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Biomedical subjects

C A Wiley

Publications and source records attributed to C A Wiley.

At least 55 records · Page 3Linked to original sources
PubMed1996

The Agar sandwich technique for retinal biopsy processing.

BACKGROUND: The authors developed an agar sandwich technique for retinal biopsy processing. This tissue agar embedding technique allows for a rapid and reliable method to handle and transport retinal biopsies from the operative field to the histology laboratory. METHODS: Biopsies from rabbit retinas infected with herpes simplex virus, epiretinal membranes from patients with macular pucker, and retinas from patients with acute retinal necrosis were studied. Each retinal biopsy was fixed, mounted on an agar disc, and covered with liquid agar. Light microscopy, electron microscopy, immunocytochemistry, and polymerase chain reaction were employed on the agar-embedded tissue. RESULTS: The tissues remained mounted in the agar sandwich and maintained their orientation throughout the processing. The morphologic integrity, histologic characteristics, antigenic properties, and DNA quality all were preserved using the agar sandwich technique. CONCLUSION: The agar sandwich technique is an efficient and simple technique for handling small biopsy specimens that require various analyses.

Agar↗
PubMed1996

Inflammation in AIDS and the role of the macrophage in brain pathology.

HIV-associated dementia complex is the most severe neurologic complication of AIDS. The pathologic substrate of the complex, termed HIV encephalitis, is marked by abundant infection and activation of brain macrophages. The pathogenesis of neurologic damage in HIV encephalitis is essentially undefined. Most current investigations are focused on potential viral or macrophage neurotoxins.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Macrophage Activation Factors in the Brains of AIDS Patients.

HIV, soluble HLA class I (sHLA-I), quinolinic acid (QUIN), and the monokines IL-1β, IL-6, and TNF-α were measured by ELISA and PCR in brain tissue of 60 AIDS autopsies without evidence of CNS opportunistic infections. Individual cases showed good interrogational correlations for the factors measured. There was a positive correlation between concentrations of IL-1β and IL-6. Brain viral burden correlated with intraparenchymal levels of sHLA-I, IL-1β, and IL-6. Comparison of neuritic damage and levels of immune mediators implicates macrophage activation factors in the etiology of neurologic damage in AIDS.

AIDS Dementia Complex↗
PubMed1995

A serum-free, pyruvate-free medium that supports neonatal neural/glial cultures.

Tissue culture media with serum generally cause excessive astrocyte proliferation in neonatal brain cultures, and often fail to support neonatal neurons. Published serum-free media for brain cultures contain sodium pyruvate, which interferes with lactate dehydrogenase (LDH) assays for cell death. We wanted to use neonatal neural-glial cultures in LDH assays while avoiding astrocyte proliferation, so we developed a serum-free medium without sodium pyruvate. Our initial medium was based on that of Romijn et al. (J Neurosci Methods 23:75-83, 1988), testing selected additives. Cell survival in 8-10-day-old cultures was measured using 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT). N-acetylcysteine, citrate, superoxide dismutase, ascorbate, supplemental amino acids, and high levels of transferrin improved survival. The optimized medium supported neonatal brain cells in reaggregates or in monolayers of 400 cells/mm2 for several weeks with large, healthy-appearing neurons and very little astrocyte proliferation. Neurons stained strongly for the neuronal marker class III beta-tubulin and the synapse marker synaptophysin. Electron microscopy of reaggregate cultures demonstrated abundant neurons with synapses in a dense neuropil. This medium will be useful for various in vitro applications, especially those using LDH assays or requiring the use of neonatal cells.

Animals↗
PubMed1995

The predictive value of cytomegalovirus retinitis for cytomegalovirus encephalitis in acquired immunodeficiency syndrome.

Cytomegalovirus (CMV) infection of the brain, optic nerves, and retinas from 47 consecutive autopsies of patients with acquired immunodeficiency syndrome (AIDS) were examined. Immunocytochemistry demonstrated CMV infection in 11 (23%) brains, two (2%) of 94 optic nerves, and 38 (40%) of 94 retinas. Ten (91%) of 11 patients with CMV encephalitis had concurrent retinitis. While 10 (42%) of 24 patients with CMV retinitis had CMV encephalitis, when the retinitis included the peripapillary region, 75% had encephalitis. Usually, the optic nerve parenchyma was not infected histologically despite extensive peripapillary retinitis. The strength of these associations suggests that CMV retinitis defines a group of patients with AIDS at risk for development of CMV encephalitis (relative risk, 9.5), particularly when the retinitis involves the peripapillary region (relative risk, 13). Furthermore, in patients with AIDS without CMV retinitis, central nervous system symptoms are unlikely to be attributable to CMV encephalitis.

