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Biomedical subjects

D H Gilden

Publications and source records attributed to D H Gilden.

At least 109 records · Page 6Linked to original sources
PubMed1983

A low thymidine kinase-producing mutant of herpes simplex virus type 1 causes latent trigeminal ganglia infections in mice.

The wild type NIH strain of herpes simplex virus type 1 (HSV-1) has a mixed plaque morphology of both large and small plaques. From this virus we selected a large plaque isolate that was a high producer of thymidine kinase (TK) activity (designated TK+) and a small plaque isolate that produced 25 per cent of the TK activity of the large plaque mutant (designated TK 1/4). A TK- mutant of the large plaque virus was obtained after passage of the virus in the presence of BUdR. The pathogenicity of the TK 1/4 virus strain in relation to the TK+ and TK- strains was investigated in mice after inoculation of the virus into the eyes by corneal scarification. The TK+ strain was highly pathogenic, caused encephalitis and killed most of the mice, whereas the TK- strain did not cause latent infections in the trigeminal ganglia or kill the mice. The TK 1/4 virus strain replicated in the eyes within 24 hours after inoculation and entered the trigeminal ganglia, establishing a latent infection in almost all of the mice. By increasing the infectious dose tenfold, the TK 1/4 virus caused an active infection in the trigeminal ganglia (ganglionitis), migrated to the brain, and killed the mice. The results indicate that not only is a low level of TK required to establish latent infections in mice, but also the degree of virulence is determined by the amount of TK produced by the infecting virus.

Animals↗
PubMed1983

Slow virus diseases of the CNS. 1. Subacute sclerosing panencephalitis, progressive rubella panencephalitis, and progressive multifocal leukoencephalopathy.

Several slowly progressive diseases of the human CNS are now known to be caused by viruses. Subacute sclerosing panencephalitis (SSPE) is caused by a measles virus that may be sequestered in the cell rather than eradicated; the disease occurs between the ages of 4 and 20. Progressive rubella panencephalitis (PRP) is caused by a rubella virus that persists in the CNS; its onset is about a decade after rubella-virus infection. Progressive multifocal leukoencephalopathy (PML) is caused by a papovavirus that lyses oligodendrocytes; it usually occurs between the ages of 50 and 60. All three disorders are characterized by usually slow mental and motor deterioration; patients with SSPE and PRP also have myoclonic seizures. The pathogenesis of these diseases is not yet understood, and there is no effective treatment. Death occurs within months to years.

Adolescent↗
PubMed1982

The production of varicella Zoster virus antiserum in laboratory animals. Brief report.

Hyperimmune anti-varicella zoster virus (VZV) antisera were prepared in BALB/c mice, Lewis rats and New Zealand rabbits by subcutaneous inoculations of purified VZ virions suspended in Freund's adjuvant. VZV antibodies were demonstrated both by an enzyme-linked immunosorbent assay (ELISA) and by indirect immunofluorescence (IF). VZV could not be detected in organs of any inoculated animals by IF or by cocultivation of tissue fragments from infected animals with human diploid fibroblasts.

Animals↗
PubMed1982

Demonstration of JC virus by immunofluorescence in multiple cell types in experimentally infected adult human brain cell cultures.

JC virus (JCV)-induced T antigen developed in the nuclei of approximately 50% of adult human brain (AHB) cells infected with JCV. Approximately 10% of these T antigen-positive cells contained glial fibrillary acidic protein (GFAP) and were identified as astrocytes in immunofluorescence studies. About 50% of these T antigen-positive cells bound antiserum to fibronectin on their surface and were identified as fibroblasts. No cells binding antiserum to galactocerebroside (GC), an oliodendrocyte-specific marker, were detected in infected or non-infected AHB cultures. the cell type of AHB that constitutes the remaining 40-50% of T antigen-positive cells that are GFAP-, fibronectin- and GC-negative remains to be determined.

Adult↗
PubMed1982

Extraction of cell-associated varicella-zoster virus DNA with triton X-100-NaCl.

Varicella-zoster virus (VZV) DNA was extracted from infected cells with 0.25% Triton X-100-0.2 M NaCl and purified by isopycnic centrifugation in CsCl. In each of eight experiments, 1.8-9.8 micrograms VZV DNA was obtained from 107 infected cells. The VZV DNA obtained by this procedure had a molecular weight of 88-100 x 106 as determined by sucrose gradient sedimentation and electron microscopy, and cleavage patterns after digestion with four restriction enzymes that corresponded to patterns previously described with six strains of VZV; the pattern of BamHI-cleaved Triton-NaCl-extracted VZV DNA was identical to the pattern seen after DNA extraction from virions. These studies expand the usefulness of Triton X-100-NaCl for extraction of large molecular weight viral DNA from a system where considerable cell-free virus is produced (Pignatti et al., 1979, Virology 93, 260) to a system known for its marked cell association.

Animals↗
PubMed1982

The internal organization of the varicella-zoster virus genome.

