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Biomedical subjects

C A Wiley

Publications and source records attributed to C A Wiley.

At least 127 records · Page 7Linked to original sources
PubMed1990

Experimental endoretinal biopsy.

We performed transvitreal endoretinal biopsy in rabbit eyes to develop a reliable and safe technique to obtain retinal specimens from attached retina. Pars plana vitrectomy without lensectomy was followed by injection of Ringer's solution into the subretinal space to produce a focal retinal detachment. The apex of the focal detachment was excised by intraocular scissors and removed from the eye by pneumohydraulic expulsion. A fluid-air exchange reattached the retina. The biopsy sites were evaluated clinically and by light and electron microscopy at regular intervals up to 20 weeks postoperatively. The initial five procedures were performed without heparin in the infusion fluid, and they were complicated by severe fibrin reaction and early retinal detachment. Of the remaining 17 eyes, 15 were without intraoperative complication and maintained attached retinas. The biopsy site developed an early ring of hyperpigmentation along the border, and the biopsy bed became increasingly hyperpigmented because of cytoplasmic hyperplasia and hypertrophy of the pigment epithelium. Epiretinal membranes and subretinal neovascularization were observed histologically. Retinal biopsy specimens were reproducible and suitable for diagnostic studies.

Animals↗
PubMed1990

Human immunodeficiency virus: infection of the nervous system.

Cynics would say it has taken the scientific community a long time to achieve very little progress in our understanding of HIV-mediated CNS damage. We cannot yet say with surity how neuronal function is affected. However, when viewed through the perspective that retroviral diseases of the human nervous system are newly recognized diseases, significant progress has been made in the 3 years since HIV infection was noted within the CNS. We have a lot to learn about how retroviruses damage the CNS, but at least the questions are better defined.

Central Nervous System Diseases↗
PubMed1990

Lobar atrophy with dense-core (brain stem type) Lewy bodies in a patient with dementia.

A 62-year-old man presented with memory impairment progressing over 6 years to dementia with near mutism and was diagnosed as having Alzheimer's disease. At autopsy his brain showed lobar atrophy suggestive of Pick's disease and there were spherical intracytoplasmic neuronal inclusions in the fascia dentata, hippocampal pyramidal cell layer, and temporal cortex. Unlike Pick bodies, however, the inclusions were eosinophilic with H&E stains, non-argyrophilic, and failed to react immunohistochemically with antibodies to paired helical filaments or Alz-50. They did label with antibodies to ubiquitin, however, and electron microscopy disclosed dense-cored granular structures with thin filamentous coronas which resembled brain stem-type Lewy bodies. The substantia nigra and locus coeruleus were not affected.

Atrophy↗
PubMed1990

Cultured human brain capillary endothelial cells are permissive for infection by human cytomegalovirus.

Human cytomegalovirus (HCMV) infection is associated with a variety of systemic and neurologic diseases. In vitro HCMV growth is usually studied in fibroblasts, while in vivo HCMV growth is frequently observed in a wide variety of cell types including glia, neurons, and human brain capillary endothelial (HBCE) cells. To examine the biology of HCMV in HBCE cells, we have established a procedure for isolating these cells from human brain temporal lobectomies. Greater than 99.0% of these cultured cells were identified as HBCE cells on the basis of positive staining for factor VIII-related antigen-Von Willebrand's factor (F VIII) and Ulex Europaeus agglutinin I (UEA I). HCMV antigens were detected by immunocytochemistry in HBCE cells after infection with strain AD 169. Intracellular virions were observed in infected cells by electron microscopy and infectious virus was released from HBCE cells. In addition, infected cells were confirmed as endothelial cells by double staining with antibodies to F VIII and HCMV.

Antibodies, Viral↗
PubMed1990

Immunohistochemical localization of neurotropic ecotropic murine leukemia virus in moribund mice.