AIDS-Related Opportunistic Infections↗
PubMed1995

Absence of infectious retinitis after injection of human cytomegalovirus into rabbit eyes.

The rabbit model of human cytomegalovirus (HCMV) retinitis was evaluated by preretinal and intravitreal injection of HCMV into rabbit eyes. Ocular disease was evaluated by indirect ophthalmoscopy, histopathology, and immunohistochemistry. Vitritis, optic nerve congestion, multiple small white infiltrates in the cortical vitreous or on the retinal surface, and retinal detachments were seen. Histopathologic examination showed inflammatory cell infiltration in the preretinal vitreous, optic nerve, and transiently in the superficial inner retina. Retinal structure was preserved except for changes in areas of retinal detachment. No necrosis or destruction of the retina was seen. Immunohistochemistry showed no evidence of cytomegalovirus infection. Inoculation of culture medium containing fetal calf serum caused a similar reaction. It is concluded that vitreous and retinal inoculation of HCMV in the rabbit eye caused nonspecific inflammation without evidence of infection, so this is not a suitable model for HCMV retinitis.

Animals↗
PubMed1995

Differential vulnerability of calbindin-immunoreactive neurons in HIV encephalitis.

Recent studies have suggested that the neuronal damage during human immunodeficiency virus encephalitis (HIVE) might be mediated by increased intracellular calcium. Since in vitro studies have shown that calcium-binding proteins protect neurons from calcium-mediated toxicity, we hypothesized that calbindin-expressing neurons might be resistant to HIV1-mediated damage. We compared patterns of calbindin immunoreactivity in the cortex and subcortex of autopsied AIDS cases with and without HIVE. Calbindin-immunoreactive neurons in the neocortex were significantly reduced in HIVE (one-way ANOVA, p < 0.001), while these neurons in the basal ganglia and hippocampus were unaffected. The loss of calbindin-immunolabeled neurons in the neocortex was correlated with viral burden (r = -0.45, p < 0.001). Differential loss of calbindin-immunoreactive neurons in HIVE suggests that neuronal damage in different regions of the CNS may be mediated by different pathogenic mechanisms.

Basal Ganglia↗
PubMed1995

Antiviral effect in human cytomegalovirus-infected cells, pharmacokinetics, and intravitreal toxicology in rabbits of acyclovir diphosphate dimyristoylglycerol.

Acyclovir diphosphate dimyristoylglycerol (ACVDP-DG) is a lipid prodrug which is active against ACV-resistant strains of herpes simplex virus because of its intracellular metabolism to ACV monophosphate. In human cytomegalovirus (HCMV)-infected MRC-5 cells, ACVDP-DG was ninefold more active than ACV. When liposomal [8-3H]ACVDP-DG was injected intravitreally at the maximum nontoxic dose of 1 mumol in rabbits, the drug remained above its estimated 90% HCMV-inhibitory concentration for 18 days. Intravitreal ganciclovir persists above its 90% inhibitory concentration for only 1 to 2 days. ACVDP-DG may be useful as a local treatment for HCMV retinitis.

Acyclovir↗
PubMed1995

Evaluation of retinal toxicity and efficacy of the anticytomegalovirus compound 2-amino-7-[(1,3-dihydroxy-2-propoxy)methyl]purine.

Compound 2242, also known as 2-amino-7-[(1,3-dihydroxy-2-propoxy)methyl]purine, is the first known antivirally active nucleoside analog with the side chain substituted at the N-7 position of the purine ring system. Our purpose was to evaluate its retinal toxicity and assess the efficacy of its highest nontoxic concentration in a rabbit model of herpes simplex retinitis. Concentrations of the drug from 0.5 to 2,000 microM were injected intravitreally in twelve New Zealand White rabbits. Fundoscopic, histologic, and electrophysiologic data revealed no evidence of toxicity even at the highest dose of the compound. Dutch pigmented rabbits (n = 34) had their left eyes injected with herpes simplex virus type 1 3 days after, concurrently, or 3 days before intravitreal injection of either 2,000 microM compound 2242 or 480 microM ganciclovir (final concentration in the eye). Both compound 2242 and ganciclovir were equally effective compared with saline when administered simultaneously with the virus (P < 0.0001). In the 3-day pretreatment paradigm, compound 2242 was superior to ganciclovir (P < 0.04), but there was no clear difference between the two with regard to their effects on an established infection. The pharmacokinetics of compound 2242 in 10 rabbits injected intravitreally with 30 microM showed an intravitreal half-life of 8 h. This compound, which may be orally active in its pro form, has a very high therapeutic index in the eye and is more efficient than ganciclovir in this animal model of herpes retinitis.