DNA was extracted from varicella-zoster (VZ) virions prepared in sucrose gradients. Thirty-eight molecules examined by electron microscopy were found to have a mean length of 46.7 micrometers. Examination of self-annealed VZV DNA molecules revealed that the virus genome was composed of a unique linear large sequence with a mol. wt. of 74.4 X 10(6) to 78.4 X 10(6), and a unique short sequence of mol. wt. approx. 9.8 X 10(6) flanked by inverted repeat sequences of 4.7 X 10(6) mol. wt.

Base Sequence↗
PubMed1981

Human brain in tissue cultures. VI. Presence of glial fibrillary acidic protein in subcultivated human fetal brain cells as demonstrated by immunofluorescent and immunoperoxidase staining.

Glial fibrillary acidic protein (GFAP) was present in cell cultures derived from human fetal brain tissue as determined by indirect immunofluorescence (IF) and immunoperoxidase (IP) staining using rabbit anti-human GFAP antisera. The IF and IP techniques were comparable in localizing the cytoplasmic distribution and the frequent perinuclear concentration of GFAP in brain cells. The horseradish peroxidase technique was more sensitive and a 1:20-1:40 dilution of anti-GFAP serum could be applied in the initial step of the peroxidase staining as compared to a 1:10 dilution of anti-GFAP serum for IF staining. Sequential studies of subcultivated human fetal brain cell lines by these techniques indicated that some brain cell lines become GFAP-negative rapidly, whereas other cell lines remain GFAP-positive for no less than ten subcultivations in vitro. GFA protein was never present in any PML-SV40-transformed human brain cells.

Animals↗
PubMed1981

The use of vesicular stomatitis (visna virus) pseudotypes to demonstrate visna virus receptors in cells from different species.

Superinfection of visna virus (VV)-infected cells with vesicular stomatitis virus (VSV) resulted in the formation of a pseudotype virus population containing a VSV genome within a VV coat [designated VSV (VV)] as determined by plaque reduction neutralization with antisera to VSV and VV. These VSV (VV) virions were capable of infecting cell cultures from a number of species that were non-permissive for VV alone. Limited propagation of VV in some mammalian species would thus appear to be due to an intracellular restriction rather than to absence of VV receptors.

Animals↗
PubMed1981

Herpes simplex type 1 DNA in human brain tissue.

Herpes simplex virus type 1 (HSV-1) is known to reside latently in the trigeminal ganglia of man. Reactivation of this virus causes skin lesions and may occasionally infect other tissues, including the brain. To determine whether the brain tissue of humans free of clinical signs of HSV-1 infection contains any trace of HSV-1, we examined the DNA from brain tissue by endonuclease digestion, separation of the fragments by gel electrophoresis, and hybridization with labeled HSV-1 DNA probes. Hybrid bands were detected autoradiographically in experiments using cloned and virion-purified fragments of the HSV-1 genome. HSV-1 DNA sequences were found in 6 of 11 human brain DNA samples tested. In some cases, these bands corresponded to the bands expected for the complete viral genome, whereas others contained bands representing only a part of the genome. In some cases, the terminal fragments could be found, suggesting that the DNA was in a linear, nonintegrated form.

Brain↗
PubMed1980

Growth of murine cytomegalovirus in murine and heterologous brain cell cultures. Brief report.

Murine cytomegalovirus (MCMV) produced a cytopathic effect in mouse brain, guinea pig embryonic brain, human brain and fibroblast cells. Virus-specific antigen was detected by immunofluorescence in these cells after primary infection with MCMV. MCMV also replicated in ouse embryo brain and guinea pig brain cells. Although definite evidence of MCMV replication could not be demonstrated in human cells, MCMV infectivity was maintained for 12 days in human cell cultures.

Animals↗
PubMed1979

Growth of the WW strain of Theiler virus in mouse central nervous system organotypic culture.

Myelinated organotypic cultures of mouse central nervous system (CNS) provide a favorable milieu for growth of the WW strain of Theiler virus (TV). WW-TV induced a cytopathic effect characterized by neuronal destruction and swelling of myelin sheaths. Tissue culture medium and homogenates of infected cultures produced neurologic disease in mice, and TV was demonstrated in cultures by indirect immunofluorescence and electron microscopy. Ultrastructurally, severe alterations in neurons and the presence of cytoplasmic inclusions containing paracrystalline arrays of 30-nm virus particles were evident in astrocytes. Demyelination appeared to be secondary to lysis of oligodendrocytes by virus. CNS organotypic cultures provide an environment for the study of TV-induced demyelination.

Animals↗
PubMed1979

Acute demyelinating disease in a chimpanzee three years after inoculation of brain cells from a patient with MS.

Brain cells from a patient with classic multiple sclerosis were inoculated intracerebrally into the frontal lobe of a newborn chimpanzee. The animal developed acute quadriplegia three years, two months later and was killed four days after the onset of symptoms. Central nervous system lesions were primarily localized in the spinal cord at root entry zones; these were characterized by demyelination and regeneration of myelin by Schwann cells.

