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Biomedical subjects

K T Schultz

Publications and source records attributed to K T Schultz.

At least 37 records · Page 2Linked to original sources

Antiidiotypic antibody mimicry of a bluetongue virus neutralizing antigen.

Syngeneic antiidiotypic (Anti-Id) mAb were produced to the Bluetongue virus (BTV) serotype 17 neutralizing mAb. Three anti-Id mAb had the characteristics of an internal image of the Id as demonstrated by 1) the internal image anti-Id mAb were capable of mimicking BTV by blocking the neutralizing activity of the idiotypic neutralizing mAb and 2) the anti-Id mAb bound specifically to the surface of BTV susceptible cells in indirect binding experiments as determined by immunocytochemistry and flow cytometric analysis. The potential application of these internal image anti-Id mAb in this arbovirus system is discussed.

Animals↗

A novel population of cells in the peripheral blood of a cow with a neurofibrosarcoma.

An unusual population of leukocytes was observed in the peripheral blood of a cow with a large tumor burden, using flow microfluorimetry. This new population accounted for 50% of the total cells in the peripheral blood of this animal. These cells expressed the p150,95 molecule (bovine CD11c equivalent), identified by the monoclonal antibody C5B6, a molecule found on myeloid cells and activated lymphocytes. The new population did not express the pan T molecules BoCD2 (the bovine T11 equivalent), BoCD5 (the bovine CD5 equivalent) or surface IgM. Isolated peripheral blood mononuclear cells maintained in bulk culture were able to kill autologous tumor cells and BHV-1 infected A549 in an NK-like assay. In vitro cytotoxicity by cells cultured from the peripheral blood of this animal was augmented 2- to 4-fold by the addition of IL-2.

Animals↗

Antigenic topography of bluetongue virus 17.

Neutralizing monoclonal antibodies (mAbs) have been produced and used to map the topographical relationship of the surface antigenic determinants of bluetongue virus (BTV) 17 that mediate neutralization. Eight monoclonal antibodies, at least five of which were directed to the major outer coat protein of BTV 17, P2, were studied in neutralization assays using variant BTV 17 and in competition binding experiments. Five different epitopes were identified that are involved in neutralization of viral infectivity. Three of the five epitopes are clearly associated with P2, while the location of the other two epitopes is not known. The potential association of these two epitopes with one or both outer coat proteins of BTV is discussed.

Antibodies, Monoclonal↗

SIV, STLV-I and type D retrovirus antibodies in captive rhesus macaques and immunoblot reactivity to SIV p27 in human and rhesus monkey sera.

The prevalence of simian immunodeficiency virus (SIV), simian T-cell lymphotropic virus type 1 (STLV-I), and type D retrovirus (SRV-D) antibodies was determined for 1229 rhesus monkeys (Macaca mulatta) from two research colonies. Serum samples were tested by using enzyme-linked immunosorbent assay (ELISA), immunoblot (IB), and radioimmunoprecipitation assay (RIPA). Seropositive results for the three retroviruses tested were 0 for SIV, 270 (22%) for STLV-I, and 103 (8.4%) for type D retrovirus. Of the rhesus monkey sera, 61 (5.0%) were reactive to SIV gag p27 only, when tested by IB, but were negative when further tested by RIPA. Virus isolation was attempted from cultured peripheral blood mononuclear cells of 35 monkeys whose sera contained only p27 reactivity and none were positive by reverse transcriptase and core antigen assays to detect SIV. No overt clinical signs of immunodeficiency disease or unexplained deaths were evident in either monkey colony. Additionally, 63 of 165 (38%) human sera from various groups (primate center workers, normal donors, health care workers) had weak to moderate IB reactivity only to SIV p27, but 31 of 31 sera tested were negative by RIPA. These sera remained reactive to SIV p27 following absorption with an uninfected cell lysate, after blocking IB strips with various blocking solutions and were reactive to different SIV antigen preparations while remaining negative to human immunodeficiency virus type 1 (HIV-1) by IB and negative to HIV-2 by ELISA. These data underscore the need to adopt criteria for a positive SIV serologic test requiring reactivity against more than one viral gene product. These results also illustrate a potential problem in the testing of human sera for antibodies against simian retroviruses and demonstrate the need for caution in the interpretation of immunoblot results.

Animals↗

Effects of a specific thromboxane synthetase inhibitor on thromboxane generation and excretion in healthy dogs.

