Biomedical subjects
Publications and source records attributed to J F Edwards.
Cache Valley Virus (CVV) is a causative agent of a mosquito-borne disease syndrome of sheep and, possibly, of all ruminants, characterized by embryonic and fetal death, stillbirths, and multiple congenital malformations. CVV is endemic in Canada, Mexico, and the United States. Several related Bunyaviruses also may play a role in syndromes of congenital malformations and embryonic losses in North America.
Two, 8-month-old Rambouillet half-sister ewes with signs of visual loss and decreased mentation were examined. Ewe No. 1 was necropsied at 10 months of age, and after being held under observation for a further 6 months, ewe No. 2 was necropsied at 16 months of age. At that time, the ewe was blind and severely depressed. Both ewes had deposition of an autofluorescent lipopigment, identified as ceroid-lipofuscin, in neurons of the brain, spinal cord, eye, and dorsal root ganglia. The disease process was progressive and characterized by deposition of lipopigment with neuronal degeneration and severe fibrillary astrogliosis. This progressive loss of neurons in the older ewe led to severe retinal degeneration. No pigment was observed in cells outside of the nervous system and eye. Controlled breeding studies have shown that this disease has an autosomal, recessive inheritance. The disease referred to here as juvenile-onset neuronal ceroid-lipofuscinosis of Rambouillet sheep is unlike the majority of the hereditary ceroid-lipofuscinoses that occur in human beings and animals in that only the nervous system is affected. Therefore, this disease could serve as an excellent model for the study of lipopigment deposition that affects the nervous system as a result of various disease states and during aging.
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Citrinin (a mycotoxin produced as a frequent contaminant of food and feed by numerous species of Aspergillus and Penicillium fungi) is embryo/fetotoxic and embryocidal in mice and rats. The present study was designed to examine whether the in vivo observed developmental toxicity of citrinin could be recapitulated using the Hydra attenuata (HA) bioassay and then be confirmed in rat whole embryo culture (WEC). Results from the HA assay indicated that the minimal affective concentrations of citrinin required to elicit a toxic response in the adult hydra (MACA) and in the regenerating hydra (MACD) were 30 mg/l and 20 mg/l, respectively. The Hydra developmental hazard index (A/D ratio) was equal to 1.5, classifying citrinin as a coaffective developmental toxin. In WEC, rat embryos were cultured in homologous (rat) serum containing citrinin at various concentrations ranging from 0.0 and 300 micrograms/ml for a period of 45 h. The results indicated a concentration-dependent reduction in yolk sac diameter, crown-rump length, somite number, protein and DNA contents. No embryonic dysmorphogenesis was observed in any treatment group. Histological examination revealed severe diffuse mesodermal and ectodermal necrosis in embryos treated with 250 micrograms/ml citrinin. At lower concentrations of citrinin, embryos were neither grossly nor histologically different from controls. Both the HA and WEC bioassays demonstrated that citrinin is not a primary developmental toxin. The use of HA and WEC bioassays in tandem may facilitate the rapid detection and ranking of the developmental hazards of food and feedborne mycotoxins.
Transcription of pathogenic equine infectious anemia virus (EIAV) in an acutely infected horse was examined by using the polymerase chain reaction and nucleotide sequencing. Four spliced transcripts were identified in liver tissue, in contrast to the multiplicity of alternatively spliced messages reported for in vitro-propagated human immunodeficiency virus, simian immunodeficiency virus, and, to a lesser extent, EIAV. Nucleotide sequence analysis demonstrated that three of these mRNAs encode known viral proteins: the envelope precursor, the product of the S2 open reading frame, and the regulatory proteins Tat and Rev. The fourth transcript encodes a novel Tat-TM fusion protein, Ttm. Ttm is a 27-kDa protein translated from the putative tat CTG initiation codon and containing the carboxy-terminal portion of TM immediately downstream from the membrane-spanning domain. p27ttm is expressed in EIAV-infected canine cells and was recognized by peptide antisera against both Tat and TM. Cells transfected with ttm cDNA also expressed p27ttm, which appeared to be localized to the endoplasmic reticulum or Golgi apparatus by indirect immunofluorescence. The carboxy terminus of lentiviral TM proteins has previously been shown to influence viral infectivity, growth kinetics, and cytopathology, suggesting that Ttm plays an important role in the EIAV life cycle.
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Rectal bleeding in a 7-month-old 13-kg sexually intact female mixed-breed dog was determined to be associated with vascular ectasia of the small intestine, descending colon, rectum, and anus. Microscopically, the telangiectasia was associated with lymphangiectasia and focal ulceration. Surgical intervention resulted in incomplete resection of the lesion and only temporary amelioration of clinical signs. The dog's age was compatible with a congenital origin for the defect, but an acquired cause could not be excluded.