The CasBrE strain of neurotropic ecotropic murine leukemia virus (NE-MuLV) infects susceptible mice and induces a noninflammatory, slowly degenerative nervous system disease. We employed immunohistochemistry to identify which cells in the nervous system and other tissues contained viral antigen in the chronically infected mouse. Rabbit antiserum to the virus was prepared using different combinations of whole virus and synthetic peptides corresponding to a 14-amino-acid sequence of the viral envelope protein. Twenty-four of forty-four (55%) mice neonates inoculated intracranially with NE-MuLV developed symptoms ranging from tremulousness to hindlimb paralysis within 3-9 months. They were subsequently sacrificed and their tissues used for histology and immunohistochemistry. The major locations of viral antigen outside of the central nervous system (CNS) were skeletal muscle and spleen. Skeletal muscle was the only non-nervous system tissue that exhibited degenerative changes as atrophy of viral antigen-bearing oxidative myofibers. In the CNS, viral antigen was detected in neurons, endothelium, and glial cells. Immunohistochemical double-labeling studies for viral antigen and the astrocytic marker glial acidic fibrillary protein (GFAP) demonstrated that the viral antigen-containing glia were oligodendrocytes and not astrocytes. Tissue damage in the brain consisted of vacuolar changes and gliosis principally in the brainstem. Viral antigen was most abundantly localized in these regions of pathologic change. In the spinal cord a different pattern was observed. Although tissue damage was observed throughout the cord, viral antigen was located at the border of the gray and white matter. These findings indicate direct and indirect virus-mediated mechanisms of damage to the CNS.

Amino Acid Sequence↗
PubMed1990

T-cell-induced expression of human immunodeficiency virus in macrophages.

Macrophages are major reservoirs of human immunodeficiency virus (HIV) in the tissues of infected humans. As monocytes in the peripheral blood do not show high levels of infection, we have investigated the expression of HIV in T-cell-activated, differentiated macrophages. Peripheral blood mononuclear cells were isolated from HIV-seropositive individuals and stimulated with antigens or mitogens, and the nonadherent fraction was removed. Macrophages were cultured alone for 2 weeks, and HIV expression was assessed. Results from p24 antigen capture assays demonstrated that the presence of autologous T cells and concanavalin A or autologous T cells and allogeneic cells for the initial 24 h of culture induced HIV expression in 35 of 47 (74%) HIV-seropositive patients tested. The macrophage monolayers could be immunostained with anti-HIV antibodies to reveal discrete infectious centers, indicating that complete virus replication was occurring in the macrophages and that infection of adjacent cells was mediated by cell-cell contact. Time course studies of the interval of coculture of the adherent and nonadherent cells indicated that 24 h (but not 2 h) was sufficient for induction of HIV in the macrophages. Direct contact between the adherent cells and activated T cells was required as well. Since the presence of autologous T cells also appeared to be necessary, induction of HIV expression in macrophages may be genetically restricted. HIV-seronegative nonadherent cells were able to induce HIV expression in macrophages from HIV-seropositive donors, demonstrating that the virus originated in the monocytes and was reactivated in the context of a classic T-cell-mediated immune reaction. The high percentage of monocytes from HIV-seropositive donors which can be induced to replicate HIV by activated T cells suggests that infection of monocytes may be critical to the pathogenesis of this lentivirus infection.

Cell Communication↗
PubMed1990

Encephalitis caused by human immunodeficiency virus: CT and MR imaging manifestations with clinical and pathologic correlation.

To determine the computed tomographic (CT) and magnetic resonance (MR) imaging manifestations of central nervous system (CNS) infection by the human immunodeficiency virus (HIV), the authors analyzed the results of imaging of the CNS in 24 patients with HIV encephalitis confirmed at autopsy. Careful pathologic correlation demonstrated that neither CT nor MR imaging enabled detection of microglial nodules with multinucleated giant cells, the hallmark of HIV encephalitis seen in all 24 affected patients. The most common abnormality observed on images of the CNS was atrophy, demonstrated in 18 patients. Demyelination and vacuolation of white matter tracts accompanying severe HIV infection caused hypoattenuation on CT scans and hyperintensity on T2-weighted MR images. These lesions had no mass effect. MR imaging was more sensitive than CT in the detection of lesions caused by HIV or other superimposed infectious agents. Although it is often difficult to attribute any radiologic appearance to a single etiologic agent in patients with acquired immunodeficiency syndrome, the combination of atrophy and symmetric, periventricular or diffuse white matter disease suggests HIV encephalitis.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Neurological and neuropsychological complications of HIV infection, Monterey, California, June 16-19, 1990.

