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Biomedical subjects

J R Baringer

Publications and source records attributed to J R Baringer.

At least 55 records · Page 3Linked to original sources
PubMed1981

Theiler's virus persists in glial cells during demyelinating disease.

Theiler's murine encephalomyelitis virus (T-MuEV) is the agent of a persistent, demyelinating infection of the central nervous system of mice, T-MuEV RNA was detected in histological sections of brain and spinal cord of experimentally infected animals by in situ hybridization. Both neurons and glial cells contained viral RNA during the early acute phase of the disease, The amount of viral RNA in neurons, however, was considerably higher than in glial cells. During the late demyelinating phase of the disease, viral RNA was found in low amounts only in glial cells of the white matter of spinal cord. At that stage, no viral RNA was found in neurons. These results demonstrate that T-MuEV persists in glial cells of the white matter. A reconstruction of the pathogenesis of this persistent infection is proposed, based on the different levels of virus replication in neurons and glial cells.

Animals↗
PubMed1981

Scrapie-associated particles in postsynaptic processes. Further ultrastructural studies.

Both tubular and spherical densities have been described in postsynaptic processes of mice with clinical scrapie. To determine whether the tubular appearances resulted from tubular structures or from overlap of spherical particles, electron microscopic examination was performed by tilting the specimen through large angles. In every instance where such could be analyzed, the tubular appearances resulted from overlapping of tightly aggregated spherical particles.

Animals↗
PubMed1981

Biochemistry of Theiler's murine encephalomyelitis virus isolated from acutely infected mouse brain: identification of a previously unreported polypeptide.

The WW strain of Theiler's murine encephalomyelitis virus (WW-TMEV) was purified from homogenates of acutely infected mouse brain. Infectious WW-TMEV was found to have an estimated sedimentation coefficient of 156 (s20,w) and a density of 1.35 g/cm3 in CsCl. Electron microscopy revealed a homogeneous population of 26-nm nonenveloped particles. Iodination of sodium dodecyl sulfate (SDS)-disrupted virions revealed four major capsid proteins with molecular weights of 58,000, 37,000, 34,000, and 27,000. A 6,000-dalton polypeptide was observed after long exposures of autoradiograms. The 37,000-, 24,000-, 27,000-, and 6,000-dalton polypeptides corresponded to picornaviral VP1, VP2, VP3, and VP4 capsid polypeptides, respectively. Comparison of autoradiograms of virions radiolabeled before and after SDS disruption indicated that the 58,000-dalton protein, VP2, and VP3 preferentially bound 125I under the labeling conditions used. Direct evidence was obtained that VP2 and VP3 were derived from the 58,000-dalton polypeptide by isolation of the 58,000-dalton polypeptide from polyacrylamide gels run under nonreducing conditions and subjecting it to reelectrophoresis under reducing conditions. The effect of trypsin on purified virions and their polypeptides was also investigated. Trypsin-sensitive sites were found in the 58,000-dalton protein, VP1, and VP2. Our results indicate that, in addition to the four typical picornaviral capsid polypeptides, there is a 58,000-dalton polypeptide present in WW-TMEV, which is sensitive to trypsin and can be reduced into two of the capsid proteins, VP2 and VP3.

Animals↗
PubMed1981

Use of monoclonal antibody directed against herpes simplex virus glycoproteins to protect mice against acute virus-induced neurological disease.

Monoclonal antibodies HCl and HD1, directed against herpes simplex virus type 1 (HSV-1) glycoproteins gC and gD, respectively, were evaluated for their ability to passively immunize mice against acute virus-induced neurological disease after footpad inoculation with HSV-1 or herpes simplex virus type 2 (HSV-2). Control virus-infected mice receiving a single intraperitoneal injection of normal serum died within 7 to 10 days after the spread of virus from footpad to spinal cord and brain. However, a single intraperitoneal injection of either HCl or HD1 antibody protected mice from neurological illness and death when administered to HSV-1 (strain HTZ)-infected mice at either 2 h before virus challenge or at 24 h after virus inoculation. To determine the in vivo specificity of the antibodies, passive transfer studies were performed with mice infected with the MP strain of HSV-1, a mutant of HSV-1 (mP) which is defective in the production of glycoprotein gC. Whereas HD1 antibody decreased the incidence of neurological illness in MP- and mP-infected mice, HCl antibody, which protected mP-infected animals, failed to protect mice infected with the MP strain. When HD1 antibody was administered to HSV-2 (strain G)-infected mice at either 2 h before virus challenge or at 6 h (but not 24 h) after virus inoculation, 100% of the infected animals receiving HD1 antibody survived. In contrast, 100% of HSV-2 (strain G)-infected animals passively immunized with HCl antibody developed neurological illness and died. These results provide in vivo evidence that the HSV-induced glycoprotein gC expresses type-specific antigenic determinants, whereas glycoprotein gD expresses type-common determinants.

