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Biomedical subjects

W E Collins

Publications and source records attributed to W E Collins.

At least 109 records · Page 6Linked to original sources
PubMed1992

Susceptibility of Macaca fascicularis monkeys from Mauritius to different species of Plasmodium.

Macaca fascicularis monkeys from Mauritius were shown to be susceptible via sporozoite inoculation to 7 species of Plasmodium (P. fragile, P. coatneyi, P. gonderi, P. inui, P. cynomolgi, P. knowlesi, and P. fieldi), indigenous to macaques in southeastern Asia. Four monkeys were sequentially infected with different species of Plasmodium to determine maximum and course of parasitemia. In 2 nonsplenectomized monkeys, P. fragile developed maximum parasite counts of only 134 and 155/microliters. For Plasmodium knowlesi, a parasite that is life-threatening to rhesus monkeys, maximum parasite counts were 4,278 and 7,440/microliters. Plasmodium coatneyi developed to what must be considered as moderate levels. After animals underwent splenectomy, parasite counts of P. coatneyi were 58,280, 89,094, 4,464, and 43,524/microliters. The maximum parasite counts for P. gonderi (13,508 and 21,576/microliters) and P. fieldi (1,767 and 17,836/microliters) were lower than would be expected in M. mulatta. In 2 monkeys that developed patent parasitemia with P. inui, the maximum parasite counts (95,046 and 728,748/microliters) indicated that this parasite may be the best adapted species for development in these animals once infection is established. Finally, the reinfection of 2 monkeys with P. cynomolgi suggested that some animals may be basically more resistant than others, whether splenectomized or not, to the production of high-density parasitemia.

Animals↗
PubMed1991

Inability of malaria vaccine to induce antibodies to a protective epitope within its sequence.

Saimiri monkeys immunized with a recombinant protein containing 20 copies of the nine amino acid repeat of the Plasmodium vivax circumsporozoite (CS) protein developed high concentrations of antibodies to the repeat sequence and to sporozoites, but were not protected against challenge. After intravenous injection of an immunoglobulin G3 monoclonal antibody (NVS3) against irradiated P. vivax sporozoites, four of six monkeys were protected against sporozoite-induced malaria, and the remaining two animals took significantly longer to become parasitemic. Epitope mapping demonstrated that NVS3 recognizes only four (AGDR) of the nine amino acids within the repeat region of the P. vivax CS protein. The monkeys immunized with (DRAADGQPAG)20 did not produce antibodies to the protective epitope AGDR. Thus, determination of the fine specificity of protective immune responses may be critical to the construction of successful subunit vaccines.

Amino Acid Sequence↗
PubMed1991

Induction of antigen-specific CD8+ cytolytic T cells by the exogenous bacterial antigen streptolysin O in rhesus monkeys.

We have characterized the T cell responses induced by streptolysin O (SLO), a sulfhydryl-activated hemolysin secreted by streptococci, by applying long-term in vitro culture and cloning rhesus monkey (Macaca mulatta) T cells. T cell lines specific for SLO were obtained from three rhesus monkeys. These T cell lines required autologous antigen-presenting cells (APC) to proliferate in response to SLO and did not respond to purified protein derivative. Phenotypic analysis showed that the cells from two of three SLO-specific T cell lines were more than 85% CD3+CD4-CD8+ after prolonged in vitro culture. The rh 1842 CD8+ T cell line proliferative response to SLO was inhibited by the addition of anti-major histocompatibility complex (MHC) class I and anti-CD8 but not of anti-MHC class II and anti-CD4 monoclonal antibody (mAb). This cell line was able to lyse P815 target cells in the presence of anti-CD3 mAb and did not show natural killer activity. Moreover, specific lysis of autologous but not allogeneic non-rosetting E- cell targets pulsed with SLO was observed. Such lysis was inhibited by the addition of anti-MHC class I mAb. In the attempt to identify the restriction elements involved in SLO presentation APC from six unrelated rhesus monkeys and three humans were used. A CD4+ rh 1842 T cell clone responded when SLO was presented by one of six, and a CD8+ rh 1842 T cell clone by four of six rhesus monkeys APC. Both CD4+ and CD8+ T cell clones did not respond when SLO was presented by human APC. However, both clones responded when APC from all donors were used in conjunction with anti-CD3 mb. Furthermore, SLO required active processing to be presented to CD4+ and CD8+ T cell clones as glutaraldehyde fixation of APC before but not after antigen pulsing inhibited T cell proliferation. The SLO-specific CD8+ cytolytic T cells described here could play a role in the regulation of the immune response occurring during streptococcal infections and/or could participate in the pathogenesis of poststreptococcal nonsuppurative sequelae.

