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E D Roberts

Publications and source records attributed to E D Roberts.

At least 19 recordsLinked to original sources
PubMed1998

Pathogenesis of Lyme neuroborreliosis in the rhesus monkey: the early disseminated and chronic phases of disease in the peripheral nervous system.

The histopathologic and immunohistochemical features of early and late neuroborreliosis of the peripheral nervous system were investigated in rhesus macaques infected with the JD1 strain of Borrelia burgdorferi. Infection was proven by culture or polymerase chain reaction analysis of skin biopsies and indirectly by Western blot analysis. Three months after infection, neuritis involving multiple nerves was the most consistent neurologic manifestation. Both macrophages and B lymphocytes but not T lymphocytes were present in the cellular infiltrates. Axonal structures surrounding infiltrates had changes consisting of demyelination and axonal phagocytosis. Some of the Schwann cells in lesions stained with anti-nitrotyrosine and anti-tumor necrosis factor-alpha antibodies. B. burgdorferi, or antigens thereof, were visualized immunohistochemically within macrophages. Forty-six months after infection, the most common changes were regenerative, whereas neuritis was infrequent. Aberrant axonal regeneration, irregularly sized myelinated fibers, and fibrosis were frequently observed. Possible mechanisms to explain the appearance and subsidence of Lyme neuritis are discussed.

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PubMed1997

Mononeuropathy multiplex in rhesus monkeys with chronic Lyme disease.

Peripheral neuropathy is a recognized but poorly understood manifestation of Lyme disease. We performed serial electrophysiological studies on 8 rhesus monkeys chronically infected with the JD1 strain of Borrelia burgdorferi and compared the results with those of similar studies on 10 uninfected control monkeys. Four infected and 2 uninfected animals underwent sural nerve biopsy. Five of the infected and 1 of the uninfected animals also had postmortem neuropathological examinations. Altogether, 5 of the infected monkeys demonstrated primarily axonal-loss-variety multifocal neuropathies. Only one nerve lesion exhibited findings compatible with demyelination. Pathologically, peripheral nerve specimens showed multifocal axonal degeneration and regeneration and occasional perivascular inflammatory cellular infiltrates without vessel wall necrosis. Free spirochetal structures were not seen, but several macrophages exhibited positive immunostaining with a highly specific anti-B. burgdorferi, 7.5-kd lipoprotein monoclonal antibody. In the infected animals, serial analysis of serum antibodies to B. burgdorferi showed increasing numbers of IgG specificities and new IgM specificities, suggesting persistent infection. Thus, peripheral neuropathy in the form of a mononeuropathy multiplex develops frequently in rhesus monkeys chronically infected with B. burgdorferi. The pathogenesis of these nerve lesions is not yet known, but our studies suggest an immune-mediated process perhaps driven by persistent infection with B. burgdorferi.

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PubMed1997

The outer surface protein A (OspA) vaccine against Lyme disease: efficacy in the rhesus monkey.

The efficacy of an outer surface protein A (OspA) vaccine in three different formulations was investigated in the rhesus monkey. The challenge infection was administered using Ixodes scapularis ticks that were infected with the B31 strain of Borrelia burgdorferi. Protection was assessed against both infection and disease, by a variety of procedures. Some of the animals were radically immune suppressed, as an attempt to reveal any putative low level infection in the vaccinated animals. The significant difference found between the spirochaetal infection rates of ticks that had fed on vaccinated vs. control monkeys, lack of seroconversion in the vaccinated animals, and the absence of spirochaetal DNA in the skin of vaccinated animals in the weeks following the challenge, indicate that vaccinated monkeys were protected against tick challenge. The post-mortem immunohistochemical and polymerase chain reaction analyses, however, suggest that these monkeys may have undergone a low-level infection that was transient.

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PubMed1997

Lyme neuroborreliosis in the rhesus monkey.

Although there are several animal models of Lyme disease, only the rhesus monkey model exhibits all of the key manifestations of the disease. After infection with Borrelia burgdorferi, rhesus monkeys develop signs of early localized, early disseminated, and chronic Lyme disease. Specific features include erythema migrans, uveitis, myocarditis, arthritis, and disease of the peripheral and central nervous system. One of the unique features of the rhesus monkey model is the development of Lyme neuroborreliosis. Peripheral nervous system (PNS) involvement is usually in the form of a mononeuropathy multiplex with primarily axonal-loss features. Evidence of central nervous system (CNS) disease has included CSF pleocytosis, meningeal inflammation, spinal cord lesions, and polymerase chain reaction (PCR) data consistent with chronic CNS infection. The pathogenesis of Lyme neuroborreliosis is not well understood, but it is likely to involve complex interactions between B. burgdorferi and host immune mechanisms.

