Current vaccines for the avian respiratory disease infectious laryngotrachetitis consist of naturally attenuated strains of the causative agent--the herpesvirus infectious laryngotracheitis virus (ILTV). Due to the dissemination of these viruses from vaccinated chickens as well as their possible reversion to more pathogenic forms, the use of genetically engineered viral vaccines lacking virulence factors while retaining antigenicity is being considered. Since the thymidine kinase (TK) activity of herpesviruses has been associated with virulence, inactivation of the encoding gene in the ILTV genome should attenuate the virus. Moreover, by analogy to other TK- herpesviruses, the ability of such ILTV mutants to induce a protective response in chickens should not be compromised. Therefore, the deliberate genetic alteration of ILTV was attempted. In order to prevent reversion and also to enable identification of the modified virus, a "marker" transcriptional unit (Escherichia coli lacZ gene fused to a SV-40 3'-polyadenylation signal sequence and regulated by the pseudorabies virus gX gene promoter) was inserted via homologous recombination at one of two loci within the ILTV TK gene. Recombinant viruses were identified and plaque-purified on the basis of their ability to produce beta-galactosidase. Retention of the foreign DNA at the predicted sites in the genomes of the recombinant ILTV was verified by Southern hybridization. Since their replication was unaffected by the thymine analog 1-(2-fluoro-2-deoxy-beta-D-arabinofuranosyl)-5-methyluracil, the recombinants appeared to have a TK- phenotype. Despite this apparent deficiency, prior inoculation of either recombinant virus into chickens afforded the birds protection against a lethal challenge of virulent ILTV. Moreover, the degree of respiratory distress in the chickens vaccinated with the recombinants was relatively mild compared to the severe reaction in birds receiving the parental virus. Thus, ILTV can be genetically attenuated without an accompanying loss of immunogenicity.
Abstract.A 2-year-old sow aborted her entire near-term litter of 1 I . Gross and histologic examination of a fetus suggested a tuberculous infection, and a yellow-pigmented Mycobacterium avium serotype 1 was subsequently isolated from the fetal tissue. Efforts to rebreed the sow were unsuccessful. She was anergic to skin tests with purified protein derivative of M. avium on two occasions but had M. avium specific in vitro lymphocyte immunostimulation.Gross granulomatous lesions were found in the liver, kidneys, and endometrium when the sow was necropsied 5 months after the abortion. Histologic examination showed diffuse and focal non-encapsulated granulomas in lymph nodes, tonsils, kidney, liver, spleen, lung, and uterine and vaginal walls. There were a few encapsulated calcified foci in the endometrium. The centers of some granulomas in the tonsils, liver. kidneys, and some lymph nodes were caseated. The yellow-pigmented M . avium was isolated from the reproductive organs and from 1 I of 12 other tissues cultured.Localized tuberculous lymphadenitis caused by Mycobacterium avium is a common infection in swine in the United States. A search of the literature written since 1930, however, revealed reports of only five cases of M. avium-associated swine abortion, all from Europe [l, 2, 4, 7, 121. Case ReportIn March 1977, an aborted near-term porcine fetus was submitted from northwest Iowa to the South Dakota Animal Disease Research and Diagnostic Laboratory. All the pigs in the litter of I 1 were dead at birth. The abortion occurred in the sow's third pregnancy, which was uneventful until the end of gestation. Necropsy of the fetus showed slight postmortem autolysis and numerous, small (less than I millimeter diameter), white foci in the liver. No other lesions were seen. The placenta was not available for examination. Results FetusHistologic examination of liver sections stained with hematoxylin and eosin (HE) showed randomly scattered, non-encapsulated, sharply circumscribed, non-mineralized granulomas ranging in size from 0.2 to I millimeter. Lymphocytes and granulocytes surrounded the granulomas and the centers of the lesions contained large 3 10
Key Clinical MessageThe diagnosis of cutaneous metastasis of renal cell carcinoma is challenging in a young person in absence of a prior history of cancer. In such situation, fine needle aspiration alone as a minimally invasive procedure can provide rapid, accurate and cost effective diagnosis, even in case of unknown primary.
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