Animals↗
PubMed1991

Plasmodium cynomolgi: immunization of a rhesus monkey with exoerythrocytic stages cultured in autologous hepatocytes.

To investigate the immune response to exoerythrocytic stages of malaria parasites, a rhesus monkey was immunized with autologous primary hepatocyte cultures infected with 7-day-old liver stage parasites of Plasmodium cynomolgi. A primary antibody response against EE stage antigens was obtained, and boosted after injection of homologous viable sporozoites. Antibodies directed against sporozoites and blood stages were also detected. The polyvalent immune response observed demonstrates the antigenicity of the liver stages and suggests their involvement in the general immune response against malaria.

Animals↗
PubMed1991

Evaluation of monoclonal antibodies against Plasmodium vivax sporozoites for ELISA development.

Nine monoclonal antibodies (MAbs) developed against Plasmodium vivax (Grassi & Feletti) salivary gland sporozoites were evaluated for use in an enzyme-linked immunosorbent assay (ELISA), using sporozoites developed in Anopheles dirus Peyton & Harrison An. gambiae Giles and An.maculatus Theobald. Four of the antibodies were unsuitable due to the low sensitivity of the resulting assays or the requirement for high concentrations of capture antibody. An additional two MAbs were rejected because they resulted in assays with high background absorbance, attributed to self-binding. Of the three remaining MAbs, the use of Navy vivax sporozoite (NVS) 3 resulted in an ELISA with the highest sensitivity and the lowest concentration requirement for capture antibody. Assay sensitivity varied with sporozoite strain indicating possible quantitative epitope heterogeneity. None of the MAbs cross-reacted with the heterologous sporozoites tested by immunofluorescence antibody assay (IFA). The IFA activity was not an indicator of ELISA sensitivity. The use of MAb NVS 3 in a standardized ELISA method resulted in an assay 10 times more sensitive than reported previously for P. vivax sporozoites, with a detection limit of fewer than 100 sporozoites per mosquito.

Animals↗
PubMed1991

Epstein-Barr virus transformation of Saimiri sciureus (squirrel monkey) B cells and generation of a Plasmodium brasilianum-specific monoclonal antibody in P. brasilianum-infected monkeys.

The new-world monkeys Saimiri sciureus (squirrel monkeys) are currently used as a model to test the efficacy of vaccines against human malaria. To improve our knowledge on this model, we tested the susceptibility of S. sciureus B cells to Epstein-Barr virus (EBV) infection. B-lymphoblastoid cell lines were obtained from six of six healthy animals after infection with the B95-8 source of EBV. The frequency distributions of spleen B cells clonally committed to the production of immunoglobulins M and G, as measured by limiting dilution analysis, were from 1 in 179 to 1 in 1,085 and from 1 in 45 to 1 in 60, respectively, in three monkeys naturally infected with Plasmodium brasilianum. In the same three animals, the frequency of spleen B cells committed to the production of P. brasilianum-specific antibody ranged from 1 in 2,211 to 1 in 9,099. One B-lymphoblastoid cell line producing anti-P. brasilianum-specific antibody was cloned twice, and the immunoglobulin G produced was purified. This monoclonal antibody recognized a parasite component of 197 kDa and was specific for Plasmodium malariae and P. brasilianum parasites. These data document that squirrel monkey B cells naturally primed by an infectious agent can be efficiently used to produce monospecific antibodies against the infectious agent.

Animals↗
PubMed1991

Immunization of owl monkeys with the ring-infected erythrocyte surface antigen of Plasmodium falciparum.

Aotus nancymai were immunized with the 4-mer, 8-mer, and 11-mer repeat peptides of the ring-infected erythrocyte surface antigen molecule of Plasmodium falciparum conjugated to diphtheria toxoid with muramyl dipeptide (MDP) as adjuvant. Immunization failed to induce protective immunity against the Uganda Palo Alto strain of P. falciparum as judged by maximum levels of parasitemia of immunized monkeys relative to those of controls. The fused polypeptide FPAg632, when combined with MDP, also failed to induce protective immunity. However, the maximum level of parasitemia and serologic response to the 11-mer peptide were inversely correlated. The safety of the use of MDP was evident.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1991

Renal pathology in Saimiri monkeys during a vaccine trial using the recombinant circumsporozoite protein of Plasmodium vivax.