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PubMed1995

Squamous epithelial proliferative lesions associated with rhesus Epstein-Barr virus in simian immunodeficiency virus-infected rhesus monkeys.

Proliferative lesions were found on the squamous epithelium of the tongue, esophagus, or penis or haired skin of the lip, hand, or thorax of 8 simian immunodeficiency virus-infected rhesus monkeys that died of simian AIDS. The lesions were focal and consisted of hyperkeratosis, parakeratosis, and acanthosis in the skin, with additional ballooning degeneration in the tongue, esophagus, and penis. The epithelial surfaces were frequently colonized by Candida species or gram-positive cocci. Intranuclear inclusion bodies were seen in cells in the middle and superficial layers. Herpesvirus virions were found in inclusion-bearing cells by transmission electron microscopy. An Epstein-Barr-like virus was identified in inclusion-bearing cells by immunohistochemistry and in situ hybridization. No virus was detectable in basal layers of the epithelium. These lesions resemble oral hairy leukoplakia in AIDS patients and may thus provide a useful primate model to study permissive epithelial infection by Epstein-Barr-like viruses.

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PubMed1995

Chronic lyme disease in the rhesus monkey.

BACKGROUND: We have previously reported the clinical, pathologic, and immunologic features of "early" Borrelia burgdorferi infection in rhesus monkeys (3). We have now evaluated these features during the chronic phase of Lyme disease in this animal model. EXPERIMENTAL DESIGN: Clinical signs, and pathologic changes at the gross and microscopic levels, were investigated 6 months post-infection in several organ systems of five rhesus macaques (Macaca mulatta), which were infected with Borrelia burgdorferi by allowing infected Ixodes scapularis nymphal ticks to feed on them. A sixth animal was used as an uninfected control. Borrelia antigens recognized by serum antibody were identified longitudinally by Western blot analysis, and C1q-binding immune complexes were quantified. Localization of the spirochete in the tissues was achieved by immunohistochemistry and in vitro culture. The species of spirocheta cultured was confirmed by the polymerase chain reaction. RESULTS: Chronic arthritis was observed in five out of five animals. The knee and elbow joints were the most consistently affected. Articular cartilage necrosis and/or degenerative arthropathy were the most severe joint structural changes. Synovial cell hyperplasia and a mononuclear/lymphocyte infiltrate were commonly seen. Nerve lesions were also observed, including nerve sheath fibrosis and focal demyelinization of the spinal cord. Peripheral neuropathy was observed in five out of five animals and could be correlated in the most severely affected monkey with the presence of higher levels of circulating immune complexes. Differences in disease severity did not correlate with differences in the antigens recognized on Western blot analysis. CONCLUSIONS: B. burgdorferi infection in rhesus macaques mirrors several aspects of both the early and chronic phases of the disease in humans. This animal model will facilitate the study of the pathogenesis of Lyme arthritis and neuroborreliosis.

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PubMed1994

Effects of U-75875, a peptidomimetic inhibitor of retroviral proteases, on simian immunodeficiency virus infection in rhesus monkeys.

U-75875 inhibits human immunodeficiency virus types 1 and 2 and simian immunodeficiency virus (SIV) proteases and blocks Gag-Pol protein processing and viral maturation and replication in vitro. Rhesus monkeys were treated with vehicle alone or with formulated U-75875 at doses of 7 or 20 mg/kg of body weight per day for 26 days by continuous intravenous infusion beginning 6 h prior to intravenous inoculation with 10 monkey 50% infectious doses of SIV Delta B670, and the monkeys were monitored until death. The effects of treatment on the level of SIV p26 antigenemia, the infectious virus titer in serum, and the level of proviral DNA in blood mononuclear cells evaluated by PCR were assessed. SIV infection of the controls resulted in an initial viral antigenemia that began 5 to 10 days postinoculation (p.i.), reached peak values on days 10 to 14 p.i., and lasted for more than 15 days. Proviral DNA was detectable in peripheral blood mononuclear cells by 7 to 11 days p.i., reached the mean peak level by 11 days p.i., and remained at high levels through day 24 p.i. Infectious virus was detected in serum from all of the infected controls by 24 days p.i. Treatment with U-75875 for 26 days resulted in a dose-related delay in the day of the peak level of antigenemia (P = 0.034). The level of proviral DNA in peripheral blood mononuclear cells at 11 days p.i. was significantly decreased in a dose-related fashion in the treated monkeys ( P </- 0.048), with a delay in the attainment of the peak level of proviral DNA in the treated groups. The titer of infectious virus in the serum of the group treated with 20 mg/kg/day was significantly decreased on day 24 p.i. compared with that in the serum of controls ( P = 0.046). Treatment with formulated U-75875 was well tolerated in rhesus monkeys and resulted in an inhibitory effect of SIV in vivo.

