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Biomedical subjects

W H Stone

Publications and source records attributed to W H Stone.

At least 19 recordsLinked to original sources
PubMed1992

Effects of chronic blood loss in a marsupial (Monodelphis domestica).

Monodelphis domestica, the gray short-tailed opossum, is used increasingly as an animal model in studies that require repeated blood sampling. Consequently, it is important to establish safe bleeding regimens. We investigated the effects of repeated blood loss on various hematologic values and on different organs in this species. Approximately 2 ml of blood were taken weekly from 20 animals for 13 weeks. The animals were then necropsied; members of an age- and sex-matched control group were bled (2 ml) once and necropsied immediately to obtain baseline data. Ultimately, each animal in the experimental group lost approximately three times its total blood volume. After the first bleeding in the chronically bled group, the red blood cell counts, hemoglobin, and hematocrit values decreased significantly but remained constant thereafter. In another experimental group bled only once, the hematologic values rose to higher than baseline levels after a rest of 2 weeks. Thereafter the values slowly returned to baseline levels. A notable increase in Howell-Jolly bodies occurred in the chronically bled group. Histologically, there was marked erythroid hyperplasia in the bone marrow and extramedullary hematopoiesis in the spleen, but none in the liver. Because there were no obvious detrimental physiologic effects, we conclude that M. domestica is markedly tolerant of chronic blood loss.

Animals↗
PubMed1991

Cellular immune response of a marsupial, Monodelphis domestica.

Marsupials are interesting subjects for studies of comparative and developmental immunology because they separated from eutherian mammals over 100 million years ago and because the newborns are still in a fetal state. We studied cellular immunity in a fully pedigreed colony of the marsupial, M. domestica (commonly called the gray short-tailed opossum). Peripheral blood lymphocytes were separated on nylon wool columns into adherent cells bearing surface immunoglobulin (B cells) and nonadherent cells (T cells) recovered in the ratio of 1:3. Peripheral blood lymphocytes responded by proliferation to Con A and other mitogens. Nonadherent cells were responsive to Con A, but adherent cells were not. Peripheral blood lymphocytes were stimulated weakly or not at all by allogeneic or xenogeneic (mouse) cells in mixed lymphocyte culture. Despite the weak MLC response, which was not due to genetic homogeneity, allogeneic and xenogeneic tail skin grafts were rejected promptly. These data suggest that the cellular immune response of M. domestica is similar to that of eutherian mammals with the notable exception of weak MLC responses.

Animals↗
PubMed1991

Ontogeny of the thymus gland of a marsupial (Monodelphis domestica).

The gray short-tailed opossum (Monodelphis domestica) has recently been established as a laboratory animal; consequently, its utility as an animal model is enhanced as more of its basic biologic characteristics become defined. To this end, we studied the ontogeny of the thymus gland in M. domestica ranging in age from the day of birth to over three years. In contrast to most Australian marsupials, M. domestica possesses only a thoracic thymus. The thymus is large in neonates and remains large until young adulthood (six months of age). It has a well-defined cortex, medulla and Hassall's corpuscles. At about six months of age, the thymuses of most animals begin to atrophy, the cortex and medulla being replaced by fat. By 28 months of age, about 50% of animals have thymuses that are completely atrophied. Thus, the ontogeny of the thymus of M. domestica appears to be similar to that of eutherian mammals.

Adipose Tissue↗
PubMed1989

Immune response of a marsupial (Monodelphis domestica) to sheep red blood cells.

A study of the humoral immune response of a marsupial, Monodelphis domestica, was performed using sheep red blood cells as the immunogen and a hemolytic titration as the assay. The primary response to a single intramuscular injection was similar to that observed in other mammalian species, except that the titers remained high for as long as 37 weeks after the initial injection. The secondary response was weaker than the primary response and diminished as early as 15 weeks after the initial injection (and only 11 weeks after the single booster injection). The hyperimmune response was similar to the secondary response, except that the titers remained consistent for up to 10 weeks and then fell to very low levels at 35 weeks. The data support the view that the primary humoral response of this marsupial is similar to that of eutherian mammals. However, the secondary and hyperimmune responses appear to be very weak, if present at all.

Animals↗
PubMed1987

Genetic research with nonhuman primates: serving the needs of mankind. Symposium summary and future prospects.

