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Biomedical subjects

W C Satterfield

Publications and source records attributed to W C Satterfield.

At least 19 recordsLinked to original sources
PubMed1999

Guided tissue fabrication from periosteum using preformed biodegradable polymer scaffolds.

A successful tissue engineering method for bone replacement would imitate natural bone graft by providing the essential elements for new bone formation using synthetic scaffolds, osteogenic cell populations, and bone induction factors. This is a study of the suitability of various formulations of poly(DL-lactic-co-glycolic acid) (PLGA) foams to provide a tissue conducting scaffold in an ovine model for bone flap fabrication. Three formulations were used of different copolymer ratio and molecular weight. Porous wafers of PLGA were stacked into rectangular chambers (volume 4 cm3) enclosed on five sides. Some chambers also contained autologous morcellized bone graft (MBG). The chambers were inserted with the open face adjacent to the cambium layer of the periosteum in rib beds of seven sheep and harvested after 8 weeks in vivo. Gross and histologic examination of the resulting tissue specimens demonstrated molded units of vascularized tissue generally conforming to the shape of the chambers and firmly attached to the periosteum. Polymer degradation appeared to occur by varying degrees based on polymer formulation. New bone formation was observed only in areas containing MBG. There was no evidence of significant inflammatory reaction or local tissue damage at 8 weeks. We conclude that a PLGA foam scaffold is (1) an efficient conductor of new tissue growth but not osteoinductive, (2) contributes to the shape of molded tissue, and (3) biocompatible when used in this model. Further studies are warranted to develop practical methods to deliver bone induction factors to the system to promote osseous tissue generation throughout the synthetic scaffold.

Absorbable Implants↗
PubMed1999

A sheep model for continuous intrathecal infusion of test substances.

Pharmaceutical research and new drug development rely extensively on animal research. The development of novel agents for intrathecal administration requires preclinical studies of toxic effects in an animal model. We have developed a nonrodent animal model for this purpose. Our sheep model: 1 Is an animal whose neural axis is similar to the human 2 Allows for the percutaneous placement of intrathecal catheters 3 Has minimal possibilities of infection because the infusion system is totally implanted 4 Provides continuous infusion of the test agent 5 Generates behavioral, motor, neurological and histopathological information so that safety guidelines can be established prior to preclinical studies.

Animals↗
PubMed1998

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↗
PubMed1997

Reactivation of HIV type 1 in chronically infected chimpanzees following xenostimulation with human cells or with pulses of corticosteroid.

Following resolution of a primary HIV-1 infection initially induced by inoculating a mixture of three different virus strains, a chimpanzee was exposed to both immunostimulatory and immunosuppressive agents in an attempt to assess the contributions of different components of the immune system in suppressing circulating virus. The infusion of human leukocytes as an xenogeneic stimulus induced the replication of one of the input virus strains that had not previously been isolated or detected by PCR. The administration of high-dose, 17-day courses of corticosteroids resulted in coordinate and transient increases of each of the three viruses present in the original inoculum and elevation of HIV-1-specific ELISA antibody levels. Steroids administered to a second chimpanzee, chronically infected with a single HIV-1 isolate, also induced elevations of cell-associated virus. These results highlight the intimate relationship between immune system activation/immunosuppression and HIV replication in an animal model.

Animals↗
PubMed1995

Paralytic illness resembling inflammatory polyradiculoneuropathy in a chimpanzee.

An adult male chimpanzee housed in an outdoor corral with a group of other chimpanzees had an acute onset of ascending motor paresis that progressed to flaccid tetraplegia over 3 days. Tendon reflexes were weak, and CSF protein concentration was high. The chimpanzee regained normal mobility over several months. This chimpanzee's ascending, symmetrical, monophasic, flaccid paralytic illness, with albuminocytologic dissociation in CSF, and recovery following supportive treatment, was characteristic of inflammatory polyradiculoneuropathy, known as Guillain-Barré syndrome in human beings. Coonhound paralysis and experimentally induced allergic neuritis are the counterparts in dogs and laboratory animals, respectively, of the syndrome. In human beings, the syndrome is apparently immunologically mediated, as it is known to develop after bacterial and viral infections, vaccinations, and surgery or injury. The chimpanzee of this report had been given a rabies vaccination and had been treated for dental abscess 12 days prior to onset of signs, and had been inoculated with material containing neuronal antigens 20 years prior to onset of signs.

Animals↗
PubMed1995

Studies on V3-specific cross-reactive T-cell responses in chimpanzees chronically infected with HIV-1IIIB.