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PubMed1993

Comparison of magnetic resonance imaging (MRI) and histopathology in rabbit models of osteoarthritis and immune arthritis.

Osteoarthritis was surgically induced in mature male Dutch Belted rabbits by sectioning the fibular collateral and sesamoid ligaments and removal of the anterior horn of the lateral meniscus. The site of surgical intervention was detectable by MRI. Histopathologic analysis revealed severe focal cartilage lesions on opposing surfaces of the tibia and femur. Histology of cartilage adjacent to the osteoarthritic lesions appeared normal. In another animal model, arthritis was induced by immunization against ovalbumin followed by intra-articular injection of ovalbumin. MRI of immune arthritic rabbit knees showed accumulation of synovial fluid and cartilage degradation. Histopathology was characterized by vascular necrosis of the synovium and depletion of cartilage proteoglycan. MRI can be used to non-invasively follow the therapeutic effects of drug treatment on synovial inflammation and cartilage degradation in rabbit knees.

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PubMed1993

Pathogenesis of Lactobacillus casei-induced polyarthritis in Lewis rats: 1. Time related changes in histopathological scores and hematology.

Intraperitoneal injection of cell wall fragments from L. casei (ATCC 11578) induces an acute and a chronic inflammatory arthritis of the distal joints of LEW/N female rats. Histopathological changes in four distal joints and hematologic changes were analyzed on days 3, 10, 20, 30, 40, 50 and 59. All joints were scored for changes in inflammation, pannus, cartilage and bone. The acute inflammatory response consisted of fluid exudate, fibrin, neutrophils and some macrophages concentrated along the periosteum of the longer bones. The disease progressed with synovial fibroblast proliferation and infiltration of lymphocytes and macrophages. On day 10, cartilage changes were associated with pannus formation and subchondral fibrosis. Both localized bone resorption and periosteal new bone formation were features of the chronic phase. Lymphocytes were elevated above normal (p < 0.05) on day 3, 10, 20, 30 and 40; returning to the normal range on day 50 and 59. Neutrophils were elevated on days 10, 20, 30, 40 and 59. L. casei-induced polyarthritis in Lewis rats appears to be a fibroblast-, macrophage-mediated disease with a prominent lymphoid component.

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PubMed1993

A human respiratory syncytial virus (RSV) primate model of enhanced pulmonary pathology induced with a formalin-inactivated RSV vaccine but not a recombinant FG subunit vaccine.

Human respiratory syncytial virus (RSV) is the leading cause of severe bronchiolitis and pneumonia in infants. RSV vaccine development has been stifled for the past 23 years because infants vaccinated with formalin-inactivated (FI) RSV have experienced exacerbated disease upon RSV infection. This exacerbated disease phenomenon is poorly understood, in part because of the lack of a primate model that exhibits a similar exacerbated disease state. Vaccination of African green monkeys with either FI RSV or a genetically engineered subunit vaccine termed FG glycoprotein reduced replication of challenge virus. However, only vaccination with FI RSV induced an enhanced pulmonary pathologic response to RSV infection. Pulmonary inflammatory scores in the FG glycoprotein-vaccinated monkeys were no greater than in monkeys vaccinated with adjuvant alone. This is the first demonstration of RSV vaccine-induced enhanced pathology in a primate and illustrates that a subunit vaccine has the potential of circumventing this exacerbated disease phenomenon.

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PubMed1993

Early and early disseminated phases of Lyme disease in the rhesus monkey: a model for infection in humans.