The wide array of papers delivered at this symposium, ranging from population genetics to molecular genetics, is convincing evidence that genetic research with nonhuman primates is in full bloom. In fact, progress has been quite remarkable considering that a significant number of pedigreed colonies of nonhuman primates have been available for less than 25 years, which is hardly enough time to raise 3 generations of chimpanzees, 5 generations of baboons or 6 generations of rhesus monkeys. Were it not for these pedigreed colonies, we would not have been privileged to have this assemblage of papers on behavior, social structure, predisposition to disease and management of breeding colonies. It is indeed exciting that preliminary evidence has been obtained for major genes that play a role in susceptibility to dyslipoproteinemias in baboons, and that monoclonal antibodies and DNA markers are helping us to understand cholesterol metabolism. And thanks to computers, we can now rank animals in a colony in terms of their useful genotypes as well as their productivity. One can not help but be impressed with the commonality of humans and nonhuman primates at the structural and functional levels. For example, the major histocompatibility systems and the maternal-fetal relationships are very similar. We heard that this similarity is even more striking at the chromosomal, biochemical and DNA levels. A provocative question yet to be answered is, "what accounts for the obvious differences between humans and nonhuman primates in view of these incredible similarities?" In light of these advances, this symposium was at the cutting edge of primate genetics and the papers published in this issue of Genetica are certain to be hallmarks in the literature.

Animals↗
PubMed1987

Further characterization of the G blood group system of rhesus monkeys.

We describe a new antiserum that has the unique ability to distinguish homozygous from heterozygous genotypes in the G blood group system of rhesus monkeys. With this new typing serum (reagent), all 10 possible genotypes in this system can be distinguished and the utility of blood typing for genetic studies has been greatly increased.

Animals↗
PubMed1987

Genetic significance of some common primate models in biomedical research.

Nonhuman primates are excellent animal models for human diseases because of their close relationship to humans. Indeed, comparisons of the chromosomes and DNA homologies between primates and humans testify to the commonality of the genetic material between these phylogenetically related species. Not surprisingly, this close relationship at the genotypic level extends to the phenotypic level. Thus, the patho-physiological responses of humans and nonhuman primates to internal and external insults are remarkably similar. Two types of human diseases for which nonhuman primates are paramount animal models are discussed. One type includes diseases with defined, single agent etiologies and to which all members of the species are genetically susceptible. Examples of these are leprosy, AIDS, hepatitis and Parkinson's disease. A second type represents diseases that have a substantial genetic component, but are multifactorial and are greatly influenced by the environment. Examples of these are diabetes, lymphoma, atherosclerosis, alcoholic cirrhosis and anxiety disorders. Nonhuman primates are also ideally suited to the role of animal models in the new area of human gene therapy. In the future, biomedical research will focus increasingly on genetic manipulations such as the transfer of genes from one individual to another to correct genetic diseases, particularly those diseases caused by single recessive gene defects. Before gene transfers are attempted in humans, they should be done in nonhuman primates. In a real sense, nonhuman primates, as animal models, represent the "step to man."

Animals↗
PubMed1986

A microagglutination test for blood typing rhesus monkeys, Macaca mulatta.

We have developed a microagglutination test for typing rhesus monkey erythrocytes that is sensitive, accurate and easy to perform. The technique requires only microliter quantities of antiserum and cells, and agglutination is easily detected using an inverted microscope. An advantage of this technique is that the typing plates can be stored at -70 degrees C without loss of activity. The results of typing over 400 rhesus blood samples with this technique were 95% concordant with results using the standard microtitre agglutination technique. Preliminary results indicate that this test is also adaptable to typing human blood.

Agglutination Tests↗
PubMed1986

Passively acquired immunity in the newborn of a marsupial (Monodelphis domestica).

A colony of fully pedigreed Monodelphis domestica has been used to investigate the maternal-fetal relationship in this unique marsupial species. To determine how immunity is transferred from mothers to young in M. domestica, we hyperimmunized females with sheep red blood cells (SRBC) before and during gestation. Offspring from these females were collected at various times after birth, and saline extracts of the neonates were assayed for hemolysins against SRBC. Antibodies were present in extracts of newborn that had been allowed to suckle their mothers; none were detected in extracts of infants that were not allowed to suckle. Antibodies were present in the milk of immunized mothers, but were not detected in the milk of nonimmunized mothers. The titer of antibodies in the extracts of newborns generally increased proportionately to the time that the newborn had been allowed to suckle. We conclude that the transfer of passive immunity from mothers of M. domestica to their offspring occurs primarily via the milk.

