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Biomedical subjects

S J Schapiro

Publications and source records attributed to S J Schapiro.

12 recordsLinked to original sources

Manipulating the affiliative interactions of group-housed rhesus macaques using positive reinforcement training techniques.

Social housing, whether continuous, intermittent, or partial contact, typically provides many captive primates with opportunities to express affiliative behaviors, important components of the species-typical behavioral repertoire. Positive reinforcement training techniques have been successfully employed to shape many behaviors important for achieving primate husbandry goals. The present study was conducted to determine whether positive reinforcement training techniques could also be employed to alter levels of affiliative interactions among group-housed rhesus macaques. Twenty-eight female rhesus were divided into high (n = 14) and low (n = 14) affiliators based on a median split of the amount of time they spent affiliating during the baseline phase of the study. During the subsequent training phase, half of the low affiliators (n = 7) were trained to increase their time spent affiliating, and half of the high affiliators (n = 7) were trained to decrease their time spent affiliating. Trained subjects were observed both during and outside of training sessions. Low affiliators significantly increased the amount of time they spent affiliating, but only during nontraining sessions. High affiliators on the other hand, significantly decreased the amount of time they spent affiliating, but only during training sessions. These data suggest that positive reinforcement techniques can be used to alter the affiliative behavior patterns of group-housed, female rhesus monkeys, although the two subgroups of subjects responded differently to the training process. Low affiliators changed their overall behavioral repertoire, while high affiliators responded to the reinforcement contingencies of training, altering their proximity patterns but not their overall behavior patterns. Thus, positive reinforcement training can be used not only as a means to promote species-typical or beneficial behavior patterns, but also as an important experimental manipulation to facilitate systematic analyses of the effects of psychosocial factors on behavior and potentially even immunology.

Animals↗

Differences in functional immune responses of high vs. low hardy healthy individuals.

An association between the personality trait of hardiness and immune responses was explored. Blood samples were collected from 21 healthy individuals under nonstressful conditions, who had either high or low levels of hardiness. Functional immune assays tested for natural killer (NK) cell activity and proliferation responses to Candida albicans (Candida), purified protein derivative from Mycobacterium tuberculosis (PPD), lipopolysaccharide (LPS), concanavalin A (Con A), and Staphylococcus enterotoxin A (Staph A). Differences between high and low hardy groups on these immune responses were examined using Bonferroni adjusted independent t-tests. Results revealed significant differences between the groups for Candida, PPD, Con A, and Staph A. In all instances, the high hardy group had larger mean proliferative responses than the low hardy group. Implications of the study as well as avenues for future research are discussed.

Adult↗

Religious beliefs and opinions on clinical xenotransplantation--a survey of university students from Kenya, Sweden and Texas.

This study investigated the association between religious beliefs and opinions on xenotransplantation among students from three different countries. A lower proportion of religious students accepted xenotransplantation than did non-religious students. A higher proportion of Protestant students seemed to accept xenotransplantation than did Muslim and Roman Catholic students. A higher proportion of the religious respondents had not formed an opinion on xenotransplantation compared to non-religious students. There was no difference according to gender on views on xenotransplantation, but a higher proportion of older students seemed to accept xenotransplantation than did younger students. A higher proportion of non-vegetarians reported acceptance of xenotransplantation than did vegetarians. Acceptance of xenotransplantation was higher in Sweden compared to the two other regions, and the proportion of students who had formed an opinion was higher as well.

Adult↗

Evidence for specific immune response against P210 BCR-ABL in long-term remission CML patients treated with interferon.

Interferon-alpha treatment induces complete cytogenetic remission in 25% of Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML) patients. These remissions are durable unlike remissions induced with other therapies and yet residual leukemia is detectable in most of these patients. Total peripheral blood mononuclear cells (PBMCs) from CML patients in long-term remission following interferon treatment exhibited significantly higher proliferative responses (four- to 15-fold over background) than normals directed against P210 BCR-ABL in extracts of transfected monkey fibroblast cells. Surprisingly, similar enhanced levels of specific proliferative responses were observed with extracts from cells expressing Bcr and/or Abl proteins. In contrast, extracts from vector only or v-Mos-expressing cells had background level responses. Control monkey fibroblast cells lacking BCR-ABL expression failed to induce proliferation over background levels. Normal individuals had no significant responses to Bcr/Abl extracts. On the other hand, peripheral blood mononuclear cells from allogeneic bone marrow transplant CML patients had proliferative responses to cell extracts independent of Bcr-Abl. These data indicate that patients in remission due to alpha-interferon treatment have significantly higher levels of specific cellular immunoreactivity against Bcr/Abl sequences than normal controls, which could play a role in maintaining cytogenetic remission in Ph-positive CML patients.

Adult↗

A synthetic peptide from the first conserved region in the envelope protein gp160 is a strong T-cell epitope in HIV-infected chimpanzees and humans.