Renal specimens of squirrel monkeys (Saimiri sciureus boliviensis) were studied by light microscopy and immunohistochemistry to examine the pathologic changes during vaccine trials with four recombinant circumsporozoite (CS) proteins (rPvCS-1, rPvCS-2, rPvCS-3, NS1(81) V20) of Plasmodium vivax. The monkeys were vaccinated and later challenged with P. vivax sporozoites. Among the 33 posttrial biopsies, 17 had mild to moderate mesangial proliferation and nine had interstitial nephritis. Immunohistochemistry by the peroxidase-antiperoxidase (PAP) method revealed IgG deposits in only three of 24 specimens and failed to demonstrate C3 deposits and P. vivax antigens in their glomeruli. There was no relationship between the severity of nephropathy and intensity of parasitemia. The intensity of parasitemia was the same in the vaccinated and control groups. Vaccinated monkeys from the groups (rPvCS-1, rPvCs-2, rPvCS-3) had no differences in renal pathology from the unvaccinated controls, but one group vaccinated with NS1(81) V20 did not develop renal changes.

Amino Acid Sequence↗
PubMed1991

Cellular proliferative responses in squirrel monkeys immunized with recombinant and synthetic Plasmodium vivax circumsporozoite peptides.

The role of circulating peripheral blood momonuclear cells (PBMC) in mediating protective immunity was examined during an immunization trial in Saimiri monkeys. Three engineered constructs representing different but overlapping regions of the circumsporozoite (CS) protein of Plasmodium vivax were used to immunize the Saimiri monkeys. Monkeys were randomly placed into three immunization groups: rPvCS2, rPvCS3, and LCV3 (representing three different but overlapping portions of the P. vivax CS protein) and two control groups: an alum adjuvant control group and an unimmunized control group. Collections of PBMC were made throughout the study at weeks 0, 2, 8, challenge (week 16), and two weeks after challenge. Proliferative responses to all immunogens and pokeweed mitogen were measured in all monkeys. Fourteen of 18 monkeys immunized with either rPvCS2 or rPvCS3 responded on the day of challenge to the appropriate immunogen with a stimulation index less than 2. Immunization with LCV3, which represents the repeat region only, elicited a specific response in only one monkey. However monkeys in both control groups also responded to rPvCS2 and rPvCS3, regardless of immunization, suggesting the presence of epitopes in rPvCS2 and rPvCS3 capable of associating with differing MHC antigens. Furthermore, the frequency of these cells in the periphery was increased by immunization, as demonstrated by a greater number of responding monkeys in the rPvCS2 and rPvCS3 immunized groups.

Animals↗
PubMed1991

Hypnozoites of Plasmodium simiovale.

Hypnozoites of Plasmodium simiovale were detected in liver biopsies from a rhesus monkey (Macaca mulatta) inoculated eight days previously with sporozoites from heavily infected anopheline mosquitoes. The tissue forms, 6 mu in diameter, were found within the cytoplasm of hepatic parenchymal cells by immunofluorescence and restained with Giemsa. This is the first report of latent, pre-erythrocytic stages from an ovale-type relapsing malaria.

Animals↗
PubMed1991

Strain specificity in the liver-stage development of Plasmodium falciparum in primary cultures of new world monkey hepatocytes.

Primary cultures of Aotus and Saimiri monkey hepatocytes were infected with sporozoites of the Plasmodium falciparum NF 54 strain from mosquitoes fed on gametocyte cultures, and with sporozoites of the P. falciparum Santa Lucia strain from mosquitoes fed on an infected Aotus monkey. After 4-8 days, one exoerythrocytic (EE) parasite per 30,000 sporozoites was detected in one of three experiments performed with the P. falciparum NF54 strain. However, numerous EE parasites were detected in Aotus and Saimiri cells infected with sporozoites of the P. falciparum Santa Lucia strain. At day 6, most of the parasites contained several hundred nuclei, and were morphologically similar to those previously described in vivo using light or electron microscopy. A monoclonal antibody directed against the repeat region of the circumsporozoite protein of P. falciparum labeled the plasma and parasitophorous vacuole membrane of five-day-old EE parasites by immunoelectron microscopy, thus supporting previous observations by immunofluorescence indicating that the CS protein persists throughout the EE development of P. falciparum. These results demonstrate that liver stages of P. falciparum can be obtained in Aotus and Saimiri monkey cells, they also suggest a parasite strain specificity for hepatocytes.

Animals↗
PubMed1991

Inhibitory activity against Plasmodium vivax sporozoites induced by plasma from Saimiri monkeys immunized with circumsporozoite recombinant proteins or irradiated sporozoites.