A 1.5-year-old Suffolk ewe with acute onset of incoordination and blindness unresponsive to antibiotic treatment was examined at necropsy. The meninges were congested, opaque, and thick. Microscopically, focal areas of hypercellularity in the left cortical gray matter and the meninges were observed. The inflammatory response consisted of gliosis and perivascular cuffing (lymphocytes, plasma cells, and variable numbers of eosinophils). An amebic organism in 2 life stages was found in the cerebral parenchyma. Numerous large (15 to 35 microns in diameter) organisms, interpreted as trophozoites, were characterized by vacuolated cytoplasm and small nuclei with a prominent eosinophilic nucleolus (karyosome). The smaller (10 to 17 microns in diameter) encysted stage was surrounded by a capsule-like membrane, and contained a large central body sometimes surrounded by a clear halo. Immunofluorescence studies for amebic antigens were strongly positive for an ameba recently isolated in human beings and baboons (Leptomyxid sp).
The medical records of 11 horses with idiopathic muscular hypertrophy (MH) of the small intestine were reviewed to determine the clinical and pathological features of the disease. The median age of affected horses was 10.0 years (range 5-18 years). No breed or sex predisposition was apparent. Ten horses (91%) had chronic (23 days to 2.4 years) signs of mild, intermittent colic, and 1 horse had signs of severe colic of only 3 days' duration. Partial anorexia and chronic weight loss of variable duration (1-6 months) were prominent historical findings in 5 (45%) horses. Diagnostic tests, with the exception of exploratory caeliotomy, were ineffective for definitive diagnosis of intestinal MH as a cause of colic. In 2 horses, however, a thickened, rigid ileum was detected by palpation per rectum, and in 5 horses, multiple loops of distended small intestine were detected by palpation per rectum. Hypertrophy of both the circular and longitudinal layers of muscularis was determined as the cause of intestinal thickening in all horses. Muscular hypertrophy of the ileum was present in 9 (82%) horses. Two horses (18%) had MH of a section of jejunum only, and 4 (36%) horses had MH of the ileum in combination with MH of other sections of small intestine. Two (18%) horses had MH of the entire small intestine. In 9 (82%) horses, intestinal MH resulted in narrowing of the luminal diameter at the site of MH. Small diverticula were present on the mesenteric border of the hypertrophied ileum of 5 (45%) horses. Five linear (up to 150-cm) diverticula were present in the hypertrophied jejunum of 1 (9%) horse. Haemomelasma ilei was present on the antimesenteric serosal surface of affected intestine of 8 (73%) horses. Full-thickness rupture of the ileum with subsequent diffuse, septic peritonitis occurred in 3 (27%) horses.
Cecal rupture has been reported as a complication of tape-worm infestation or parturition in horses. Often it occurs with no apparent predisposing factors. Spontaneous rupture on the medial surface of the cecum occurred in 2 of 19 foals, 12 to 24 hours after gastric endoscopy. The sites of rupture were identical in both foals. Rupture occurred despite prior deworming, withholding of food and water before anesthesia, and care in induction of anesthesia and recovery. Surgeons should be aware of the potential of cecal rupture in horses anesthetized for elective surgery.
A Thoroughbred stallion developed priapism that was unresponsive to medical treatment and lavage of the corpus cavernosum penis with heparinized 0.9% NaCl solution. Three weeks after onset of priapism, the penis was firm and noncompliant, and penile pain sensation and ability to retract the penis were lost. Ultrasonography confirmed thrombosis of the corpus cavernosum penis. The stallion was euthanatized because of poor prognosis for return to breeding soundness. Necropsy revealed enlargement of numerous lymph nodes. The dorsal penile nerves were demyelinated distal to the crura of the penis. A diagnosis of generalized malignant melanoma was made; however, neither metastasis to the vertebral canal nor compression of spinal nerve roots as they exited the vertebral foramen was found. Priapism is a persistent erection without sexual arousal and is initially unassociated with penile paralysis, but if prolonged, leads to irreversible venous occlusion where collecting veins join the cavernous spaces. Damage to the dorsal penile nerves may explain the long-term penile paralysis and loss of sensation that accompanied priapism in this stallion. Priapism unassociated with the use of phenothiazine-derivative tranquilizers is uncommon in horses.