OBJECTIVE AND DESIGN: In this study we used synthetic peptides corresponding to the third variable region (V3) in the envelope protein gp120 of 14 different HIV-1 strains, and tested whether V3-specific T-cell responses are HIV-1 strain-specific or broadly cross-reactive in nine chimpanzees chronically infected with HIV-1IIIB. METHODS: Peripheral blood mononuclear cells isolated from nine HIV-infected chimpanzees and two uninfected controls were tested, by the [3H]-thymidine incorporation assay, for proliferative responses against phytohemagglutinin, control peptide and V3-loop peptides corresponding to 14 different HIV-1 strains. Serum samples collected from the chimpanzees were analyzed by enzyme-linked immunosorbent assay for antibodies against the V3 peptides. RESULTS: Chimpanzees 100, 139 and 175 exhibited high level of proliferative response directed against the cognate V3 peptide from HIV-1IIIB and also showed cross-reactivity to V3 peptides from 13, seven and 13 of 13 other HIV-1 strains, respectively. Additionally, five out of nine chimpanzees showed cross-reactive proliferative responses to V3 peptides from at least eight different HIV-1 strains, while significant proliferation to V3 peptides from two or more HIV-1 strains was observed in seven out of nine chimpanzees. On the other hand, four out of nine chimpanzees showed antibody response directed against the cognate V3 peptide from HIV-1IIIB, and serum from only one chimpanzee (100) showed cross-reactive antibody to six different V3 peptides. CONCLUSIONS: Overall, these studies in chimpanzees chronically infected with HIV-1IIIB indicate that with respect to the immunodominant V3 region, the virus-induced T-cell immunity is directed against a broad spectrum of HIV-1 strains.

Amino Acid Sequence↗
PubMed1994

Clinical efficacy and toxicity of doxorubicin encapsulated in glutaraldehyde-treated erythrocytes administered to dogs with lymphosarcoma.

Doxorubicin was encapsulated in canine erythrocytes, treated with 0.32% glutaraldehyde, and administered at a dosage equivalent to 30 mg of free doxorubicin/m2 of body surface area to dogs with diagnosis of lymphosarcoma. Compared with administration of free doxorubicin, this method of drug delivery substantially reduced peak plasma concentration and prolonged higher plasma concentration of doxorubicin. As such, this method was comparable to continuous IV infusion. Previous studies have indicated this method's potential for reduction in toxic side effects, particularly cardiotoxicosis, while allowing higher total doses of doxorubicin to be administered. In this study, doxorubicin encapsulated in glutaraldehyde-treated erythrocytes induced a triphasic exponential decay of doxorubicin from plasma, the highest relative contribution to the total area of the curve being the terminal phase. The treatment was effective in inducing complete and partial remissions of lymphosarcoma, with minimal acute toxicosis and no evidence of cardiotoxicosis. However, substantial, unanticipated, chronic, nonregenerative myelosuppression developed, and was mot strikingly expressed as profound thrombocytopenia. Efforts to ameliorate or circumvent this toxic effect will be required prior to further consideration of this doxorubicin delivery system for treatment of systemic neoplasia.

Animals↗
PubMed1993

Induction of human immunodeficiency virus-specific T cell responses in rhesus monkeys by synthetic peptides from gp160.

We have previously identified several synthetic peptides from conserved regions of the human immunodeficiency virus (HIV) envelope protein gp160 that have the capacity to induce broadly reactive T cell responses against gp160 in mice of several major histocompatibility complex (MHC) haplotypes. In the present investigation three rhesus monkeys were immunized with a mixture of eight synthetic peptides that are capable of inducing T cell activity in mice. Peripheral blood mononuclear cells (PBMCs) from these monkeys were monitored every 2 weeks for a period of 34 weeks for proliferative responses against individual peptides and recombinant gp160. Peripheral blood mononuclear cells from all three rhesus monkeys showed good proliferative responses with peptides 104 (aa 45-55), 111 (aa 118-130), and 63 (aa 519-543), whereas weak responses were observed with peptides 113 (aa 204-216) and 116 (aa 240-252). Two of the three rhesus monkey-derived PBMC preparations also showed good proliferative responses with peptide 61 (aa 586-598). Significant responses were not observed with peptides 105 (aa 48-61) and R15K (aa 315-329) in any of the monkeys immunized. However, PBMCs from all three monkeys showed significantly high proliferative responses with recombinant gp160, the HIV-1 envelope protein precursor. These results demonstrate that mixtures of synthetic peptides from HIV env gene product can prime gp160-specific T cell responses in rhesus monkeys.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1990

Avian endoscopy.