We demonstrate that Borrelia burgdorferi infection in the rhesus monkey mimics the early and early disseminated phases of human Lyme disease. Clinical, bacteriological, immunological, and pathological signs of infection were investigated during 13 weeks after inoculation of the spirochete. Three animals were given B. burgdorferi (strain JD1) by needle inoculations, six animals were exposed to the bite of B. burgdorferi-infected Ixodes dammini ticks, and three animals were uninfected controls. B. burgdorferi could be recovered from all animals that were given the spirochete. Bacteria were detectable until week 6 postinoculation (p.i.) in blood, until week 8 p.i. in skin biopsies, and at 10 weeks p.i. in the conjunctiva of one of two animals which developed conjunctivitis. Erythema migrans (EM) appeared in one of the three animals infected by needle inoculation and in five of the six animals infected by ticks. Deep dermal perivascular lymphocytic infiltrations (characteristic of human EM) were observed in all animals showing EM clinically. Both EM and conjunctivitis were documented concomitantly with the presence of the spirochete. Lethargy, splenomegaly, and cerebrospinal fluid pleocytosis were also noted in some animals, but the direct connection of these signs with the infection was not shown. The appearance rate of immunoglobulin M and immunoglobulin G antibodies to B. burgdorferi, as well as the antigen spectra recognized, were remarkably similar to those seen in humans. Serum antibodies from infected animals were able to kill B. burgdorferi in vitro in the presence of rhesus complement. The rhesus monkey model appears to be useful for the investigation of the immunology and pathogenesis of Lyme disease and for the development of immunoprophylactic, diagnostic, and chemotherapeutic protocols.

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PubMed1993

Magnetic resonance imaging and morphometric quantitation of cartilage histology after chronic infusion of interleukin 1 in rabbit knees.

Cartilage pathology in rabbit knees was monitored by noninvasive magnetic resonance imaging (MRI) and evaluated using morphometric histologic measurements. Infusion of rabbit knees with the cytokine interleukin 1 induces cartilage degradation and inflammation. A miniosmotic pump was implanted subcutaneously to deliver interleukin 1 through a polyethylene catheter inserted into the rabbit knee. Rabbit knees were imaged using MRI and prepared for histologic examination at 5 and 12 days after chronic infusion of interleukin 1. MRI obtained 0.7-mm sections for three-dimensional reconstruction of cartilage image. Cartilage deterioration near the site of infusion was visible on MRI. MRI measurements indicated a reduction in cartilage thickness. Histology revealed a loss of staining of cartilage matrix proteoglycan, synovial hypertrophy, and perichondral bone resorption. Morphometric analysis of cartilage histology indicated a reduction in both cellularity (chondrocytes/m mu 2 area) and cell to matrix area ratio. These observations suggest that a loss of proteoglycan, an early event in cartilage degeneration, can be detected by MRI.

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PubMed1992

Effects of intra-articular administration of methylprednisolone acetate on normal articular cartilage and on healing of experimentally induced osteochondral defects in horses.

The effects of intra-articular administration of methylprednisolone acetate (MPA) on the healing of full-thickness osteochondral defects and on normal cartilage were evaluated in 8 horses. In group-1 horses (n = 4), a 1-cm-diameter, full-thickness defect was created bilaterally in the articular cartilage on the dorsal distal surface of the radial carpal bone. Cartilage defects were not created in group-2 horses (n = 4). One middle carpal joint was randomly selected in each horse (groups 1 and 2), and treated with an intra-articular injection of 100 mg of MPA, once a week for 4 treatments. Injections began 1 week after surgery in group-1 horses. The contralateral middle carpal joint received intra-articular injections of an equivalent volume of 0.9% sodium chloride solution (SCS), and served as a control. Horses were evaluated for 16 weeks, then were euthanatized, and the middle carpal joints were examined and photographed. Synovial and articular cartilage specimens were obtained for histologic and histochemical evaluation. Gross morphometric evaluation of the healing defects in group-1 horses revealed that 48.6% of the defect in control joints and 0% of the defect in MPA-treated joints was resurfaced with a smooth, white tissue, histologically confirmed as fibrocartilage. This replacement tissue was a firmly attached fibrocartilage in control joints and a thin fibrous tissue in MPA-treated joints. The articular cartilage in joints treated with MPA had morphologic changes, including chondrocyte cluster formation, loss of palisading architecture, and cellular necrosis in both groups of horses.(ABSTRACT TRUNCATED AT 250 WORDS)

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PubMed1992

Field recovery and analysis of horse skeletal remains.

In response to a request from an insurance company investigating a claim relative to the death of four race and show horses, allegedly as a result of deliberate starvation, physical anthropologists of the Louisiana State University (LSU) Department of Geography and Anthropology undertook the recovery and analysis of skeletal remains said to be those of the animals. The objectives were to determine the number and kinds of animals represented, their ages, and sexes, and, through morphometric evaluation of bone density at the LSU School of Veterinary Medicine, whether there was evidence of nutritional osteodystrophy. The skeletons were the remains of four horses. In comparisons of data derived from these skeletons with breeding records for the horses described in the insurance claim, it was established that the skeletons were those of mares, as were the insured animals, and that the relative ages of the four approximated those of the insured horses. The skeletal samples submitted for morphometric evaluation showed no evidence of nutritional osteodystrophy and, thus, provided no support for the contention that death had resulted from starvation. In one horse, the superior aspect of the right ascending ramus of the lower jaw below the coronoid process revealed a gunshot wound; the other skeletons showed no evidence of trauma.

