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Biomedical subjects

L B Cummins

Publications and source records attributed to L B Cummins.

13 recordsLinked to original sources
PubMed1992

Virus safety of human immunoglobulins: efficient inactivation of hepatitis C and other human pathogenic viruses by the manufacturing procedure.

Human immunoglobulins are plasma derivatives with a low risk of transmitting viral infections. To the present, no proven case of human immunoglobulins transmitting human immunodeficiency viruses has been reported. However, there have been a few reports on the transmission of hepatitis C virus by these plasma proteins. To improve further the safety of both 5s iv human immunoglobulins and 7s im immunoglobulins, we introduced a 10-hour heat treatment of the aqueous solutions at 60 degrees C (i.e., pasteurization) into the manufacturing procedure. This treatment was not added to the manufacturing procedure of 7s iv immunoglobulin that already contained the S-sulfonation as a virus inactivating method. We now report on experimental data that show that the whole manufacturing procedures of the above immunoglobulins inactivate efficiently hepatitis C virus and that the specific virus inactivation methods alone, namely, pasteurization or S-sulfonation, also inactivate completely viruses of the flavivirus family, to which the hepatitis C virus belongs. The inactivation of the Flaviviridae bovine viral diarrhea virus, tick-borne encephalitis virus, and yellow fever virus by pasteurization or S-sulfonation was at least 10(5). The clearance of HCV achieved by the entire manufacturing process of each of these immunoglobulins was also at least 10(5). The experiments therefore show that pasteurization or S-sulfonation provides a high margin of safety to human immunoglobulins regarding the transmission of hepatitis C virus.

Animals↗
PubMed1992

Primate responses to a vaccinia-rabies glycoprotein recombinant virus vaccine.

Over the past decade, a vaccinia-rabies glycoprotein (V-RG) recombinant vaccine virus has been developed for the potential control of wildlife rabies through oral immunization via baits. Prior to widespread field applications in varying ecological settings, extensive laboratory safety testing is necessary in a number of target and non-target species to quantify real or perceived risks and to monitor potential adverse health effects. Moreover, in order to mitigate concerns over inadvertent human exposure to a vaccine targeted for environmental release and intended for wildlife consumption, it was necessary to document the safety of the vaccine in primates following direct consumption orally and indirectly through transdermal administration. In the ensuing study, no significant differences were observed in the comparative pathogenicity of vaccinia and vaccinia-recombinant viruses by intradermal scarification of squirrel monkeys. In addition, eight of eleven chimpanzees administered the V-RG vaccine (10(9) plaque forming units/ml) per os developed rabies virus-neutralizing antibodies. Sentinel chimpanzee controls and human animal handlers did not show evidence of virus exposure. No adverse health effects were noted in any experimental animals as a result of V-RG vaccine administration.

Administration, Cutaneous↗
PubMed1992

Follow-up of hepatitis C virus infection in chimpanzees: determination of viraemia and specific humoral immune response.

Chimpanzees were inoculated intravenously with the H strain of hepatitis C virus (HCV), and analysed for viraemia using the polymerase chain reaction and for a humoral immune response using first and second generation anti-HCV ELISAs and an immunoblot assay (4-RIBA). In all seven chimpanzees studied, viraemia occurred several weeks before a significant increase in serum alanine transferase (ALT) activity, whereas the first circulating anti-HCV antibodies became detectable at the time of significant increase in ALT levels, provided the second generation ELISA or 4-RIBA was used. On the basis of the duration of viraemia the chimpanzees studied could be assigned to two different groups: those in which viraemia disappeared in conjunction with or shortly after seroconversion, and those remaining viraemic for many weeks after the appearance of antibodies. The clearance of HCV from the circulation did not correlate with the antibody pattern determined using 4-RIBA, i.e. the HCV-specific assays currently available do not enable us to predict whether an infected chimpanzee will develop persistent viraemia. Only two of the seven chimpanzees analysed developed anti-core protein (c-22) antibodies, which appeared at the same time as the first ALT peak, whereas all animals developed antibodies to the non-structural protein, c-33, and these antibodies persisted.

Alanine Transaminase↗
PubMed1980

Retinal tumor induced in the baboon by human adenovirus 12.

Three of 21 newborn baboons injected intraocularly with human adenovirus type 12 developed an intravitreal mass 12 to 36 months later. Two of the masses were indistinguishable from human retinoblastoma, a retinal tumor that afflicts children. To our knowledge this is the first time a retinoblastoma-like tumor has been induced experimentally by adenovirus type 12 in a nonhuman primate.

Adenoviruses, Human↗
PubMed1980

Production and standardization of the chimpanzee for research.