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An outbreak of congenital abnormalities occurred in sheep at San Angelo, Texas, between December 1986 and February 1987. Of 360 lambs born, 19.2% had arthrogryposis or other musculo-skeletal problems and hydranencephaly (AGH), and the total neonatal loss was 25.6%. In 1987, all ewes that were tested with AGH lambs had antibody to Cache Valley virus (CVV), whereas 62% of the ewes with normal lambs had CVV-specific antibody. Pre-colostral serum samples from AGH lambs had neutralizing antibody to CVV. An increase in prevalence of CVV-specific antibody, from 5% during the spring of 1986 to 63.4% during the winter of 1987, occurred during a time that included the gestation of these affected lambs, as well as a period of increased rainfall. The isolation of a CVV-related strain from a sentinel sheep in October 1987 confirmed the continued presence of this virus in the pasture where this outbreak occurred and provided a recent field strain for future studies.
The transmembrane (TM) envelope protein of lentiviruses, including equine infectious anemia virus (EIAV), is significantly larger than that of other retroviruses and may extend in the C-terminal direction 100 to 200 amino acids beyond the TM domain. This size difference suggests a lentivirus-specific function for the long C-terminal extension. We have investigated the synthesis and processing of the EIAV TM protein by immune precipitation and immunoblotting experiments, by using several envelope-specific peptide antisera. We show that the TM protein in EIAV particles is cleaved by proteolysis to an N-terminal glycosylated 32- to 35-kilodalton (kDa) segment and a C-terminal nonglycosylated 20-kDa segment. The 20-kDa fragment was isolated from virus fractionated by high-pressure liquid chromatography, and its N-terminal amino acid sequence was determined for 13 residues. Together with the known nucleotide sequence, this fixes the cleavage site at a His-Leu bond located 240 amino acids from the N terminus of the TM protein. Since the 32- to 35-kDa fragment and the 20-kDa fragment are not detectable in infected cells, we assume that cleavage occurs in the virus particle and that the viral protease may be responsible. We have also found that some cells producing a tissue-culture-adapted strain of EIAV synthesize a truncated envelope precursor polyprotein. The point of truncation differs slightly in the two cases we have observed but lies just downstream from the membrane-spanning domain, close to the cleavage point described above. In one case, virus producing the truncated envelope protein appeared to be much more infectious than virus producing the full-size protein, suggesting that host cell factors can select for virus on the basis of the C-terminal domain of the TM protein.
Serologic evidence indicated that an episode of congenital abnormalities in sheep was caused by Cache Valley virus (CVV), a bunyavirus indigenous to the United States. To determine the teratogenic potential of CVV in sheep, fetuses were infected in utero between 27 and 54 days of gestation with an isolate (CK-102) obtained in 1987 from a sentinel sheep in San Angelo, Texas. The dams of these fetuses were euthanatized between 28 and 75 days after inoculation, and the fetuses were examined for malformations. Twenty-eight of 34 fetuses had congenital abnormalities, including arthrogryposis, hydranencephaly, mummification, reabsorption, and oligohydroamnion. Virus was isolated from the allantoic fluid of 11 of 17 fetuses euthanatized at less than 70 days of gestation. The virus-positive fetuses, which were all negative for CVV-neutralizing antibody, had lesions ranging from none to severe arthrogryposis and hydranencephaly. Virus was not recovered from the allantoic fluid of fetuses after 76 days' gestation when CVV-specific antibody could be detected in 5 of 8 fetuses examined. The 2 fetuses infected on days 50 and 54 of gestation appeared normal and 1 had antibody to CVV.
At an abattoir, lesion specimens from 140 condemned sheep livers were collected for bacteriologic culture and for pathologic examination. Grossly, 23 lesions were abscesses; from 9 of which, Fusobacterium necrophorum biovar A (3 in pure culture and 6 in mixed culture) was isolated and from 14 of which, biovar B (6 in pure culture and 8 in mixed culture) was isolated. Escherichia coli was the predominant facultative anaerobic bacterium and Clostridium perfringens was the predominant obligate anaerobic bacterium isolated from the 14 lesions with mixed bacterial infection. Histologically, these lesions had a core of coagulation necrosis, encircled by a zone of necrotic phagocytic cells and bacteria with cellular characteristics of F necrophorum biovars A or B, and a connective tissue capsule. Of the 117 lesions without F necrophorum, 49 were culture-positive (for other organisms) and 69 were culture-negative. These 117 lesions were fibrous and were smaller than the 23 abscesses. A variety of gram-positive and gram-negative facultative anaerobic and obligate anaerobic bacteria was isolated from the culture-positive lesions, but always in low numbers. Eleven culture-negative and 18 culture-positive lesions were examined and had histologic characteristics of parasite-induced granulomas, with numerous eosinophils and epithelioid giant cells. Results of the study indicated that the histologic appearance of ovine hepatic lesions with F necrophorum was similar to bovine liver abscesses caused by F necrophorum, but unlike bovine liver abscesses, F necrophorum biovar B was isolated more frequently than was biovar A and often in pure culture. Most of the lesions in the condemned livers were parasite-induced granulomas.