Animals↗
PubMed1981

Progressive retinal degeneration in scrapie-infected hamsters: a light and electron microscopic analysis.

Scrapie is considered a prototype of the spongiform encephalopathies. This group of diseases is characterized by a prolonged incubation period, without symptoms, followed by an insidious onset of clinical disease leading to death. Attention has mainly been focused on central nervous system pathology, and reports of pathology in the retina have been limited. In this study, hamsters were inoculated intracerebrally with the scrapie agent and serially sacrificed to determine agent titers and pathologic changes in the eyes over time. Scrapie infectivity rises progressively in the eye to maximal levels between 6 and 8 weeks after inoculation, then it reaches a plateau. Ocular abnormalities are first visible 8 weeks after infection. The process begins with a gradual loss of rod outer segments, after which progressive loss of rod inner segments and photoreceptor nuclei occurs. By 10 weeks, only a vestige of the outer nuclear layer remains. Ultrastructurally, this destruction is attended by the presence of macrophages, although the importance of this finding is unknown. Later, Müller cells increase their pericellular investment of remaining photoreceptor cell nuclei. The limitation of the lesion to the outer retinal layers suggests this tissue site may be important in the investigation of basic pathogenetic mechanisms in the spongiform encephalopathies.

Animals↗
PubMed1981

Detection of Theiler's virus RNA in mouse central nervous system by in situ hybridization.

The location and distribution of viral RNA were examined in the central nervous system tissues of weanling mice acutely infected with the GDVII strain of Theiler's murine encephalomyelitis virus. Viral RNA was detected by autoradiography following in situ hybridization of a 3H-labeled DNA synthesized in vitro complementary to purified viral RNA. Viral RNA was detected in pyramidal neurons of the hippocampus, cerebral cortex, brainstem nuclei, thalamus, basal ganglia, and spinal cord. Autoradiographic grains could be detected in the axonal and dendritic processes of many infected neurons. No viral RNA was detected in any cell of the cerebellum or white matter. In addition to demonstrating the location of viral RNA in infected central nervous system tissues, and hence the sites of viral replication during this acute polioencephalomyelitis, they indicate that necrosis of hippocampal neurons is due to lytic infection, rather than to hypoxia.

Animals↗
PubMed1980

Type-common and type-specific monoclonal antibody to herpes simplex virus type 1.

Hybridoma cells produced by fusing mouse myeloma cells with spleen cells from mice primed with herpes simplex virus (HSV) type 1 yielded five clones producing neutralizing antibody against homologous virus. Two clones, HCl and HC2, produced antibody capable of precipitating glycoprotein C and its precursor, whereas three clones, HD1, HD2, and HD3, produced antibody capable of precipitating glycoprotein D and its precursor. Antibody produced by the HC1 and HC2 clones neutralized HSV type 1 but not HSV type 2 or HSV type 1 strain MP, which is known to lack glycoprotein C. Antibody produced by the HD1 and HD2 clones neutralized both HSV type 1 and HSV type 2, whereas antibody produced by the HD3 clone neutralized HSV type 1 but not HSV type 2. The two clones which produced antibody to glycoprotein C and the two clones which produced type-common antibody to glycoprotein D were independently derived and not clonally related inasmuch as the antibody in each pair belonged to a different subclass of immunoglobulin.

Animals↗
PubMed1980

Delayed stroke following carotid occlusion.

A 60-year-old patient suffered a lethal hemispheric infarction 3 days after angiographically documented occlusion of the ipsilateral cervical internal carotid artery and while receiving anticoagulant therapy. Pathologic evidence is consistent with embolism from the distal "tail" of a propagated carotid thrombus as the mechanism of his stroke.

Carotid Artery Thrombosis↗
PubMed1979

Progressive myelopathy due to extramedullary hematopoiesis: case report and review of the literature.

Extramedullary hematopoiesis (EMH) in the spinal epidural space is a rare but treatable cause of progressive paraparesis in patients with a variety of hematological and systemic disorders. We report a case of extensive thoracic epidural EMH causing progressive spastic paraparesis in a patient with agnogenic myeloid metaplasia. The literature describes 11 additional cases of myelopathy due to epidural EMH. All patients had EMH in the midthoracic region with elevated cerebrospinal fluid protein and abnormal spine roentgenograms or myelograms. Treatment with decompressive laminectomy, radiation therapy, or both, resulted in marked or complete recovery in 7 of 10 patients. Patients who develop paraparesis and who have a disorder associated with EMH should be evaluated rapidly for this treatable condition.

Humans↗
PubMed1979

Host defenses in herpes simplex infections of the nervous system: effect of antibody on disease and viral spread.