Laboratory born and reared chimpanzees are essential for quality biomedical research and to ensure that adequate numbers of the animal model will be available to the research community without the depletion of wild populations. Production of progeny in sufficient numbers for research efforts is an expensive and time consuming task, encompassing cost efficiency factors of harem breeding, high birth rates, low maternal-infant interaction times, efficient nursery systems, and appropriate husbandry. Standardization methods provide for identical diets, handling procedures, and laboratory evaluation of all animals. Applied psychological techniques utilizing non-isolate rearing, juvenile-peer socialization, and adolescent-adult adaptation methods complete the generation cycle of the laboratory chimpanzee. Continuous microbiological and clinical chemistry monitoring provides baseline data, as well as revealing any alterations from the normal.

Animals↗
PubMed1980

Age estimation in baboons (Papio cynocephalus) using dental characteristics.

Criteria for estimating the age of baboons using dental characteristics have been developed and tested. These criteria used eruption, wear, and color of the premolars and molars to characterize the ages of baboons in the range of 4--11 years of age. Ages greater than 11 were grouped into a single category. Using the criteria, three judges estimated independently the ages of 49 baboons, of known and unknown ages and of both sexes, with good agreement and precision. The rank order of the estimated ages was similar to the rank order of true ages for colony born animals.

Age Determination by Teeth↗
PubMed1979

Acute demyelinating disease in a chimpanzee three years after inoculation of brain cells from a patient with MS.

Brain cells from a patient with classic multiple sclerosis were inoculated intracerebrally into the frontal lobe of a newborn chimpanzee. The animal developed acute quadriplegia three years, two months later and was killed four days after the onset of symptoms. Central nervous system lesions were primarily localized in the spinal cord at root entry zones; these were characterized by demyelination and regeneration of myelin by Schwann cells.

Animals↗
PubMed1979

Experimental smallpox in chimpanzees.

In an attempt to prepare highly specific antiserum to variola virus, a chimpanzee was inoculated with a virulent human strain of this virus. Three uninoculated chimpanzees were housed in the same room; two of these developed clinical disease with seroconversion, while the third developed no evidence of infection and no antibody. The three animals that became ill also developed antibody to vaccinia and monkeypox viruses. Human contacts during the study and following a break in containment showed no evidence of infection as determined by serological tests and lack of clinical disease.

Animals↗
PubMed1978

Tuberculosis in nonhuman primates as a threat to humans.

Nonhuman primates are used in many laboratories either as modest systems for studies of disease processes or as a source of these tissues for cell culture and vaccine production. Much too frequently, the health of these donor animals is taken for granted, although T.B. testing is one of the few procedures routinely performed. In spite of this screening, outbreaks of T.B. among various simian species are still sufficiently commonplace to make maintenance and use of these animals a continuing source of danger to the human population. Development of rampant fatal tuberculosis in established colony animals (chimpanzees, baboons, others) previously tested as tuberculin negative suggests the need for continuing monitoring as well as extreme caution in handling of these animals, especially at necropsy. Further, use of complete Freund's adjuvant or isoniazid either experimentally or therapeutically will obscure the interpretation of the skin test. Present lack of concern by many investigators for biohazards associated with use of nonhuman primates makes the problem of laboratory-associated infections a major source of concern. Positive conversion of animal handlers has occurred a sufficient number of times to make development of tuberculosis in a colony of animals a matter of more than academic interest.

Animals↗
PubMedDate not supplied

Infection and disease induced in chimpanzees with 6/94, a parainfluenza type 1 virus isolated from human multiple sclerosis brain.

A parainfluenza type 1 virus (6/94) recovered from brain cell cultures of two patients with multiple sclerosis (MS) was inoculated into newborn chimpanzees by the intranasal (IN) or intracerebral (IC) routes. Four of the five animals receiving the virus IN developed clinical signs ranging from mild fever, with or without rhinorrhea, to severe respiratory disease. Two of the chimpanzees died as a result of pneumonia. Virus could be recovered from respiratory tracts for as long as 9 days after exposure and was followed by development of specific neutralizing antibody to the 6/94 virus but not to the HA2 strain of parainfluenza type 1. Brain examination showed astrocytosis, especially of posterior fossa structures, activation of microgliacytes and, in one animal, round cell infiltration of leptomeninges. Of thse three animals receiving virus IC, two developed recurrent seizures beginning 14 months after inoculation. One of these was sacrificed at 23 months of age after progressive neurologic disease, with electroencephalographic abnormalities, developed. The third animal died at 3 months of age of intercurrent pneumonia. No virus was recovered from these animals, although all showed antibody conversion to 6/94 but not HA2 virus. A variety of pathologic lesions were seen in the brains of both animals coming to necropsy particularly in the sacrificed chimpanzee. These included subacute encephalitis, extensive cortical and subcortical degeneration, vascular sclerosis, white matter gliosis and axonal dystrophy.

Animals↗