We reported earlier that synthetic peptides corresponding to highly conserved regions in the envelope protein gp160 of the human immunodeficiency virus type 1 (HIV-1), in particular an 11-amino acid sequence (peptide 104) from the first conserved region at the amino-terminus, were capable of inducing strong HIV-specific T-cell proliferative responses in several inbred mouse strains as well as in outbred Rhesus monkeys. We have now obtained evidence of the presence of significant levels of proliferative response to peptide 104 in 7 of 9 chimpanzees chronically infected with HIV-1 (p < or = 0.05) and 8 of 17 HIV+ individuals (p < or = 0.001). Further, four other conserved HIV envelope-derived peptides, identified previously in our murine and Rhesus monkey model systems, were widely recognized as T-cell epitopes in both chimpanzees and humans infected with HIV-1. In none of the infected subjects did peripheral blood mononuclear cells show proliferative responses to unrelated control peptides. Also, neither the control normal chimpanzees nor HIV-seronegative individuals showed proliferative responses to the conserved peptides. With respect to the humoral responses, serum samples from none of the chimpanzees showed reactivity with any of the conserved peptides, and only low levels of antibody responses against peptide 104 were observed in 3 of the 17 patients (p > 0.05). Importantly, three of the conserved envelope-derived peptides, including peptide 104, overlap with sequences that were reported in the literature to be epitopes for virus-induced cytotoxic T lymphocytes in asymptomatic HIV+ individuals. These observations, together with our results in multiple animal models and humans, establish that these conserved HIV envelope-derived peptides, particularly peptide 104, are significant T-cell epitopes with potential usefulness for induction of HIV-specific cell-mediated immune responses in humans.

Amino Acid Sequence↗

Cross-reactive T-cell proliferative responses to V3 peptides corresponding to different geographical HIV-1 isolates in HIV-seropositive individuals.

We have investigated the proliferative response of peripheral blood mononuclear cells from individuals infected with human immunodeficiency virus type 1 (HIV-1) to synthetic peptides from the third variable loop region (V3) in the envelope protein gp120. We tested a total of 14 peptides, corresponding to 14 HIV-1 isolates belonging to four geographical locations (clades U, A, B, and D). Although differences in relative level of responses exist between individual peptides and patients, the proliferation in response to all 14 V3 peptides was significantly greater than that to unrelated control peptides. Additionally, we observed that proliferative responses of blood cells from the 10 HIV-seropositive individuals studied from the clade B region to peptides from within clades U, A, B, and D were not significantly different, indicating the cross-reactive nature of the V3-specific cell-mediated immune responses. Even though the majority of patients also exhibited antibody responses against several V3 peptides, serum samples from 50% of clade B patients exhibited antibody cross-reactivity, while proliferative responses to V3 peptides from more than one clade were observed in 80% of patients. Importantly, in two patients, decreased CD4+ cell numbers, an important surrogate marker of disease progression, significantly correlated with loss of V3 peptide-specific proliferative responses but not antibody responses. These results have important implications toward evaluating the utility of V3 peptides for designing therapeutic and/or vaccine reagents against HIV-1.

Amino Acid Sequence↗

Behavioral management of specific pathogen-free rhesus macaques: group formation, reproduction, and parental competence.

Breeding colonies of specific pathogen-free (SPF) rhesus macaques were established to eradicate the transmission of Herpesvirus simiae and several retroviruses in this species. Strategies to attain this goal included the combination of large numbers of monkeys into groups, the establishment of small unimale groups, and a program using animals that were temporarily socially restricted. All methods required the establishment of new social groups from unfamiliar animals. In using these methods, we encountered important behavioral questions related to the group formation process, as well as reproductive and parental competence. Age and prior social experience were important determinants of social and parental success. New multimale-multifemale SPF group formations were successful initially and involved the least aggression during the first breeding season when young females and older males were used. Formation of unimale groups was successful, even when males and females were of similar ages. Breeding competence did not seem to be affected by any of the SPF colony management procedures, but animals with restricted early social experience exhibited impaired parental competence when compared with animals with more social experience. Males were more sensitive to the effects of early social restriction than females. A variety of behavioral obstacles will be encountered when attempting to establish an SPF breeding colony by forming groups by use of these methods. Skilled behavioral management is necessary to surmount these obstacles and to achieve satisfactory social integration, reproduction, and parenting.

Aging↗

Weight gain among juvenile rhesus macaques: a comparison of enriched and control groups.