Administration, Oral↗
PubMed1995

Immune predispositions for cytomegalovirus retinitis in AIDS. The HNRC Group.

CMV retinitis develops in approximately 28-35% of all AIDS patients at later stages of disease, often leading to blindness. To determine whether the subset of AIDS patients who developed CMV retinitis (CMV-R) were immunologically predisposed, T cell proliferation responses to CMV were examined prospectively in an HIV infected, HLA typed, longitudinal study population. Individuals who developed CMV-R had significantly lower T cell proliferation responses to CMV, both early and late in disease, compared to CD4 matched controls who have not developed CMV-R. Since HLA proteins influence T-cell recognition, phenotypes of 21 CMV-R patients were examined to determine whether certain HLA alleles were associated with low immune response and predisposed AIDS patients to CMV-R. HLA DR7 and B44 were at increased (nearly twice the expected) frequency in those with CMV-R. The combined association of either B44, 51 or DR7 with CMV-R was highly significant (P = .008, relative risk of CMV-R = 15) with correction for multiple comparisons. Low immune responses were twice as frequent in those with (61%) compared to those without (30%) predisposing alleles. Thus, AIDS patients with immunogenetically related hyporesponsiveness to CMV antigens may be at increased risk of retinitis.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Chronic myelopathy associated with human herpesvirus-6.

Human herpesvirus-6 (HHV-6) is implicated in a variety of neurologic diseases. We report a previously healthy elderly woman with progressive spastic paraparesis. At autopsy the spinal cord showed widespread demyelination, axonal loss, and chronic inflammation. HHV-6 DNA was amplified, using polymerase chain reaction, from spinal cord tissue, and glial cells were immunoreactive with an HHV-6 antibody. These findings suggest that HHV-6 may cause myelopathy.

Aged↗
PubMed1995

Neuropathology of the retina in acquired immunodeficiency syndrome.

The pathogenesis of HIV-mediated neurodegeneration is unknown. Presently, work is focused on two main hypotheses: direct (caused by HIV or component proteins) versus indirect (monocyte-mediated) neurotoxicity. In HIV-induced retinal disease, the high incidence of opportunistic infections and the low HIV viral burden found in most clinical specimens present challenges in defining the roles played by potential factors. Future studies will see the resolution of these controversies by showing the mechanism of HIV-induced neuronal damage and its relationship to retinal disease.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Intraocular tolerance of perfluorooctylbromide (perflubron)

PURPOSE: To determine the intraocular tolerance of perfluorooctylbromide (perflubron) in vitrectomized rabbit and pig eyes and evaluated its use as a vitreous substitute in virteoretinal surgery. METHODS: Pars plana vitrectomy was performed on 33 Dutch pigmented rabbits and 11 micro mini pigs. After vitrectomy the eyes were filled with perflubron for 2 hours, 1 week, 2 weeks, 1 month, and up to 6 months. RESULTS: No clinical, electroretinographic, or light and electron microscopic evidence of adverse effects on the retina and lens were observed. Perflubron emulsified and dispersed into small bubbles after 2-3 weeks. The lens showed mild posterior subcapsular cataracts in pig eyes after long-term retention of perflubron. CONCLUSION: These findings indicate that perflubron is safe for intraoperative and for long-term use intravitreally. However, emulsification and the breakdown into small bubbles limits the view of the retina when perflubron is used as a long-term tamponade.

Animals↗
PubMed1994

Cytokine receptor alterations during HIV infection in the human central nervous system.

Cytokines are potent factors mediating interactions between the immune and nervous systems. Cytokines released by macrophages/microglia, the predominant immune cell within the brain, have been proposed to modulate neuronal survival and death. In human immunodeficiency virus-encephalitis (HIVE), cytokines could modulate neurologic damage if nervous system cells possessed appropriate receptors. We hypothesized that the populations of neurons vulnerable to the toxic effects of cytokines in HIVE might contain specific receptors for these molecules. We examined the distribution of cytokine receptors in the human brain utilizing fluorescent-labeled cytokines combined with confocal laser microscopy imaging. Phycoerythrin-conjugated interleukin-1 beta and phycoerythrin-Avidin/biotin conjugated transforming growth factor beta 1 labeled dendritic processes of neurons in the neocortex. Labeling was abolished by pre-incubation with unlabeled cytokines. In cases with moderate HIVE, an average 35% increase in intensity of labeling was observed compared to cases without HIVE or with cases with severe HIVE. The patterns of interleukin 2 labeling were not altered in HIVE. These results suggest that neurons susceptible to cytokine-mediated damage during the progression of HIVE display abnormal patterns of cytokine receptor labeling.

AIDS Dementia Complex↗