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Meeting report: human fetal tissue transplantation research panel.

On September 14 through 16, 1988, a meeting on the use of human fetal tissue in transplantation was held at the National Institutes of Health, Bethesda Maryland, USA. The meeting sponsored by NIH for the Human Fetal Tissue Transplantation Research Panel, a consultant group to the Advisory Committee to the Director. The consultant group was convened to deal with the scientific, judicial and moral questions associated with research involving transplantation of human fetal tissue obtained after induced abortions. The first day of the meeting was devoted to presentations addressing scientific issues. Included among the speakers was Dr. Lars Olson, Professor of Neurobiology, Karolinska Institute, Stockholm, who described the use of transplanted human fetal tissue in the treatment of patients with Parkinson's disease and Dr. Eugene Redmond, Professor of Psychiatry, Yale University School of Medicine, who showed results of work with transplantation of tissue to correct induced Parkinson-like disease in monkeys. Other speakers addressed the present, past or potential use of fetal tissue in the treatment of diabetes, immune disorders, and other diseases, as well as the use of fetal cells in the production of biologicals. At the conclusion of the meeting the panel did not recommend that research be halted on fetal tissue within the context discussed, although the recommendation of the committee is not binding, and an additional assembly of the panel will probably occur before the final recommendation to an NIH advisory committee is made in November. Other meetings on this subject include a meeting on the use of fetal tissue sponsored by the American Association of Tissue Banks, March 6-7, 1989, in Washington D. C. (Crystal City) and a meeting June 10, 1989, the day before the annual meeting of the Tissue Culture Association, USA, in Orlando, Florida, on fetal cells and ownership of cultured cells and products derived from clinical specimens. Following are statements to the Human Fetal Tissue Transplantation Research Panel presented September 14, 1988, by Dr. David Barnes, Associate Professor of Biochemistry and Biophysics in the Environmental Health Sciences Center at Oregon State University, USA, who was asked to address for the panel recent advances in cell culture related to fetal tissue, and Dr. Robert E. Stevenson, Director of the American Type Culture Collection, President of the Tissue Culture Association, USA, and Chairman of the Committee on Cells and Tumors of the American Association of Tissue Banks.

Cells, Cultured↗

A common-source outbreak of callitrichid hepatitis in captive tamarins and marmosets.

Callitrichid hepatitis (CH) is a highly fatal, emerging arenavirus disease of captive South American marmosets and tamarins (Callitrichidae), including the endangered golden lion tamarin. A common-source outbreak of CH in golden lion tamarins and pygmy marmosets at a US zoo resulted from a single feeding of the primates with newborn mice in apparently infected with lymphocytic choriomeningitis virus (LCMV). Isolates from livers of mice and primates were related to isolates from previous CH outbreaks and to laboratory strains of LCMV by serology and nucleic acid hybridization, and 2 surviving animals developed antibody to other LCMVCH isolates and to laboratory strains of LCMV. Thus, LCMV, an arenavirus prevalent in wild mice in the US, can cause sporadic fatal hepatic disease in primates. Exposure of humans to wild or laboratory mice or to marmosets and tamarins that are infected with wild-type strains of LCMV poses the danger of serious disease.

Animals↗

Primate malaria.

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Animal Diseases↗

Localization of persistent Enterocytozoon bieneusi infection in normal rhesus macaques (Macaca mulatta) to the hepatobiliary tree.

Enterocytozoon bieneusi is the most common microsporidian parasite recognized in human patients with AIDS. Recently, we identified a virtually identical organism causing a spontaneous infection associated with hepatobiliary and intestinal disease in simian immunodeficiency virus (SIV)-infected macaques. To examine the natural history of the infection, we examined captive rhesus macaques for E. bieneusi by PCR, in situ hybridization, and cytochemical techniques. PCR performed on fecal DNA detected enterocytozoon infection in 22 (16.7%) of 131 normal rhesus macaques (Macaca mulatta), compared to 18 (33.8%) of 53 rhesus macaques experimentally inoculated with SIV. In normal rhesus macaques, persistence of infection was demonstrated for up to 262 days and was usually not associated with clinical signs. In six of seven normal rhesus animals, E. bieneusi was detected by PCR in bile obtained through percutaneous cholecystocentesis but not by in situ hybridization performed on endoscopic biopsies of duodenum and proximal jejunum.

Animals↗

Biohazards and simian viruses.

