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Biomedical subjects

J R Baringer

Publications and source records attributed to J R Baringer.

At least 37 records · Page 2Linked to original sources
PubMed1989

Porphyrin-laser photodynamic induction of focal brain necrosis.

A noninvasive photodynamic method has been developed to produce focal brain necrosis using porphyrin activated in vivo with laser light. After peripheral injection of the photosensitive porphyrin derivative, Photofrin I, mice were irradiated on the posterior lateral aspect of the head through the intact depilated scalp with 632 nm argon-dye laser light. Animals were studied at one, two and seven days after irradiation. Blood-brain barrier damage was detected by the intravenous injection of Evans blue, horseradish peroxidase and heterologous immunoglobulins. At one and two days after irradiation, the lesions were characterized by extravasation of immunoglobulin and Evans blue, and by edema, ischemia and infiltration by monocytes. On the seventh day after irradiation, the lesion was smaller than it had been two days after irradiation, and had reactive changes at its edges and coagulative necrosis at its center. Extravasation of Evans blue and immunoglobulin was markedly reduced by the seventh day after irradiation, but uptake of horseradish peroxidase by macrophages located at the periphery of the lesion was evident.

Animals↗
PubMed1987

Nocardial cerebral abscess in the acquired immunodeficiency syndrome.

Nocardial cerebral abscess is an unusual neurologic manifestation of the acquired immunodeficiency syndrome. A 20-year-old woman with the acquired immunodeficiency syndrome presented with headache and fever. Nocardia asteroides was cultured from a stereotaxic brain biopsy specimen. Despite antibiotic therapy to which the pathogen was sensitive, resolution of the abscess followed only after complete surgical excision.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Scrapie infection diminishes spines and increases varicosities of dendrites in hamsters: a quantitative Golgi analysis.

An altered morphology of neuronal dendrites has been shown to be associated with many degenerative diseases of the central nervous system (CNS). Scrapie is a CNS degenerative disorder caused by a novel infectious particle or prion. Golgi impregnation studies showed that neurons in the scrapie-infected brains of hamsters contained varicose swellings and diminished numbers of dendritic spines. In order to ascertain whether or not these differences were statistically significant, quantitative methods were applied to brain samples from scrapie-infected hamsters and compared to uninfected controls. Golgi impregnated layer III pyramidal neurons from both motor and visual cortex exhibited two types of changes in infected animals. First, loss of dendritic spines on the apical shaft of both motor and visual neurons were found from 50 to 200 microns from the cell body (p less than 0.001). Second, spherical varicosities on dendritic stalks ranging from 7 to 25 microns in diameter were found. The average number of varicosities per cell was 18.1 in infected animals with varicosities on dendrites of controls numbering less than 3 per cell. Less than 2% of the control cells exhibited these varicosities, while greater than 80% of the scrapie dendrites exhibited varicosities. These changes in scrapie are similar to those reported in Creutzfeldt-Jakob and Alzheimer's disease in human patients.

Animals↗
PubMed1986

Effect of antiviral agents on replication of herpes simplex virus type 1 in brain cultures.

An in vitro tissue culture system consisting of reaggregated embryonic brain cells was used to evaluate the inhibition of herpes simplex type 1 (HSV-1) by several antiviral compounds. The efficacy of acyclovir, vidarabine, bromovinyldeoxyuridine, and 9-(1,3-dihydroxy-2-propoxymethyl) guanine in HSV-1-infected Vero cell monolayer cultures was compared with that seen with brain cell aggregates. At a mean 50% inhibitory dose with Vero cells, acyclovir showed a 99% reduction of virus titer in brain cell aggregates. Vidarabine and 9-(1,3-dihydroxy-2-propoxymethyl) guanine gave a dose-dependent reduction in virus titer with Vero cells; however, in aggregate cultures treated with the same drugs a dose-dependent decrease at 24 h was followed by an increase to a point of no inhibition at 72 h postinfection. Pretreatment of brain cell aggregates with a hybrid human leukocyte interferon (Le IF-AD) reduced virus titers at 48 h postinfection but did not maintain this reduction at 72 h. In contrast, infected Vero cell monolayer cultures demonstrated a dose-dependent reduction in virus titers with Le IF-AD. Postinfection treatment with Le IF-AD did not reduce plaque formation in Vero cells but was effective in reducing virus titer in HSV-1-infected brain cell aggregates at 48 h postinfection. Antiviral concentrations of up to 200 micrograms or 200,000 IU/ml for interferon did not appear morphologically toxic to brain cells. Antiviral therapy of HSV-1-infected brain cell aggregates may more closely mimic in vivo responses than monolayer cultures.