Environmental enrichment techniques for captive primates are aimed at improving their psychological well-being. While behavioral variables are used to measure changes in psychological well-being, physiologic measures (e.g., heart rate, cortisol response) are sometimes gathered in addition to the behavioral evidence. Some of these physiologic indices measure acute changes in the animals' well-being, limiting their usefulness. Body weight, however, is a measure of physical well-being that may have meaning as a long-term indicator of psychological well-being. We therefore collected body weight data from two groups of rhesus macaques (Macaca mulatta group 1: n = 34, group 2: n = 30) every 8 weeks beginning at the age of 1 year, as they passed through various housing conditions as part of a program to develop a specific pathogen-free breeding colony. One-half of the subjects in each group received a variety of environmental enhancements during all housing conditions; the other half received no enrichment and served as controls. At the beginning of the study (age 1 year), control and enriched subjects did not differ in body weight. Among group-1 subjects, enriched animals weighed significantly more than controls after 4 months of enrichment, and the weight difference was maintained 24 months later. Enriched animals in group 2 never differed in weight from their controls. The order in which different types of enrichment were presented and the extra-cage environment of the two groups differed, which may account for this discrepancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Husbandry↗

Guidelines for developing and managing an environmental enrichment program for nonhuman primates.

Before implementing an environmental enrichment program for nonhuman primates, several issues should be considered. The assignment of enrichment tasks can be made to caretakers, a dedicated "enrichment technician," volunteers, students or individuals with training in behavioral science. Determining the enrichment techniques to be used must take into account personnel time available; the species, age, sex, and individual histories of the nonhuman primates; and experimental protocols for which animals are being maintained. Identifying the most beneficial way to use the available personnel time must be tailored for each institution. To meet federal regulations, records must be kept of the environmental enhancements available to each nonhuman primate. Good record-keeping will allow appropriate evaluation of the program. This evaluation should involve the animals' responses to the enrichment opportunity, cost and durability of enrichment items, human and nonhuman safety considerations, and personnel required. The well-being of captive nonhuman primates will be most improved if well-informed decisions are made in developing and managing environmental enrichment programs.

Animal Husbandry↗

Evaluation of cellular immune responses in rhesus monkeys subjected to adenovirus-mediated gene transfer into the cervix.

We reported previously that direct injection of a recombinant adenovirus (rAd), Ad5CMV-beta-gal, into the cervix of the rhesus monkey resulted in efficient beta-galactosidase expression in the cervix within 3 days. In these studies, we also observed the induction of anti-adenovirus (Ad)-specific immunoglobulin G responses after 22 days. In the continuation of evaluating the anti-Ad-specific immune responses resulting from this approach of gene targeting to the cervix, we measured the cellular immune responses. The introduction of Ad5CMV-beta-gal into the cervix by direct injection, but not by the abrasion technique, resulted in the induction of strong proliferative responses against extracts of cells infected with Ad5CMV-beta-gal but not against control uninfected cells. These responses were initially detected at 22 days postinjection and coincided with the abrogation of transgene expression. Significant levels of proliferative responses were maintained for < or =83 days. Multiple injections of rAds had no significant enhancing effect on either the level or longevity of the proliferative responses. At 3 days after the injection of Ad5CMV-beta-gal, when the transgene expression in the cervix was clearly evident, proliferative responses against the rAd were not detectable. However, the production of low but significant amounts of interleukin-10, a cytokine characteristic of T helper type 2 responses that promote humoral immune responses, was observed at the 3-day point in these animals. These results suggest that significant differences exist between the kinetics of transgene expression and the priming of specific host immune responses, and that these differences may be important for devising alternate strategies to improve techniques for Ad-mediated gene therapy of cervical cancer.

Adenoviridae↗

Accumulated means analysis: a novel method to determine reliability of behavioral studies using continuous focal sampling.

During the past decade, the behavioral needs, and especially the social needs, of laboratory animals have received increasing attention. New captive care guidelines have been developed, and these advocate group housing of laboratory animals whenever possible and appropriate. Analyses of behavioral observations are commonly used to assess the effects of experimental manipulations on behavioral responses. In studies of animal welfare, stress levels and effects on well being can be measured in this manner. Collecting the proper amount of data both to allow statistical analyses and to optimize time investment in data collection is a practical concern in behavioral research. The aim of the present study was to develop a simple method to estimate how much behavioral data should be collected in order to achieve a preset level of reliability across observations. This paper examines the behavior of 12 rhesus monkeys (Macaca mulatta) housed in two small social groups. Each monkey was observed for a total of two hours in 10 minute observation periods spread over 12 days. Accumulated Means Analysis, in which the accumulated mean for a behavior across successive observation sessions must meet several criteria, is proposed as a method to assess reliability across observations, thereby providing information concerning the optimum number of observational data sessions that need to be collected. The data in this study indicate that this optimum number of observations varies with the behavior being measured and with the group observed, as does the value of the Accumulated Means Analysis technique. Six hours of observation of rhesus macaques may be sufficient to provide the type of simple, yet reliable time budget (for a specific window of time) needed by those managing groups of primates. Accumulated Means Analysis should be applicable to behavioral data collected during multiple time periods on other non-human primate species, both in captivity and in the field.

Animal Welfare↗