In summary this important conference covered the entire gamut of issues regarding retroviral damage of the central nervous system. Neuropathologists interested in this rapidly moving field should strongly consider attending the next satellite conference to be held in June 1991 in Florence, Italy. Given the almost carnival atmosphere that the parent International AIDS Conference has fallen into, this is an important satellite conference that lends itself well to the close sharing of data from a wide spectrum of neuroscience fields.

AIDS Dementia Complex↗
PubMed1990

Pathologic observations made by retinal biopsy.

The authors report four cases in which retinal biopsy findings yielded unexpected or previously unreported diagnoses in patients with inflammatory retinitis. The tissue diagnoses included Wegener's retinal vasculitis in an immunosuppressed patient with a clinical diagnosis of cytomegalovirus retinitis, a novel viral form in the retina of a patient with cytomegalovirus retinitis, a case of acute retinal necrosis due to cytomegalovirus infection in an immunologically normal adult, and a case of ganciclovir-resistant herpes family viral retinitis. These cases illustrate the use of retinal biopsy in obtaining tissue for diagnosis and guiding treatment in selected cases of retinitis.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Severe visual loss related to isolated peripapillary retinal and optic nerve head cytomegalovirus infection.

We examined ten patients from a consecutive series of 73 patients with either isolated cytomegalovirus papillitis or limited cytomegalovirus retinitis contiguous with the optic disk. Patients with peripheral retinitis and other areas of retinitis were excluded. All patients were treated with ganciclovir. Two distinct types of cytomegalovirus infection of the peripapillary area were identified. Type I was characterized by spread of limited retinitis to the optic disk margin, good central visual acuity, and permanent arcuate and altitudinal visual field defects that enlarged and became more complete as the retinitis progressed toward the disk. Type II appeared to be a true cytomegalovirus infection of the optic nerve characterized by primary, isolated papillitis with peripapillary retinitis, an early afferent pupillary defect, and good initial visual acuity, which rapidly deteriorated despite prompt antiviral therapy. Peripapillary cytomegalovirus retinitis appears to be an important and underreported cause of visual morbidity in patients with AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1989

The agar-albumin sandwich technique for processing retinal biopsy specimens.

Retinal biopsy may be useful procedure in the diagnosis of certain cases of infectious retinitis complicated by retinal detachment. The small, delicate pieces of retina obtained by retinal biopsy are difficult to handle and prepare for histologic processing. The tissue is friable, may curl upon itself, and is often lost during normal processing. Routine methods for handling small biopsy specimens of other tissues are inadequate for preparing retinal specimens. We developed an agar-albumin tissue mount for the sterile recovery and transport of small pieces of retina from the operative field to the laboratory. The agar-albumin sandwich mount facilitates tissue processing without interfering with histologic sectioning or interpretation. The ability to recover small, friable pieces of retina in a manner that allows good histologic examination is essential if retinal biopsy specimens are to be used in the diagnosis and management of patients with infectious retinitis where the causative agent is unclear.

Agar↗
PubMed1989

Pneumocystis carinii choroidopathy. A new clinical entity.