A specific thromboxane synthetase inhibitor, 3-methyl-2 (3-pyridyl)-1-indoleoctanoic acid (CGS 12970) was administered orally to 6 healthy adult Beagles at a dosage of 30 mg/kg of body weight. Blood generation of thromboxane B2 and urinary excretion of thromboxane B2 were measured before and after administration of CGS 12970. Although 97 +/- 0.4% inhibition of thromboxane B2 generation was observed within 2 hours after a single dose of CGS 12970 was administered orally, an effect on urinary excretion of thromboxane B2 was not observed. Additionally, oral administration of 30 mg/kg every 12 hours resulted in 80 +/- 14% inhibition of thromboxane B2 generation but had no effect on urinary thromboxane B2 excretion.

Administration, Oral↗

Evaluation of a commercial staphylococcal bacterin for management of idiopathic recurrent superficial pyoderma in dogs.

Twenty-one dogs with idiopathic superficial recurrent pyoderma were entered into a double-blind, placebo-controlled study to evaluate the efficacy of a commercial staphylococcal bacterin. The study spanned an 18-week period. All dogs were administered sodium oxacillin orally for the initial 6 weeks of the study. Dogs were given the bacterin or placebo SC, twice weekly at 3- or 4-day intervals, beginning at week 0 and continuing for 18 weeks. Dogs given antibiotics plus the bacterin (n = 13) had a significantly (P less than 0.05) better treatment response than those given antibiotic plus placebo.

Animals↗

Enzyme processing of La Crosse virus glycoprotein G1: a bunyavirus-vector infection model.

Efficient transmission, amplification, and dissemination of arboviruses require viral replication in vertebrate and invertebrate hosts. As a result, virions are exposed to two significantly different environments. Exposure of LaCrosse virus (LACV) to proteolytic enzymes, such as those that may be found in the mosquito midgut, increases virus affinity for mosquito cells. These enzymes remove the major envelope glycoprotein (G1) while leaving the second glycoprotein (G2) intact. Processing of LACV glycoproteins in the mosquito midgut may be necessary to expose attachment proteins on the virion surface before attachment to, and infection of, midgut cells can occur. This model may suggest answers to questions regarding the molecular basis for midgut infection barriers and species susceptibility to arbovirus infection in nature.

Animals↗

Identification of anti-idiotypic antibody in dogs.

There is general agreement that idiotype/anti-idiotype (id/anti-id) networks are important mechanisms of immune regulation, based primarily on studies conducted using inbred laboratory animals. To determine if anti-idiotypic antibody (anti-id) could be induced during an immune response in outbred dogs, the dogs were immunized to the hapten-carrier combination dinitrophenol-ascaris (DNP-ASC) and subsequently immunized with autologous antibody in complete Freund's adjuvant (CFA). Auto-anti-id was detected in three of five dogs during the DNP-ASC response. A cross-reactive anti-id was detected in dogs immunized with autologous antibody when a mouse monoclonal antibody was used as the id. These experiments further suggest that the regulation of the immune response via network interaction, as first illucidated in inbred animals, may occur in dogs.

Animals↗

Exogenous immunosuppression with methylprednisolone does not reactivate a type D retrovirus in rhesus monkeys.

To determine whether immunosuppression would result in retrovirus expression in previously infected rhesus monkeys, chronic high dose methyl prednisolone therapy was administered to two groups of animals for 4 weeks. One group was antibody positive for a type D retrovirus, designated Type D/3/wisc. The second group of animals had no known exposure to Type D/3/wisc and was antibody negative to this virus. The monkeys were evaluated for immunosuppression and retrovirus re-expression following the corticosteroid therapy. Although this treatment induced a marked cellular immunosuppression in all animals, as measured by in vitro assays, in none of the animals was retrovirus viremia or retrovirus-associated disease detected.

Animals↗

Conformationally dependent epitopes of bluetongue virus neutralizing antigen.

The neutralizing epitopes of Bluetongue virus serotype 17 (BTV 17) were evaluated by virus neutralization assay, flow cytometry, radioimmuno-precipitation, and Western blot. We showed that neutralizing monoclonal antibodies (MABs) raised to BTV 17 bound to viral proteins on intact virus when examined by virus neutralization and by an indirect binding assay analyzed by flow cytometry. In contrast, when the viral proteins were solubilized, a loss in reactivity with some of the neutralizing MABs was observed. Additionally, when the viral proteins were subjected to denaturing conditions, none of the neutralizing MABs reacted with the viral proteins. The results indicate that these neutralizing MABs bind conformationally dependent epitopes.

Animals↗

ELISA for detection of antibodies to a type D retrovirus, SRV-W.

An ELISA was developed to detect antibodies to a Type D retrovirus, SRV-W. The interpretation of the ELISA results were based on: 1) Comparisons of known antibody positive (to a closely related type D retrovirus) and negative serum samples, 2) the ability of ELISA reactivity to be absorbed with a Type D virus but not a mock virus preparation, and 3) analysis by a Western Blot assay as an alterative way to identify antibody to the Type D retrovirus.