Animals↗
PubMed1984

Mononuclear phagocyte receptors in rhesus monkeys (Macaca mulatta) and their role in hemolytic disease of the newborn.

Hemolytic disease of the newborn does not develop in rhesus monkeys because placentally-transferred maternal antibodies do not induce immune clearance of the newborn's erythrocytes. In an in vitro RBC adherence assay, rhesus peripheral blood monocytes did not bind newborn's RBC which had been coated in utero or in vitro with maternal antibodies. Nevertheless, rhesus phagocytes possess receptors that are specific for the Fc portion of IgC and for the C3b. Using purified human IgG subclasses as inhibitors of RBC adherence, rhesus Fc receptors preferentially bind IgG1 and IgG3. Thus, it may be that maternal antibodies are non-opsonic because they belong to IgG subclasses that do not bind effectively to rhesus Fc receptors. Also, RBC adherence appears to be controlled by the level of antibody coating which in turn is determined by avidity of the antibodies and by the number of RBC membrane determinants. The failure of maternal antibodies to opsonize the newborn's RBC and thus cause hemolytic disease is very likely due to the low avidity of antibodies and to the weak expression of blood group determinants on the membranes of these RBC.

Animals↗
PubMed1982

The absence of hemolytic disease in the newborn rhesus monkey (Macaca mulatta).

Hemolytic disease of the newborn has not been observed in rhesus monkeys even though the newborn's erythrocytes may be coated with maternal antibodies. Using a 51chromium-erythrocyte survival assay, we found that maternal antibodies do not mediate immune elimination of newborn's red blood cells. However, certain allogeneic or xenogeneic antibodies mediate clearance via sequestration by the reticuloendothelial system, or by intravascular hemolysis, or by a combination of these. The class of antibody plays a major role in elimination since red cells coated with IgG but not with IgM were rapidly cleared. In addition, the quantity of antibody controls the rate and extent of clearance. A comparison of rhesus alloantisera suggests that coating of multiple antigenic sites is necessary for clearance. Passive immunization with selected high-titered anti-erythrocyte alloantisera can induce some hematologic signs of erythrocyte destruction in newborn monkeys.

Animals↗
PubMed1982

Sources of bovine lymphocyte antigen (BoLA) typing reagents.

Sera from about 1000 cows were tested for cytotoxicity against a panel of up to 100 lymphocyte samples. Cytotoxic antibodies presumably resulting from transplacental immunization of the cow by her calf were found in about 45% of these sera. The antibody titers of sera from parous cows rarely exceed 4(2), some persisted for over one year, but decreased notably at calving. Thirty-five immune sera were also produced by alloimmunization with lymphocytes. They usually reached peak titers of up to 4(4) at 2 or 3 weeks after the initial immunization. Subsequent immunizations produced sera with very high titers but they were much more polyspecific. High-titered antibodies were also produced by skin graft recipients. Useful cytotoxic antibodies were found in 19 of 111 colostrum whey samples. Studies on 13 dam-calf pairs showed that the newborn calf may acquire cytotoxic antibodies from its mother's colostrum, but the only cytotoxic antibodies detectable in this calf's serum are those not directed against its own lymphocyte antigens. It is concluded that efficient lymphocyte typing requires antibodies from a variety of sources.

Animals↗
PubMed1982

A simple technique using skin implants to produce histocompatability (BoLA) typing sera.

We describe a technique to produce high-titered bovine lymphocytotoxic antisera using skin implants. The main advantage of this technique is that the skin does not need to be processed prior to implantation and no surgical skill is required. In addition, the skin can be stored for up to 2 weeks and can be shipped to other laboratories without special handling and without loss of immunogenicity.

Animals↗
PubMed1981

The bovine major histocompatibility complex (BoLa): close linkage of the genes controlling serologically defined antigens and mixed lymphocyte reactivity.

Detection of linkage between genetic loci in cattle has been hampered by the lack of large full -sib families. A unique source of full-sib families is now available from embryo transplantation. Lymphocytes from six full-sib families, ranging in size from three to seven siblings, were tested for serologically defined BoLA antigens (BoLA-A). In addition, mixed lymphocyte reactivity (MLR) was tested between all paired combinations of cells within each family to distinguish BoLA-D specificities. Serologically identical siblings within each family were reciprocally nonreactive in MLR, and vice versa; thus, no recombinants were detected between the BoLA-A and the BoLA-D loci. Classical genetic linkage analysis revealed that these loci are significantly closer than 11.9 centimorgans.

Animals↗