Acyclovir↗
PubMed1986

Replication of scrapie prions in hamster eyes precedes retinal degeneration.

Progressive degeneration of outer retinal structures occurs in hamsters with scrapie. In order to determine the relationship between histopathologic changes and replication of the scrapie agent, hamsters were inoculated intracerebrally with approximately 10(7) ID50 units. Animals sacrificed at 50 days after inoculation showed no signs of neurologic dysfunction, but had high titers of the scrapie agent or prions in both neural and nonneural portions of the eye. Prion titers in retina were greater than 10(7) ID50 units/ml of 10% (w/v) homogenate and equal to those found in optic nerve and brain. No histopathologic changes were seen by light microscopy in any ocular structure. At 70 days after inoculation, neurologic dysfunction was profound. The titers of the scrapie agent in brain, lens, retinal pigment epithelium, cornea, retina, and optic nerve were not significantly changed compared to those found at 50 days; however, retinal degeneration was severe. No morphologic changes were observed in cornea, pigment epithelium or optic nerve. These findings show that scrapie prion replication to maximal levels precedes the onset of degenerative changes in retina. Furthermore, the retina is preferentially susceptible to the degeneration induced by the scrapie agent while the other ocular structures containing significant levels of prions seem to escape injury.

Animals↗
PubMed1984

Use of aggregating brain cultures to study the replication of herpes simplex virus types 1 and 2 in central nervous system tissue.

A novel tissue culture system consisting of reaggregated embryonic mouse brain cells was used to examine the replication of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) within central nervous system tissue. Brain aggregates cultured 30-40 days in vitro demonstrated progressive maturation and differentiation into cells recognizable as neurons, astrocytes and oligodendrocytes, with the latter cell type exhibiting myelin production. Mature aggregates were infected with HSV and sampled at timed intervals postinfection for morphological, virological, and biochemical assays. By electron microscopy mature nucleocapsids were observed in the nucleus of peripheral cells at 9 h and in all cell types by 33 h. Virus-specific antigens were observed, using the immunoperoxidase test, within peripheral cells at 12 h postinfection (p.i.). By 24 h p.i., antigen production had progressed throughout the infected aggregates. Growth curves of HSV-1 and HSV-2 for intracellular and extracellular infectious virus production correlated well with virus-induced morphological changes and antigen production. SDS-polyacrylamide slab gel electrophoresis of isotopically-labelled proteins and glycoproteins synthesized from 4 to 24 h p.i. in virus-infected aggregates revealed typical HSV-1 polypeptide profiles and HSV-1 and HSV-2 glycoprotein profiles. Our results suggest that aggregating brain cultures may provide a useful and more accurate in vitro model for the study of HSV-induced neurological disease.

Animals↗
PubMed1983

Recurrent herpes simplex encephalitis: recovery of virus after Ara-A treatment.

A 54-year-old man developed clinical findings consistent with herpes simplex virus (HSV) encephalitis. These signs included an abrupt onset of focal central nervous system disease, cerebrospinal fluid pleocytosis, localized electroencephalographic abnormalities, and a computerized tomographic scan showing right temporal lobe involvement. Treatment with adenine arabinoside (Ara-A) resulted in improvement. Two months later he again became confused, and a left hemiparesis developed. Although biopsy revealed extensive necrosis and inflammatory response, HSV antigens and herpesvirus particles were not detected. Culture of biopsy tissue yielded HSV type 1 only after 18 days. A second course of Ara-A was administered but the patient failed to improve and died four months later. Extensive inflammatory necrosis of both temporal lobes involving gray and white matter was found. Cultures were negative for HSV. The recovery of virus from our patient during the second encephalitic episode should raise concerns regarding the efficacy of Ara-A treatment and the role of the virus in recurrent disease. In addition, the importance of maintaining biopsy tissue in culture for prolonged periods is emphasized.

Biopsy↗
PubMed1983

Impaired migratory and chemotactic activity of neutrophils during murine cytomegalovirus infection.

