICG was studied 3 weeks following the last dose of toxin. A rapid IV injection of 0.5 mg of ICG/kg was administered and serum samples were obtained at certain intervals during 60-minute periods. Serum ICG was analyzed by use of visible spectrophotometry. Disposition kinetics were determined from serum ICG concentrations vs 15- and 60-minute time curves and compared between one another and among groups. Data based on 60-minute time curves were not significantly different from those based on 15-minute curves. Area under the curve for ICG was greatest in group 3. Clearance of ICG was decreased and mean resident time was increased in groups 3 and 4, compared with those in groups 1 and 2. When disposition data (60 minutes) were normalized for differences in hepatic weight among dogs, group-3 mean resident time was significantly greater than that of group 4. This study supports the diagnostic benefits of using ICG disposition kinetics as a method of evaluating hepatic function in dogs with progressive liver disease.
Animals↗
Dimethylnitrosamine-induced hepatotoxicosis in dogs as a model of progressive canine hepatic disease.
A model of toxin-induced progressive hepatitis is described in Beagles. The toxin, dimethylnitrosamine, was administered orally to 18 Beagles; 6 dogs comprised a control group. Clinical signs and laboratory test results were monitored as disease progressed and were used to determine the end point of disease. Following euthanasia, histologic lesions were scored and used to derive a total severity score for each dog. Severity scores were then used to allot the 18 dogs to 3 groups of hepatic disease, defined as mild, moderate, or severe. Changes in clinical laboratory test results, including tests of hepatic function, and clinical signs indicative of liver disease were described chronologically for all dogs. Group means of clinical laboratory test results and quantifiable clinical signs (eg, weight loss and ascitic fluid accumulation) were compared. This model offers several advantages, compared with other experimental models of canine hepatic disease. These include hepatospecificity, similarity to natural disease (eg, the development of multiple extrahepatic portosystemic shunts), and the ability to titrate the disease to a desired end point. The major disadvantages of this model were the toxic nature of the drug to human beings and the variation in individual animal response to the toxin, which precludes preassignment of animals into groups.
Animals↗
Colonic adenocarcinoma with osseous metaplasia in a horse.
Rectal palpation of a 30-year-old mixed-breed mare with chronic weight loss and intermittent, refractory abdominal pain revealed a mass in the right caudoventral portion of the abdomen. Hematologic and serum biochemical findings were normal except for slight mature neutrophilia and mildly high alkaline phosphatase activity and total bilirubin concentration. Cytologic examination of a specimen obtained by abdominocentesis revealed equal numbers of nondegenerative neutrophils and macrophages, but no evidence of neoplastic cells. The mare continued to have signs of abdominal discomfort and was euthanatized. Necropsy revealed a large mass at the junction of the right dorsal colon and transverse colon, and several smaller masses in the liver. Histologic characteristics of the small-colon mass were consistent with colonic adenocarcinoma with osseous metaplasia.
Adenocarcinoma↗
Do propriospinal projections contribute to hindlimb recovery when all long tracts are cut in neonatal or weanling rats?
Lateral hemisection lesions separated by 1 to 3 spinal segments were made on opposite sides of the mithoracic spinal cord in 1-month-old (N = 15; weanling operates) and newborn albino rats (N = 16; neonatal operates). Hindlimb behavior was assessed between 1 and 6 months p.o. for both groups of operates using a protocol and rating system that have previously proved effective in differentiating behavioral recovery of the hindlimbs as a function of age of spinal transection. In addition, at the conclusion of behavioral testing, operates received spinal injections of [3H]proline and HRP caudal to the spinal lesions to determine if lesions were complete and if neurons within the region between the two lesions (interlesion zone) projected into the caudal spinal cord. In both groups of operates, neurons were retrogradely labeled within the interlesion zone bilaterally, primarily in laminae VII-VIII. When both lesions were complete lateral hemisections in weanling operates, little behavioral recovery was observed, similar to complete spinal cord transection (N = 3). However, much greater behavioral recovery was seen, including supporting reactions and locomotor responses, when one or both lesions spared axons along the ventrolateral rim of the white matter. Neurons were retrogradely labeled in the brain stem reticular formation (N = 12) in these cases. All lesions were complete lateral hemisections in neonatal operates but much greater behavioral recovery was seen than in weanling operates with the same lesions, including supporting, placing, and locomotor responses. In an additional group of eight neonatal operates, the spinal cord rostral to the spinal hemisections was transected at 1 month of age. Supportive, placing, and locomotor responses were seen immediately after recovery from anesthesia and responses returned to pretransection levels in six of eight operates over the 10-day survival period. Fink-Heimer impregnation showed that degeneration argyrophilia from the transection bilaterally filled the interlesion zone but little argyrophilia was seen caudal to this region. Our results indicate that an intact propriospinal circuit remains in both neonatal and weanling operates but does not appear to contribute to hindlimb response development or recovery. The greater behavioral recovery in neonatal operates appears due to intrinsic connections (doral root, interneuronal) continuing to be able to drive the spinal circuitry underlying the spared behaviors.
Aging↗
The cytotoxin of Actinobacillus pleuropneumoniae (pleurotoxin) is distinct from the haemolysin and is associated with a 120 kDa polypeptide.