A 43-year-old black woman with acquired immunodeficiency syndrome developed bilateral multifocal choroidopathy characterized by slowly enlarging round to oval lesions in the posterior pole and midperiphery. Systemic evaluation revealed no evidence of mycobacterial, fungal, or spirochetal disease. Fluorescein angiography of the lesions showed early hypofluorescence with late staining of the lesions, which appeared deep to the retinal circulation. There was no evidence of retinal involvement. Over a 4-month period of observation, the lesions appeared to enlarge slowly, with no evidence of vitreous cells or debris in the overlying retina. A transscleral choroidal biopsy was performed, and electron microscopy showed numerous cystic structures characteristic of Pneumocystis carinii within necrotic choroid. The lack of inflammatory changes clinically, by fluorescein angiography, and histopathologically was striking.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Spinal cord and peripheral nerve pathology in AIDS: the roles of cytomegalovirus and human immunodeficiency virus.

We examined spinal cords, nerve roots, or peripheral nerves of 27 patients who died with acquired immunodeficiency syndrome (AIDS) for the presence of cytomegalovirus (CMV) and human immunodeficiency virus (HIV) by immunoperoxidase techniques in paraffin-embedded tissue. Vacuolar myelopathy was seen in 8 of 26 spinal cords (31%) and microglial nodules were seen in 13 (50%). All of the patients with lateral column vacuolar myelopathy showed severe brain pathology. HIV antigens had been detected in the brains of 15 (55%) of the 27 patients but were detected in only 3 (11%) of 26 spinal cords and were not localized to regions of vacuolar myelopathy. This suggests that the vacuolar myelopathy may be due to a remote or indirect effect of HIV or other infectious agent. CMV antigens were detected in none of the patients who showed vacuolar myelopathy but were detected in 2 of the 13 with microglial nodules. Focal nerve root or peripheral nerve inflammation was seen in 7 patients; 4 had CMV antigens and none had HIV antigens. CMV appears to be an important cause of inflammatory peripheral neuropathy in AIDS patients.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Endoretinal biopsy in immunosuppressed and healthy patients with retinitis. Indications, utility, and techniques.

Endoretinal biopsies were taken using pars plana vitrectomy techniques in 13 eyes with inflammatory or infectious retinitis complicated by retinal detachment (RD). The surgical technique has evolved over a 4-year period. The authors review the surgical technique including techniques of removal of the vitreous, appropriate hemostasis, selection of the biopsy site, and atraumatic removal of the tissue from the vitreous cavity. Careful processing of the material for histopathology, immunopathology, and electron microscopy is necessary and has provided useful information in patient diagnosis and management. The authors have used the technique in cases of rhegmatogenous RD complicating presumed viral retinitis. The technique has proven to be useful in confirming the clinical diagnosis and is relatively safe when used in selected cases.

Biopsy↗
PubMed1989

Neuromuscular diseases of AIDS.

Neuromuscular diseases are common in acquired immune deficiency syndrome (AIDS). Although the clinical incidence of peripheral neuropathy has not been systematically studied, various reports suggest that up to 40% of AIDS patients have clinical symptoms. Biopsy and autopsy studies have shown an inflammatory neuropathy with a variable component of demyelination and axonal loss. Evidence of direct involvement by the human immunodeficiency virus (HIV) is scant. Immunosuppression followed by cytomegalovirus (CMV) infection appears to be a direct cause of polyradiculoneuropathy and perhaps other forms of peripheral neuropathy in AIDS. The clinical incidence of myopathy in AIDS is less clear, and clinically less appreciated than the neuropathy. Scattered reports have identified an inflammatory myopathy that does not appear to be due to direct HIV infection, but could be mediated by another human retrovirus. HIV seropositive patients being treated with antiviral drugs develop a unique set of neuromuscular diseases that must be distinguished from the non-drug-related conditions.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Absence of humorally mediated damage within the central nervous system of AIDS patients.

The pathogenesis of CNS damage by human immunodeficiency virus infection is unclear. Because there is little detectable virus within the CNS, we evaluated the role of the humoral immune system in mediating CNS tissue destruction. The paucity and nonspecific nature of immunoglobulin deposition rules against significant involvement of humorally mediated injury in the pathogenesis of AIDS encephalopathy.

Acquired Immunodeficiency Syndrome↗