Mice have been shown to have increased susceptibility to bacterial and fungal superinfections between days 1 and 5 of acute murine cytomegalovirus (MCMV) infection. The current study demonstrated that, during the same period of the MCMV infection, migration of neutrophils into a subcutaneous sponge was impaired (1,300-2,000 cells/mm3 in MCMV-infected animals vs 6,000-7,000 cells in controls; P less than 0.01) and chemotaxis of neutrophils harvested from the sponge was decreased (chemotactic index of 1.5-2.1 in infected animals vs 5.4-5.7 in controls; P less than 0.01). The number of neutrophils in peripheral blood was not altered. Infectious MCMV was present in the neutrophil-rich fraction of peripheral white blood cells, suggesting that direct viral infection of neutrophils may contribute to altered function. These studies suggest that abnormalities in neutrophil function during acute cytomegalovirus infection may contribute to the enhanced susceptibility to bacterial and fungal infections that occurs in both experimental animals and humans.

Animals↗
PubMed1983

Replication of the scrapie agent in hamster brain precedes neuronal vacuolation.

The scrapie agent causes a degenerative neurological disorder in sheep and goats after a prolonged incubation period. Hamsters inoculated intracerebrally with 10(7) ID50 units of the scrapie agent develop clinical signs of neurological dysfunction 60-65 days later. The titers of scrapie agent in selected regions of the central nervous system (CNS) of hamsters were determined prior to the onset of clinical illness. At 48 days after inoculation, the cerebrum, cerebellum, brain stem, and spinal cord contained 9.3, 9.1, 9.3, and 8.6 log ID50 units/g of tissue, respectively. Sections from the cerebrum showed minimal vacuolation without any astrogliosis. The spinal cord and cerebellum revealed no lesions. At 71 days after inoculation, when clinical signs of scrapie were prominent, another group of hamsters was evaluated. The mean titers of the agent in the same CNS regions were virtually unchanged, but severe vacuolation and moderate astrogliosis were present in the cerebral cortex. A moderate degree of vacuolation and astrogliosis were observed in the cerebellum, brain stem, and spinal cord. These studies indicate that replication of the scrapie agent in the hamster is uniform throughout the CNS and precedes the development of pathological changes.

Animals↗
PubMed1983

Comparative neurovirulence of herpes simplex virus type 1 strains after peripheral or intracerebral inoculation of BALB/c mice.

Twenty-three strains of herpes simplex virus type 1 were compared for their pathogenicity in 4-week-old BALB/c mice after peripheral (footpad) or intracerebral inoculation. Among those strains examined were (i) six clinical isolates of brain or cerebrospinal fluid origin, (ii) seven clinical isolates of oral or genital origin, (iii) five prototype laboratory strains that have been passaged numerous times in culture, and (iv) five syncytial variants capable of producing cell fusion in culture. Based on comparative 50% lethal dose values, the strains appeared to segregate into one of three classes of neurovirulence. Class I strains were highly virulent by both the peripheral and intracerebral routes of inoculation, class II strains were highly virulent by the intracerebral route only, and class III strains were highly attenuated by both routes of inoculation. In vivo growth curves for whole brain homogenates infected with class III strains revealed titers of infectious virus approaching those found in the brains of animals infected with class I or II strains. These results would therefore suggest that (i) a strain-dependent variation in neural spread exists that may influence the ability of the virus to cause acute neurological disease and (ii) the amount of infectious virus present within an infected brain does not necessarily determine or reflect the clinical status of the animal. Of the clinical isolates examined, the strains recovered from brain tissue of humans after fatal episodes of encephalitis were found to be no more neurovirulent in mice than the strains isolated from nonneural sites. However, although syncytial variants were found to be highly attenuated by the peripheral route, as a group these strains proved to be among the most virulent when inoculated directly into the central nervous system.

Acute Disease↗
PubMed1983

Retinal degeneration in experimental Creutzfeldt-Jakob disease.