Nonhuman primates are extensively used in laboratories as experimental animals. It is necessary, however, to realize that their employment may be dangerous to man and other species of primates, if recognition of their flora and fauna, especially viral, is not considered and if appropriate controls are not followed. Several outbreaks have occurred, resulting in high mortality and morbidity of man and simian. A number of recommendations are provided which, if followed, will minimize the waste of time, money, and life.

Animals↗

Adrenal lesions in the baboon (Papio spp).

A histological survey was conducted on 604 pairs of adrenal glands from yellow (Papio cynocephalus) and olive (Papio anubis) baboons used in drug safety evaluation studies. Spontaneous lesions were found in 372 glands--34 of which had more than one change. Cortical lesions consisted of accessory nodules (190), nodular hyperplasia (7), hepatoadrenal adhesion (18) and partial fusion (1), focal mineralization (20), ectopic bone marrow (6), and focal fatty change (60). Medullary lesions were confined to focal lymphocytic (66) and plasma cell (1) infiltrates.

Adrenal Cortex↗

West Nile virus vaccines.

West Nile virus (WNV) is a mosquito-borne flavivirus that is emerging as a global pathogen. In the last decade, virulent strains of the virus have been associated with significant outbreaks of human and animal disease in Europe, the Middle East and North America. Efforts to develop human and veterinary vaccines have taken both traditional and novel approaches. A formalin-inactivated whole virus vaccine has been approved for use in horses. DNA vaccines coding for the structural WNV proteins have also been assessed for veterinary use and have been found to be protective in mice, horses and birds. Live attenuated yellow fever WNV chimeric vaccines have also been successful in animals and are currently undergoing human trials. Additional studies have shown that immunisation with a relatively benign Australian variant of WNV, the Kunjin virus, also provides protective immunity against the virulent North American strain. Levels of efficacy and safety, as well as logistical, economic and environmental issues, must all be carefully considered before vaccine candidates are approved and selected for large-scale manufacture and distribution.

Animals↗

Outbreak of Orthoreovirus-induced meningoencephalomyelitis in baboons.

BACKGROUND AND PURPOSE: Spontaneous viral encephalitis is rare in the baboon; yet, during a 13-month period (1993-1994), eight juvenile baboons (Papio cynocephalus spp.) developed acute, progressive nonsuppurative meningoencephalomyelitis caused by an unknown agent. Clinical signs of disease included disorientation and truncal ataxia that rapidly progressed to hemiparesis or paraparesis. Clinicopathologic findings were not remarkable and appreciable gross lesions were not seen at necropsy. Microscopic examination revealed CNS lesions that were characterized by lymphoplasmacytic perivascular cuffing, microglial nodules, demyelination, axonal degeneration, vacuolization, and hemorrhage. Subsequently, a novel syncytium-inducing mammalian orthoreovirus was isolated from the brain tissue of five baboons with clinical signs of infection. METHODS: To confirm the etiologic role of the orthoreovirus, two juvenile baboons were inoculated with the virus, then were monitored for 6 weeks. RESULTS: Lesions similar to those seen in spontaneous cases were found in the CNS, and orthoreovirus was isolated from the brain of both animals. CONCLUSION: Analysis of the outbreak indicated juvenile baboons were most susceptible to disease and the virus had a possible incubation time of 46 to 66 days, but did not indicate a source of the virus or mode of transmission.

Animals↗

Enrofloxacin treatment of long-tailed macaques with acute bacillary dysentery due to multiresistant Shigella flexneri IV.

Thirty-four cases of acute bacillary dysentery occurred within 90 days among macaques housed at the California Regional Primate Research Center. Cases were identified by depression, diarrhea with blood and leukocytic exudate, and/or leukocytosis with a left shift. Antimicrobial susceptibility testing of enteric isolates and plasmid profile analyses established an etiologic diagnosis of multiple antibiotic resistant Shigella flexneri IV infection. When standard therapies were invalidated by high frequencies of resistance among the isolates, therapy with enrofloxacin, a fluoroquinolone antimicrobial, was initiated to interrupt the epidemic. Serum concentrations of enrofloxacin and its primary metabolite ciprofloxacin were measured in selected cases. A serum concentration-time data analysis was performed to evaluate the oral enrofloxacin dose and dosing interval for nonfasted macaques. Once daily administration of 5 mg/kg enrofloxacin by gastric intubation produced 24-hour serum concentrations above the MICs for the Shigella isolates from this outbreak.

Animals↗