BALB/c mice passively immunized with antibody to herpes simplex virus type 1 and challenged in the footpad with 10(5.7) plaque-forming units of herpes simplex virus type 1 were shown to be protected from neurological disease and death compared with control mice treated with normal serum or antibody to Sindbis virus. One hundred percent of untreated mice had virus recoverable from dorsal root ganglia by 48 h after infection. Whereas amputation of the infected limb at 48 h had no effect, antibody administration (resulting in titers of 1:8 and 1:16) was found to prevent acute neurological disease if administered no later than 48 h after infection. Antibody also restricted the extent of latent infection in the lumbosacral ganglia. The data provide strong evidence that antibody is effective in preventing spread of virus both in the peripheral nervous system and in central nervous system (spinal cord) tissue.

Animals↗
PubMed1979

Morphology of central nervous system disease in immunosuppressed mice after peripheral herpes simplex virus inoculation. Trigeminal root entry zone.

Inoculation of mice and rabbits on the cornea with herpes simplex type 1 virus has been shown to cause an ascending infection of the trigeminal nerve, ganglion, and descending tract within the brainstem (2, 3, 7). A discrete, destructive, and primarily demyelinative lesion is seen on the central nervous system side of the trigeminal root entry zone 5 to 8 days after infection (8, 15, 16). This study, utilizing Swiss mice, demonstrated that immunosuppression with cyclophosphamide prior to infection with herpes simplex type virus causes a marked reduction of the mononuclear infiltrate within the central nervous system and a significant decrease in myelin destruction when compared with the infected, nonimmunosuppressed control animals. The content of virus in the brainstem was similar in both groups by day 8 as were the neutralizing antibody titers to herpes simplex type 1 virus. These results suggest that the cellular response plays a definitive role in the destruction of central nervous system tissue after peripheral infection with herpes simplex type 1 virus.

Animals↗
PubMed1978

Partial purification and evidence for multiple molecular forms of the scrapie agent.

A procedure for the partial purification of the scrapie agent from mouse spleen was developed based on its sedimentation profile. Differential centrifugation and detergent treatment with sodium deoxycholate yielded a fraction designated "P5" which was enriched for scrapie infectivity approximately 20-fold with respect to cellular protein. The P5 fraction was devoid of cellular membranes but heavily contaminated with ribosomes as judged by electron microscopy. On centrifugation of the fraction P5 to near equilibrium in a sucrose gradient scrapie infectivity was distributed over a range of densities from 1.08 to 1.30 g/cm3. Parallel rate-zonal analysis showed that the infectivity was distributed over a range of particle sizes with s20.w values from approximately 40 S to greater than 500 S. Incubation of P5 at 37 or 80 degrees C, under conditions that disrupt ribosomes, dramatically altered the rate-zonal gradient profile of the agent. Under these conditions, the agent sedimented as particles with s20.w greater than 500 S. The apparent heterogeneity of the scrapie agent with respect to both size and density and its ability to shift from one form to another suggest that the agent may contain hydrophobic domains on its surface.

Animals↗
PubMed1978

Experimental scrapie in mice: ultrastructural observations.

Scrapie, kuru, and Creutzfeldt-Jakob disease are characterized by a similar spongiform pathology, prolonged incubation periods, and an agent with unique physical, chemical, and biological properties. Swiss mice were inoculated with the scrapie agent and sacrificed three to five months later for light and electron microscopy. At three months, small vacuoles were seen within the neuropil of the cerebral cortex and basal ganglia. By the fifth month these vacuoles had increased in number and size and were accompanied by moderate astrocytic proliferation. The brainstem, cerebellum, and spinal cord showed variable changes of much less intensity. Many dilated postsynaptic processes contained osmiophilic particles in random or crystalline arrays. The particles, measuring approximately 23 nm in diameter, appeared consistently in postsynaptic processes of brain from scrapie-infected mice, were lacking in controls, and were a size consistent with sedimentation and filtration data for the scrapie agent. Whether these particles represent the scrapie agent must await further studies.

Animals↗
PubMed1978

Central nervous system susceptibility to herpes simplex infection.

Four days after inoculation of herpes simplex virus (HSV) on the rabbit cornea, distinctive and reproducible lesions appear in the trigeminal root entry zone. These viral lesions, situated in the central nervous system (CNS) portion of the root, consist of severe myelin destruction accompanied by mononuclear cell infiltration and partial sparing of axons. Immunofluorescent study demonstrated abundant viral antigen, and by electron microscopy viral nucleocapsids were found to be numerous within astrocytes and were rarely found in other cell types. In contrast, the adjacent peripheral nervous system (PNS) tissue appears unaffected by the presence of virus. The mechanism for this marked difference in response of the central nervous system and the peripheral nervous system may depend upon the susceptibility of astrocytes to viral infection and replication. The selective nature of the lesion provides an easily reproducible model for further investigation of the response of nervous system tissue to HSV.

Animals↗