Mutants of Actinobacillus pleuropneumoniae strain HK 361 (serotype 2) were isolated which were deficient in type II (Ca2(+)-dependent) haemolysin activity (Hly-). Some of the Hly- mutants secreted a potent, heat-labile extracellular cytotoxic activity against porcine alveolar macrophages. Comparison of cell-free culture supernatant from the parent strain and some Hly- mutants by SDS-PAGE and immunoblotting revealed the loss of a major extracellular polypeptide of 109 kDa. Two Hly- mutants which in addition failed to secrete a 120 kDa polypeptide produced no extracellular cytotoxic activity, suggesting that the 120 kDa protein was the cytotoxin. Antiserum raised to the culture supernatant from a Hly- mutant lacking the 109 kDa polypeptide recognized the 120 kDa band, but not the 109 kDa band, in immunoblots and neutralized the cytotoxic activity, but not the haemolytic activity, of A. pleuropneumoniae. The 120 kDa polypeptide and extracellular cytotoxic activity were widespread among A. pleuropneumoniae strains, but absent from related bacterial pathogens of the pig: Actinobacillus suis, Haemophilus parasuis and Pasteurella multocida. A clear correlation was found between the presence of the 120 kDa polypeptide and cytotoxic activity in culture supernatants. The cytotoxic activity of all the strains tested was neutralized by antibody to the Hly- extracellular material and by convalescent pig serum. It is proposed that the 120 kDa polypeptide represents the cytotoxin of A. pleuropneumoniae, that it is distinct from the haemolysin, and that it be termed pleurotoxin.
Actinobacillus↗
Scirpentriol toxicity in young broiler chickens.
Scirpentriol (STO) (3 alpha,4 beta,15-trihydroxy-12,13-epoxytrichothec-9- ene), the parent alcohol of the family of acetylated scirpenol mycotoxins produced by several Fusarium species, has been implicated in mixed toxicoses of animals, but there is not a general description of its toxicity in chickens. Dietary STO (0, 2, 4, 8, 16, and 32 micrograms/g feed) was fed to four groups of 10 male day-old broiler chickens for 3 wk. The minimum effective dose (MED) for reducing growth rate significantly (P less than .05) was 4 micrograms/g. The same MED was found for increased serum alkaline phosphatase and relative weight of the gizzard. Unlike literature reports for two other trichothecene mycotoxins, T-2 toxin and diacetoxyscirpenol (DAS), STO impaired feed conversion efficiency but did not alter spleen or pancreas size. The MED of STO for decreases in serum lactic dehydrogenase and aspartate aminotransferase was 8 micrograms/g, but the MED for decreased serum albumin and total proteins and regression of the bursa of Fabricius was 16 micrograms/g. Serum sodium, potassium, and calcium were not altered at the highest dose, 32 micrograms/g, but serum phosphate, uric acid, and cholesterol were decreased by 32 micrograms/g. Serum chloride was increased slightly but significantly (P less than .05) at 16 and 32 micrograms/g. Based on these results, STO toxicosis of chickens can be differentiated from those of T-2 toxin and DAS and its toxicity appears sufficient to warrant further attention.
Alkaline Phosphatase↗
Bovine viral diarrhea virus-induced cerebellar disease in a calf.
Bovine viral diarrhea virus (BVDV) was isolated from buffy coat cells of a 10-day-old calf with signs of cerebellar disease--ataxia, hypermetria, and intention head tremor. The tentative diagnosis was BVDV-induced cerebellar hypoplasia. At necropsy, gross lesions were not identified. Histologic findings suggested BVDV-induced diffuse hypomyelination throughout the CNS, as reported in the United Kingdom and The Netherlands.
Animals↗
Hepatic neoplasms in aflatoxin B1-treated, congenital duck hepatitis B virus-infected, and virus-free pekin ducks.
To assess the effects of the combination of persistent hepadnavirus infection and chemical carcinogen exposure, aflatoxin B1 (AFB) was administered p.o. for 60 days to congenitally duck hepatitis B virus (DHBV)-infected and virus-free Pekin ducks, starting at 3 days of age, during a 28-month study. Hepatic neoplasia occurred only in AFB-dosed ducks. Hepatocellular carcinomas or biliary carcinomas occurred in 4 of 8 DHBV-infected and 3 of 4 DHBV-free ducks, and hepatocellular adenomas developed in 2 DHBV-infected AFB-dosed ducks that survived 20 months or longer. Altered foci of hepatocytes similar to those observed in chemical carcinogen-dosed rodents, characterized by enlarged eosinophilic hepatocytes or vacuolated cytoplasm, occurred in AFB-dosed ducks. Cells in foci or hepatic neoplasms did not contain histochemically detectable gamma-glutamyltranspeptidase but were distinguished from uninvolved parenchyma by altered glycogen content. Immunohistochemical staining indicated that DHBV core antigen persisted in liver, spleen, pancreas, and, to a lesser extent, kidney of most congenitally infected ducks up to 28 months of age. Hepatic neoplasms contained only patches of hepatocytes were detectable viral antigen. Southern blot analysis of restriction endonuclease-digested neoplastic and normal liver DNA revealed high molecular weight forms of DHBV DNA consistent with integration of viral DNA into the genome of hepatic neoplasms from 3 of 4 DHBV-infected ducks but not nontumorous liver. These findings indicate that AFB is a potent hepatic carcinogen in ducks and that persistent congenital DHBV infection did not contribute significantly to the emergence of hepatic neoplasia in ducks under these conditions.
Aflatoxin B1↗