Animals↗

Aging and immunity in non-human primates. II. Lymphocyte response in thymosin treated middle-aged monkeys.

Thymic hormone production declines with age, and recent strategies for enhancing immune function in elderly people include the administration of various thymic preparations. In an effort to develop an animal model for such therapeutic intervention, the current study was undertaken. Fourteen female rhesus monkeys (Macaca mulatta), aged 18-25 years, received a 7-day course of either Thymosin Alpha One (TA1) or placebo, and in vitro and in vivo immunologic analyses were performed. The relative percentage of T-cells and T-cell subsets declined during treatment in both TA1 and placebo groups. Nevertheless, mitogen-induced proliferation and NK-cell function were increased in most monkeys that received TA1, a trend that was apparent but not statistically significant. The antibody response to tetanus toxoid vaccine was not greater in the TA1 treatment group when compared to the placebo group. These findings suggest that TA1 can be safely administered to old monkeys and that such treatment, if undertaken in a larger or more sustained trial, may be associated with demonstrable biologic activity. Further studies are warranted to determine the potential for this or similar agents to reduce the consequences of age-associated immune deficiency.

Aging↗

Specific antibody synthesis in vitro. IV. The correlation of in vitro and in vivo antibody response to influenza vaccine in rhesus monkeys.

Fourteen female monkeys (Macaca mulatta) received a trivalent influenza vaccine and antibody response was determined by a change in plasma antibody content (ELISA) before and after vaccine. Lymphocyte cultures were also established from these monkeys and the level of antibody response did not correlate with mitogen-induced lymphocyte blastogenesis or natural killer cell function. In vitro anti-influenza antibody synthesis, however, was found to correlate well with the in vivo response. That is, monkeys who were non-responders, as determined by lack of change in plasma antibody content, were also non-responders in vitro. Accordingly, we believe that vaccine response is not necessarily a measure of immune competence but its measurement may, none the less, have clinical utility. The excellent correlation of in vivo and in vitro response provides predictive value for the in vitro test. Furthermore, because the correlation is good, the in vitro test may be useful as a tool in immunopharmacology and toxicology.

Animals↗

Immunobiology of bluetongue virus.

Following BTV infection or vaccination, sheep develop both anti-virus antibody (which may include neutralizing antibody) and a cellular immune response. Yet, it still is unclear what aspects of the response are most critical in preventing infection and disease from this virus. This is, in part, the result of a lack of knowledge of all of the viral virulence factors. However, with the current work involving subunit vaccines and the efforts to more carefully characterize virulence factors and tissue tropism, there will be a more thorough understanding of the immunobiology of the Bluetongue virus.

Animals↗

Structure and function of the immune system.

The major function of the immune system is to protect the host from environmental agents such as microbes or chemicals, thereby preserving the integrity of the body. This is done by the recognition of self and response to non-self. The immune response has been artificially divided into innate immunity (resistance) and specific immunity. Specific immunity is further divided into humoral immunity, the one involved with antibody, and cellular immunity, which is orchestrated by T cells. It is essential to understand that although these divisions have helped in understanding and analyzing the immune response, the system functions as a single unit rather than as a separate entity. In this paper, a simplified analysis of specific immunity will be given. However, the importance of nonspecific immunity, especially as it pertains to its role in preventing exposure of environmental substances, should not be forgotten.

Animals↗

The induction and kinetics of an anti-DNP IgE response in dogs.

Twenty-eight dogs immunized to dinitrophenol-ascaris (DNP-ASC) at birth and then three times at two week intervals produced serum anti-DNP antibody. The IgM response was detected one week after primary immunization and lasted for up to five weeks. The IgE and IgG antibody response in general was not present until week three but persisted through the immunization schedule. Although variation in the level and duration of the antibody response was detected between individual dogs, each dog did have a response that included all three isotypes examined.

Animals↗

The evaluation of cell-mediated immunity in vivo.

This paper has briefly described the history, mechanisms and in vivo measurements of cell-mediated immune responses. The focus of this paper was to examine the methods available to measure cell-mediated responsiveness in domestic animals. It was concluded that a practical way of evaluating the integrity of the cellular response would be to combine the measurement of an anamnestic response with the measurement of the cellular response following active immunization with an antigen. The anamnestic response can be evaluated by measuring the response to a battery of antigens given intradermally. In this case the animals (presumably or actually) have had previous exposed to these antigens. The measurement of an induced cell-mediated immune response could be accomplished concurrently by cutaneous sensitization and challenge to a low molecular weight hapten. By using both of these procedures, the ability of the animal's immune system to develop both a primary and secondary response to an antigen can be evaluated in vivo.

Animals↗