Mice with experimental Creutzfeldt-Jakob disease (CJD) develop a progressive retinal degeneration after a prolonged incubation period. Sections of the eyes stained with hematoxylin and eosin revealed pathologic changes in the optic nerve and a marked degeneration of photoreceptor cell inner and outer segment areas. Both peripheral and central retina, normally 10 cells thick, were reduced to one photoreceptor cell or less in thickness. Ultrastructural analysis revealed total loss of outer segment and most inner segment elements. Only Müller cell microvilli and macrophages remained in the subretinal space. Macrophages were also visible in the remnant photoreceptor cell layer. The inner nuclear layer and pigment epithelial cell layers appeared normal. Müller cell hypertrophy was evident but was not accompanied by spongiform vacuolation. Several of the degenerative changes of the eye in mice with experimental Creutzfeldt-Jakob disease differ from those observed for scrapie in rodents. The pathologic similarities between the retinal degenerations occurring in mice with experimental Creutzfeldt-Jakob disease and those found in some forms of human retinal degeneration are provocative. These similarities raise the question whether or not other retinal degenerative diseases might be caused by infectious agents such as prions or slow viruses.

Animals↗
PubMed1982

Herpetic proctitis and meningitis: recovery of two strains of herpes simplex virus type 1 from cerebrospinal fluid.

A patient with simultaneous proctitis and meningitis due to herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) was extensively investigated. In both disease locations the infection was clinically evident and culture-proven. Analysis by sodium dodecylsulfate-polyacrylamide gel electrophoresis of rectal isolates revealed both HSV-1 and HSV-2. The cerebrospinal fluid harbored two apparently different strains of HSV-1, one of which was shown by restriction endonuclease analysis to be identical with the rectal isolate of HSV-1.

Adult↗
PubMed1982

Detection of tissue culture-adapted Theiler's virus RNA in spinal cord white matter cells throughout infection.

The appearance of histological lesions and the localization of viral RNA in the central nervous system of mice infected with tissue culture-adapted Theiler's murine encephalomyelitis virus (WW strain) (TMEV-WW) was studied. Viral RNA was detected by autoradiography after in situ hybridization, using a (3)H-labeled DNA probe complementary to virion RNA, which was applied to deparaffinized sections of central nervous system tissues from infected mice. Subjacent histological sections of tissues were used to assess the location and extent of lesions. Lesions were first observed at 20 days post-inoculation and appeared to enlarge throughout infection. They consisted of infiltrates of mononuclear cells and lymphocytes in spinal cord white matter and leptomeninges; at 78 days post-inoculation severe necrotizing and demyelinative myelitis and gliosis were observed. In contrast to the pathogenesis of brain-derived TMEV-WW-infected mice, no lesions were found in the central nervous system gray matter of mice infected with tissue culture-adapted TMEV-WW at any time post-infection. Tissue culture-adapted viral RNA was found in the cells of spinal cord white matter throughout infection; only one neuron in close proximity to the injection site was found to contain viral RNA shortly after infection. At early times after infection, spinal cord white matter cells containing viral RNA were found before development of inflammatory lesions; at later days post-inoculation, positive cells were found within, at the periphery of, or at a distance from lesions. The number of infected cells and the amount of viral RNA per cell appeared to remain constant from 20 to 78 days post-inoculation despite the increasing intensity of the inflammatory response. The nearly exclusive spinal cord white matter tropism of tissue culture-adapted TMEV-WW appeared to directly correlate with the disease-inducing potential of this virus.

Animals↗
PubMed1982

Immunochemical features of a case of progressive rubella panencephalitis.

Progressive rubella panencephalitis (PRP), a slowly progressive and fatal central nervous system (CNS) disorder due to rubella virus, is characterized by high cerebrospinal fluid (CSF) levels of immunoglobulins, oligoclonal bands and high CSF:serum rubella antibody titre ratios. Sera, CSF and neutral extracts of brain, spleen, lymph node and kidney obtained at autopsy from a case were analysed for immunoglobulin isotype and content by enzyme linked immunosorbent assays. Comparable titres of rubella specific IgA and IgG were found in sera and CSF, but accounted for a disproportionate amount of the isotype specific immunoglobulins of CSF (0.19%, 14.0%) as compared to serum (0.02%, 0.69%). The percentage of isotype specific immunoglobulins were not increased in extracts of most visceral tissues compared to serum, however, rubella specific IgA and IgG were disproportionately increased in extracts from most regions of brain sampled (1-60-fold and 8-27-fold respectively). No rubella specific IgM could be conclusively demonstrated in any specimen. Immunoprecipitation studies showed that the IgG reacted with the major glycoproteins (gp62, gp47-56 complex) and non-glycosylated polypeptide (p38) of radiolabelled rubella virions and infected cell lysates. These studies support the conclusion that a major portion of the rubella specific antibody is produced within the CNS of patients with PRP.

Antibodies, Viral↗