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PubMed1992

Arthrotomy versus arthroscopy and partial synovectomy for treatment of experimentally induced infectious arthritis in horses.

To evaluate the clinical, laboratory, and histologic effects of 2 methods of treatment for infectious arthritis in horses, Staphylococcus aureus (3.4 to 3.9 x 10(3) colony-forming units) was inoculated into the tarsocrural joints of 8 horses on day 0. Each horse was treated with phenylbutazone (2 g, PO, q 24 h) and gentamicin sulfate (2.2 mg/kg of body weight, IV, q 8 h) for 14 days. On day 2, general anesthesia was induced, and each horse had 1 tarsocrural joint treated by arthrotomy, with removal of accessible fibrin and lavage with 3 L of sterile balanced electrolyte solution. An indwelling plastic drain was placed in the standing horse to provide a means for lavage with 3 L of balanced electrolyte solution twice daily for 72 hours. The contralateral tarsocrural joint was treated via arthroscopic debridement, synovectomy, and lavage with 3 L of balanced electrolyte solution. Arthrotomy and arthroscopic portals were allowed to heal by second intention. Lameness and thermographic examinations, analysis and bacteriologic culture of synovia, CBC, and WBC differential count were performed prior to inoculation and on days 1, 3, 6, 8, and 13. On day 14, each horse was euthanatized, and the joints were measured, opened, and photographed. Synovium and articular cartilage were obtained for semiquantitative histologic (H&E stain) and histochemical (safranin O fast green stain) evaluation. Lameness and joint circumference were significantly (P less than 0.05) greater in limbs treated by arthroscopy, synovectomy, and lavage. Arthrotomy with lavage eliminated the S aureus infection significantly (P less than 0.05) earlier than arthroscopy, synovectomy, and lavage, however, both treatments eliminated the infection in all but a single joint.(ABSTRACT TRUNCATED AT 250 WORDS)

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PubMed1991

Lactobacillus casei-induced polyarthritis in Lewis rats: histopathological scoring system for evaluation of anti-rheumatic drugs.

A histopathological scoring system which grades drug effects on cellular infiltration, pannus formation, cartilage degradation and bone resorption in L. casei-induced polyarthritis in rats is described. Reference anti-rheumatic and anti-inflammatory agents administered on days 2-60 after induction of arthritis were evaluated for effects on paw swelling weekly and graded histopathologic changes on day 60. This animal model affords a tool to evaluated therapeutic agents on the joint destruction resulting from chronic inflammation.

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PubMed1991

Experimental haemarthrosis in rhesus monkeys: morphometric, biochemical and metabolic analyses.

The effects of a single episode of massive haemarthrosis in rhesus monkeys were studied. Autologous whole blood was injected into a femorotibial joint of 16 anaesthetized monkeys, equally divided into four groups and killed 7 days, 2, 3 and 6 months post-injection (PI). Synovial membrane and femoral articular cartilage were analysed morphometrically and articular cartilage was further analysed biochemically and metabolically. At 7 days PI, morphometric evaluation revealed a significant increase (P less than 0.05) in synovial membrane cellularity and synovial intimal thickness of injected joints versus control joints. This change was no longer evident 2 months PI. There was also an overall (n = 16) significant increase (P less than 0.05) in femoral articular cartilage cellularity in injected joints. The average chondrocyte lacuna area of injected joints was not statistically different from the control joints. Biochemical analyses of femoral articular cartilage revealed a significant decrease in hexosamine concentration (P less than 0.05) of injected joints. There was no significant difference between the injected and control joints in hydroxyproline or total protein concentration. Metabolic analyses revealed a significant increase (P less than 0.05) in cartilage collagenous protein production by injected joints compared with control joints. There were no significant differences in cartilage or secreted total protein production between injected and control joints. There were also no significant differences in cartilage or secreted proteoglycan production between joints. Morphometric evaluation of articular tissues following massive haemarthrosis has quantified a temporary hyperplastic reaction. A significant decrease in cartilage hexosamine concentration in haemarthrotic joints suggests this is a crucial biochemical event in the pathogenesis of blood-induced cartilage destruction.

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