Two Saimiri monkey vaccine trials have been conducted comparing four recombinant Plasmodium vivax circumsporozoite proteins and irradiated sporozoites. Only a small number of animals immunized with certain recombinants or irradiated sporozoites became fully protected against sporozoite challenge. Preimmunization and postimmunization plasma samples obtained from 30 monkeys on the day of challenge were tested in an in vitro assay based on sporozoite development into exoerythrocytic stages in primary cultures of Saimiri monkey hepatocytes. The percentage of inhibition was determined by comparison of the number of exoerythrocytic stages developing from sporozoites preincubated with a preimmunization and a postimmunization plasma sample of each animal. The plasma samples of the day of challenge of nearly all the immunized animals had a variable, but significant inhibitory effect, when compared with the corresponding preimmunization sample. We found no correlation between the degree of in vitro inhibition of liver stage development, and the in vivo protection against sporozoite challenge of individual animals. The variable results of the incubation of sporozoites with "normal" plasma of different animals indicates that the in vitro results were affected by plasma factors unrelated to anti-sporozoite antibodies.

Animals↗
PubMed1991

Anopheles gambiae as a host for geographic isolates of Plasmodium vivax.

The G-3 strain of Anopheles gambiae was compared with 2 other strains of An. gambiae and An. freeborni, An. stephensi, and An. dirus for susceptibility to infection with 7 different geographic strains of Plasmodium vivax. Ratios of infection varied, indicating that certain strains of P. vivax were more infectious to the G-3 strain of An. gambiae than to other anopheline species/strains. Based on the comparative number of oocysts per mosquito, the relationships between the 3 strains of An. gambiae were closer than between the G-3 strain of An. gambiae and the 3 other species of Anopheles. Anopheles gambiae appears to be a very useful host for laboratory studies with P. vivax from different geographic origins.

Animals↗
PubMed1991

Infection of Aotus vociferans monkeys with different strains of Plasmodium falciparum.

Twenty-one splenectomized Aotus vociferans monkeys were infected with the different strains/clones of Plasmodium falciparum. Maximum parasitemia ranged from 1,302 to 1,460,000 parasites per mm3. Only the Santa Lucia strain was shown to produce gametocytes for extended periods. Gametocytes produced during the primary episode of parasitemia were highly infective to Anopheles freeborni mosquitoes. Gametocytes produced during recrudescence were not infective to mosquitoes feeding directly on the animals. This lack of mosquito infection during recrudescence periods suggests the presence of transmission-blocking immunity, which may be important in understanding the control of malaria through immunologic initiatives.

Amodiaquine↗
PubMed1991

Relationships of anxiety scores to screening and training status of air traffic controllers.

The present study assessed the relationship between anxiety, as measured by the State-Trait Personality Inventory (STPI), and success of post-strike air traffic control specialist (ATCS) trainees at the FAA Academy and during field training. The STPI was administered to students who entered the FAA Academy between June 1984 and September 1985. Academy test scores were obtained for 1,790 students in the en route option. Criterion data included the field training status of the Academy graduates as of July 1988. Statistical analyses determined the relationships between ATCS student scores on the STPI measures and a) normative data and b) Academy screening and field training results. ATCS students reported significantly lower state (current level) and trait (proneness) levels of anxiety than did either college students or military recruits. Trainees who had relatively high scores (for ATCSs) on a combined index of the trait and state measures of anxiety exhibited significantly higher a) percentages of Academy failures/withdrawals, b) percentages of option switches in the field, and c) overall field attrition, than did trainees with low scores. Results support the operation of some personality-related self-selection among ATCS applicants regarding anxiety and the importance of this low anxiety characteristic for ATCS job success.

Aerospace Medicine↗
PubMed1990

Infection of chimpanzees with the Uganda I/CDC strain of Plasmodium malariae.

Nine splenectomized chimpanzees were infected with the Uganda I/CDC strain of Plasmodium malariae. Two had no history of previous malarial infection, whereas 6 had been infected with P. vivax and 1 with P. vivax and P. ovale. The animals with no previous infection had maximum parasitemias of 8,740 and 10,800/mm3. The other animals had maximum parasite counts of 930-75,700/mm3. Anopheles freeborni, An. stephensi, An. dirus, An. maculatus, An. quadrimaculatus, An. culicifacies, An. arabiensis, and An. gambiae were readily infected by feeding through membranes on heparinized blood from these animals.

Animals↗
PubMed1990

Renal pathology in owl monkeys in Plasmodium falciparum vaccine trials.

Renal specimens of 16 owl monkeys (Aotus vociferans) were studied by light microscopy and immunohistochemistry during a vaccine trial with recombinant proteins of the ring-infected erythrocyte surface antigen (RESA) of Plasmodium falciparum. Deposition of IgG, C3, and P. falciparum antigens in the mesangium was demonstrated by the peroxidase anti-peroxidase (PAP) method. A relationship between the severity of parasitemia at the time of death and the presence of nephropathy was not apparent.

Animals↗