Endoscopic techniques in birds provide invaluable information on the medical care and husbandry of avian species. The instruments required to perform these examinations have been adapted from human arthroscopic instruments. With the advances in avian anesthetic techniques, endoscopic techniques can be readily and successfully applied to the avian patient in a general practice setting.

Anesthesia↗
PubMed1989

Reappearance of hepatitis D virus (HDV) replication in chronic hepatitis B virus carrier chimpanzees rechallenged with HDV.

Four chronic hepatitis B virus (HBV) carrier chimpanzees, which had apparently cleared hepatitis D virus (HDV) after a first experimental challenge with HDV, were reinoculated with a homologous strain of HDV. All animals had reappearance of low levels of serum HDV RNA and transient, mild alanine aminotransferase (ALT) elevations, which in two cases correlated with HDV RNA positivity. Plasmas obtained from two chimpanzees after rechallenge were inoculated into two other chronic HBV carrier animals that had recovered from a previous HDV infection. A similar reappearance of HDV RNA in serum (without ALT elevation) was noticed. These same plasmas, however, when inoculated into a chronic HBV carrier chimpanzee never exposed to HDV caused a severe acute hepatitis D. Rechallenge with HDV in chimpanzees apparently recovered from a first HDV infection resulted in the reappearance of HDV replication, sometimes associated with hepatitis. This can be interpreted as reinfection with HDV, but other explanations are possible. Although the serum level of HDV RNA observed after rechallenge with HDV is low, its transmission to individuals susceptible to HDV infection can result in severe acute hepatitis D.

Alanine Transaminase↗
PubMed1988

Chronic hepatitis D virus (HDV) infection in hepatitis B virus carrier chimpanzees experimentally superinfected with HDV.

Chimpanzees that were chronic hepatitis B virus carriers and that were superinfected with hepatitis D virus (HDV) apparently developed acute, self-limited type D hepatitis. Reevaluation with a sensitive hybridization-based assay using RNA probes specific for the HDV genome, however, demonstrated that greater than 50% of these animals still had detectable signs of ongoing HDV replication an average of 2.4 y (range, 1-6.4 y) after inoculation. The only positive marker for the presence of HDV was serum HDV RNA; HDV antigen was undetectable in both serum and the liver by an immunoblot assay and immunofluorescence, respectively. Because the detected amount of viral genome was very low, the previous failure to identify the chronic HDV carrier state in the chimpanzee can be attributed to the lower sensitivity of previously described assays.

Animals↗
PubMed1987

Nonhuman primates and the practitioner.

This article presents a practical introduction to nonhuman primate medicine for the private practitioner. The general approach to handling these animals for examination as well as methods of restraint are described. Preventive medicine and husbandry programs are discussed and common disease problems are outlined.

Animal Diseases↗
PubMed1981

Glutaraldehyde coagulation test for detection of hypogammaglobulinemia in neonatal nondomestic ruminants.

Sera were collected from 103 individuals of 26 species of nondomestic ruminant animals in 2 zoological collections. Eighteen were presumed not to have absorbed colostral proteins (group 1), 32 had consumed colostrum at least 12 hours before testing (group 2), and 53 were healthy adults (group 3). The gamma-globulin concentration, as determined by zone electrophoresis, was less than or equal to 0.4 g/dl in 16 of 18 samples from the group 1 animals, and greater than 0.4 g/dl in 31 of 32 group 2 animals. The glutaraldehyde coagulation test was performed on each serum sample. The results were negative in 15 of 17 samples, with gamma-globulin concentration less than or equal to 0.4 g/dl, and positive in 85 of 86 samples, with gamma-globulin concentration greater than 0.4 g/dl. The glutaraldehyde coagulation test appeared to be a practical field test for determining failure of passive transfer of maternal antibody in newborn nondomestic ruminant animals in zoological collections.

Agammaglobulinemia↗
PubMed1977

Short-term group therapy for people in crisis.

The author describes a short-term group therapy program that he believes is more effective than the traditional one-to-one approach for people in crisis. The group focuses on the problems of one member at a time and helps him examine his role, identity, and value system, the significant people in his community, and his ability to appreciate the positive things that exist within himself. Short-term goal-setting, self-evaluation, and written homework assignments are used to teach the client a new process that can help him look at his life positively and accept defeats and failures as a part of the growth process.

Community Mental Health Services↗