Animals↗
PubMed1978

Morphological studies of hamster brain cells transformed in vitro by a human papovavirus BK.

The cytomorphology and cytogenesis of BK virus-transformed hamster brain cells (HBBK cells) were studied. HBBK cells with indistinct processes showed a tendency to epithelial arrangement as well as characteristics of malignant tumor cells in vitro, and developed long, delicate processes when cell growth was suppressed. Glial fibrillary acidic protein was demonstrated by immunofluorescence in the cytoplasm of almost all HBBK cells. The tumors arising in hamsters after subcutaneous inoculation of HBBK cells were classified as poorly differentiated gliomas. These findings suggest that selective transformation of glial cells in hamster brain cells by BK virus occurred.

Animals↗
PubMed1978

Enhanced parainfluenza I (6/94) virus detection in latently infected human brain cell cultures by treatment with cytochalasin D and dimethyl sulfoxide.

The ability of cytochalasin D (CD) and dimethyl sulfoxide (DMSO) to enhance parainfluenza I (6/94) virus replication was studied in various cell culture systems. Treatment of CV1 cells with CD (1 microgram/ml) dissolved in DMSO prior to primary 6/94 virus exposure at 10(0)--10(5) multiplicities of infection did not substantially enhance virus replication. However, there was a transient increase in cell associated virus one day after infection of DMSO-treated cultures. CD treatment of cultures of human brain cells latently infected with 6/94 virus (LIHB cells) did not enhance 6/94 virus detection. Cocultivation of CV1 cells with CD-treated LIHB cell cultures, and cocultivation of LIHB cell cultures with CD-treated CV1 cells, resulted in the production of both cell-associated and cell-free 6/94 virus three and five days after cocultivation. No virus was detected after similar cocultivation of untreated LIHB cell cultures with untreated CV1 cells. The usefulness of CD-DMSO treatment in the rescue of virus from 6/94 LIHB cell cultures appears limited to a cocultivation system. The use of these techniques to enhance virus rescue from human tissues suspected of harboring latent viral genomes is discussed.

Animals↗
PubMed1978

Rat tracheal organ culture supports replication of parainfluenza 1 (6/94) virus and promotes 6/94 virus rescue from latently infected human brain cells.

Rat tracheal organ culture (TOC) supported replication of parainfluenza 1 (6/94) virus. Cell-associated and cell-free viruses were found after primary infection of TOC. In contrast to other mammalian systems, rat TOC was capable of maintaining 6/94 virus infectivity after primary infection. Rat TOC may be considered a potential indicator system that could be used to detect virus latent in human tissue.

Animals↗
PubMed1978

Varicella-zoster virus infection of human brain cells and ganglion cells in tissue culture.

The growth of varicella-zoster virus (VZV) in cultures of human brain (HB) and human ganglion (HG) cells was compared to VZV growth in human fibroblasts. Infected cultures were monitored by histologic, electron microscopic (EM), and virologic techniques. Two to three days after VZV infection of all cell cultures at a multiplicity of infection (MOI) of 0.1, a multifocal cytopathic effect (CPE) developed. CPE was characterized by multinucleated cells and virus-specific intranuclear inclusions as determined by immunofluorescence and EM. In VZV- infected HB and HG cells only, large vacuoles were also seen in the cytoplasm of dying cells. Some vacuoles were almost devoid of structures. Within and at the limiting membranes of other vacuoles, aggregates of VZV particles (measuring 210--230 nm) were seen enveloped in osmiophilic material. VZV infection of HB and HG cultures was strongly cell-associated. Clarified tissue culture medium removed at maximum CPE failed to infect homologous HB or HG cells. When an inoculum of VZV-infected HB or HG cells was transferred to homologous uninfected cultures for 10--15 passages, the incubation period for CPE remained constant, and the titer of VZV in cells sampled randomly corresponded to the amount of virus that was used for original infection.

Brain↗
PubMed1978

Virology and histopathology of the trigeminal ganglia of Americans and Japanese.

Herpes simplex virus in the trigeminal ganglia of humans was studied in Philadelphia, Pennsylvania, United States of America, and in Kyoto, Japan. The prevalence of recurrent herpes labialis and of clinically latent herpes simplex virus within trigeminal ganglia was determined in inhabitants of the two cities. In addition, a comparison was made of the prevalence of mononuclear cell infiltration in the trigeminal ganglia of Americans and Japanese. Recurrent herpes labialis was found to be significantly less common in the Japanese city than in the American city. Herpes simplex virus was rescued less commonly from the trigeminal ganglia of cadavers in Japan than in America. The difference was significant. The frequency of mononuclear cell infiltration in the trigeminal ganglia of Americans and Japanese is not significantly different. These observations, as well as previously reported serological studies, suggest that despite the ubiquitous nature of herpes simplex virus in America and Japan, the Japanese have less clinically overt disease caused by this virus.

Adolescent↗